Efficacy and safety of rituximab versus cyclophosphamide in primary membranous nephropathy: A systematic review and meta-analysis

Efficacy and safety of rituximab versus cyclophosphamide in primary membranous nephropathy: A systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy and safety of rituximab versus cyclophosphamide in primary membranous nephropathy: A systematic review and meta-analysis Fangjiao Huang, Chenxin Fu, Maorong Liu, Peiyu Wu, Yanfang Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8173549/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Mar, 2026 Read the published version in BMC Nephrology → Version 1 posted 15 You are reading this latest preprint version Abstract Background PMN is a leading cause of nephrotic syndrome in adults. In some patients, PMN can be severe or continue to worsen even after 6 months of supportive treatment. Rituximab and cyclophosphamide are used to treat moderate-risk or high-risk PMNs, but the efficacy and safety of rituximab and cyclophosphamide in patients with PMN are still unclear. Methods We searched PubMed, Embase and the Cochrane Library for the time period through November 2025 to identify randomized controlled trials and cohort studies that evaluated rituximab compared with cyclophosphamide for the treatment of PMN. The primary outcomes were complete remission (CR), partial remission (PR), and total remission (TR = PR + CR). The secondary outcomes included the relapse rate, adverse events, and serious adverse events. The random effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results Thirteen studies (N = 1228) were eligible for final inclusion. Rituximab demonstrated similar efficacy to cyclophosphamide in inducing complete or partial remission at 18 months (RR, 0.98; 95% CI, 0.86–1.10; p = 0.70) and 24 months (RR, 1.01; 95% CI, 0.91–1.13; p = 0.82). Similarly, rates of complete remission were comparable between the two treatment groups at 18 months (RR, 0.83; 95% CI, 0.62–1.11; p = 0.21) and 24 months (RR, 0.93; 95% CI, 0.76–1.15; p = 0.51). There were significant differences in the incidence of AEs or SAEs between RTX and cyclophosphamide. The RRs were 0.77 (95% CI, 0.68–0.87; p < 0.0001) and 0.60 (95% CI, 0.42–0.86; p = 0.005), respectively. Conclusions The current limited evidence suggests that RTX treatment has comparable long-term efficacy to cyclophosphamide in PMN patients at moderate risk or high risk. Compared with cyclophosphamide treatment, rituximab treatment was associated with significantly fewer adverse events and serious adverse events. Further large-scale, longer follow-up, well-designed RCTs on head-to-head comparisons of the safety and efficacy of rituximab versus cyclophosphamide are urgently needed. Membranous nephropathy Primary membranous nephropathy In idiopathic membranous nephropathy Rituximab Cyclophosphamide Systematic review Meta-analysis Treatment Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Membranous nephropathy is an immune-mediated disease that results from the deposition of IgG and complement components onto the subepithelial layer of the glomerular capillary wall[ 1 ]. MNs occur in all regions and all ethnicities[ 2 ]. The annual incidence rates of MN are estimated at 10–12 per million in North America and 2–17 per million in Europe[ 3 – 7 ]. Primary membranous nephropathy (PMN) remains the most common cause of primary nephrotic syndrome in adults[ 8 ]. Previous studies reported that untreated PMNs had spontaneous complete remission rates ranging from 20% to 30% and 10-year renal survival rates ranging from 60–80% [ 2 , 8 – 11 ]. However, 30–40% of patients progress toward end-stage renal failure within 5–15 years[ 12 ]. Treatments for PMN are based on risk assessment of the progressive loss of kidney function. For patients with MN and at least one risk factor for disease progression, KDIGO (2021) recommends the use of rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months or CNI-based therapy for ≥6 months, with the choice of treatment depending on the risk estimate[ 13 ]. Although rituximab and cyclophosphamide are used to treat moderate-risk or high-risk PMNs, the efficacy and safety of rituximab and cyclophosphamide in patients with PMN are still unclear. We performed a head-to-head comparison to assess the long-term benefits and risks of the rituximab and cyclophosphamide protocols in patients with PMN. Methods The present systematic review and meta-analysis was conducted according to the PRISMA statement[ 14 ]. Search strategy We searched PubMed, Embase and the Cochrane Library for the time period through November 2025 to identify randomized controlled trials and cohort studies that evaluated rituximab compared with cyclophosphamide for the treatment of primary membranous nephropathy (PMN). The detailed search strategy is available in the Supplementary Materials. Inclusion and Exclusion Criteria Studies were considered acceptable for inclusion in the meta-analysis if they met the following criteria: (1) adult primary membranous nephropathy patients (age older than 18 years); (2) RCT or cohort studies; (3) rituximab treatment compared with cyclophosphamide as a control; and (4) 1 or more of the following clinical outcomes reported: complete or partial remission, relapse, side events, and serious side events. Trials were excluded if they (1) were abstracts, letters, or meeting proceedings; (2) had repeated data or did not report outcomes of interest; or (3) were placebo, supportive therapy, TAC, or CNIs. Data Extraction and Outcome Measures Two authors (F.-J.H. and C.-X.F.) independently extracted the following data: first author, year of publication, country of author, number of patients, study design/Jadad score or study design/NOS score, rituximab group (dosage, route, and duration), cyclophosphamide group (control group: dosage, route, and duration), site (single-center or multicenter), follow-up, primary outcomes, secondary outcomes, and definition of outcomes. The primary outcomes were complete remission (CR), partial remission (PR), and total remission (TR = PR + CR). The secondary outcomes included the relapse rate, adverse events, and serious adverse events. The extracted data were entered into a standardized Excel file. Quality Assessment Two authors (Yifeng Xie and Fangjiao Huang) independently assessed the risk of bias of the included studies via a validated Jadad 5-point scale[ 15 ] and the quality of cohort studies via the NOA score [ 17 ]. Any disagreements were resolved by discussion and consensus. The methodological quality of each RCT was evaluated via the Jadad scale[ 15 ]. The quality scale ranges from 0–5 points. Higher scores indicate better reporting. The studies are said to be of low quality if the Jadad score is ≤ 2 and high quality if the score is ≥ 3[ 16 ]. The Newcastle‒Ottawa Scale (NOS) was employed in this meta-analysis to assess the quality of cohort studies [ 17 ]. The scale consists of 3 items describing selection (0–4 points), comparability (0–2 points), and outcome (0–3 points) in the report of a cohort study. Scores of 7–9, 4–6, and < 4 were classified as having a low, moderate, or high risk of bias, respectively. Statistical analysis We estimated the relative risks (RRs) with 95% confidence interval (CI) for dichotomous outcomes. Heterogeneity of treatment effects across studies was reported using the I 2 statistic, and I 2 statistic > 50% indicated significant heterogeneity[ 18 ]. We pooled effect estimates via a random-effects model, taking clinical heterogeneity between studies into account. To examine the influence of various factors on the treatment effects of rituximab therapy for IMN patients, we performed post hoc subgroup analyses according to baseline urinary protein levels (proteinuria > 8 g/24 h versus proteinuria 80 RU/mL versus Anti-PLA2R 60 mL/min/1.73 m 2 versus eGFRs 100 for large sample studies versus n < 100 for small sample studies), and risk of bias (low quality versus high quality). Publication bias was assessed visually via funnel plots. The presence of publication bias was also evaluated by using the Egger’s test and Begg’s test[ 19 , 20 ]. We performed all the statistical analyses via RevMan 5.3 (Nordic Cochrane Centre). Results were considered as statistically significant for P < .05. Results Study identification and selection The PRISMA flowchart shows the process of study identification, screening, selection, and reasons for exclusion, as shown in Fig. 1 . The combined search identified a total of 477 records, 441 of which were excluded after removing duplicates and screening the titles and abstracts. A full-text assessment of 36 potentially eligible articles identified 13 studies. Finally, 3 RCTs[ 21 – 23 ] and 10 cohort studies[ 24 – 33 ] were included in the meta-analysis. Figure 1 PRISMA flow diagram for study selection Characteristics of the studies The main characteristics of the 3 RCTs and 10 cohort studies included in the meta-analysis are presented in Table 1 (see appendix ), and the outcome data of each included trial or study are described in Table 2 (see appendix ). The sample size ranged from 35 to 203, with a total of 1228 patients. Only four studies[ 26 , 27 , 30 , 33 ] had more than 100 participants. The rituximab dose is 0.375 g[ 29 ], 1 g[ 21 , 23 ], 1.5 g[ 25 – 31 , 33 ], 2 g[ 22 , 25 , 28 , 31 – 33 ], or 3 g[ 24 ]. Cyclophosphamide treatment is cyclical[ 21 – 23 , 29 ] or continuous[ 24 – 27 , 30 , 32 , 33 ]. Twelve studies defined complete remission as a reduction in proteinuria from baseline to a value ≤ 0.3 g/24 h plus stable kidney function, and 11 studies defined partial remission as a reduction in proteinuria > 50% from baseline and a value < 3.5 g/24 h plus stable renal function. One study[ 26 ] defined partial remission as a UPCR (urinary protein‒creatinine ratio) of 0.3‒3.0 g/g with at least a 50% reduction from baseline, a serum ALB concentration ≥ 30 g/l and stable renal function, whereas complete remission was defined as a UPCR < 0.3 g/g, a normal serum ALB concentration and stable renal function. Nine studies[ 21 – 27 , 29 , 30 ] reported relapse rate data. All studies reported adverse events, and six studies[ 21 – 23 , 27 , 30 , 33 ] reported serious adverse events. Table 1 Main characteristics of the studies included in the meta-analysis Author Year Country Sample Size(n) Study Design/Jadad or NOS Score Site Treatment Regimens Follow-up Outcomes Fernandez-Juarez[ 21 ] (STARMEN) 2020 Spain & Netherlands 43 RCT/3 M RTX + TAC intravenous rituximab (1 g) and tacrolimus dosage was reduced by 25% per month, with complete withdrawal after 3 months 24 months CR,PR,TR at 6/9/12/18/24 months Relapse, AEs, SAEs 43 CYC + CS methylprednisolone at months 1, 3, and 5 (1 g intravenously at days 1, 2, and 3, then 0.5 mg/kg/day orally from day 4 to day 30). At months 2, 4, and 6, patients received oral cyclophosphamide adjusted for age and renal function (1.0–2.0 mg/kg/day for 30 days) Scolari[ 22 ] (RI-CYCLO) 2021 Italy & Switzerland 37 RCT/3 M RTX received two courses of rituximab at a dose of 1 g on days 1 and 15 36 months CR,PR,TR at 6/9/12/18/24/36 months Relapse, AEs, SAEs 37 CYC + CS three consecutive cycles lasting for 2 months each (for a total of 6 months), where steroids were alternated with cyclophosphamide every other month; the cumulative dose of cyclophosphamide per patient was 180 mg/kg Suresh[ 23 ] 2025 India 34 RCT/3 S RTX RTX injection (500 mg) IV given on days 1 and 15. Each patient received premedication with injection methylprednisolone (125 mg), injection Pheniramine (45.5 mg), and tablet Paracetamol (500 mg) 12 months CR,PR,TR at 6/12 months Relapse, AEs, SAEs 34 CYC + CS Cyclical therapy with 1 g IV methylprednisolone daily (Days 1–3), then oral prednisolone (0.5 mg/kg/day) for 27 days (Days 4–30) on months 1, 3, and 5, alternating with oral cyclophosphamide (2.0 mg/kg/day) for 30 days on months 2, 4, and 6. Van den Brand[ 30 ] 2017 Italy & Switzerland 100 RC/7 M RTX four weekly doses of 375 mg/m2 RTX infused intravenously. 40 months CR,PR,TR at last follow-up, Relapse, AEs, SAEs 103 CYC + CS Oral cyclophosphamide (1.5 mg/kg daily) was administered for 6–12 months, and methylprednisolone pulses (1 g) were infused on days 1–3, 61–63, and 121–123 in combination with 0.5 mg/kg oral prednisone every other day for 5 months before tapering. Zhou[ 32 ] 2025 China 21 RC/5 S RTX 1000 mg on day 1 and day 15 12 months CR,PR,TR at 6/12 months, AEs 14 CYC + CS intravenous infusion (0.5 to 0.75 g/m2/month, maximum dose is 1 g/month, the cumulative dose of cyclophosphamide − 9 to 10 g Ramachandran[ 28 ] 2021 India 13 PC/6 S RTX 3 received weekly (×4) doses of 375 mg/m 2 , 4 received 2 doses of 1 g (×2) 15 days apart, and 6 re ceived CD-19 targeted dosing 26 months TR at 12/24 months, AEs 49 CYC + CS Cyclical Regimen Fenoglio[ 29 ] 2020 Italy 14 RC/6 M Low-Dose RTX one dose of RTX 375 mg/m 2 24 months CR, PR, TR at 24 months, Relapse, AEs 14 Standard RTX four weekly doses of rituximab 375 mg/m 2 14 CYC + CS Ponticelli Regimen: patients received methylprednisolone at months 1, 3, and 5 (1 g intravenously at days 1, 2, and 3, then 0.5 mg/kg/day orally from day 4 to day 30). At months 2, 4, and 6, patients received oral cyclophosphamide adjusted for age and renal function (1.0–2.0 mg/kg/day for 30 days) Medrano[ 31 ] 2014 Spain 53 RC/5 S RTX + TAC The first 23 patients treated with this regime received a total of four weekly doses of 375 mg/m 2 , and the last 30 patients received two 1-gram doses administered at an interval of 15 d. 12 months CR, PR, TR at 12 months 26 CYC + CS Ponticelli Regimen Nie[ 24 ] 2023 China 43 RC/5 S RTX one dose of rituximab 375 mg/m 2 , once weekly 6 months CR, PR, TR at 6 months, Relapse, AEs 43 CYC + CS 0.8–1.0 g intravenously, once monthly; If clinical complete or partial remission is achieved after 6 months of treatment, continue therapy for an additional 3 months (cumulative dose < 10 g) Lu[ 26 ] 2024 China 86 RC/6 S RTX a dose of 375 mg/m 2 intravenous rituximab once every two weeks until their peripheral blood B-cell count was 0/µl. 18 months CR, PR, TR at 6/12/18 months, Relapse, AEs 86 CYC + CS a single dose of 500–750 mg/m 2 by intravenous infusion monthly for the initial 6 months, and once every 2–3 months for the later period. All patients in CYC group received a combination of oral prednisone 0.6–0.8 mg/kg/d for 4–8 weeks, and gradually tapered. Wang[ 25 ] 2024 China 40 RC/6 M RTX received intravenous RTX at a dose of 375 mg/m 2 once a week for 4 consecutive weeks or 1 g every 2 weeks (a total of two times as a course of treatment). At least two doses of 375 mg/m 2 or one dose of 1 g RTX therapy was repeated 4–6 months later to maintain the effect of RTX. 24 months CR, PR, TR at 6/12/24 months, Relapse, AEs 27 CYC + CS the initial oral corticosteroid dose was 1 mg/kg/day (maximum dose was 60 mg), tapered after 8–12 weeks until withdrawal. Intermittent intravenous CYC was given monthly at 10–15 mg/kg for six months (generally 0.6–1.0 g/month), followed by an additional dose of the same approximately every 3 months for the next 6 months. The total dose of CTX generally reached 6–8 g and did not exceed 10 g. Hu[ 27 ] 2024 China 70 PC/6 S RTX a dose of 375 mg/m2 every week for a total of 4 doses. Methylprednisolone 40 mg i.v. will be given before the first dose. Chlorpheniramine (10 mg) and acetaminophen (500 mg) or other similar drugs will be given orally before each infusion to prevent allergic reactions 24 months CR, PR, TR at 6/12/18/24 months, Relapse, AEs, SAEs 71 CYC + CS oral prednisone starting at 0.8 mg/kg/24 h combined with intravenous CTX at a dose of 500 mg/m2 every 4 weeks until the total amount administered reached 6–8 g. Oral prednisone was maintained for 8 weeks and then tapered gradually to 5–10 mg every 4 weeks and may be stopped at 1 year Wu[ 33 ] 2025 China 58 RC/6 S RTX received either a weekly intravenous infusion of 375 mg/m² for four consecutive weeks, or 1 g every two weeks (for a total of two doses as one treatment course). To reduce infusion reactions, patients received 40 mg of intravenous methylprednisolone prior to each infusion. 18 months CR, PR, TR at 6/12/18 months, AEs, SAEs 55 CYC + CS the initial oral corticosteroid dose was 1 mg·kg⁻¹·d⁻¹ (maximum 60 mg), which was gradually tapered off and discontinued after 8–12 weeks. Cyclophosphamide was administered intermittently via intravenous infusion at a monthly dose of 10–15 mg/kg for 6 months (typically 0.6–1.0 g/month), followed by additional doses administered approximately every 3 months over the next 6 months. The total cumulative dose generally reached 6–8 g and did not exceed 10 g. RCT : randomized controlled trial, PC : prospective cohort, RC : retrospective cohort, M : multicenter, S : single-center, RTX : rituximab, TAC : tacrolimus, CYC : cyclophosphamide, CS : glucocorticoids. CR: complete remission , a reduction in proteinuria from baseline to a value ≤ 0.3 g/24 h plus stable kidney function (eGFR > 45 ml/min per 1.73 m2); PR: partial remission , a reduction in proteinuria > 50% from baseline; and a value 45 ml/min per 1.73 m2). TR: total remission, TR = CR + PR . Relapse : a reappearance of proteinuria > 3.5 g/24 h and at least a > 50% increase from the lowest value at 3 or more consecutive visits in patients with previous partial or complete remission. AEs: adverse events , any untoward medical occurrence; SAEs: serious adverse events , any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or resulted in persistent or significant disability/incapacity. Table 2 Outcome data of the 13 included studies Author Year Treatment Sample Size(n) CR TR(PR + TR) Relapse AEs SAE patients Follow-up 6 months 12 months 18 months 24 months 6 months 12 months 18 months 24 months Fernandez-Juarez[ 21 ] (STARMEN) 2020 RTX + TAC 43 0/43 4/43 7/43 11/43 19/43 22/43 23/43 25/43 3/25 39/43 6/43 24 months CYC + CS 43 6/43 14/43 19/43 26/43 32/43 34/43 36/43 36/43 1/36 42/43 8/43 Scolari[ 22 ] (RI-CYCLO) 2021 RTX 37 3/37 6/37 10/32 11/26 19/37 23/37 21/32 22/26 3/23 16/37 7/37 24 months CYC + CS 37 2/37 12/37 7/34 11/31 24/37 27/37 27/34 25/31 6/27 16/37 5/37 Suresh[ 23 ] 2025 RTX 34 3/30 3/27 NA NA 15/30 16/27 NA NA 5/20 13/34 6/34 12 months CYC + CS 34 4/29 4/23 NA NA 17/29 16/23 NA NA 4/21 22/34 8/34 Van den Brand[ 30 ] 2017 RTX 100 NA NA NA 26/100a NA NA NA 64/100a 3/64 41/100 9/100 40 months CYC + CS 103 NA NA NA 34/103a NA NA NA 89/103a 6/89 58/103 30/103 Zhou[ 32 ] 2025 RTX 21 4/21 5/21 NA NA 14/21 18/21 NA NA NA 4/21 NA 12 months CYC + CS 14 3/14 7/14 NA NA 11/14 13/14 NA NA NA 6/14 NA Ramachandran[ 28 ] 2021 RTX 13 NA NA NA NA NA 3/13 NA 5/13a NA 9/13 NA 24 months CYC + CS 49 NA NA NA NA NA 23/49 NA 24/49a NA 24/49 NA Fenoglio[ 29 ] 2020 Low-dose RTX 14 NA NA NA 12/14 NA NA NA 13/14 1/13 1/14 NA 24 months Standard RTX 14 NA NA NA 13/14 NA NA NA 13/14 1/13 3/14 NA CYC + CS 14 NA NA NA 12/14 NA NA NA 12/14 1/12 3/14 NA Medrano[ 31 ] 2014 RTX + TAC 53 NA 28/53 NA NA NA 49/53 NA NA NA NA NA 12 months CYC + CS 26 NA 6/26 NA NA NA 19/26 NA NA NA NA NA Nie[ 24 ] 2023 RTX 43 7/43 NA NA NA 26/43 NA NA NA 1/26 5/43 NA 6 months CYC 43 6/43 NA NA NA 23/43 NA NA NA 2/23 6/43 NA Lu[ 26 ] 2024 RTX 86 2/86 9/74 18/86 NA 31/86 51/74 59/86 NA 2/59 23/86 NA 12 months CYC + CS 86 3/86 11/66 18/86 NA 33/86 36/66 47/86 NA 2/47 25/86 NA Wang[ 25 ] 2024 RTX 40 2/40 9/40 NA 22/40 27/40 35/40 NA 37/40 2/37 15/40 NA 24 months CYC 27 2/27 7/27 NA 9/27 20/27 21/27 NA 20/27 7/20 23/27 NA Hu[ 27 ] 2024 RTX 70 3/70 10/70 15/59 22/61 43/70 43/70 42/59 46/61 2/46 20/70 2/70 24 months CYC + CS 71 8/71 24/71 21/64 22/58 44/71 54/71 44/64 40/58 2/40 29/71 6/71 Wu[ 33 ] 2025 RTX 58 6/58 8/31 7/19 NA 36/58 26/31 14/19 NA NA 21/58 11/58 18 months CYC + CS 55 8/55 14/48 13/38 NA 38/55 34/48 28/38 NA NA 26/55 11/55 a: data at the last follow-up; Table 1 Main characteristics of the studies included in the meta-analysis Table 2 Outcome data of the 13 included studies Quality of the included studies The details of the risk of bias are listed in Tables 3 and 4 (see the appendix ). Overall, three RCTs[ 21 – 23 ] and one cohort study[ 30 ] were categorized as having high methodological quality. Nine cohort studies[ 24 – 29 , 31 – 33 ] were categorized as having moderate methodological quality. Table 3 Assessing the risk of bias of the included studies via the validated Jadad 5-point scale RCTs Sample size (n) Study Design Randomization (0–2 points) Double-blind (0–2 points) Drop-outs and withdrawals (0–1 points) Jadad score STARMEN 2020[ 21 ] 86 multicenter, open-labeled, parallel 2 0 1 3 RI-CYCLO 2021[ 22 ] 74 multicenter, open-labeled, parallel 2 0 1 3 Suresh 2025[ 23 ] 68 single-center, open-labeled, parallel 2 0 1 3 Table 4 Assessment of the quality of the included cohort studies by the NOS. Studies Selection Comparability Outcome assessment NOS score 1) 2) 3) 4) 5) 6) 7) 8) Medrano 2014[ 31 ] a a a a a b b d 5 van den Brand 2017[ 30 ] a a a a a b a b 7 Fenoglio 2021[ 29 ] a a a a a b a d 6 Ramachandran 2021[ 28 ] a a a a a b a d 6 Zhou 2025[ 32 ] a a a a a b b d 5 Nie 2023[ 24 ] a a a a a b b d 5 Lu 2024[ 26 ] a a a a a b a d 6 Wang 2024[ 25 ] a a a a a b a d 6 Hu 2024[ 27 ] a a a a a b a d 6 Wu 2025[ 33 ] a a a a a b a d 6 Table 3 . Assessing the risk of bias of the included studies via the validated Jadad 5-point scale Table 4 . Assessment of the quality of the included cohort studies by the NOS Primary outcome: Composite remission (complete or partial remission) Compared with cyclophosphamide treatment, RTX treatment had similar efficacy in inducing complete or partial remission at 6 months, 12 months, 18 months and 24 months. The RRs were 0.89 (3 RCTs + 6 Cohorts; 95% CI, 0.79–1.00; p = 0.05), 0.96 (3 RCTs + 7 Cohorts; 95% CI, 0.88–1.06; p = 0.43), 0.98 (2 RCTs + 3 Cohorts; 95% CI, 0.86–1.10; p = 0.70), and 1.01 (2 RCTs + 3 Cohorts; 95% CI, 0.91–1.13; p = 0.82) (Fig. 2 ) (see appendix ). The I 2 values were 0%, 62%, 69%, and 53%, respectively, indicating no evidence of heterogeneity, moderate heterogeneity, moderate heterogeneity, and moderate heterogeneity, respectively (Fig. 2 ). We subsequently performed sensitivity analyses to explore potential sources of heterogeneity. In the RCT subgroup, the statistical I 2 values for composite remission at 6 months, 12 months, 18 months and 24 months were 0%, 0%, 27%, and 81%, respectively, whereas in the cohort subgroup, the statistical I 2 values were 0%, 57%, 0%, and 0%, respectively (Fig. 2 ). In the RCT subgroup with a statistic I 2 = 81%, only 2 trials were included, and more RCTs are needed to explore potential sources of heterogeneity. In the cohort subgroup with a statistic of I 2 = 57%, Exclusion of three studies[ 27 , 31 , 32 ] with baseline proteinuria > 8 g/24 h yielded similar results (RR, 1.13; 95% CI, 0.97–1.32; P = 0.11), with no evidence of heterogeneity ( I 2 = 8%). Cyclophosphamide induced more complete remission or partial remission at 6 months, 12 months, and 18 months than did rituximab, as revealed by the RCT subgroup. The RRs were 0.72 (3 RCTs; 95% CI, 0.57–0.91; p = 0.006), 0.76 (3 RCTs; 95% CI, 0.62–0.93; p = 0.008), and 0.72 (2 RCTs; 95% CI, 0.58–0.89; p = 0.003), respectively (Fig. 2 ). The I 2 statistics were 0%, 0%, and 27%, respectively, indicating no evidence of heterogeneity and low heterogeneity. Figure 2 Composite remission (CR + PR) rates in PMNs treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months Primary outcome: Complete remission Cyclophosphamide induced more complete remission at 12 months than did rituximab. The RR was 0.70 (3 RCTs + 6 Cohorts; 95% CI, 0.53–0.91; p = 0.008) (Fig. 3 ). (see appendix ). The I 2 statistic was 52%, indicating moderate heterogeneity (Fig. 3 ). Sensitivity analyses were performed to explore potential sources of heterogeneity. The I 2 statistic of the RCT subgroup was 0%, whereas that of the cohort subgroup was 60% (Fig. 3 ). In the cohort subgroup, Exclusion of three studies[ 27 , 31 , 32 ] in which the baseline proteinuria was > 8 g/24 h yielded similar results (RR, 0.62; 95% CI, 0.43–0.89; P = 0.01), with no evidence of heterogeneity ( I 2 = 0%). Exclusion of three studies[ 25 , 31 , 33 ] in which the baseline anti-PLA2R concentration > 80 RU/mL yielded similar results (RR, 0.48; 95% CI, 0.38–0.68; P < 0.0001), with no evidence of heterogeneity ( I 2 = 0%). Compared with cyclophosphamide treatment, RTX treatment had similar efficacy in inducing complete remission at 18 months and 24 months. The RRs were 0.83 (2 RCTs + 3 Cohorts; 95% CI, 0.62–1.11; p = 0.21) and 0.93 (2 RCTs + 3 Cohorts; 95% CI, 0.76–1.15; p = 0.51), respectively (Fig. 3 ). The I 2 values were 46% and 62%, respectively, indicating low heterogeneity and moderate heterogeneity, respectively (Fig. 3 ). We performed sensitivity analyses to explore potential sources of heterogeneity. The statistical I 2 values of the RCT subgroup were 84% and 82%, whereas those of the cohort subgroup were both 0% (Fig. 3 ). In the RCT subgroup, only 2 trials were included, and more RCTs are needed to explore potential sources of heterogeneity. Figure 3 Complete remission (CR) rates in PMN patients treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months Secondary outcome: Relapse Compared with cyclophosphamide treatment, RTX treatment had a similar relapse rate during follow-up. The RR was 0.71 (3 RCTs + 6 cohorts; 95% CI, 0.43–1.15; p = 0.17) (Fig. 4 ). (see appendix ). The I 2 statistic was 0%, indicating that there was no evidence of heterogeneity. Cyclophosphamide had a higher relapse rate during the follow-up than did rituximab, as revealed by the cohort subgroup. The RR was 0.50 (6 cohorts; 95% CI, 0.26–0.98; p = 0.04) (Fig. 4 ). The I 2 statistic was 0%, indicating that there was no evidence of heterogeneity. Figure 4 Relapse rates in PMN patients treated with rituximab versus cyclophosphamide Secondary outcome: adverse events and severe adverse events There were significant differences in the incidence of AEs or SAEs between the Rituximab group and the Cyclophosphamide group. The RRs were 0.77 (3 RCTS + 9 Cohorts; 95% CI, 0.68–0.87; p < 0.0001) and 0.60 (3RCTs + 3 Cohorts; 95% CI, 0.42–0.86; p = 0.005) (Fig. 5 ) (see appendix ). The I 2 values were 59% and 40%, indicating moderate heterogeneity and low heterogeneity, respectively. We performed sensitivity analyses to explore potential sources of heterogeneity. The statistical I 2 values of the RCT subgroup were 61% and 0%, whereas those of the cohort subgroup were 41% and 60%, respectively (Fig. 5 ). (1) In the RCT subgroup of AEs (Fig. 5 a), exclusion of one study[ 23 ] in which baseline proteinuria > 8 g/24 h yielded similar results (RR, 0.79; 95% CI, 0.69–0.90; P = 0.003), with no evidence of heterogeneity ( I 2 = 0%). (2) In the cohort subgroup of AEs (Fig. 5 a ), exclusion of two studies[ 27 , 32 ] that reported baseline proteinuria > 8 g/24 h yielded similar results (RR, 0.79; 95% CI, 0.69–0.90; P = 0.0004), yet heterogeneity was still present ( I 2 = 52%). Exclusion of four studies[ 24 , 25 , 28 , 33 ] in which the baseline anti-PLA2R concentration was > 80 RU/mL yielded similar results (RR, 0.78; 95% CI, 0.68–0.90; P = 0.0009), with no evidence of heterogeneity ( I 2 = 0%). Exclusion of two studies[ 28 , 30 ] in which the baseline eGFR was < 60 mL/min/1.73m 2 yielded similar results (RR, 0.75; 95% CI, 0.65–0.87; P = 0.0001), with no evidence of heterogeneity ( I 2 = 4%). (3) In the SAE cohort subgroup (Fig. 5 b), Exclusion of one study[ 27 ] in which baseline proteinuria > 8 g/24 h yielded similar results (RR, 0.63; 95% CI, 0.43–0.91; P = 0.01) however, heterogeneity was still present ( I 2 = 79%). Exclusion of one study[ 33 ] in which the baseline anti-PLA2R concentration was > 80 RU/mL yielded similar results (RR, 0.53; 95% CI, 0.35–0.80; P = 0.003), with no evidence of heterogeneity ( I 2 = 0%).Exclusion of one study[ 30 ] in which the baseline eGFR < 60 mL/min/1.73 m 2 changed the overall estimate (RR, 0.83; 95% CI, 0.54–1.27; P = 0.39), with low heterogeneity ( I 2 = 28%). Figure 5 Adverse events and serious adverse events in PMN patients treated with rituximab versus cyclophosphamide Publication Bias Publication bias was not assessed because of the limited number (< 10) of studies included in each analysis. Discussion This meta-analysis demonstrated that rituximab was effective as cyclophosphamide for promoting disease remission (CR + PR or CR) in patients with primary membranous nephropathy. In addition, the RTX group had significantly fewer adverse events and serious adverse events than did the cyclophosphamide group. Rituximab demonstrated comparable long-term efficacy to cyclophosphamide in patients with primary membranous nephropathy. Specifically, there were no significant differences between the two treatments in the rates of complete or partial remission at 18 and 24 months or in complete remission at 18 months and 24 months. However, a subgroup analysis of the three randomized controlled trials (RCTs) revealed that the cyclophosphamide group was associated with significantly higher rates of complete or partial remission at 6, 12, and 18 months, as well as higher rates of complete remission at 12 months. This short-term superior efficacy of cyclophosphamide may be partially attributed to the delayed onset of action of rituximab[ 1 , 2 ]. Immunosuppressive therapy is associated with side effects[ 13 ]. The anti-CD20 monoclonal antibody rituximab was well tolerated, with minimal adverse events[ 1 , 34 ]. Our meta-analysis revealed a significant difference in the incidence of adverse events and serious adverse events between RTX and cyclophosphamide in patients with primary membranous nephropathy. The superior safety profile and comparable efficacy of rituximab support its use as a first-line therapy for primary membranous nephropathy. However, moderate heterogeneity was observed among these studies, which was not surprising given the differences in the characteristics of the populations, dosage regimens, definitions of complete or partial remission, types of included studies (RCTs vs. cohorts), and study designs. Compared with recently published meta-analyses[ 35 – 39 ], however, this meta-analysis revealed several differences. First, cohort studies were included because MN is a disease with serious, objective, clinical outcomes such as morality or kidney failure[ 13 ]. This meta-analysis uses information from cohort studies as part of the evidence base. Second, this meta-analysis demonstrated that rituximab had a superior safety profile to cyclophosphamide in patients with primary membranous nephropathy. Third, this meta-analysis included recently published studies and thus had a larger sample size. This meta-analysis has several potential limitations that should be taken into account. First, the number of included RCTs was small, and the studies had small sample sizes and short follow-up periods. Second, the number of included trials was too small to evaluate publication bias in our meta-analysis, either visually via funnel plots or quantitatively via Egger’s test[ 19 ] and Begg’s test[ 20 ]. There may be potential publication bias in this meta-analysis. Third, comparisons between rituximab and cyclophosphamide are based on clinical responses (complete remission or partial remission), and clinical outcomes such as kidney failure, ESRD, and quality of life were not reported. Further studies should focus on the following points. There is an urgent need for large-scale, adequately powered, well-designed RCTs that compare the long-term efficacy and safety of rituximab treatment and cyclophosphamide treatment. Next, such RCTs should have longer follow-up periods (10–20 years) to assess the risk of SAEs, such as malignancies that occur as late as 10–20 years after treatment[ 40 ], and to assess whether rituximab treatment can reduce the risk of kidney failure or prevent ESRD. Third, such RCTs should report long-term efficacy and safety outcomes, such as the rate of kidney failure, rate of ESRD, quality of life, incidence of SAEs such as malignancies, and death. Finally, such RCTs should standardize the treatment protocol (i.e., further consistency regarding dosage, route, follow-up, duration of administration, and long-term outcomes). Conclusions The current limited evidence suggests that rituximab treatment has comparable long-term efficacy to cyclophosphamide in patients with primary membranous nephropathy. Compared with cyclophosphamide treatment, rituximab treatment was associated with significantly fewer adverse events and serious adverse events. The results should be interpreted with caution because of the heterogeneity among study designs. Further large-scale, longer follow-up, well-designed RCTs on head-to-head comparisons of the safety and efficacy of RTX vs. cyclophosphamide are urgently needed. Abbreviations PMN primary membranous nephropathy RTX rituximab TAC tacrolimus CYC cyclophosphamide CS glucocorticoids RCT randomized controlled trial PC prospective cohort RC retrospective cohort M multicenter S single-center CI confidence interval CR complete remission PR partial remission TR total remission, TR = CR + PR AEs adverse events SAEs serious adverse events KDIGO Kidney Disease: Improving Global Outcomes PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses RR relative risk ALB albumin Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Guangxi University of Chinese Medicine Joint Fund Project (2024LZ006) and the Self-funded Research Project of the Guangxi Autonomous Region Administration of Traditional Chinese Medicine (GXZYB20220409). Author Contribution Yifeng Xie contributed to concept and design of the study, acquisition, analysis and interpretation of data, drafting and revising the article, and final approval of the manuscript. Fangjiao Huang, Chenxin Fu, Maorong Liu and Peiyu Wu contributed to acquisition, analysis and interpretation of data, drafting the article, and final approval of the manuscript. Yanfang Li, Zhuguang Lu and Yanlei Li contributed to concept and design of the study, analysis and interpretation of data, revising the article. Data Availability All the data generated or analyzed during this study are included in this published article and its supplementary information files. References Ruggenenti P, Fervenza FC, Remuzzi G. 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Supplementary Files DatasetsforIMN1119.xlsx Cite Share Download PDF Status: Published Journal Publication published 16 Mar, 2026 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 08 Jan, 2026 Reviews received at journal 07 Jan, 2026 Reviews received at journal 22 Dec, 2025 Reviews received at journal 22 Dec, 2025 Reviewers agreed at journal 15 Dec, 2025 Reviews received at journal 15 Dec, 2025 Reviewers agreed at journal 12 Dec, 2025 Reviewers agreed at journal 12 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviewers agreed at journal 09 Dec, 2025 Reviewers invited by journal 09 Dec, 2025 Editor assigned by journal 09 Dec, 2025 Editor invited by journal 01 Dec, 2025 Submission checks completed at journal 01 Dec, 2025 First submitted to journal 30 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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16:50:13","extension":"png","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":141272,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/0c71f3afa5e5be03fffdfd73.png"},{"id":98246036,"identity":"ee7530e5-0db5-4c81-b660-fc795c6e175f","added_by":"auto","created_at":"2025-12-15 16:18:45","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65416,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/a39098613676eb772e3911bd.png"},{"id":98245870,"identity":"70da2aa4-f862-49d8-93d9-de123ebd25e9","added_by":"auto","created_at":"2025-12-15 16:18:32","extension":"png","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":108994,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/69809b2a1f70069ffc2be131.png"},{"id":98245793,"identity":"9c5b8e3a-7a9a-402b-a542-565973049088","added_by":"auto","created_at":"2025-12-15 16:18:24","extension":"xml","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":170670,"visible":true,"origin":"","legend":"","description":"","filename":"53cbc70fa2ba4b86adad952f0df897f21structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/1be92abe6fd7545c86143d5f.xml"},{"id":98245993,"identity":"b16d34fa-74a0-49ba-90bd-ef9bb6b79b0e","added_by":"auto","created_at":"2025-12-15 16:18:44","extension":"html","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":178916,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/03703af8b006517915aeefa9.html"},{"id":98245935,"identity":"e9f643fc-7939-4476-a76a-aaff4b05f87c","added_by":"auto","created_at":"2025-12-15 16:18:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94816,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram for study selection\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/6211283339bdcc82f974af26.png"},{"id":98245944,"identity":"f88514b1-6b32-4783-b730-9815d413eec3","added_by":"auto","created_at":"2025-12-15 16:18:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2733501,"visible":true,"origin":"","legend":"\u003cp\u003eComposite remission (CR+PR) rates in PMNs treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/dd34b55e523ee1e1484e845f.png"},{"id":98246116,"identity":"dfe11eef-5bf2-4152-a9a7-d555f7db7ae7","added_by":"auto","created_at":"2025-12-15 16:18:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2732096,"visible":true,"origin":"","legend":"\u003cp\u003eComplete remission (CR) rates in PMN patients treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/425789d79688e191918fa184.png"},{"id":98246078,"identity":"4d4c62d1-4a34-4d6c-b049-fd021ab623de","added_by":"auto","created_at":"2025-12-15 16:18:48","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":304678,"visible":true,"origin":"","legend":"\u003cp\u003eRelapse rates in PMN patients treated with rituximab versus cyclophosphamide\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/9dd4f0a418b5d2f1bde300f0.png"},{"id":98246082,"identity":"8c2410cc-d2db-4eee-aa26-cf6857b82c56","added_by":"auto","created_at":"2025-12-15 16:18:48","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":647769,"visible":true,"origin":"","legend":"\u003cp\u003eAdverse events and serious adverse events in PMN patients treated with rituximab versus cyclophosphamide\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/11df8357d0fe1c974503d65f.png"},{"id":105223274,"identity":"a065cd3b-8063-4b68-89d6-e4044f35e17b","added_by":"auto","created_at":"2026-03-23 16:01:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7978691,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/85da24c8-2f1b-42e2-8228-a7d8a38a1eb2.pdf"},{"id":98245826,"identity":"df43640c-e794-4ef3-b0bf-4e15065d4321","added_by":"auto","created_at":"2025-12-15 16:18:27","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":25297,"visible":true,"origin":"","legend":"","description":"","filename":"DatasetsforIMN1119.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8173549/v1/9944cd21edd70a74fc0ac20b.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of rituximab versus cyclophosphamide in primary membranous nephropathy: A systematic review and meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMembranous nephropathy is an immune-mediated disease that results from the deposition of IgG and complement components onto the subepithelial layer of the glomerular capillary wall[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. MNs occur in all regions and all ethnicities[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The annual incidence rates of MN are estimated at 10\u0026ndash;12 per million in North America and 2\u0026ndash;17 per million in Europe[\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Primary membranous nephropathy (PMN) remains the most common cause of primary nephrotic syndrome in adults[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Previous studies reported that untreated PMNs had spontaneous complete remission rates ranging from 20% to 30% and 10-year renal survival rates ranging from 60\u0026ndash;80% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, 30\u0026ndash;40% of patients progress toward end-stage renal failure within 5\u0026ndash;15 years[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTreatments for PMN are based on risk assessment of the progressive loss of kidney function. For patients with MN and at least one risk factor for disease progression, KDIGO (2021) recommends the use of rituximab or cyclophosphamide and alternate month glucocorticoids for 6 months or CNI-based therapy for \u0026ge;6 months, with the choice of treatment depending on the risk estimate[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although rituximab and cyclophosphamide are used to treat moderate-risk or high-risk PMNs, the efficacy and safety of rituximab and cyclophosphamide in patients with PMN are still unclear.\u003c/p\u003e\u003cp\u003eWe performed a head-to-head comparison to assess the long-term benefits and risks of the rituximab and cyclophosphamide protocols in patients with PMN.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe present systematic review and meta-analysis was conducted according to the PRISMA statement[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSearch strategy\u003c/h2\u003e\u003cp\u003eWe searched PubMed, Embase and the Cochrane Library for the time period through November 2025 to identify randomized controlled trials and cohort studies that evaluated rituximab compared with cyclophosphamide for the treatment of primary membranous nephropathy (PMN). The detailed search strategy is available in the Supplementary Materials.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003eStudies were considered acceptable for inclusion in the meta-analysis if they met the following criteria: (1) adult primary membranous nephropathy patients (age older than 18 years); (2) RCT or cohort studies; (3) rituximab treatment compared with cyclophosphamide as a control; and (4) 1 or more of the following clinical outcomes reported: complete or partial remission, relapse, side events, and serious side events.\u003c/p\u003e\u003cp\u003eTrials were excluded if they (1) were abstracts, letters, or meeting proceedings; (2) had repeated data or did not report outcomes of interest; or (3) were placebo, supportive therapy, TAC, or CNIs.\u003c/p\u003e\n\u003ch3\u003eData Extraction and Outcome Measures\u003c/h3\u003e\n\u003cp\u003eTwo authors (F.-J.H. and C.-X.F.) independently extracted the following data: first author, year of publication, country of author, number of patients, study design/Jadad score or study design/NOS score, rituximab group (dosage, route, and duration), cyclophosphamide group (control group: dosage, route, and duration), site (single-center or multicenter), follow-up, primary outcomes, secondary outcomes, and definition of outcomes. The primary outcomes were complete remission (CR), partial remission (PR), and total remission (TR\u0026thinsp;=\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;CR). The secondary outcomes included the relapse rate, adverse events, and serious adverse events. The extracted data were entered into a standardized Excel file.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eTwo authors (Yifeng Xie and Fangjiao Huang) independently assessed the risk of bias of the included studies via a validated Jadad 5-point scale[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and the quality of cohort studies via the NOA score [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Any disagreements were resolved by discussion and consensus.\u003c/p\u003e\u003cp\u003eThe methodological quality of each RCT was evaluated via the Jadad scale[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The quality scale ranges from 0\u0026ndash;5 points. Higher scores indicate better reporting. The studies are said to be of low quality if the Jadad score is \u0026le;\u0026thinsp;2 and high quality if the score is \u0026ge;\u0026thinsp;3[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe Newcastle‒Ottawa Scale (NOS) was employed in this meta-analysis to assess the quality of cohort studies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The scale consists of 3 items describing selection (0\u0026ndash;4 points), comparability (0\u0026ndash;2 points), and outcome (0\u0026ndash;3 points) in the report of a cohort study. Scores of 7\u0026ndash;9, 4\u0026ndash;6, and \u0026lt;\u0026thinsp;4 were classified as having a low, moderate, or high risk of bias, respectively.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eWe estimated the relative risks (RRs) with 95% confidence interval (CI) for dichotomous outcomes. Heterogeneity of treatment effects across studies was reported using the I\u003csup\u003e2\u003c/sup\u003e statistic, and \u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e statistic\u0026thinsp;\u0026gt;\u0026thinsp;50% indicated significant heterogeneity[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. We pooled effect estimates via a random-effects model, taking clinical heterogeneity between studies into account. To examine the influence of various factors on the treatment effects of rituximab therapy for IMN patients, we performed post hoc subgroup analyses according to baseline urinary protein levels (proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/24 h versus proteinuria\u0026thinsp;\u0026lt;\u0026thinsp;8 g/24 h), anti-PLA2R levels (Anti-PLA2R\u0026thinsp;\u0026gt;\u0026thinsp;80 RU/mL versus Anti-PLA2R\u0026thinsp;\u0026lt;\u0026thinsp;80 RU/mL), eGFRs\u0026thinsp;\u0026gt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e versus eGFRs\u0026thinsp;\u0026lt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e), study type (RCT versus cohort), sample size (\u003cem\u003en\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;100 for large sample studies versus \u003cem\u003en\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;100 for small sample studies), and risk of bias (low quality versus high quality). Publication bias was assessed visually via funnel plots. The presence of publication bias was also evaluated by using the Egger\u0026rsquo;s test and Begg\u0026rsquo;s test[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. We performed all the statistical analyses via RevMan 5.3 (Nordic Cochrane Centre). Results were considered as statistically significant for \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eStudy identification and selection\u003c/h2\u003e\u003cp\u003eThe PRISMA flowchart shows the process of study identification, screening, selection, and reasons for exclusion, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The combined search identified a total of 477 records, 441 of which were excluded after removing duplicates and screening the titles and abstracts. A full-text assessment of 36 potentially eligible articles identified 13 studies. Finally, 3 RCTs[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and 10 cohort studies[\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] were included in the meta-analysis.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e PRISMA flow diagram for study selection\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCharacteristics of the studies\u003c/h3\u003e\n\u003cp\u003eThe main characteristics of the 3 RCTs and 10 cohort studies included in the meta-analysis are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e), and the outcome data of each included trial or study are described in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). The sample size ranged from 35 to 203, with a total of 1228 patients. Only four studies[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] had more than 100 participants. The rituximab dose is 0.375 g[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], 1 g[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], 1.5 g[\u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29 CR30\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], 2 g[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], or 3 g[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Cyclophosphamide treatment is cyclical[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] or continuous[\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Twelve studies defined complete remission as a reduction in proteinuria from baseline to a value\u0026thinsp;\u0026le;\u0026thinsp;0.3 g/24 h plus stable kidney function, and 11 studies defined partial remission as a reduction in proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;50% from baseline and a value\u0026thinsp;\u0026lt;\u0026thinsp;3.5 g/24 h plus stable renal function. One study[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] defined partial remission as a UPCR (urinary protein‒creatinine ratio) of 0.3‒3.0 g/g with at least a 50% reduction from baseline, a serum ALB concentration\u0026thinsp;\u0026ge;\u0026thinsp;30 g/l and stable renal function, whereas complete remission was defined as a UPCR\u0026thinsp;\u0026lt;\u0026thinsp;0.3 g/g, a normal serum ALB concentration and stable renal function. Nine studies[\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25 CR26\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] reported relapse rate data. All studies reported adverse events, and six studies[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] reported serious adverse events.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMain characteristics of the studies included in the meta-analysis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCountry\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSample Size(n)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStudy Design/Jadad or NOS Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRegimens\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eFollow-up\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c11\" namest=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFernandez-Juarez[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e(STARMEN)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSpain \u0026amp; \u003c/p\u003e\u003cp\u003eNetherlands\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRCT/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u0026thinsp;+\u0026thinsp;TAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eintravenous rituximab (1 g) and tacrolimus dosage was reduced by 25% per month, with complete withdrawal after 3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR,PR,TR at 6/9/12/18/24 months\u003c/p\u003e\u003cp\u003eRelapse, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003emethylprednisolone at months 1, 3, and 5 (1 g intravenously at days 1, 2, and 3, then 0.5 mg/kg/day orally from day 4 to day 30). At months 2, 4, and 6, patients received oral cyclophosphamide adjusted for age and renal function (1.0\u0026ndash;2.0 mg/kg/day for 30 days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eScolari[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e(RI-CYCLO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eItaly \u0026amp; \u003c/p\u003e\u003cp\u003eSwitzerland\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRCT/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ereceived two courses of rituximab at a dose of 1 g on days 1 and 15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e36 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR,PR,TR at 6/9/12/18/24/36 months\u003c/p\u003e\u003cp\u003eRelapse, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ethree consecutive cycles lasting for 2 months each (for a total of 6 months), where steroids were alternated with cyclophosphamide every other month; the cumulative dose of cyclophosphamide per patient was 180 mg/kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSuresh[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eIndia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRCT/3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eRTX injection (500 mg) IV given on days 1 and 15. Each patient received premedication with injection methylprednisolone (125 mg), injection Pheniramine (45.5 mg), and tablet Paracetamol (500 mg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR,PR,TR at 6/12 months\u003c/p\u003e\u003cp\u003eRelapse, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCyclical therapy with 1 g IV methylprednisolone daily (Days 1\u0026ndash;3), then oral prednisolone (0.5 mg/kg/day) for 27 days (Days 4\u0026ndash;30) on months 1, 3, and 5, alternating with oral cyclophosphamide (2.0 mg/kg/day) for 30 days on months 2, 4, and 6.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVan den Brand[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eItaly \u0026amp; \u003c/p\u003e\u003cp\u003eSwitzerland\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003efour weekly doses of 375 mg/m2 RTX infused\u003c/p\u003e\u003cp\u003eintravenously.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e40 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR,PR,TR at last follow-up,\u003c/p\u003e\u003cp\u003eRelapse, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eOral cyclophosphamide (1.5 mg/kg daily) was administered for 6\u0026ndash;12 months, and methylprednisolone pulses (1 g) were infused on days 1\u0026ndash;3, 61\u0026ndash;63, and 121\u0026ndash;123 in combination with 0.5 mg/kg oral prednisone every other day for 5 months before tapering.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eZhou[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1000 mg on day 1 and day 15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR,PR,TR at 6/12 months,\u003c/p\u003e\u003cp\u003eAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eintravenous infusion (0.5 to 0.75 g/m2/month, maximum dose is 1 g/month, the cumulative dose of cyclophosphamide \u0026minus;\u0026thinsp;9 to 10 g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRamachandran[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eIndia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3 received weekly (\u0026times;4) doses of 375 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e, 4 received 2 doses of 1 g (\u0026times;2) 15 days apart, and 6 re ceived CD-19 targeted dosing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e26 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTR at 12/24 months, AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCyclical Regimen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eFenoglio[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eItaly\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eRC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLow-Dose RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eone dose of RTX 375 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eCR, PR, TR at 24 months, Relapse, AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eStandard RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003efour weekly doses of rituximab 375 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePonticelli Regimen: patients received methylprednisolone at months 1, 3, and 5 (1 g intravenously at days 1, 2, and 3, then 0.5 mg/kg/day orally from day 4 to day 30). At months 2, 4, and 6, patients received oral cyclophosphamide adjusted for age and renal function (1.0\u0026ndash;2.0 mg/kg/day for 30 days)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMedrano[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSpain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u0026thinsp;+\u0026thinsp;TAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eThe first 23 patients treated with this regime received a total of four weekly doses of 375 mg/m\u003csup\u003e2\u003c/sup\u003e, and the last 30 patients received two 1-gram doses administered at an interval of 15 d.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePonticelli Regimen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNie[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eone dose of rituximab 375 mg/m\u003csup\u003e2\u003c/sup\u003e, once weekly\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 6 months, Relapse, AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.8\u0026ndash;1.0 g intravenously, once monthly; If clinical complete or partial remission is achieved after 6 months of treatment, continue therapy for an additional 3 months (cumulative dose\u0026thinsp;\u0026lt;\u0026thinsp;10 g)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLu[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea dose of 375 mg/m\u003csup\u003e2\u003c/sup\u003e intravenous rituximab once every \u003c/p\u003e\u003cp\u003etwo weeks until their peripheral blood B-cell count was \u003c/p\u003e\u003cp\u003e0/\u0026micro;l.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 6/12/18 months, Relapse, AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea single dose of 500\u0026ndash;750 mg/m\u003csup\u003e2\u003c/sup\u003e by intravenous infusion monthly for the initial 6 months, and once every 2\u0026ndash;3 months for the later period. All patients in CYC group received a combination of oral prednisone 0.6\u0026ndash;0.8 mg/kg/d for 4\u0026ndash;8 weeks, and gradually tapered.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eWang[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ereceived intravenous RTX at a dose of 375 mg/m\u003csup\u003e2\u003c/sup\u003e once a week for 4 consecutive weeks or 1 g every 2 weeks (a total of two times as a course of treatment). At least two doses of 375 mg/m\u003csup\u003e2\u003c/sup\u003e or one dose of 1 g RTX therapy was repeated 4\u0026ndash;6 months later to maintain the effect of RTX.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 6/12/24 months, Relapse, AEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ethe initial oral corticosteroid dose was 1 mg/kg/day (maximum dose was 60 mg), tapered after 8\u0026ndash;12 weeks until withdrawal. Intermittent intravenous CYC was given monthly at 10\u0026ndash;15 mg/kg for six months (generally 0.6\u0026ndash;1.0 g/month), followed by an additional dose of the same approximately every 3 months for the next 6 months. The total dose of CTX generally reached 6\u0026ndash;8 g and did not exceed 10 g.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHu[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea dose of 375 mg/m2 every week for a total of 4 doses. Methylprednisolone 40 mg i.v. will be given before the first dose. Chlorpheniramine (10 mg) and acetaminophen (500 mg) or other similar drugs will be given orally before each infusion to prevent allergic reactions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 6/12/18/24 months, Relapse, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eoral prednisone starting at 0.8 mg/kg/24 h combined with intravenous CTX at a dose of 500 mg/m2 every 4 weeks until the total amount administered reached 6\u0026ndash;8 g. Oral prednisone was maintained for 8 weeks and then tapered gradually to 5\u0026ndash;10 mg every 4 weeks and may be stopped at 1 year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eWu[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRC/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ereceived either a weekly intravenous infusion of 375 mg/m\u0026sup2; for four consecutive weeks, or 1 g every two weeks (for a total of two doses as one treatment course). To reduce infusion reactions, patients received 40 mg of intravenous methylprednisolone prior to each infusion.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCR, PR, TR at 6/12/18 months, AEs, SAEs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ethe initial oral corticosteroid dose was 1 mg\u0026middot;kg⁻\u0026sup1;\u0026middot;d⁻\u0026sup1; (maximum 60 mg), which was gradually tapered off and discontinued after 8\u0026ndash;12 weeks. Cyclophosphamide was administered intermittently via intravenous infusion at a monthly dose of 10\u0026ndash;15 mg/kg for 6 months (typically 0.6\u0026ndash;1.0 g/month), followed by additional doses administered approximately every 3 months over the next 6 months. The total cumulative dose generally reached 6\u0026ndash;8 g and did not exceed 10 g.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003cb\u003eRCT\u003c/b\u003e: randomized controlled trial, \u003cb\u003ePC\u003c/b\u003e: prospective cohort, \u003cb\u003eRC\u003c/b\u003e: retrospective cohort, \u003cb\u003eM\u003c/b\u003e: multicenter, \u003cb\u003eS\u003c/b\u003e: single-center, \u003cb\u003eRTX\u003c/b\u003e: rituximab, \u003cb\u003eTAC\u003c/b\u003e: tacrolimus, \u003cb\u003eCYC\u003c/b\u003e: cyclophosphamide, \u003cb\u003eCS\u003c/b\u003e: glucocorticoids. \u003cb\u003eCR: complete remission\u003c/b\u003e, a reduction in proteinuria from baseline to a value\u0026thinsp;\u0026le;\u0026thinsp;0.3 g/24 h plus stable kidney function (eGFR\u0026thinsp;\u0026gt;\u0026thinsp;45 ml/min per 1.73 m2); \u003cb\u003ePR: partial remission\u003c/b\u003e, a reduction in proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;50% from baseline; and a value\u0026thinsp;\u0026lt;\u0026thinsp;3.5 g/24 h plus stable renal function (eGFR\u0026thinsp;\u0026gt;\u0026thinsp;45 ml/min per 1.73 m2). \u003cb\u003eTR: total remission, TR\u0026thinsp;=\u0026thinsp;CR\u0026thinsp;+\u0026thinsp;PR\u003c/b\u003e. \u003cb\u003eRelapse\u003c/b\u003e: a reappearance of proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;3.5 g/24 h and at least a\u0026thinsp;\u0026gt;\u0026thinsp;50% increase from the lowest value at 3 or more consecutive visits in patients with previous partial or complete remission. \u003cb\u003eAEs: adverse events\u003c/b\u003e, any untoward medical \u003cb\u003eoccurrence; SAEs: serious adverse events\u003c/b\u003e, any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or resulted in persistent or significant disability/incapacity.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcome data of the 13 included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"16\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYear\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTreatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSample \u003c/p\u003e\u003cp\u003eSize(n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c8\" namest=\"c5\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c12\" namest=\"c9\"\u003e\u003cp\u003eTR(PR\u0026thinsp;+\u0026thinsp;TR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eRelapse\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003eAEs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\"\u003e\u003cp\u003eSAE patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c16\"\u003e\u003cp\u003eFollow-up\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eFernandez-Juarez[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e(STARMEN)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u0026thinsp;+\u0026thinsp;TAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e19/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e22/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e23/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e25/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3/25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e39/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e6/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e32/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e34/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e36/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e36/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1/36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e42/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e8/43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eScolari[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e(RI-CYCLO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10/32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11/26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e19/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e23/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e21/32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e22/26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e16/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e7/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7/34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e24/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e27/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e27/34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e25/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e6/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e16/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e5/37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSuresh[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3/30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e15/30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e16/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e5/20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e13/34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e6/34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4/29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e17/29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e16/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e4/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e22/34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e8/34\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVan den Brand[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26/100a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e64/100a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3/64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e41/100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e9/100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e40 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e34/103a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e89/103a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e6/89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e58/103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e30/103\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eZhou[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e14/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e18/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e4/21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e13/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e6/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRamachandran[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e3/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e5/13a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e9/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e23/49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e24/49a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e24/49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eFenoglio[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow-dose RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e13/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStandard RTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e13/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e13/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e3/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e12/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e3/14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMedrano[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u0026thinsp;+\u0026thinsp;TAC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28/53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e49/53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6/26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e19/26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eNie[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e26/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e1/26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e5/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e23/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e6/43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLu[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9/74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e31/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e51/74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e59/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e23/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11/66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e33/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e36/66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e47/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e25/86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eWang[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e27/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e35/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e37/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e15/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e20/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e21/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e20/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e7/20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e23/27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHu[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15/59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22/61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e43/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e43/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e42/59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e46/61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e20/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e2/70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e24 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8/71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e24/71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e21/64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e44/71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e54/71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e44/64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e40/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e2/40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e29/71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e6/71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eWu[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e7/19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e36/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e26/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e14/19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e21/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e11/58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c16\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e18 months\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCYC\u0026thinsp;+\u0026thinsp;CS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8/55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14/48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13/38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e38/55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e34/48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e28/38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e26/55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e11/55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"16\"\u003ea: data at the last follow-up;\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e Main characteristics of the studies included in the meta-analysis\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e Outcome data of the 13 included studies\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eQuality of the included studies\u003c/h2\u003e\u003cp\u003eThe details of the risk of bias are listed in Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e (see the \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). Overall, three RCTs[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and one cohort study[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] were categorized as having high methodological quality. Nine cohort studies[\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] were categorized as having moderate methodological quality.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssessing the risk of bias of the included studies via the validated Jadad 5-point scale\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRCTs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSample \u003c/p\u003e\u003cp\u003esize (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudy Design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRandomization \u003c/p\u003e\u003cp\u003e(0\u0026ndash;2 points)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDouble-blind\u003c/p\u003e\u003cp\u003e (0\u0026ndash;2 points)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDrop-outs and withdrawals \u003c/p\u003e\u003cp\u003e(0\u0026ndash;1 points)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eJadad score\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSTARMEN 2020[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emulticenter, open-labeled, parallel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRI-CYCLO 2021[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emulticenter, open-labeled, parallel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuresh 2025[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003esingle-center, open-labeled, parallel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssessment of the quality of the included cohort studies by the NOS.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eSelection\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eComparability\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e\u003cp\u003eOutcome assessment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNOS score\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedrano 2014[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003evan den Brand 2017[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFenoglio 2021[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRamachandran 2021[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eZhou 2025[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNie 2023[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLu 2024[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWang 2024[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHu 2024[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWu 2025[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Assessing the risk of bias of the included studies via the validated Jadad 5-point scale\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Assessment of the quality of the included cohort studies by the NOS\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePrimary outcome: Composite remission (complete or partial remission)\u003c/h2\u003e\u003cp\u003eCompared with cyclophosphamide treatment, RTX treatment had similar efficacy in inducing complete or partial remission at 6 months, 12 months, 18 months and 24 months. The RRs were 0.89 (3 RCTs\u0026thinsp;+\u0026thinsp;6 Cohorts; 95% CI, 0.79\u0026ndash;1.00; p\u0026thinsp;=\u0026thinsp;0.05), 0.96 (3 RCTs\u0026thinsp;+\u0026thinsp;7 Cohorts; 95% CI, 0.88\u0026ndash;1.06; p\u0026thinsp;=\u0026thinsp;0.43), 0.98 (2 RCTs\u0026thinsp;+\u0026thinsp;3 Cohorts; 95% CI, 0.86\u0026ndash;1.10; p\u0026thinsp;=\u0026thinsp;0.70), and 1.01 (2 RCTs\u0026thinsp;+\u0026thinsp;3 Cohorts; 95% CI, 0.91\u0026ndash;1.13; p\u0026thinsp;=\u0026thinsp;0.82) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e values were 0%, 62%, 69%, and 53%, respectively, indicating no evidence of heterogeneity, moderate heterogeneity, moderate heterogeneity, and moderate heterogeneity, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWe subsequently performed sensitivity analyses to explore potential sources of heterogeneity. In the RCT subgroup, the statistical I\u003csup\u003e2\u003c/sup\u003e values for composite remission at 6 months, 12 months, 18 months and 24 months were 0%, 0%, 27%, and 81%, respectively, whereas in the cohort subgroup, the statistical I\u003csup\u003e2\u003c/sup\u003e values were 0%, 57%, 0%, and 0%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In the RCT subgroup with a statistic I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;81%, only 2 trials were included, and more RCTs are needed to explore potential sources of heterogeneity. In the cohort subgroup with a statistic of I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;57%, Exclusion of three studies[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] with baseline proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/24 h yielded similar results (RR, 1.13; 95% CI, 0.97\u0026ndash;1.32; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.11), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 8%).\u003c/p\u003e\u003cp\u003eCyclophosphamide induced more complete remission or partial remission at 6 months, 12 months, and 18 months than did rituximab, as revealed by the RCT subgroup. The RRs were 0.72 (3 RCTs; 95% CI, 0.57\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.006), 0.76 (3 RCTs; 95% CI, 0.62\u0026ndash;0.93; p\u0026thinsp;=\u0026thinsp;0.008), and 0.72 (2 RCTs; 95% CI, 0.58\u0026ndash;0.89; p\u0026thinsp;=\u0026thinsp;0.003), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e statistics were 0%, 0%, and 27%, respectively, indicating no evidence of heterogeneity and low heterogeneity.\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e Composite remission (CR\u0026thinsp;+\u0026thinsp;PR) rates in PMNs treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003ePrimary outcome: Complete remission\u003c/h2\u003e\u003cp\u003eCyclophosphamide induced more complete remission at 12 months than did rituximab. The RR was 0.70 (3 RCTs\u0026thinsp;+\u0026thinsp;6 Cohorts; 95% CI, 0.53\u0026ndash;0.91; p\u0026thinsp;=\u0026thinsp;0.008) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e statistic was 52%, indicating moderate heterogeneity (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Sensitivity analyses were performed to explore potential sources of heterogeneity. The I\u003csup\u003e2\u003c/sup\u003e statistic of the RCT subgroup was 0%, whereas that of the cohort subgroup was 60% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the cohort subgroup, Exclusion of three studies[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] in which the baseline proteinuria was \u0026gt;\u0026thinsp;8 g/24 h yielded similar results (RR, 0.62; 95% CI, 0.43\u0026ndash;0.89; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 0%). Exclusion of three studies[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] in which the baseline anti-PLA2R concentration\u0026thinsp;\u0026gt;\u0026thinsp;80 RU/mL yielded similar results (RR, 0.48; 95% CI, 0.38\u0026ndash;0.68; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 0%).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCompared with cyclophosphamide treatment, RTX treatment had similar efficacy in inducing complete remission at 18 months and 24 months. The RRs were 0.83 (2 RCTs\u0026thinsp;+\u0026thinsp;3 Cohorts; 95% CI, 0.62\u0026ndash;1.11; p\u0026thinsp;=\u0026thinsp;0.21) and 0.93 (2 RCTs\u0026thinsp;+\u0026thinsp;3 Cohorts; 95% CI, 0.76\u0026ndash;1.15; p\u0026thinsp;=\u0026thinsp;0.51), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e values were 46% and 62%, respectively, indicating low heterogeneity and moderate heterogeneity, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). We performed sensitivity analyses to explore potential sources of heterogeneity. The statistical I\u003csup\u003e2\u003c/sup\u003e values of the RCT subgroup were 84% and 82%, whereas those of the cohort subgroup were both 0% (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the RCT subgroup, only 2 trials were included, and more RCTs are needed to explore potential sources of heterogeneity.\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e Complete remission (CR) rates in PMN patients treated with rituximab versus cyclophosphamide. (a) 6 months, (b) 12 months, (c) 18 months, and (d) 24 months\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eSecondary outcome: Relapse\u003c/h2\u003e\u003cp\u003eCompared with cyclophosphamide treatment, RTX treatment had a similar relapse rate during follow-up. The RR was 0.71 (3 RCTs\u0026thinsp;+\u0026thinsp;6 cohorts; 95% CI, 0.43\u0026ndash;1.15; p\u0026thinsp;=\u0026thinsp;0.17) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e statistic was 0%, indicating that there was no evidence of heterogeneity.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCyclophosphamide had a higher relapse rate during the follow-up than did rituximab, as revealed by the cohort subgroup. The RR was 0.50 (6 cohorts; 95% CI, 0.26\u0026ndash;0.98; p\u0026thinsp;=\u0026thinsp;0.04) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e statistic was 0%, indicating that there was no evidence of heterogeneity.\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e Relapse rates in PMN patients treated with rituximab versus cyclophosphamide\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eSecondary outcome: adverse events and severe adverse events\u003c/h2\u003e\u003cp\u003eThere were significant differences in the incidence of AEs or SAEs between the Rituximab group and the Cyclophosphamide group. The RRs were 0.77 (3 RCTS\u0026thinsp;+\u0026thinsp;9 Cohorts; 95% CI, 0.68\u0026ndash;0.87; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and 0.60 (3RCTs\u0026thinsp;+\u0026thinsp;3 Cohorts; 95% CI, 0.42\u0026ndash;0.86; p\u0026thinsp;=\u0026thinsp;0.005) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) (see \u003cspan refid=\"Sec19\" class=\"InternalRef\"\u003eappendix\u003c/span\u003e). The I\u003csup\u003e2\u003c/sup\u003e values were 59% and 40%, indicating moderate heterogeneity and low heterogeneity, respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWe performed sensitivity analyses to explore potential sources of heterogeneity. The statistical I\u003csup\u003e2\u003c/sup\u003e values of the RCT subgroup were 61% and 0%, whereas those of the cohort subgroup were 41% and 60%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). (1) In the RCT subgroup of AEs (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea), exclusion of one study[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] in which baseline proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/24 h yielded similar results (RR, 0.79; 95% CI, 0.69\u0026ndash;0.90; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 0%). (2) In the cohort subgroup of AEs (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003ea ), exclusion of two studies[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] that reported baseline proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/24 h yielded similar results (RR, 0.79; 95% CI, 0.69\u0026ndash;0.90; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0004), yet heterogeneity was still present (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 52%). Exclusion of four studies[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] in which the baseline anti-PLA2R concentration was \u0026gt;\u0026thinsp;80 RU/mL yielded similar results (RR, 0.78; 95% CI, 0.68\u0026ndash;0.90; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0009), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 0%). Exclusion of two studies[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] in which the baseline eGFR was \u0026lt;\u0026thinsp;60 mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e yielded similar results (RR, 0.75; 95% CI, 0.65\u0026ndash;0.87; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 4%). (3) In the SAE cohort subgroup (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003eb), Exclusion of one study[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] in which baseline proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/24 h yielded similar results (RR, 0.63; 95% CI, 0.43\u0026ndash;0.91; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) however, heterogeneity was still present (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 79%). Exclusion of one study[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] in which the baseline anti-PLA2R concentration was \u0026gt;\u0026thinsp;80 RU/mL yielded similar results (RR, 0.53; 95% CI, 0.35\u0026ndash;0.80; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), with no evidence of heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 0%).Exclusion of one study[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] in which the baseline eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e changed the overall estimate (RR, 0.83; 95% CI, 0.54\u0026ndash;1.27; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.39), with low heterogeneity (\u003cem\u003eI\u003c/em\u003e \u003csup\u003e2\u003c/sup\u003e = 28%).\u003c/p\u003e\u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e Adverse events and serious adverse events in PMN patients treated with rituximab versus cyclophosphamide\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003ePublication Bias\u003c/h2\u003e\u003cp\u003ePublication bias was not assessed because of the limited number (\u0026lt;\u0026thinsp;10) of studies included in each analysis.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis demonstrated that rituximab was effective as cyclophosphamide for promoting disease remission (CR\u0026thinsp;+\u0026thinsp;PR or CR) in patients with primary membranous nephropathy. In addition, the RTX group had significantly fewer adverse events and serious adverse events than did the cyclophosphamide group.\u003c/p\u003e\u003cp\u003eRituximab demonstrated comparable long-term efficacy to cyclophosphamide in patients with primary membranous nephropathy. Specifically, there were no significant differences between the two treatments in the rates of complete or partial remission at 18 and 24 months or in complete remission at 18 months and 24 months. However, a subgroup analysis of the three randomized controlled trials (RCTs) revealed that the cyclophosphamide group was associated with significantly higher rates of complete or partial remission at 6, 12, and 18 months, as well as higher rates of complete remission at 12 months. This short-term superior efficacy of cyclophosphamide may be partially attributed to the delayed onset of action of rituximab[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImmunosuppressive therapy is associated with side effects[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The anti-CD20 monoclonal antibody rituximab was well tolerated, with minimal adverse events[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our meta-analysis revealed a significant difference in the incidence of adverse events and serious adverse events between RTX and cyclophosphamide in patients with primary membranous nephropathy. The superior safety profile and comparable efficacy of rituximab support its use as a first-line therapy for primary membranous nephropathy. However, moderate heterogeneity was observed among these studies, which was not surprising given the differences in the characteristics of the populations, dosage regimens, definitions of complete or partial remission, types of included studies (RCTs vs. cohorts), and study designs.\u003c/p\u003e\u003cp\u003eCompared with recently published meta-analyses[\u003cspan additionalcitationids=\"CR36 CR37 CR38\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], however, this meta-analysis revealed several differences. First, cohort studies were included because MN is a disease with serious, objective, clinical outcomes such as morality or kidney failure[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This meta-analysis uses information from cohort studies as part of the evidence base. Second, this meta-analysis demonstrated that rituximab had a superior safety profile to cyclophosphamide in patients with primary membranous nephropathy. Third, this meta-analysis included recently published studies and thus had a larger sample size.\u003c/p\u003e\u003cp\u003eThis meta-analysis has several potential limitations that should be taken into account. First, the number of included RCTs was small, and the studies had small sample sizes and short follow-up periods. Second, the number of included trials was too small to evaluate publication bias in our meta-analysis, either visually via funnel plots or quantitatively via Egger\u0026rsquo;s test[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and Begg\u0026rsquo;s test[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. There may be potential publication bias in this meta-analysis. Third, comparisons between rituximab and cyclophosphamide are based on clinical responses (complete remission or partial remission), and clinical outcomes such as kidney failure, ESRD, and quality of life were not reported.\u003c/p\u003e\u003cp\u003eFurther studies should focus on the following points. There is an urgent need for large-scale, adequately powered, well-designed RCTs that compare the long-term efficacy and safety of rituximab treatment and cyclophosphamide treatment. Next, such RCTs should have longer follow-up periods (10\u0026ndash;20 years) to assess the risk of SAEs, such as malignancies that occur as late as 10\u0026ndash;20 years after treatment[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e], and to assess whether rituximab treatment can reduce the risk of kidney failure or prevent ESRD. Third, such RCTs should report long-term efficacy and safety outcomes, such as the rate of kidney failure, rate of ESRD, quality of life, incidence of SAEs such as malignancies, and death. Finally, such RCTs should standardize the treatment protocol (i.e., further consistency regarding dosage, route, follow-up, duration of administration, and long-term outcomes).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe current limited evidence suggests that rituximab treatment has comparable long-term efficacy to cyclophosphamide in patients with primary membranous nephropathy. Compared with cyclophosphamide treatment, rituximab treatment was associated with significantly fewer adverse events and serious adverse events. The results should be interpreted with caution because of the heterogeneity among study designs. Further large-scale, longer follow-up, well-designed RCTs on head-to-head comparisons of the safety and efficacy of RTX vs. cyclophosphamide are urgently needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePMN\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprimary membranous nephropathy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRTX\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erituximab\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTAC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etacrolimus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCYC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecyclophosphamide\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eglucocorticoids\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erandomized controlled trial\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprospective cohort\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eretrospective cohort\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emulticenter\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esingle-center\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003econfidence interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecomplete remission\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epartial remission\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etotal remission, TR\u0026thinsp;=\u0026thinsp;CR\u0026thinsp;+\u0026thinsp;PR\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAEs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eadverse events\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSAEs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eserious adverse events\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eKDIGO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKidney Disease: Improving Global Outcomes\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePRISMA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePreferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erelative risk\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eALB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ealbumin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis work was supported by the Guangxi University of Chinese Medicine Joint Fund Project (2024LZ006) and the Self-funded Research Project of the Guangxi Autonomous Region Administration of Traditional Chinese Medicine (GXZYB20220409).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYifeng Xie contributed to concept and design of the study, acquisition, analysis and interpretation of data, drafting and revising the article, and final approval of the manuscript. Fangjiao Huang, Chenxin Fu, Maorong Liu and Peiyu Wu contributed to acquisition, analysis and interpretation of data, drafting the article, and final approval of the manuscript. Yanfang Li, Zhuguang Lu and Yanlei Li contributed to concept and design of the study, analysis and interpretation of data, revising the article.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll the data generated or analyzed during this study are included in this published article and its supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRuggenenti P, Fervenza FC, Remuzzi G. Treatment of membranous nephropathy: time for a paradigm shift. Nat Rev Nephrol. 2017;13(9):563\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRonco P, Beck L, Debiec H, et al. Membranous nephropathy. Nature reviews. Disease primers. 2021;7(1):69.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transpl. 2011;26(2):414\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDebiec H, Ronco P. Immunopathogenesis of membranous nephropathy: an update. Semin Immunopathol. 2014;36(4):381\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKumar V, Ramachandran R, Kumar A, et al. Antibodies to m-type phospholipase A2 receptor in children with idiopathic membranous nephropathy. Nephrol (Carlton). 2015;20(8):572\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Vriese AS, Glassock RJ, Nath KA, Sethi S, Fervenza FC. A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2017;28(2):421\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCattran DC, Brenchley PE. Membranous nephropathy: integrating basic science into improved clinical management. Kidney Int. 2017;91(3):566\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTroyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC. Idiopathic membranous nephropathy: definition and relevance of a partial remission. Kidney Int. 2004;66(3):1199\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchieppati A, Mosconi L, Perna A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med. 1993;329(2):85\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePonticelli C, Zucchelli P, Passerini P, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int. 1995;48(5):1600\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJha V, Ganguli A, Saha TK, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy. J Am Soc Nephrol. 2007;18(6):1899\u0026ndash;904.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Y, Schieppati A, Chen X, et al. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2014;2014(10):Cd004293.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4s):S1\u0026ndash;276.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. 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The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. 2012:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ohri.ca/programs/clinical_epidemiology/oxford.asp\u003c/span\u003e\u003cspan address=\"http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHiggins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clinical research ed.). 2003;327(7414):557\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEgger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed.). 1997;315(7109):629\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBegg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFern\u0026aacute;ndez-Ju\u0026aacute;rez G, Rojas-Rivera J, Logt AV, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021;99(4):986\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScolari F, Delbarba E, Santoro D, et al. Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial. J Am Soc Nephrol. 2021;32(4):972\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSuresh S, Konnur A, Rajapurkar MM, Gang S, Hegde UN, Patel H. Low-Dose Rituximab vs. Modified Ponticelli Regimen in the Treatment of Primary Membranous Nephropathy \u0026ndash; A Randomized Controlled Trial. Indian J Nephrol. 2025;35(5):545\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNie Limin YX, Rong Xue Z, Shanshan Z, Bing, et al. Effecy of rituximab combined with cyclophosphamide in treatment of idiopathic membranous nephropathy effect and on immune function of patients. Drug Evaluation Res. 2023;46(6):1307\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Ma X, Yang X, et al. A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy. Ren Fail. 2024;46(2):2409353.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu L, Cai S, Zhu H, et al. Comparations of efficacy and safety of rituximab, calcineurin inhibitors and cyclophosphamide in primary membranous nephropathy: a single-center retrospective analysis. BMC Nephrol. 2024;25(1):473.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu X, Ren H, Xu J, et al. Treatment of Membranous Nephropathy in Chinese Patients: Comparison of Rituximab and Intravenous Cyclophosphamide with Steroids. Kidney Dis (Basel). 2024;10(5):359\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRamachandran R, Prabakaran R, Priya G, et al. Immunosuppressive Therapy in Primary Membranous Nephropathy with Compromised Renal Function. Nephron. 2022;146(2):138\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFenoglio R, Baldovino S, Sciascia S, et al. Efficacy of low or standard rituximab-based protocols and comparison to Ponticelli's regimen in membranous nephropathy. J Nephrol. 2021;34(2):565\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan den Brand J, Ruggenenti P, Chianca A, et al. Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous Nephropathy. J Am Soc Nephrol. 2017;28(9):2729\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMedrano AS, Escalante EJ, C\u0026aacute;ceres CC, et al. Prognostic value of the dynamics of M-type phospholipase A2 receptor antibody titers in patients with idiopathic membranous nephropathy treated with two different immunosuppression regimens. Biomarkers. 2015;20(1):77\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou Z, Zou Y, Ke B, Shen W. How to Choose Treatment Regimens for Idiopathic Membranous Nephropathy Patients with PLA2R-Negative: A Single-Center Retrospective Cohort Study. ImmunoTargets therapy. 2025;14:515\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu S, Yu Q, Yang Q, et al. Comparing the efficacy and safety of cyclophosphamide and rituximab in idiopathic membranous nephropathy. Chin J Clin Pharmacol Ther. 2025;30(5):657\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBomback AS, Derebail VK, McGregor JG, Kshirsagar AV, Falk RJ, Nachman PH. Rituximab therapy for membranous nephropathy: a systematic review. Clin J Am Soc Nephrol. 2009;4(4):734\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMao B, Han J, Wang J, Ye K. Efficacy and safety of rituximab for membranous nephropathy in adults: a meta-analysis of RCT. Front Nephrol. 2025;5:1548679.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMathew GG, Sundaramurthy S, Muthuperumal P, Jayaprakash V. Low-Dose Rituximab in the Treatment of Primary Membranous Nephropathy - A Systematic Review and Meta-Analysis. G Ital Nefrol. 2024;41(5).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXue C, Wang J, Pan J, et al. Cyclophosphamide induced early remission and was superior to rituximab in idiopathic membranous nephropathy patients with high anti-PLA2R antibody levels. BMC Nephrol. 2023;24(1):280.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOu JY, Chen YW, Li TL, et al. Evaluation of efficacy of rituximab for membranous nephropathy: A systematic review and meta-analysis of 11 studies. Nephrol Ther. 2022;18(2):104\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDai P, Xie W, Yu X, Sun J, Wang S, Kawuki J. Efficacy and cost of different treatment in patients with idiopathic membranous nephropathy: A network meta-analysis and cost-effectiveness analysis. Int Immunopharmacol. 2021;94:107376.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFaurschou M, Sorensen IJ, Mellemkjaer L, et al. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rhuematol. 2008;35(1):100\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Membranous nephropathy, Primary membranous nephropathy, In idiopathic membranous nephropathy, Rituximab, Cyclophosphamide, Systematic review, Meta-analysis, Treatment","lastPublishedDoi":"10.21203/rs.3.rs-8173549/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8173549/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePMN is a leading cause of nephrotic syndrome in adults. In some patients, PMN can be severe or continue to worsen even after 6 months of supportive treatment. Rituximab and cyclophosphamide are used to treat moderate-risk or high-risk PMNs, but the efficacy and safety of rituximab and cyclophosphamide in patients with PMN are still unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe searched PubMed, Embase and the Cochrane Library for the time period through November 2025 to identify randomized controlled trials and cohort studies that evaluated rituximab compared with cyclophosphamide for the treatment of PMN. The primary outcomes were complete remission (CR), partial remission (PR), and total remission (TR\u0026thinsp;=\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;CR). The secondary outcomes included the relapse rate, adverse events, and serious adverse events. The random effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThirteen studies (N\u0026thinsp;=\u0026thinsp;1228) were eligible for final inclusion. Rituximab demonstrated similar efficacy to cyclophosphamide in inducing complete or partial remission at 18 months (RR, 0.98; 95% CI, 0.86\u0026ndash;1.10; p\u0026thinsp;=\u0026thinsp;0.70) and 24 months (RR, 1.01; 95% CI, 0.91\u0026ndash;1.13; p\u0026thinsp;=\u0026thinsp;0.82). Similarly, rates of complete remission were comparable between the two treatment groups at 18 months (RR, 0.83; 95% CI, 0.62\u0026ndash;1.11; p\u0026thinsp;=\u0026thinsp;0.21) and 24 months (RR, 0.93; 95% CI, 0.76\u0026ndash;1.15; p\u0026thinsp;=\u0026thinsp;0.51). There were significant differences in the incidence of AEs or SAEs between RTX and cyclophosphamide. The RRs were 0.77 (95% CI, 0.68\u0026ndash;0.87; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and 0.60 (95% CI, 0.42\u0026ndash;0.86; p\u0026thinsp;=\u0026thinsp;0.005), respectively.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe current limited evidence suggests that RTX treatment has comparable long-term efficacy to cyclophosphamide in PMN patients at moderate risk or high risk. Compared with cyclophosphamide treatment, rituximab treatment was associated with significantly fewer adverse events and serious adverse events. Further large-scale, longer follow-up, well-designed RCTs on head-to-head comparisons of the safety and efficacy of rituximab versus cyclophosphamide are urgently needed.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of rituximab versus cyclophosphamide in primary membranous nephropathy: A systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 16:13:31","doi":"10.21203/rs.3.rs-8173549/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-08T08:42:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-07T12:25:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T03:35:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-22T22:22:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152178323850803575538897129019185173405","date":"2025-12-15T12:05:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T06:57:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"237549310719405809110399404853126232217","date":"2025-12-12T14:15:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"334261156024142342463552031984422800305","date":"2025-12-12T12:38:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"305330265698904408703635649917128801492","date":"2025-12-10T07:30:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152369546717778199796949312930607544650","date":"2025-12-10T04:40:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-10T02:19:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-09T12:29:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-01T12:04:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-01T08:40:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-11-30T15:15:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c0cc8ac7-62df-436c-a414-0d3a006cb557","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:00:31+00:00","versionOfRecord":{"articleIdentity":"rs-8173549","link":"https://doi.org/10.1186/s12882-026-04895-0","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2026-03-16 15:57:59","publishedOnDateReadable":"March 16th, 2026"},"versionCreatedAt":"2025-12-15 16:13:31","video":"","vorDoi":"10.1186/s12882-026-04895-0","vorDoiUrl":"https://doi.org/10.1186/s12882-026-04895-0","workflowStages":[]},"version":"v1","identity":"rs-8173549","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8173549","identity":"rs-8173549","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}