The effect of tacrolimus combined with mycophenolate mofetil or cyclophosphamide on renal response in systemic lupus erythematosus patients 

The effect of tacrolimus combined with mycophenolate mofetil or cyclophosphamide on renal response in systemic lupus erythematosus patients | 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 The effect of tacrolimus combined with mycophenolate mofetil or cyclophosphamide on renal response in systemic lupus erythematosus patients Siqin Sun, Xueyi Zhang, Qingqing Guo, Xiaojun Tang, Wei Shen, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4593245/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Dec, 2024 Read the published version in BMC Rheumatology → Version 1 posted 10 You are reading this latest preprint version Abstract Objective This study aimed to determine the therapeutic effect of tacrolimus (TAC) and its combination with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the complete response (CR) in patients with systemic lupus erythematosus (SLE). Methods A retrospective cohort study based on medical data was conducted among SLE patients taking at least one of TAC, MMF and CYC during 2010–2021. Odds ratio (OR) and 95% confidence interval (CI) were calculated and multiplicative interactions were estimated using logistic regression models. Results Among 793 SLE patients, 27.9% (221 cases) patients achieved CR after at least 3 months. TAC use was positively associated with CR with adjusted OR (95% CI) of 2.82(1.89, 4.22) in overall, as well as in subgroups of SLE patients with SLEDAI score > 12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was further observed at the dose of TAC more than 4 mg/d and more than 180 days, with adjusted OR (95% CI) of 5.65(2.35, 13.55), and 3.60(2.02, 6.41) respectively. Moreover, the combined effect of TAC with MMF or CYC was better than monotherapy with the significant multiplicative interaction, with adjusted OR (95% CI) of 2.43(1.20,4.92) and 3.14(1.49,6.64), respectively, and similar results were also observed for the combination of different doses of TAC with MMF or CYC. Conclusion TAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, suggesting that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE. Trial registration: This is a purely observational study that does not require registration. lupus nephritis tacrolimus mycophenolate mofetil cyclophosphamide dose-response Figures Figure 1 Introduction Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that affects multiple systems, organs, and tissues. 1 Renal involvement is a serious complication of SLE. About 40–60% of patients with SLE will exhibit lupus nephritis (LN), and about 26% of patients with LN will progress to end-stage renal disease (ESRD). 2, 3 The main clinical manifestations of renal involvement include urinary protein, hematuria, cellular casts, decreased glomerular filtration function, and elevated serum creatinine levels. It is recommended at least annual renal evaluations for SLE patients and more frequent evaluations (every 3 months) for high-risk patients. 4, 5 The primary treatment options for SLE include glucocorticoids (GCs), immunosuppressants, and biological agents. 6 Tacrolimus (TAC), a calcineurin inhibitor, works by binding to the FK506 binding protein 12 in T-lymphocytes, thereby inhibiting T-cell activation and calcineurin. 7 It also suppresses B-cell, plasma cell, and CD40 receptor signaling. 8–11 TAC is effective in improving renal function in SLE patients. 8, 9 Moreover, multitarget therapy has demonstrated significant efficacy in LN patients, and TAC is often used in combination with mycophenolate mofetil (MMF) and cyclophosphamide (CYC). 10–12 The combination therapy of TAC with other drugs can reduce dosages of TAC and other drugs, as well as drug-related organ damage and infections. 13–15 Multiple clinical studies have shown that the treatment regimen combining TAC with MMF or CYC has significant renal therapeutic effects for LN patients who have failed to respond to monotherapy. 16, 17 However, the dosage of TAC in combination with other drugs remains controversial, and few studies explored the length of TAC use. 13, 14 Although previous studies involved drug combinations, they rarely assessed the impact of drug interactions on renal response. In addition, previous studies involved fewer than 400 cases and the interactions of TAC with MMF or CYC have been rarely estimated in Chinese SLE patients. 18 Thus, we carried out a retrospective cohort study to investigate the clinical efficacy of TAC and its interactions with MMF or CYC in a Chinese patients with SLE. Methods Study design and participants This retrospective cohort study was conducted in the Affiliated Drum Tower Hospital, Nanjing University Medical School. The process of enrolling participants is illustrated in Fig. 1 . We gathered the medical records of SLE patients who visited the rheumatology and immunology department between January 1, 2010 and December 31, 2021. To be included in the study, patients had to meet at least four of the classification criteria for SLE, as revised and updated by the American College of Rheumatology. 15 Referring to the LN guidelines, we determined the criteria for renal involvement in SLE patients: ( 1 ) 24-hour protein measurement > 500 mg or urine protein / creatinine ratio > 30 mg/mmol. ( 2 ) The patient had cellular casts and pathological tube pattern. ( 3 ) The patient had active urinary sediment. 19 The exclusion criteria were: patients did not meet renal involvement, medical information was incomplete, there was no follow-up record or follow-up was less than 3 months, CR at baseline, and patients were not treated with TAC, CYC or MMF. Data collection and definition We gathered data from medical records of both inpatients and outpatients with SLE, including demographics, diagnostic information, physical exams, SLEDAI score, laboratory test data, medication records, pathology reports, and imaging information. The missing laboratory test and medication information of hospitalized patients was supplemented by the latest outpatient medical information within three months before and after hospitalization. The patient's comorbidities included one or more of hypertension, hyperlipidemia, diabetes, secondary Sjogren's syndrome and cancer. We defined the time of the patient’s first hospitalization as the baseline and defined the nearest follow-up after 3 months from baseline as the endpoint. The immunosuppressants used by the patients during this period were defined as combination therapy, and several diseases that occurred during or before this period but had not been cured were defined as comorbidities. Patients who continuously used TAC from baseline to endpoint were defined as TAC users, and those who did not use TAC at baseline were defined as non-TAC users. The patients used renal-protective agents including dinoprost sodium, hekunshenxi capsule, huangkui, hiaoduqing granules, shenfu kanglu capsule, lanthanum carbonate, sevelamer carbonate and pioglitazone hydrochloride and glimepiride. The list of abnormal ranges for each laboratory indicator is: eGFR 106 mL/min·1.73 m 2 , C3 ≤ 0.8 g/L, C4 ≤ 0.2 g/L. The urinary protein levels were divided into three groups: mild urinary protein: 24-hour urinary protein less than 1000 mg; moderate urinary protein: 24-hour urinary protein between 1000 mg and 3500 mg; severe urinary protein: 24-hour urinary protein greater than 3500 mg. 20 The patients were treated with different kinds of GC, and we converted all GC doses to prednisone doses according to “ Dexamethasone Suppression Test ” (5 mg prednisone = 5 mg prednisone dragon = 4 mg methylprednisolone = 0.75 mg dexamethasone). 21 The follow-up record was taken at least 3 months after baseline. Our primary outcome was CR of renal function, which was defined as normal urinary protein (24-hour protein measurement excretion less than 500 mg/day or urinary protein negative or weakly positive) and a serum creatinine level of 106.08 µmol/L or less (or a decrease of at least 25% from baseline). Statistical analysis The data were analyzed using IBM SPSS STATISTICS 25.0 software. The Shapiro-Wilk test was applied to test the normality of continuous variables. Non-normally distributed variables were described by the median and interquartile range (IQR) and compared using the Mann-Whitney U test. Categorical variables were described by their count (percentage) and compared using the χ 2 test or Fisher's exact test. A binary unconditional logistic regression model was used to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) between treatment with TAC and overall CR. The OR and P -value for trend were estimated for each exposure category and dose of TAC using dummy variables and ordinal coding. Stratified analyses were conducted based on factors such as sex, age, SLEDAI score at baseline, disease course, comorbidities, urinary protein, laboratory tests, and combined drug use. We used a binary logistic regression model to assess the potential multiplicative interaction between TAC and MMF or CYC. The confounding factors included in the binary regression analysis were treated with sex, age, SLE disease period, comorbidities, SLEDAI score, renal-protective agents, HCQ treatment, GCs dose, abnormal urinary protein, abnormal serum creatinine and other immunosuppressants. These adjusted variables were excluded when they were used as stratified variables. To further eliminate the influence of confounding factors and verify the credibility of the results, we employed binary logistic regression analysis for propensity score matching, controlling for sensitivity factors that have a significant impact on the outcome. The propensity score model included recipient's age, sex, SLEDAI score, abnormal urinary protein, and abnormal creatinine rate. We then conducted a secondary analysis of the main results associated with the relationship between TAC and SLE patients. Results Characteristics of the study patients Among the 793 SLE patients, 244 patients were in the TAC use group and 549 patients were in the TAC non-use group. The demographic and baseline clinical characteristics of the patients are presented in Table 1 . The age of TAC non-users was older than that of users. The median age (IQR) for TAC non-users was 37.0(28.0, 50.0), and for TAC users (IQR) was 27.0(22.0, 35.0) (P < 0.001). The median weight (IQR) was 55.00(49.00, 63.00) for TAC non-users and 57.63(55.00, 65.50) for TAC users ( P < 0.001). The dose of CYC or MMF combined with TAC was lower than that used alone. Table 1 Baseline clinical characteristics of SLE patients Variable TAC non-users TAC users P Total n = 549 n = 244 — Gender (Female), n (%) 487(88.7) 226(92.6) 0.098 Age, M (IQR), years 37.0(28.0,50.0) 27.0(22.0,35.0) < 0.001 Weight, M (IQR), kg 55.0(50.0,62.0) 57.6(55.0,65.0) < 0.001 SLE disease period, M (IQR), years 0.5(0.0,6.0) 1.0(0.0,3.0) 0.033 Renal biopsy, n (%) 52(9.5) 37(15.2) 0.028 SLEDAI score, M (IQR) 14.0(8.3,20.0) 16.0(12.0,21.0) < 0.001 Follow-up duration, M (IQR), days 126(94.0,221.0) 118.0(91.0,199.0) 0.473 Comorbidities, n (%) All 465(84.7) 217(88.9) 0.121 Hyperlipemia 206(37.5) 130(53.3) < 0.001 Hypertension 316(57.6) 167(68.4) 0.004 Diabetes 46(8.4) 20(8.2) 1.000 Tumor 30(5.5) 11(4.5) 0.728 Secondary Sjogren’s syndrome 17(3.1) 2(0.8) 0.075 Indicators of renal involvement, n (%) Urinary protein Mild 129(23.5) 31(12.7) 0.607 Moderate 141(25.7) 55(22.5) < 0.001 Severe 279(50.8) 158(64.8) < 0.001 Pathological tube pattern 126(32.0) 62(25.4) 0.470 Abnormal serum creatinine 263(48.5) 79(32.4) < 0.001 Abnormal eGFR 155(80.3) 154(77.4) 0.537 Anti-dsDNA positive, n (%) 400(72.9) 42(17.2) 0.003 Low complement, n (%) C3 ≤ 0.8 g/L 373(74.9) 175(71.7) 0.374 C4 ≤ 0.2 g/L 404(81.1) 151(61.9) < 0.001 Treatments TAC dose, M (IQR), mg/d — 3.0(2.0,3.0) — MMF, n (%) 208(24.1) 91(37.3) 0.937 MMF dose, M (IQR), g/d 1.0(1.0,1.5) 1.0(0.8,1.5) 0.001 CYC, n (%) 419(76.3) 108(44.3) < 0.001 CYC dose, M (IQR), g/m 2 0.4(0.4,0.4) 0.4(0.2,0.4) 0.012 GCs, n (%) 546(99.5) 207(84.8) < 0.001 GCs maintenance dose, M (IQR), mg/d 30.0(20.0,40.0) 30.0(15.0,50.0) 0.814 Renal-protective agents, n (%) 166(30.2) 37(15.2) < 0.001 HCQ, n (%) 488(88.9) 179(73.4) < 0.001 Other immunosuppressants, n (%) 420(76.5) 138(56.6) < 0.001 Leflunomide 116(21.1) 63(25.8) Methotrexate 11(2.0) 3(1.2) Tripterygium wilfordii 34(6.2) 10(4.1) Azathioprine 4(0.7) 8(3.3) Metronidazole 0(0.0) 2(0.8) Sunitinib 20(3.6) 9(3.7) M (IQR): median (interquartile range), eGFR: estimated glomerular filtration rate, Anti-dsDNA: anti-double stranded DNA, GCs: glucocorticoids, HCQ: hydroxychloroquine, MMF: mycophenolate mofetil, CYC: cyclophosphamide. Compared with TAC non-users, the median course of disease period, SLEDAI score, and severe urinary protein proportion were significantly higher in TAC users, while the proportion of moderate urinary, abnormal serum creatinine, anti-dsDNA, and low C4 were lower in TAC users. TAC non-users were more likely to use renal-protective agents, GCs, HCQ, CYC and other immunosuppressants. MMF were more prevalent in the TAC user group. Effect of TAC use on CR CR was achieved in 27.9% (221) of all the SLE patients, and the use of TAC was positively associated with CR, with adjusted OR (95% CI) of 2.82(1.89, 4.22). TAC dose ≥ 4 mg/d and TAC use > 180 days were found to be associated with an increased likelihood of CR compared to non-users, with adjusted OR (95% CI) of 5.65(2.35, 13.55) and 3.60(2.02, 6.41), respectively. A dose-response relationship was also observed between CR and the dose ( P for trend < 0.001) and duration ( P for trend < 0.001) of TAC use, respectively (Table 2 ). After propensity score matching, age, SLEDAI score, comorbidities, abnormal urinary protein, and abnormal creatinine rate were balanced between TAC users and non-users. A total of 396 patients were matched, including 198 patients in the TAC use group and 198 patients in the TAC non-use group, and 32.1% achieved CR (Supplementary Table 1). The use of TAC was positively correlated with CR, with adjusted OR (95% CI) of 2.40(1.48, 3.88). And a dose-response relationship between TAC dosage and duration of use and CR was also observed (Table 2 ). Table 2 Complete response rates according to TAC use in SLE patients and these patients after propensity score matching Variable Non-CR, n (%) CR, n (%) OR Adjusted OR (95% CI) (95% CI) All patients n = 572 n = 221 TAC treatment No 431(78.5) 118(21.5) 1.00 1.00 Yes 141(57.8) 103(42.2) 2.67(1.93,3.7) 2.82(1.89,4.22) TAC dose No 431(78.5) 118(21.5) 1.00 1.00 ≤ 2 mg/d 88(61.1) 56(38.9) 2.32(1.57,3.44) 2.42(1.53,3.84) 3 mg/d 43(57.3) 32(42.7) 2.72(1.65,4.49) 2.92(1.65,5.16) ≥ 4 mg/d 10(40.0) 15(60.0) 5.48(2.40,12.51) 5.65(2.35,13.55) P for trend < 0.001 180 days 37(52.9) 33(47.1) 3.26(1.95,5.43) 3.60(2.02,6.41) P for trend < 0.001 < 0.001 PSM n = 572 n = 221 TAC treatment No 155(78.3) 43(21.7) 1.00 1.00 Yes 114(57.6) 84(42.4) 2.66(1.71,4.12) 2.40(1.48,3.88) TAC dose No 155(78.3) 43(21.7) 1.00 1.00 ≤ 2 mg/d 74(63.2) 43(36.8) 2.09(1.26,3.47) 1.88(1.09,3.23) 3 mg/d 33(53.2) 29(46.8) 3.17(1.73,5.79) 2.95(1.53,5.67) ≥ 4 mg/d 7(36.8) 12(63.2) 6.18(2.29,16.65) 5.08(1.84,14.04) P for trend < 0.001 180 days 32(52.5) 29(47.5) 3.27(1.78,5.99) 2.88(1.49,5.54) P for trend < 0.001 < 0.001 The confounding factors included in the multivariate regression analysis of all patients were sex (female = 1, male = 0), age (continuous), SLE disease period (continuous), comorbidities (yes = 1, no = 0), SLEDAI score (continuous), abnormal urinary protein (yes = 1, no = 0), abnormal serum creatinine (yes = 1, no = 0), renal-protective agents (yes = 1, no = 0), MMF treatment (yes = 1, no = 0), CYC treatment (yes = 1, no = 0), HCQ treatment (yes = 1, no = 0), GCs dose (continuous) and other immunosuppressants (yes = 1, no = 0). The confounding factors included in the multivariate regression analysis of patients after propensity score matching were sex (female = 1, male = 0), SLE disease period (continuous), renal-protective agents (yes = 1, no = 0), MMF treatment (yes = 1, no = 0), CYC treatment (yes = 1, no = 0), HCQ treatment (yes = 1, no = 0), GCs dose (continuous) and other immunosuppressants (yes = 1, no = 0). We also conducted a stratified analysis of 14 factors such as gender, age, SLE disease period, SLEDAI score, urinary protein, comorbidities, laboratory tests, and therapeutic drugs (Table 3 ). CR rate was significantly higher in the TAC use group compared to the non-use group across most strata, but was not significantly different in male patients, mild urinary protein patients, patients with low complement 3 and patients without defined comorbidities, those receiving renal-protective agents treatment and those rejecting HCQ treatment. Table 3 Complete response rates using TAC in subgroups of SLE patients Variable Non-users TAC Users Non-CR/CR Non-CR/CR OR (95% CI) Adjusted OR (95% CI) Gender Male 48/14 14/4 0.98(0.28,3.46) 1.01(0.18,5.53) Female 383/104 127/99 2.87(2.04,4.04) 3.04(1.99,4.66) Age, years ≤ 30 148/41 90/67 2.69(1.68,4.29) 3.08(1.71,5.56) > 30 283/77 51/36 2.59(1.58,4.26) 2.76(1.52,4.99) SLE disease period, years ≤ 2 261/75 101/71 3.08(1.71,5.56) 2.45(1.64,3.64) > 2 170/43 40/32 2.76(1.52,4.99) 3.16(1.78,5.61) SLEDAI score ≤ 12 199/57 54/30 1.94(1.14,3.31) 1.93(1.00,3.79) > 12 253/61 87/73 3.19(2.10,4.86) 3.42(2.02,5.80) Urinary protein Mild 89/40 20/11 1.22(0.54,2.79) 0.95(0.27,3.32) Moderate 112/29 26/29 4.31(2.21,8.41) 4.62(1.94,11.00) Severe 230/49 95/63 3.11(2.00,4.85) 2.80(1.63,4.81) Complement 3, g/L ≤ 0.8 296/77 102/73 2.75(1.86,4.07) 2.91(1.81,4.68) > 0.8 89/36 39/30 1.90(1.03,3.51) 1.99(0.85,4.64) Complement 4, g/L ≤ 0.2 312/92 79/72 3.09(2.08,4.59) 2.90(1.80,4.67) > 0.2 73/21 62/31 1.74(0.91,3.33) 3.26(1.23,8.65) Comorbidities No 60/24 15/12 2.00(0.82,4.89) 1.85(0.38,8.91) Yes 371/94 126/91 2.85(2.00,4.05) 3.08(2.01,4.73) Renal-protective agents treatment No 295/88 116/91 2.63(1.83,3.78) 2.18(0.98,4.81) Yes 136/30 25/12 2.18(0.98,4.81) 2.46(0.93,6.54) GCs treatment No 3/0 18/19 — — Yes 428/118 123/84 2.48(1.76,3.49) 2.74(1.81,4.14) MMF treatment No 258/83 94/59 1.95(1.30,2.94) 2.40(1.25,4.61) Yes 173/35 47/44 4.63(2.67,8.01) 5.34(2.57,11.1) HCQ treatment No 50/11 38/27 3.23(1.43,7.32) 2.41(0.59,9.84) Yes 381/107 103/76 2.63(1.82,3.79) 2.93(1.89,4.53) CYC treatment No 101/29 77/59 2.67(1.56,4.55) 3.33(1.44,7.70) Yes 330/89 64/44 2.55(1.63,4.00) 4.10(2.32,7.26) Other immunosuppressants No 101/28 55/51 3.34(1.90,5.89) 4.85(2.12,11.09) Yes 330/90 86/52 2.22(1.46,3.36) 3.28(1.89,5.70) The confounding factors included in the multivariate regression analysis were sex (female = 1, male = 0), age (continuous), SLE disease period (continuous), comorbidities (yes = 1, no = 0), SLEDAI score (continuous), abnormal urinary protein (yes = 1, no = 0), abnormal serum creatinine (yes = 1, no = 0), renal-protective agents (yes = 1, no = 0), MMF treatment (yes = 1, no = 0), CYC treatment (yes = 1, no = 0), HCQ treatment (yes = 1, no = 0), GCs dose (continuous) and other immunosuppressants (yes = 1, no = 0) and the above adjusted variables would be excluded when it was the stratified variable. The combined effects of TAC with other drugs on CR The results of TAC combined with CYC or MMF in SLE patients are shown in Table 4 . The results showed that TAC combined with CYC or MMF had better efficacy than CYC alone in SLE patients, with adjusted OR (95% CI) of 2.15(1.15, 4.02) and 2.43(1.20, 4.92), respectively. Similarly, TAC combined with CYC or MMF also had better efficacy than MMF alone, with adjusted OR (95% CI) of 3.14(1.49, 6.64) and 3.54(1.66, 7.58), respectively. Besides, a multiplicative interaction was found between TAC and CYC or MMF, with adjusted P for interaction of 0.043 and 0.025, respectively. Table 4 Effect of TAC combined with MMF or CYC on complete response in SLE patients TAC/CYC/MMF Non-CR, n (%) CR, n (%) OR (95% CI) Adjusted OR (95% CI) CYC as reference CYC 258(75.7) 83(24.3) 1.00 1.00 TAC 51(58.6) 36(41.4) 1.72(1.04,2.85) 1.97(1.10,3.53) TAC + CYC 43(65.2) 23(34.8) 2.02(1.16,3.51) 2.15(1.15,4.02) TAC + MMF 26(53.1) 23(46.9) 2.75(1.49,5.08) 2.43(1.20,4.92) TAC + MMF + CYC 21(50.0) 21(50.0) 3.11(1.62,5.98) 2.69(1.33,5.45) P TAC * CYC 0.038 0.043 MMF as reference MMF 101(77.7) 29(22.3) 1.00 1.00 TAC 51(58.6) 36(41.4) 2.46(1.36,4.45) 2.89(1.50,5.58) TAC + MMF 26(53.1) 23(46.9) 3.08(1.54,6.18) 3.54(1.66,7.58) TAC + CYC 43(65.2) 23(34.8) 1.86(0.97,3.58) 3.14(1.49,6.64) TAC + MMF + CYC 21(50.0) 21(50.0) 3.48(1.67,7.24) 3.94(1.74,8.95) P TAC * MMF 0.013 0.025 The confounding factors included in the multivariate regression analysis were sex (female = 1, male = 0), age (continuous), SLE disease period (continuous), comorbidities (yes = 1, no = 0), SLEDAI score (continuous), abnormal urinary protein (yes = 1, no = 0), abnormal serum creatinine (yes = 1, no = 0), renal-protective agents (yes = 1, no = 0), HCQ treatment (yes = 1, no = 0), GCs dose (continuous) and other immunosuppressants (yes = 1, no = 0). P TAC * CYC is P for interaction between TAC and CYC. P TAC * MMF is P for interaction between TAC and MMF. We analyzed the efficacy of different doses of TAC in combination with MMF or CYC, and the results showed a dose-response relationship between TAC dosage and CR rates in combination therapy (Table 5 ). The optimal efficacy was achieved when ≥ 4 mg/d of TAC was combined with MMF or CYC for treatment, with adjusted OR (95% CI) of 4.87(1.17, 20.17) and 8.86(2.31, 33.94), respectively. Table 5 Effect of different doses of TAC combined with CYC or MMF on complete response in SLE patients TAC/CYC/MMF Non-CR, n (%) CR, n (%) OR (95% CI) Adjusted OR (95% CI) TAC/CYC CYC 258(75.7) 83(24.3) 1.00 1.00 TAC ≤ 2 mg/d 28(58.3) 20(41.7) 2.22(1.19,4.15) 1.74(0.87,3.48) TAC 3 mg/d 20(62.5) 12(37.5) 1.87(0.87,3.98) 1.54(0.67,3.57) TAC 4 mg/d 3(42.9) 4(57.1) 4.14(0.91,18.9) 3.02(0.61,14.93) TAC ≤ 2 mg/d + CYC 41(65.1) 22(34.9) 1.67(0.94,2.96) 1.62(0.80,3.32) TAC 3 mg/d + CYC 19(55.9) 15(44.1) 2.45(1.19,5.05) 2.48(1.06,5.80) TAC 4 mg/d + CYC 4(36.4) 7(63.6) 5.44(1.55,19.05) 4.87(1.17,20.17) P TAC dose * CYC 0.001 0.009 TAC/MMF MMF 101(77.7) 29(22.3) 1.00 1.00 TAC ≤ 2 mg/d 28(58.3) 20(41.7) 2.49(1.23,5.04) 2.74(1.27,5.90) TAC 3 mg/d 20(62.5) 12(37.5) 2.09(0.91,4.77) 2.41(0.99,5.85) TAC 4 mg/d 3(42.9) 4(57.1) 4.64(0.98,21.94) 4.64(0.94,22.86) TAC ≤ 2 mg/d + MMF 32(59.3) 22(40.7) 2.39(1.21,4.74) 2.49(1.10,5.64) TAC 3 mg/d + MMF 11(47.8) 12(52.2) 3.8(1.52,9.5) 4.58(1.47,14.27) TAC 4 mg/d + MMF 4(28.6) 10(71.4) 8.71(2.54,29.81) 8.86(2.31,33.94) P TAC dose * MMF 0.012 0.011 The confounding factors included in the multivariate regression analysis were sex (female = 1, male = 0), age (continuous), SLE disease period (continuous), comorbidities (yes = 1, no = 0), SLEDAI score (continuous), abnormal urinary protein (yes = 1, no = 0), abnormal serum creatinine (yes = 1, no = 0), renal-protective agents (yes = 1, no = 0), HCQ treatment (yes = 1, no = 0), GCs dose (continuous) and other immunosuppressants (yes = 1, no = 0). MMF treatment (yes = 1, no = 0) was further adjusted in TAC/CYC group, and CYC treatment (yes = 1, no = 0) was adjusted in TAC/MMF group. P TAC dose * CYC is P for interaction between different doses of TAC and CYC. P TAC dose * MMF is P for interaction between different doses of TAC and MMF. Discussion In this large retrospective cohort study, we confirmed TAC was effective in achieving CR in SLE patients, with a higher rate observed among those who received TAC more than 4 mg/d or more than 180 days. Furthermore, multiplicative interactions were firstly observed for the combination of TAC with MMF or CYC, with a higher CR rate than these drugs alone. Previous studies have shown that TAC can reduce urinary protein and renal involvement; and its therapeutic effect is more significant than traditional immunosuppressants such as CYC and MMF. 22, 23 Not only may TAC be effective at increasing complete response rates in SLE patients, but TAC also has a dose-response relationship. However, there are few studies on the dose-response of TAC. A five-year follow-up study of LN patients treated with TAC showed that the mean urinary protein / creatinine ratio decreased annually, and meta-analysis also showed that the efficacy of TAC increased over time. 24, 25 Due to the complex metabolism of TAC, which involves the comprehensive regulation of CYP3A5, ABCB1, MDR1 and other gene polymorphisms as well as p-glycoprotein, and the narrow therapeutic window and large differences in blood drug concentration in different populations, therapeutic drug monitoring should be carried out as far as possible during the use of TAC. 26 TAC was found to be effective in different populations, supporting its general effectiveness in improving renal function. This study reported significant therapeutic effects of TAC in patients with hypertension, diabetes, hyperlipidemia, tumors, and secondary Sjogren's syndrome. NO significant effect in reducing urinary protein and disease activity in more severe SLE patients. And previous studies have not explored the extent of treatment efficacy of TAC in patients with varying degrees of urinary protein. The significant effect of TAC may be due to TAC protecting renal function and preventing protein loss by stabilizing synaptic podocyte protein expression and podocyte cytoskeleton, preserving podocyte numbers, reducing podocyte apoptosis, inhibiting podocyte fusion, maintaining podocyte integrity and protecting the glomerular filtration barrier. 27–29 In previous studies, the multi-target therapy of TAC combined with MMF or CYC was stronger than monotherapy. 10, 18 In this study, the combined effect was also observed to be better than monotherapy, and the interactions were observed for the first time. In a meta-analysis of LN patients, the CR rate of TAC combined with MMF was 53.0%, which was significantly higher than the CR rate of 27.1% for TAC combined with CYC ( P < 0.001). 10 In a study of 368 patients, TAC combined with MMF had a significantly higher CR rate and fewer adverse reactions compared to the CYC treatment. 16 The optimal dosage of TAC combined with MMF in patients with SLE lacks literature evidence; however, our findings suggest that ≥ 4 mg/d TAC combined with MMF exhibits superior efficacy. Consistent with our findings, a long-term cohort study also found that 4 mg/d TAC combined with MMF can treat LN patients who are ineffective in standard treatment. 30 Thus, TAC combined with MMF treatment can effectively relieve the condition of SLE patients. This effectiveness may be due to MMF not only inhibiting lymphocyte proliferation and antibody formation but also inhibiting IL-2 production when combined with TAC. In vivo studies have also shown that the combination of MMF and TAC significantly reduces the expression of serum TGF-β1 and cystatin C. 31 Although the CR rate of TAC combined with CYC is not as high as that of combined with MMF in our study, it can still be an important option for multi-target drug therapy in clinical practice. For patients with refractory LN, multi-targeted therapy of TAC combined with CYC may be a potentially valuable approach. Previous studies have reported successful treatment of LN patients who did not respond to IV-CYC by adding TAC. 32 Sakai's study showed that the combination of TAC (3.0 mg/day) and CYC resulted in a significantly higher CR rate after 6 months compared to CYC alone. 33 Our study provides a clearer separation of TAC doses compared with previous studies and confirms the multiplicative interaction between different doses of TAC and CYC. As an alkylating agent that inhibits cell proliferation, CYC primarily treats SLE patients by inhibiting the proliferation of T and B lymphocytes in patients and suppressing the lymphoblast response to antigen stimulation. 34, 35 The combination therapy of TAC and CYC may have a synergistic effect due to their ability to inhibit both T and B lymphocytes. Although the treatment regimen of TAC combined with CYC has not been widely recognized, and there is insufficient research on the pharmacological effects and treatment outcomes between the two drugs, our study has discovered for the first time a multiplicative interaction between TAC and CYC. This study has several limitations that should be considered. First, this is a retrospective observation study. Second, although only 10% of patients underwent renal biopsy, kidney biopsy is not a diagnostic criterion for SLE, and we referred to the diagnostic criteria for LN proposed by the American College of Rheumatology only to ensure that patients with varying degrees of renal involvement were included. Third, although potential confounding factors have been adjusted, it is impossible to collect all other factors such as diet and family history that may affect renal function. Fourth, the assessment of renal response was based on hospital medical records. This may lead to an underestimation of renal response, as patients tend to seek medical attention due to disease flares. Fifth, the potential nephrotoxicity associated with TAC was not investigated in this study and further research is needed to assess the effects on renal function of long-term TAC use, as well as its interaction with other drugs. Despite these limitations, the cohort study has several strengths. It is a large retrospective study that included over 790 Chinese SLE patients, allowing for performing multivariate regression analyses and stratified analyses to minimize the potential confounding effects. Moreover, we firstly reported multiplicative interactions on renal response between TAC and MMF and CYC, and determined the dose-response relationship of TAC doses involved in this therapy. Conclusions In this cohort study, TAC was found to be effective in relieving the condition of SLE patients, with a dose-response relationship in the dosage and the duration of TAC use. In addition, TAC had relieving efficacy in different subgroups of SLE patients, including SLEDAI score > 12, moderate or severe urinary protein and comorbidities. Compared with monotherapy, TAC combined with MMF or CYC was positively correlated with a higher CR rate, and a multiplicative interaction was observed. Declarations Ethics approval and consent to participate The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Nanjing Drum Tower Hospital. (Project code 2022-220-02). Written informed consent was exempt from ethics approval requirements according to national legislation from National Health and Family Planning Commission of China. Consent for publication Not applicable. Availability of data and materials The data presented in this study are available on request from the corresponding author following permission by the ethics committee of the hospital. Competing interests The authors have declared no conflict of interests. Funding This research was supported by funding for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (Z.J is a recipient of grant No. 2022-YXZX-MY-02, X.T is a recipient of grant No. 2021-LCYJ-DBZ-02). Authors' contributions Conceptualization, Q.S, Z.J and L.S; methodology and writing, Q.S, X.Z, Q.G, Z.J; review and editing, X.T, W.S, J.L, G.Y, L.G, S.D, H.C, H.W, B.H, D.W, H.Z, X.F; supervision and administration, Z.J, L.S. All authors have read and agreed to the published version of the manuscript. Conflict of Interest statements The authors have declared no conflict of interests. Acknowledgements The authors would like to thank all the patients for their cooperation in the follow-up visits and the hospital information department for their kind help in the establishment of our database. References Wardowska A. The epigenetic face of lupus: Focus on antigen-presenting cells. Int Immunopharmacol . 2020;81:106262.http://dx./10.1016/j.intimp.2020.106262 Yap DY, Chan TM. Lupus nephritis in Asia: clinical features and management. Kidney diseases . 2015;1(2):100-9 Mahajan A, Amelio J, Gairy K, Kaur G, Levy RA, Roth D, et al. 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00:46:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51333,"visible":true,"origin":"","legend":"\u003cp\u003eSelection of study patients\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4593245/v1/de2eec2c8aa7bdc9569c55e7.jpg"},{"id":72202548,"identity":"9cc3712d-41b8-4b20-bd81-eb2cac04c346","added_by":"auto","created_at":"2024-12-23 16:14:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1078121,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4593245/v1/2a7685b6-a4aa-4e0a-a600-12f76fe72c06.pdf"},{"id":60630619,"identity":"53b1bd7d-985f-4914-8966-61e9de6e360f","added_by":"auto","created_at":"2024-07-19 00:46:43","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":21452,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-4593245/v1/e54e31ca891832a28733e2fb.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of tacrolimus combined with mycophenolate mofetil or cyclophosphamide on renal response in systemic lupus erythematosus patients ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSystemic Lupus Erythematosus (SLE) is a complex autoimmune disease that affects multiple systems, organs, and tissues.\u003csup\u003e1\u003c/sup\u003e Renal involvement is a serious complication of SLE. About 40\u0026ndash;60% of patients with SLE will exhibit lupus nephritis (LN), and about 26% of patients with LN will progress to end-stage renal disease (ESRD).\u003csup\u003e2, 3\u003c/sup\u003e The main clinical manifestations of renal involvement include urinary protein, hematuria, cellular casts, decreased glomerular filtration function, and elevated serum creatinine levels. It is recommended at least annual renal evaluations for SLE patients and more frequent evaluations (every 3 months) for high-risk patients.\u003csup\u003e4, 5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe primary treatment options for SLE include glucocorticoids (GCs), immunosuppressants, and biological agents.\u003csup\u003e6\u003c/sup\u003e Tacrolimus (TAC), a calcineurin inhibitor, works by binding to the FK506 binding protein 12 in T-lymphocytes, thereby inhibiting T-cell activation and calcineurin.\u003csup\u003e7\u003c/sup\u003e It also suppresses B-cell, plasma cell, and CD40 receptor signaling.\u003csup\u003e8\u0026ndash;11\u003c/sup\u003e TAC is effective in improving renal function in SLE patients.\u003csup\u003e8, 9\u003c/sup\u003e Moreover, multitarget therapy has demonstrated significant efficacy in LN patients, and TAC is often used in combination with mycophenolate mofetil (MMF) and cyclophosphamide (CYC).\u003csup\u003e10\u0026ndash;12\u003c/sup\u003e The combination therapy of TAC with other drugs can reduce dosages of TAC and other drugs, as well as drug-related organ damage and infections.\u003csup\u003e13\u0026ndash;15\u003c/sup\u003e Multiple clinical studies have shown that the treatment regimen combining TAC with MMF or CYC has significant renal therapeutic effects for LN patients who have failed to respond to monotherapy.\u003csup\u003e16, 17\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eHowever, the dosage of TAC in combination with other drugs remains controversial, and few studies explored the length of TAC use.\u003csup\u003e13, 14\u003c/sup\u003e Although previous studies involved drug combinations, they rarely assessed the impact of drug interactions on renal response. In addition, previous studies involved fewer than 400 cases and the interactions of TAC with MMF or CYC have been rarely estimated in Chinese SLE patients.\u003csup\u003e18\u003c/sup\u003e Thus, we carried out a retrospective cohort study to investigate the clinical efficacy of TAC and its interactions with MMF or CYC in a Chinese patients with SLE.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eStudy design and participants\u003c/p\u003e \u003cp\u003eThis retrospective cohort study was conducted in the Affiliated Drum Tower Hospital, Nanjing University Medical School. The process of enrolling participants is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. We gathered the medical records of SLE patients who visited the rheumatology and immunology department between January 1, 2010 and December 31, 2021. To be included in the study, patients had to meet at least four of the classification criteria for SLE, as revised and updated by the American College of Rheumatology.\u003csup\u003e15\u003c/sup\u003e Referring to the LN guidelines, we determined the criteria for renal involvement in SLE patients: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) 24-hour protein measurement\u0026thinsp;\u0026gt;\u0026thinsp;500 mg or urine protein / creatinine ratio\u0026thinsp;\u0026gt;\u0026thinsp;30 mg/mmol. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The patient had cellular casts and pathological tube pattern. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The patient had active urinary sediment.\u003csup\u003e19\u003c/sup\u003e The exclusion criteria were: patients did not meet renal involvement, medical information was incomplete, there was no follow-up record or follow-up was less than 3 months, CR at baseline, and patients were not treated with TAC, CYC or MMF.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eData collection and definition\u003c/p\u003e \u003cp\u003eWe gathered data from medical records of both inpatients and outpatients with SLE, including demographics, diagnostic information, physical exams, SLEDAI score, laboratory test data, medication records, pathology reports, and imaging information. The missing laboratory test and medication information of hospitalized patients was supplemented by the latest outpatient medical information within three months before and after hospitalization. The patient's comorbidities included one or more of hypertension, hyperlipidemia, diabetes, secondary Sjogren's syndrome and cancer. We defined the time of the patient\u0026rsquo;s first hospitalization as the baseline and defined the nearest follow-up after 3 months from baseline as the endpoint. The immunosuppressants used by the patients during this period were defined as combination therapy, and several diseases that occurred during or before this period but had not been cured were defined as comorbidities. Patients who continuously used TAC from baseline to endpoint were defined as TAC users, and those who did not use TAC at baseline were defined as non-TAC users.\u003c/p\u003e \u003cp\u003eThe patients used renal-protective agents including dinoprost sodium, hekunshenxi capsule, huangkui, hiaoduqing granules, shenfu kanglu capsule, lanthanum carbonate, sevelamer carbonate and pioglitazone hydrochloride and glimepiride. The list of abnormal ranges for each laboratory indicator is: eGFR\u0026thinsp;\u0026lt;\u0026thinsp;90 mL/min\u0026middot;1.73 m\u003csup\u003e2\u003c/sup\u003e or \u0026gt;\u0026thinsp;106 mL/min\u0026middot;1.73 m\u003csup\u003e2\u003c/sup\u003e, C3\u0026thinsp;\u0026le;\u0026thinsp;0.8 g/L, C4\u0026thinsp;\u0026le;\u0026thinsp;0.2 g/L. The urinary protein levels were divided into three groups: mild urinary protein: 24-hour urinary protein less than 1000 mg; moderate urinary protein: 24-hour urinary protein between 1000 mg and 3500 mg; severe urinary protein: 24-hour urinary protein greater than 3500 mg.\u003csup\u003e20\u003c/sup\u003e The patients were treated with different kinds of GC, and we converted all GC doses to prednisone doses according to \u0026ldquo;\u003cem\u003eDexamethasone Suppression Test\u003c/em\u003e\u0026rdquo; (5 mg prednisone\u0026thinsp;=\u0026thinsp;5 mg prednisone dragon\u0026thinsp;=\u0026thinsp;4 mg methylprednisolone\u0026thinsp;=\u0026thinsp;0.75 mg dexamethasone).\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe follow-up record was taken at least 3 months after baseline. Our primary outcome was CR of renal function, which was defined as normal urinary protein (24-hour protein measurement excretion less than 500 mg/day or urinary protein negative or weakly positive) and a serum creatinine level of 106.08 \u0026micro;mol/L or less (or a decrease of at least 25% from baseline).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data were analyzed using IBM SPSS STATISTICS 25.0 software. The Shapiro-Wilk test was applied to test the normality of continuous variables. Non-normally distributed variables were described by the median and interquartile range (IQR) and compared using the Mann-Whitney U test. Categorical variables were described by their count (percentage) and compared using the χ\u003csup\u003e2\u003c/sup\u003e test or Fisher's exact test. A binary unconditional logistic regression model was used to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) between treatment with TAC and overall CR. The OR and \u003cem\u003eP\u003c/em\u003e-value for trend were estimated for each exposure category and dose of TAC using dummy variables and ordinal coding. Stratified analyses were conducted based on factors such as sex, age, SLEDAI score at baseline, disease course, comorbidities, urinary protein, laboratory tests, and combined drug use.\u003c/p\u003e \u003cp\u003eWe used a binary logistic regression model to assess the potential multiplicative interaction between TAC and MMF or CYC. The confounding factors included in the binary regression analysis were treated with sex, age, SLE disease period, comorbidities, SLEDAI score, renal-protective agents, HCQ treatment, GCs dose, abnormal urinary protein, abnormal serum creatinine and other immunosuppressants. These adjusted variables were excluded when they were used as stratified variables. To further eliminate the influence of confounding factors and verify the credibility of the results, we employed binary logistic regression analysis for propensity score matching, controlling for sensitivity factors that have a significant impact on the outcome. The propensity score model included recipient's age, sex, SLEDAI score, abnormal urinary protein, and abnormal creatinine rate. We then conducted a secondary analysis of the main results associated with the relationship between TAC and SLE patients.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eCharacteristics of the study patients\u003c/p\u003e \u003cp\u003eAmong the 793 SLE patients, 244 patients were in the TAC use group and 549 patients were in the TAC non-use group. The demographic and baseline clinical characteristics of the patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The age of TAC non-users was older than that of users. The median age (IQR) for TAC non-users was 37.0(28.0, 50.0), and for TAC users (IQR) was 27.0(22.0, 35.0) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median weight (IQR) was 55.00(49.00, 63.00) for TAC non-users and 57.63(55.00, 65.50) for TAC users (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The dose of CYC or MMF combined with TAC was lower than that used alone.\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\u003eBaseline clinical characteristics of SLE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAC non-users\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAC users\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Female), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e487(88.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e226(92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, M (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0(28.0,50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.0(22.0,35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, M (IQR), kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.0(50.0,62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.6(55.0,65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSLE disease period, M (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5(0.0,6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0(0.0,3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal biopsy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSLEDAI score, M (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.0(8.3,20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.0(12.0,21.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up duration, M (IQR), days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126(94.0,221.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118.0(91.0,199.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities, n (%)\u003c/p\u003e \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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e465(84.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e217(88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206(37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130(53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e316(57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167(68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.728\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary Sjogren\u0026rsquo;s syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eIndicators of renal involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary protein\u003c/p\u003e \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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e129(23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31(12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141(25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55(22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e279(50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158(64.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological tube pattern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126(32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62(25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e263(48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79(32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal eGFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155(80.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154(77.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-dsDNA positive, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e400(72.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow complement, n (%)\u003c/p\u003e \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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3\u0026thinsp;\u0026le;\u0026thinsp;0.8 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e373(74.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175(71.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC4\u0026thinsp;\u0026le;\u0026thinsp;0.2 g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e404(81.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151(61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatments\u003c/p\u003e \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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC dose, M (IQR), mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0(2.0,3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMF, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e208(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91(37.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMF dose, M (IQR), g/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0(1.0,1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0(0.8,1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYC, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e419(76.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108(44.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYC dose, M (IQR), g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.4(0.4,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4(0.2,0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCs, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e546(99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e207(84.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCs maintenance dose, M (IQR), mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.0(20.0,40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.0(15.0,50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.814\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal-protective agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166(30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCQ, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e488(88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179(73.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther immunosuppressants, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e420(76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138(56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeflunomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116(21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTripterygium wilfordii\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAzathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetronidazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSunitinib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eM (IQR): median (interquartile range), eGFR: estimated glomerular filtration rate, Anti-dsDNA: anti-double stranded DNA, GCs: glucocorticoids, HCQ: hydroxychloroquine, MMF: mycophenolate mofetil, CYC: cyclophosphamide.\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\u003eCompared with TAC non-users, the median course of disease period, SLEDAI score, and severe urinary protein proportion were significantly higher in TAC users, while the proportion of moderate urinary, abnormal serum creatinine, anti-dsDNA, and low C4 were lower in TAC users. TAC non-users were more likely to use renal-protective agents, GCs, HCQ, CYC and other immunosuppressants. MMF were more prevalent in the TAC user group.\u003c/p\u003e \u003cp\u003eEffect of TAC use on CR\u003c/p\u003e \u003cp\u003eCR was achieved in 27.9% (221) of all the SLE patients, and the use of TAC was positively associated with CR, with adjusted OR (95% CI) of 2.82(1.89, 4.22). TAC dose\u0026thinsp;\u0026ge;\u0026thinsp;4 mg/d and TAC use\u0026thinsp;\u0026gt;\u0026thinsp;180 days were found to be associated with an increased likelihood of CR compared to non-users, with adjusted OR (95% CI) of 5.65(2.35, 13.55) and 3.60(2.02, 6.41), respectively. A dose-response relationship was also observed between CR and the dose (\u003cem\u003eP\u003c/em\u003e for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and duration (\u003cem\u003eP\u003c/em\u003e for trend\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of TAC use, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After propensity score matching, age, SLEDAI score, comorbidities, abnormal urinary protein, and abnormal creatinine rate were balanced between TAC users and non-users. A total of 396 patients were matched, including 198 patients in the TAC use group and 198 patients in the TAC non-use group, and 32.1% achieved CR (Supplementary Table\u0026nbsp;1). The use of TAC was positively correlated with CR, with adjusted OR (95% CI) of 2.40(1.48, 3.88). And a dose-response relationship between TAC dosage and duration of use and CR was also observed (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eComplete response rates according to TAC use in SLE patients and these patients after propensity score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNon-CR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;572\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;221\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC treatment\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e431(78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118(21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141(57.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103(42.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67(1.93,3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.82(1.89,4.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC dose\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e431(78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118(21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88(61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56(38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.32(1.57,3.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.42(1.53,3.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.72(1.65,4.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.92(1.65,5.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.48(2.40,12.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.65(2.35,13.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e \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 \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTAC length of use\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e431(78.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118(21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(61.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.27(1.30,3.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.48(1.33,4.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026ndash;180 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67(58.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47(41.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.56(1.68,3.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.60(1.59,4.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;180 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.26(1.95,5.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.60(2.02,6.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e \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 \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePSM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;572\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;221\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC treatment\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155(78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114(57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84(42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.66(1.71,4.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.40(1.48,3.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC dose\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155(78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74(63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.09(1.26,3.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.88(1.09,3.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.17(1.73,5.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.95(1.53,5.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.18(2.29,16.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.08(1.84,14.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e \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 \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTAC length of use\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155(78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(65.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.92(0.96,3.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.64(0.79,3.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026ndash;180 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.70(1.58,4.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.60(1.47,4.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;180 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(52.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.27(1.78,5.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.88(1.49,5.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e \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 \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eThe confounding factors included in the multivariate regression analysis of all patients were sex (female\u0026thinsp;=\u0026thinsp;1, male\u0026thinsp;=\u0026thinsp;0), age (continuous), SLE disease period (continuous), comorbidities (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), SLEDAI score (continuous), abnormal urinary protein (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), abnormal serum creatinine (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), renal-protective agents (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), MMF treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), CYC treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), HCQ treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), GCs dose (continuous) and other immunosuppressants (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0).\u003c/p\u003e \u003cp\u003eThe confounding factors included in the multivariate regression analysis of patients after propensity score matching were sex (female\u0026thinsp;=\u0026thinsp;1, male\u0026thinsp;=\u0026thinsp;0), SLE disease period (continuous), renal-protective agents (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), MMF treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), CYC treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), HCQ treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), GCs dose (continuous) and other immunosuppressants (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0).\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\u003eWe also conducted a stratified analysis of 14 factors such as gender, age, SLE disease period, SLEDAI score, urinary protein, comorbidities, laboratory tests, and therapeutic drugs (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). CR rate was significantly higher in the TAC use group compared to the non-use group across most strata, but was not significantly different in male patients, mild urinary protein patients, patients with low complement 3 and patients without defined comorbidities, those receiving renal-protective agents treatment and those rejecting HCQ treatment.\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\u003eComplete response rates using TAC in subgroups of SLE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-users\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eTAC Users\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-CR/CR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-CR/CR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48/14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98(0.28,3.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01(0.18,5.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e383/104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127/99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.87(2.04,4.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.04(1.99,4.66)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148/41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90/67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.69(1.68,4.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.08(1.71,5.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e283/77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.59(1.58,4.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.76(1.52,4.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSLE disease period, years\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e261/75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101/71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.08(1.71,5.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.45(1.64,3.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170/43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40/32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.76(1.52,4.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.16(1.78,5.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSLEDAI score\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199/57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.94(1.14,3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.93(1.00,3.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253/61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.19(2.10,4.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.42(2.02,5.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary protein\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89/40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.22(0.54,2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.95(0.27,3.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112/29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26/29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.31(2.21,8.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.62(1.94,11.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230/49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95/63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.11(2.00,4.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.80(1.63,4.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eComplement 3, g/L\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e296/77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.75(1.86,4.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.91(1.81,4.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.90(1.03,3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.99(0.85,4.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eComplement 4, g/L\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e312/92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79/72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.09(2.08,4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.90(1.80,4.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73/21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62/31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.74(0.91,3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.26(1.23,8.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60/24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.00(0.82,4.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.85(0.38,8.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e371/94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e126/91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.85(2.00,4.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.08(2.01,4.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eRenal-protective agents treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e295/88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116/91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.63(1.83,3.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.18(0.98,4.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25/12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.18(0.98,4.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.46(0.93,6.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eGCs treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18/19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e428/118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123/84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.48(1.76,3.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.74(1.81,4.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMMF treatment\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258/83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94/59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.95(1.30,2.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.40(1.25,4.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e173/35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47/44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.63(2.67,8.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.34(2.57,11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHCQ treatment\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50/11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38/27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.23(1.43,7.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.41(0.59,9.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e381/107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103/76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.63(1.82,3.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.93(1.89,4.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCYC treatment\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101/29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77/59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67(1.56,4.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.33(1.44,7.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e330/89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64/44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.55(1.63,4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.10(2.32,7.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOther immunosuppressants\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101/28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55/51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.34(1.90,5.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.85(2.12,11.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e330/90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86/52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.22(1.46,3.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.28(1.89,5.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eThe confounding factors included in the multivariate regression analysis were sex (female\u0026thinsp;=\u0026thinsp;1, male\u0026thinsp;=\u0026thinsp;0), age (continuous), SLE disease period (continuous), comorbidities (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), SLEDAI score (continuous), abnormal urinary protein (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), abnormal serum creatinine (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), renal-protective agents (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), MMF treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), CYC treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), HCQ treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), GCs dose (continuous) and other immunosuppressants (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0) and the above adjusted variables would be excluded when it was the stratified variable.\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\u003eThe combined effects of TAC with other drugs on CR\u003c/p\u003e \u003cp\u003eThe results of TAC combined with CYC or MMF in SLE patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The results showed that TAC combined with CYC or MMF had better efficacy than CYC alone in SLE patients, with adjusted OR (95% CI) of 2.15(1.15, 4.02) and 2.43(1.20, 4.92), respectively. Similarly, TAC combined with CYC or MMF also had better efficacy than MMF alone, with adjusted OR (95% CI) of 3.14(1.49, 6.64) and 3.54(1.66, 7.58), respectively. Besides, a multiplicative interaction was found between TAC and CYC or MMF, with adjusted \u003cem\u003eP\u003c/em\u003e for interaction of 0.043 and 0.025, respectively.\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\u003eEffect of TAC combined with MMF or CYC on complete response in SLE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC/CYC/MMF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-CR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYC as reference\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258(75.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83(24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.72(1.04,2.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.97(1.10,3.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(65.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.02(1.16,3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.15(1.15,4.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.75(1.49,5.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.43(1.20,4.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;MMF\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.11(1.62,5.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.69(1.33,5.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC * CYC\u003c/sub\u003e\u003c/p\u003e \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 \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMF as reference\u003c/b\u003e\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101(77.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.46(1.36,4.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.89(1.50,5.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.08(1.54,6.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.54(1.66,7.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(65.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.86(0.97,3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.14(1.49,6.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;+\u0026thinsp;MMF\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.48(1.67,7.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.94(1.74,8.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC * MMF\u003c/sub\u003e\u003c/p\u003e \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 \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eThe confounding factors included in the multivariate regression analysis were sex (female\u0026thinsp;=\u0026thinsp;1, male\u0026thinsp;=\u0026thinsp;0), age (continuous), SLE disease period (continuous), comorbidities (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), SLEDAI score (continuous), abnormal urinary protein (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), abnormal serum creatinine (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), renal-protective agents (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), HCQ treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), GCs dose (continuous) and other immunosuppressants (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0). \u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC * CYC\u003c/sub\u003e is \u003cem\u003eP\u003c/em\u003e for interaction between TAC and CYC. \u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC * MMF\u003c/sub\u003e is \u003cem\u003eP\u003c/em\u003e for interaction between TAC and MMF.\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\u003eWe analyzed the efficacy of different doses of TAC in combination with MMF or CYC, and the results showed a dose-response relationship between TAC dosage and CR rates in combination therapy (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The optimal efficacy was achieved when \u0026ge;\u0026thinsp;4 mg/d of TAC was combined with MMF or CYC for treatment, with adjusted OR (95% CI) of 4.87(1.17, 20.17) and 8.86(2.31, 33.94), respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of different doses of TAC combined with CYC or MMF on complete response in SLE patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC/CYC/MMF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-CR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCR, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC/CYC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258(75.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83(24.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;\u0026le;\u0026thinsp;2 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.22(1.19,4.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.74(0.87,3.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 3 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.87(0.87,3.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.54(0.67,3.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 4 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.14(0.91,18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.02(0.61,14.93)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;\u0026le;\u0026thinsp;2 mg/d\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(65.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(34.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.67(0.94,2.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.62(0.80,3.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 3 mg/d\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(55.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.45(1.19,5.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.48(1.06,5.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 4 mg/d\u0026thinsp;+\u0026thinsp;CYC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.44(1.55,19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.87(1.17,20.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC dose * CYC\u003c/sub\u003e\u003c/p\u003e \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 \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTAC/MMF\u003c/b\u003e\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101(77.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;\u0026le;\u0026thinsp;2 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.49(1.23,5.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.74(1.27,5.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 3 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.09(0.91,4.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.41(0.99,5.85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 4 mg/d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.64(0.98,21.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.64(0.94,22.86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u0026thinsp;\u0026le;\u0026thinsp;2 mg/d\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(59.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.39(1.21,4.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.49(1.10,5.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 3 mg/d\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.8(1.52,9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.58(1.47,14.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC 4 mg/d\u0026thinsp;+\u0026thinsp;MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.71(2.54,29.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.86(2.31,33.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC dose * MMF\u003c/sub\u003e\u003c/p\u003e \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 \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eThe confounding factors included in the multivariate regression analysis were sex (female\u0026thinsp;=\u0026thinsp;1, male\u0026thinsp;=\u0026thinsp;0), age (continuous), SLE disease period (continuous), comorbidities (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), SLEDAI score (continuous), abnormal urinary protein (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), abnormal serum creatinine (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), renal-protective agents (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), HCQ treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0), GCs dose (continuous) and other immunosuppressants (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0). MMF treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0) was further adjusted in TAC/CYC group, and CYC treatment (yes\u0026thinsp;=\u0026thinsp;1, no\u0026thinsp;=\u0026thinsp;0) was adjusted in TAC/MMF group. \u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC dose * CYC\u003c/sub\u003e is \u003cem\u003eP\u003c/em\u003e for interaction between different doses of TAC and CYC. \u003cem\u003eP\u003c/em\u003e\u003csub\u003eTAC dose * MMF\u003c/sub\u003e is \u003cem\u003eP\u003c/em\u003e for interaction between different doses of TAC and MMF.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large retrospective cohort study, we confirmed TAC was effective in achieving CR in SLE patients, with a higher rate observed among those who received TAC more than 4 mg/d or more than 180 days. Furthermore, multiplicative interactions were firstly observed for the combination of TAC with MMF or CYC, with a higher CR rate than these drugs alone.\u003c/p\u003e \u003cp\u003ePrevious studies have shown that TAC can reduce urinary protein and renal involvement; and its therapeutic effect is more significant than traditional immunosuppressants such as CYC and MMF.\u003csup\u003e22, 23\u003c/sup\u003e Not only may TAC be effective at increasing complete response rates in SLE patients, but TAC also has a dose-response relationship. However, there are few studies on the dose-response of TAC. A five-year follow-up study of LN patients treated with TAC showed that the mean urinary protein / creatinine ratio decreased annually, and meta-analysis also showed that the efficacy of TAC increased over time.\u003csup\u003e24, 25\u003c/sup\u003e Due to the complex metabolism of TAC, which involves the comprehensive regulation of CYP3A5, ABCB1, MDR1 and other gene polymorphisms as well as p-glycoprotein, and the narrow therapeutic window and large differences in blood drug concentration in different populations, therapeutic drug monitoring should be carried out as far as possible during the use of TAC.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTAC was found to be effective in different populations, supporting its general effectiveness in improving renal function. This study reported significant therapeutic effects of TAC in patients with hypertension, diabetes, hyperlipidemia, tumors, and secondary Sjogren's syndrome. NO significant effect in reducing urinary protein and disease activity in more severe SLE patients. And previous studies have not explored the extent of treatment efficacy of TAC in patients with varying degrees of urinary protein. The significant effect of TAC may be due to TAC protecting renal function and preventing protein loss by stabilizing synaptic podocyte protein expression and podocyte cytoskeleton, preserving podocyte numbers, reducing podocyte apoptosis, inhibiting podocyte fusion, maintaining podocyte integrity and protecting the glomerular filtration barrier.\u003csup\u003e27\u0026ndash;29\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn previous studies, the multi-target therapy of TAC combined with MMF or CYC was stronger than monotherapy.\u003csup\u003e10, 18\u003c/sup\u003e In this study, the combined effect was also observed to be better than monotherapy, and the interactions were observed for the first time. In a meta-analysis of LN patients, the CR rate of TAC combined with MMF was 53.0%, which was significantly higher than the CR rate of 27.1% for TAC combined with CYC (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003csup\u003e10\u003c/sup\u003e In a study of 368 patients, TAC combined with MMF had a significantly higher CR rate and fewer adverse reactions compared to the CYC treatment.\u003csup\u003e16\u003c/sup\u003e The optimal dosage of TAC combined with MMF in patients with SLE lacks literature evidence; however, our findings suggest that \u0026ge;\u0026thinsp;4 mg/d TAC combined with MMF exhibits superior efficacy. Consistent with our findings, a long-term cohort study also found that 4 mg/d TAC combined with MMF can treat LN patients who are ineffective in standard treatment.\u003csup\u003e30\u003c/sup\u003e Thus, TAC combined with MMF treatment can effectively relieve the condition of SLE patients. This effectiveness may be due to MMF not only inhibiting lymphocyte proliferation and antibody formation but also inhibiting IL-2 production when combined with TAC. \u003cem\u003eIn vivo\u003c/em\u003e studies have also shown that the combination of MMF and TAC significantly reduces the expression of serum TGF-β1 and cystatin C.\u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough the CR rate of TAC combined with CYC is not as high as that of combined with MMF in our study, it can still be an important option for multi-target drug therapy in clinical practice. For patients with refractory LN, multi-targeted therapy of TAC combined with CYC may be a potentially valuable approach. Previous studies have reported successful treatment of LN patients who did not respond to IV-CYC by adding TAC.\u003csup\u003e32\u003c/sup\u003e Sakai's study showed that the combination of TAC (3.0 mg/day) and CYC resulted in a significantly higher CR rate after 6 months compared to CYC alone.\u003csup\u003e33\u003c/sup\u003e Our study provides a clearer separation of TAC doses compared with previous studies and confirms the multiplicative interaction between different doses of TAC and CYC. As an alkylating agent that inhibits cell proliferation, CYC primarily treats SLE patients by inhibiting the proliferation of T and B lymphocytes in patients and suppressing the lymphoblast response to antigen stimulation.\u003csup\u003e34, 35\u003c/sup\u003e The combination therapy of TAC and CYC may have a synergistic effect due to their ability to inhibit both T and B lymphocytes. Although the treatment regimen of TAC combined with CYC has not been widely recognized, and there is insufficient research on the pharmacological effects and treatment outcomes between the two drugs, our study has discovered for the first time a multiplicative interaction between TAC and CYC.\u003c/p\u003e \u003cp\u003eThis study has several limitations that should be considered. First, this is a retrospective observation study. Second, although only 10% of patients underwent renal biopsy, kidney biopsy is not a diagnostic criterion for SLE, and we referred to the diagnostic criteria for LN proposed by the American College of Rheumatology only to ensure that patients with varying degrees of renal involvement were included. Third, although potential confounding factors have been adjusted, it is impossible to collect all other factors such as diet and family history that may affect renal function. Fourth, the assessment of renal response was based on hospital medical records. This may lead to an underestimation of renal response, as patients tend to seek medical attention due to disease flares. Fifth, the potential nephrotoxicity associated with TAC was not investigated in this study and further research is needed to assess the effects on renal function of long-term TAC use, as well as its interaction with other drugs. Despite these limitations, the cohort study has several strengths. It is a large retrospective study that included over 790 Chinese SLE patients, allowing for performing multivariate regression analyses and stratified analyses to minimize the potential confounding effects. Moreover, we firstly reported multiplicative interactions on renal response between TAC and MMF and CYC, and determined the dose-response relationship of TAC doses involved in this therapy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this cohort study, TAC was found to be effective in relieving the condition of SLE patients, with a dose-response relationship in the dosage and the duration of TAC use. In addition, TAC had relieving efficacy in different subgroups of SLE patients, including SLEDAI score\u0026thinsp;\u0026gt;\u0026thinsp;12, moderate or severe urinary protein and comorbidities. Compared with monotherapy, TAC combined with MMF or CYC was positively correlated with a higher CR rate, and a multiplicative interaction was observed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Nanjing Drum Tower Hospital. (Project code 2022-220-02). Written informed consent was exempt from ethics approval requirements according to national legislation from National Health and Family Planning Commission of China.\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eThe data presented in this study are available on request from the corresponding author following permission by the ethics committee of the hospital.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors have declared no conflict of interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThis research was supported by funding for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (Z.J is a recipient of grant No. 2022-YXZX-MY-02, X.T is a recipient of grant No. 2021-LCYJ-DBZ-02).\u003c/p\u003e\n\u003ch3\u003eAuthors\u0026apos; contributions\u003c/h3\u003e\n\u003cp\u003eConceptualization, Q.S, Z.J and L.S; methodology and writing, Q.S, X.Z, Q.G, Z.J; review and editing, X.T, W.S, J.L, G.Y, L.G, S.D, H.C, H.W, B.H, D.W, H.Z, X.F; supervision and administration, Z.J, L.S. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003ch3\u003eConflict of Interest statements\u003c/h3\u003e\n\u003cp\u003eThe authors have declared no conflict of interests.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eThe authors would like to thank all the patients for their cooperation in the follow-up visits and the hospital information department for their kind help in the establishment of our database.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWardowska A. The epigenetic face of lupus: Focus on antigen-presenting cells. \u003cem\u003eInt Immunopharmacol\u003c/em\u003e. 2020;81:106262.http://dx./10.1016/j.intimp.2020.106262\u003c/li\u003e\n\u003cli\u003eYap DY, Chan TM. 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Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide. \u003cem\u003eIntern Med\u003c/em\u003e. 2013;52(10):1125-30.http://dx./10.2169/internalmedicine.52.9366\u003c/li\u003e\n\u003cli\u003eSakai R, Kurasawa T, Nishi E, Kondo T, Okada Y, Shibata A, et al. Efficacy and safety of multitarget therapy with cyclophosphamide and tacrolimus for lupus nephritis: a prospective, single-arm, single-centre, open label pilot study in Japan. \u003cem\u003eLupus\u003c/em\u003e. 2018;27(2):273-82.http://dx./10.1177/0961203317719148\u003c/li\u003e\n\u003cli\u003eTakada K, Illei GG, Boumpas DT. Cyclophosphamide for the treatment of systemic lupus erythematosus. \u003cem\u003eLupus\u003c/em\u003e. 2001;10(3):154-61.http://dx./10.1191/096120301671376017\u003c/li\u003e\n\u003cli\u003ede Jonge ME, Huitema AD, Rodenhuis S, Beijnen JH. Clinical pharmacokinetics of cyclophosphamide. \u003cem\u003eClin Pharmacokinet\u003c/em\u003e. 2005;44(11):1135-64.http://dx./10.2165/00003088-200544110-00003\u003c/li\u003e\n\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-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"lupus nephritis, tacrolimus, mycophenolate mofetil, cyclophosphamide, dose-response","lastPublishedDoi":"10.21203/rs.3.rs-4593245/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4593245/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to determine the therapeutic effect of tacrolimus (TAC) and its combination with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) on the complete response (CR) in patients with systemic lupus erythematosus (SLE).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study based on medical data was conducted among SLE patients taking at least one of TAC, MMF and CYC during 2010\u0026ndash;2021. Odds ratio (OR) and 95% confidence interval (CI) were calculated and multiplicative interactions were estimated using logistic regression models.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 793 SLE patients, 27.9% (221 cases) patients achieved CR after at least 3 months. TAC use was positively associated with CR with adjusted OR (95% CI) of 2.82(1.89, 4.22) in overall, as well as in subgroups of SLE patients with SLEDAI score\u0026thinsp;\u0026gt;\u0026thinsp;12, moderate or severe urinary protein and comorbidities. The dose-response effect on CR was further observed at the dose of TAC more than 4 mg/d and more than 180 days, with adjusted OR (95% CI) of 5.65(2.35, 13.55), and 3.60(2.02, 6.41) respectively. Moreover, the combined effect of TAC with MMF or CYC was better than monotherapy with the significant multiplicative interaction, with adjusted OR (95% CI) of 2.43(1.20,4.92) and 3.14(1.49,6.64), respectively, and similar results were also observed for the combination of different doses of TAC with MMF or CYC.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTAC can effectively alleviate the condition of patients with SLE and may interact with MMF or CYC, suggesting that the combination therapy of TAC with MMF or CYC may produce greater benefits for patients with SLE.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eThis is a purely observational study that does not require registration.\u003c/p\u003e","manuscriptTitle":"The effect of tacrolimus combined with mycophenolate mofetil or cyclophosphamide on renal response in systemic lupus erythematosus patients ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 00:46:38","doi":"10.21203/rs.3.rs-4593245/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-14T20:50:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-13T06:22:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-02T03:24:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254930996256004136513023932753620908671","date":"2024-07-23T18:51:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78393032155436987716110729674730929886","date":"2024-07-21T11:40:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-17T15:18:54+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-25T18:58:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-25T18:57:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-25T18:57:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Rheumatology","date":"2024-06-17T09:39:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32872cb8-227d-417d-abca-9505ff043376","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:08:22+00:00","versionOfRecord":{"articleIdentity":"rs-4593245","link":"https://doi.org/10.1186/s41927-024-00439-x","journal":{"identity":"bmc-rheumatology","isVorOnly":false,"title":"BMC Rheumatology"},"publishedOn":"2024-12-18 15:58:15","publishedOnDateReadable":"December 18th, 2024"},"versionCreatedAt":"2024-07-19 00:46:38","video":"","vorDoi":"10.1186/s41927-024-00439-x","vorDoiUrl":"https://doi.org/10.1186/s41927-024-00439-x","workflowStages":[]},"version":"v1","identity":"rs-4593245","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4593245","identity":"rs-4593245","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}