Comparative Safety and Immunological Effects of Tocilizumab versus Cyclophosphamide in Takayasu Arteritis: A Retrospective Cohort Study

Comparative Safety and Immunological Effects of Tocilizumab versus Cyclophosphamide in Takayasu Arteritis: A Retrospective Cohort Study | 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 Comparative Safety and Immunological Effects of Tocilizumab versus Cyclophosphamide in Takayasu Arteritis: A Retrospective Cohort Study Hua Liao, Wei Cao, Lili Pan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9330968/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Takayasu arteritis (TAK) requires long-term immunosuppression. Cyclophosphamide (CTX) is effective but toxic, whereas tocilizumab provides targeted IL-6 inhibition; however, comparative data on efficacy and safety remain limited. Objective To compare the efficacy, safety, and immunological effects of TCZ versus CTX in patients with TAK. Methods This retrospective cohort study included 75 patients with TAK (TCZ, n = 46; CTX, n = 29). Disease activity NIH score, inflammatory markers, complement levels, and lymphocyte subsets were assessed at baseline and at 3, 6, and 12 months. Adverse events were systematically recorded. Results Both treatments significantly reduced inflammatory markers and improved NIH scores over 12 months, with TCZ achieving faster disease activity control at 3 months. Lymphocyte subset analysis showed stable B-cell counts in the TCZ group, whereas CTX was associated with marked B-cell depletion. The TCZ group had a significantly lower incidence of infections than the CTX group (10.9% vs. 31.0%, p = 0.037) and fewer menstrual disorders (p = 0.026). Other adverse events were comparable between groups. No deaths occurred during follow-up. Conclusion TCZ demonstrated comparable or improved disease control with a more favorable safety profile than CTX. Preservation of B-cell–mediated immunity may be associated with the reduced infection risk observed with TCZ, highlighting a potential mechanism underlying its clinical advantage. Takayasu arteritis tocilizumab B lymphocytes Figures Figure 1 Figure 2 Introduction Takayasu arteritis (TAK) is a rare chronic granulomatous vasculitis predominantly involving the aorta and its major branches, most frequently affecting women under the age of 40. The global incidence is estimated at approximately 1.2–2.6 cases per million person-years[ 1 , 2 ]. Pathologically, TAK is characterized by transmural vascular inflammation with variable degrees of fibrosis, which may lead to stenosis, occlusion, and ischemic complications in affected organs [ 3 ]. Clinical manifestations are diverse and may include pulselessness, refractory hypertension, and multi-organ dysfunction. Approximately half of the patients develop irreversible vascular damage within 5 years of diagnosis, indicating that the treatment window is very limited. Although advances in imaging techniques such as FDG-PET/CT have enhanced early detection [ 4 ], the etiology of TAK remains poorly understood. Current treatment strategies continue to rely on glucocorticoids and empiric immunosuppressive agents,, with limited individualization based on high-quality evidence. While glucocorticoids combined with CTX have historically remained a common induction therapy for moderate-to-severe TAK in Chinese clinical practice. This approach is reflected in recent Chinese diagnostic and treatment guidelines and national expert consensus statements, as well as in clinical reviews summarizing experiences from Chinese cohorts [ 5 , 6 ].CTX exerts immunosuppressive effects through non-selectively selective inhibition of DNA synthesis, targeting rapidly proliferating immune cells to promptly control inflammation and alleviate clinical symptoms. However, its broad cytotoxicity restrictsclinical use, with frequent adverse events including bone marrow suppression, infections, hepatotoxicity, nephrotoxicity, and gonadal toxicity. Long-term administration is associated with cumulative dose-dependent risks such as secondary malignancies. Studies indicate that approximately 30% of patients experience neutropenia and a significantly increased risk of severe infections, while nearly 40% develop disease relapses or suboptimal responses to treatment [ 7 ], highlighting the trade-off between efficacy and safety. In recent years, advances in understanding the immunopathogenesis of TAK have underscored the pivotal role of the interleukin-6 (IL-6) signaling pathway in mediating vascular inflammation[ 8 ]. Tocilizumab (TCZ), a humanized monoclonal antibody that targets the IL-6 receptor, inhibits IL-6–mediated activation of the JAK/STAT signaling pathway, thereby suppressing Th17 cell differentiation and the production of acute-phase proteins, leading to attenuation of the inflammatory cascade. Emerging evidence suggests that TCZ can rapidly reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in refractory TAK, induce clinical remission[ 9 ], and substantially reduce glucocorticoid requirements[ 10 ]. Nevertheless, its potential risk such as infections, hepatotoxicity warrant caution[ 11 ]. Due to a lack of high-quality comparative studies, it remains uncertain whether TCZ offers a more favorable risk-benefit profile compared to conventional immunosuppressants In this retrospective study, we included hospitalized TAK patients treated with either TCZ or CTX. We compared changes in laboratory parameters at 3, 6, and 12 months, the incidence of adverse events, and immunological profiles between the two treatment groups. Particular attention was paid to associations between infections, liver function abnormalities, myelosuppression, and alterations in B lymphocyte subsets. Our objective was to evaluate the comparative effectiveness and safety of these two therapeutic strategies, and to further elucidate the immunoregulatory role of the IL-6 pathway in TAK, thereby providing a clinical basis for future optimization of targeted therapies. This study provides real-world comparative evidence linking B-cell preservation to reduced infection risk in TAK. Materials and Methods Study Subjects This retrospective study included 75 patients with TAK who were hospitalized at Beijing Anzhen Hospital from December 2012 to July 2024. The inclusion criteria were a confirmed diagnosis of TAK according to the 1990 American College of Rheumatology classification criteria[ 12 ] and treatment with either TCZ or CTX. The exclusion criteria were: (1) the use of TCZ and CTX consecutively or simultaneously within 6 months; (2) presence of active infectious diseases such as hepatitis B or tuberculosis; (3) receipt of other biologic agents for TAK treatment. Ultimately, 46 patients were assigned to the TCZ group, and 29 patients to the CTX group. The retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University [No. 2026060X]. Clinical Data Collection and Indicators In this study, National Institutes of Health Stroke Scale (NIH scores) and associated indicators were utilized during the clinical data collection process to ensure data accuracy and reliability. baseline data collection encompassed patients' clinical manifestations and laboratory parameters. The NIH score[ 1 ] was employed as a quantitative tool to assess disease activity and clinical symptoms. During the treatment period, the research team systematically collected laboratory parameters at 3, 6, and 12 months to monitor therapeutic response and disease progression. The selected laboratory parameters included erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), complement 3 (C3), complement 4 (C4), C-reactive protein (CRP), and lymphocyte subset analysis, including absolute counts and percentages of B lymphocytes. All collected data went rigorous review to ensure completeness and consistency, providing a solid foundation for subsequent statistical analysis. Recording and Assessment of Adverse Events ALL adverse events occurring in participants during the treatment period were systematically recorded and evaluated. All patients were required to attend regular follow up visits t to facilitate timely identification and documentation of treatment-related adverse events. At each visit, the research team conducted detailed inquiries regarding patient-reported symptoms and complaints, recording any potential treatment-associated side effects. Adverse events included various new-onset infections, manifestations of bone marrow suppression: leukopenia(WBC < 3.5*10 9 /L, NE < 1.5*10 9 /L), thrombocytopenia(PLT 40U/L, AST>40U/L), renal dysfunction(Scr>80µmol/L), reactivation of hepatitis B(HBV-DNA positive), allergic reactions (drug allergy), menstrual disturbances (irregular menstruation or amenorrhea), newly diagnosed malignancies, or recurrence of pre-existing tumors. Statistical analysis All statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). A two-tailed P-value of < 0.05 was considered statistically significant. Continuous variables were assessed for normality using the Shapiro–Wilk test. Normally distributed data were presented as mean ± standard deviation (SD) and compared between groups using the independent-samples t-test. Non-normally distributed data were expressed as median with interquartile range (IQR) and were analyzed using the Mann–Whitney U test (rank-sum test). Categorical variables were presented as frequencies and percentages, and intergroup comparisons were performed using the Chi-square test or Fisher’s exact test as appropriate. Kaplan–Meier survival analysis was used to estimate event-free survival, and differences between groups were assessed using the log-rank test. Results 1.Baseline characteristics of patients A total of 75 patients were enrolled in this study, and assigned to either the TCZ group or the CTX group. The TCZ group, comprised 4 male and 42 female patients, with a mean age of 41 ± 15 years, and disease duration ranging from 1 to 300 months, and a median of 18 months. The CTX group, included 3 male patients and 26 female patients, with an average age of 44 ± 10 years, and disease duration ranging from 1 to 360 months, and a median of 48 months. No significant differences were observed between the two groups in terms of gender distribution or age prior to treatment (p > 0.05). Other baseline characteristics, including disease duration, ESR, CRP and related parameters showed no statistically significant differences between groups (p > 0.05), indicating comparable baseline conditions at enrollment. With respect to concomitant medication use, the proportion of methotrexate(MTX) use was significantly higher in the TCZ group than in the CTX group (p < 0.001), whereas usage rates of other agents, including mycophenolate mofetil (MMF), hydroxychloroquine (HCQ), glucocorticoids, azathioprine (AZA), and leflunomide (LEF) did not differ significantly between groups (p > 0.05) (see Table 1 ). Table 1 Baseline Comparison Between CTX and TCZ Groups general condition TCZ(n = 46) CTX(n = 29) p Age(year) 41 ± 15 44 ± 10 0.370 Sex(female), n( %) 42(91.30) 26(89.66) 1.000 Course of disease(month) 18(6,120) 48(3,126) 0.441 Onset(age) 35 ± 15 37 ± 11 0.478 BMI 21.93 ± 3.17 22.57 ± 3.44 0.565 Complication HBP, n(%) 13(34.21) 6(21.42) 0.286 T2DM, n(%) 2(5.13) 1(3.45) 1.000 Hyperlipidemia, n(%) 9(23.07) 2(6.90) 0.100 CAD, n(%) 5(12.82) 3(10.34) 1.000 Cerebrovascular disease, n(%) 5(12.82) 2(6.90) 0.690 Menopause, n(%) 7(18.91) 9(34.62) 0.240 Smoking, n(%) 5(11.82) 3(10.34) 1.000 Drinking, n(%) 2(5.13) 1(3.45) 1.000 Medication history MTX,n(%) 39(84.78) 8(27.59) < 0.001 MMF,n(%) 16(34.78) 6(20.69) 0.298 HCQ,n(%) 4(8.70) 3(10.34) 1.000 Glucocorticoid,n(%) 37(80.43) 26(89.66) 0.349 AZA,n(%) 2(4.35) 0(0) 0.519 LEF,n(%) 1(2.17) 4(13.79) 0.070 Laboratory tests and disease activity WBC(10 9 /L) 6.38(5.68,8.38) 7.58() 0.226 Lymphocytes(10 9 /L) 1.94(1.59,2.62) 1.93(,1.69,2.30) 0.986 NE(10 9 /L) 4.81 ± 2.07 4.95 ± 1.83 0.756 ALT(U/L) 11.00(9.00,18.00) 11.00(7.90,14.00) 0.473 AST(U/L) 16.00 ± 6.32 17.96 ± 8.21 0.293 Cr(µmol/L) 54.40(49.00,66.70) 56.50(49.20,65.30) 0.917 ESR(mm/h) 16.50(7.00,39.00) 29.00(12.00,62.00) 0.148 CRP(mg/L) 4.00(1.47,15.43) 8.90(2.31,57.73) 0.221 NIH Score 2(2,3) 3(2,3) 0.075 HBP, hypertension; T2DM, type 2 diabetes; CAD, coronary artery disease; MTX, methotrexate; MMF, mycophenolate mofetil; HCQ, hydroxychloroquine; AZA, azathioprine; LEF, leflunomide; WBC, white blood cell; NE, neutrophil; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, creatinine; TG, triglyceride; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein. In addition, there was no significant difference in immune indicators or lymphocyte subsets between the CTX group and the TCZ group prior to treatment, except for CD3+(%) levels, which were significantly higher in the TCZ group than in the CTX group (p = 0.028), although values in both groups remained within the normal reference range. (see Table 2 ). Table 2 Comparison of immune indicators and lymphocyte subsets between the CTX group and the TCZ group IL-6(pg/ml) TCZ(n = 46) CTX(n = 29) p 11.70(4.70,20.34) 8.06(2.88,26.68) 0.472 TNF-ɑ(pg/ml) 9.57(2.73,32.70) 8.45(2.81,18.28) 0.598 IgA(g/L) 2.48(1.83,3.45) 2.83(2.00,3.68) 0.530 IgG(g/L) 13.19 ± 4.12 14.55 ± 3.88 0.164 IgM(g/L) 1.41 ± 0.56 1.71 ± 0.93 0.090 IgE(g/L) 13.80(2.60,42.90) 18.20(10.00,107.25) 0.068 C3(g/L) 1.21 ± 0.25 1.22 ± 0.25 0.917 C4(g/L) 0.23(0.19,0.29) 0.23(0.18,0.33) 0.788 CD3+(%) 76.20(72.95,80.25) 72.95(69.03,75.13) 0.028 CD4+(%) 44.96 ± 7.01 44.92 ± 6.08 0.982 CD8+(%) 27.54 ± 7.36 25.59 ± 6.56 0.355 B lymphocyte(%) 13.64 ± 5.75 16.02 ± 6.57 0.227 NK(%) 8.60(6.25,12.25) 10.20(5.50,15.73) 0.790 CD4%/CD8% 1.75(1.23,2.11) 1.78(1.38,2.38) 0.654 CD3+(/µL) 1289.00(1100.50,1767.00) 1484.50(1299.25,1772.25) 0.316 CD4+(/µL) 780.00(647.00,938.50) 985.00(758.00,1188.50) 0.077 CD8+(/µL) 505.00(339.00,827.50) 467.00(417.25,714.00) 0.873 B lymphocytes(/µL) 261.06 ± 143.24 363.69 ± 173.91 0.051 NK(/µL) 149.00(115.50,206.00) 218.56() 0.343 2.Laboratory and Immunological Responses to Tocilizumab and Cyclophosphamide Therapy At 3 months aftertreatment initiation, significant intergroup differences emerged. The TCZ group exhibited lower ESR (p < 0.001) and CRP (p = 0.016) levels (Fig. 1A-Fig. 1B). The serum IL-6 level in the TCZ group was significantly higher than that in the CTX group (P < 0.001) (Fig. 1C). Additionally, C4 levels were significantly lower in the TCZ group (p = 0.020) (Fig. 1I). By 6 months, the TCZ group continued to show reduced ESR (p < 0.001), CRP (p = 0.002), C3 (p = 0.004), and C4 (p = 0.001) levels relative to the CTX group. Notably, B lymphocyte counts (both percentage and absolute values) were significantly higher in the TCZ group (p < 0.001), (Fig. 1). At 12 months post-treatment, the TCZ group maintained lower ESR (p = 0.006) and C4 (p = 0.025) levels. B lymphocyte counts remained elevated in the TCZ group compared with the CTX group (percentage: p = 0.005; absolute count: p = 0.008), suggesting sustained preservation of B cells. The total lymphocyte count was also higher in the TCZ group at 12 months (p = 0.005) (Fig. 1). After 3 and 6 months of treatment, the TCZ group demonstrated significantly lower NIH scores than the CTX group (p < 0.001) (Fig. 1D). Comparison of Adverse Event Probability All patients were followed up for a median of 6 months (range, 1–12 months). During the follow-up period, adverse events were reported in 16 patients in the TCZ group and 13 patients in the CTX group. Data on adverse events were unavailable for 1 patient in the TCZ group and 2 patients in the CTX group due to loss to follow-up. No deaths occurred in either group during the observation period. Infection was the most common adverse event, occurring in 5 patients (including 1 case of severe acute gastroenteritis) in the TCZ group and in 9 patients (including 2 severe cases—1 pyelonephritis and 1 herpes zoster) in the CTX group. The overall infection rate was significantly lower in the TCZ group (p = 0.021), whereas the incidence of severe infections did not differ significantly between the two groups. Abnormal liver function was observed in 9 patients in the TCZ group and 1 patient in the CTX group (p = 0.113). Reactivation of hepatitis B occurred in 1 patient in each group. Menstrual disorders were reported in 3 patients in the CTX group but none in the TCZ group (p = 0.034). Other adverse events included 1 case of corneal and oral ulcers in the TCZ group and 1 case each of vaginal bleeding and gastrointestinal symptoms in the CTX group, with no significant difference (p = 0.648) (Fig. 2). Discussion In this retrospective cohort study, designed to compare the efficacy, safety, and immunological effects of TCZ and CTX in TAK, we found that TCZ was associated with both superior disease control and a more favorable safety profile over a 12-month treatment period. TCZ treatment resulted in significantly greater improvements in key indicators of disease activity, including lower NIH scores and more pronounced reductions in inflammatory markers such as ESR and CRP, compared with CTX. At the same time, TCZ was associated with a significantly lower incidence of infections and menstrual disorders. Our findings suggest that preservation of B-cell–mediated humoral immunity may represent a key mechanism underlying the lower infection risk observed with IL-6 inhibition. Importantly, these clinical advantages were accompanied by distinct immunological differences between the two therapies. Lymphocyte subset analysis demonstrated that TCZ preserved B lymphocyte (CD19⁺) counts throughout follow-up, whereas CTX induced marked B-cell depletion. This preservation of humoral immune components provides a biologically plausible explanation for the reduced infection risk observed in the TCZ group. Collectively, these findings suggest that TCZ offers a more favorable risk–benefit profile than CTX by achieving superior control of disease activity while minimizing unnecessary immunosuppression, particularly in patients at increased risk of infection, while remaining an effective therapeutic option for the management of TAK. In this study, both the TCZ and CTX groups demonstrated significant improvement in inflammatory activity following treatment, as evidenced by marked reductions in CRP and ESR compared with baseline. These findings indicate that both conventional immunosuppressants and targeted biologic therapies can effectively control systemic inflammation in TAK. While, the therapeutic response was notably faster in the TCZ group, with a notable decline in inflammatory markers and improvement in NIH scores observed as early as 3 months after treatment initiation, whereas comparable improvements in the CTX group typically required more than 6 months of therapy. This discrepancy suggests that IL-6 signaling plays a critical role in the early inflammatory cascade of TAK, and its inhibition may rapidly suppress disease activity[ 13 , 14 , 6 ]. Tocilizumab exerts its effects by selectively binding to IL-6 receptors and inhibiting downstream JAK/STAT signaling, thereby suppressing acute-phase protein synthesis (e.g., CRP) and Th17 cell activation. This mechanism, which directly targets a central pathway of inflammation, likely accounts for its more rapid onset of therapeutic effect compared to the nonspecific cytotoxic action of CTX, which inhibits DNA synthesis in proliferating immune cells. Consequently, CTX achieves inflammation control more slowly and may delay the restoration of immune homeostasis. In this study, TCZ-treated patients showed significantly lower ESR and CRP levels at 3 months compared with those treated with CTX, alongside parallel improvement in clinical symptoms such as fatigue, fever, and vascular bruits, confirming its rapid and stable anti-inflammatory effects. In summary, tocilizumab showed superior therapeutic efficiency and a faster onset of action during the induction phase, suggesting that IL-6 blockade represents a promising strategy for optimizing future treatment approaches in TAK[ 15 ]. Importantly, our lymphocyte subset analysis revealed a key mechanistic distinction between the two agents. In the TCZ group, both total lymphocyte counts and B lymphocyte (CD19⁺) counts remained largely unchanged before and after treatment, indicating preservation of baseline immune competence. In contrast, the CTX group exhibited a marked reduction in both absolute B cell counts and B cell proportions following treatment, reflecting the broad immunosuppressive and cytotoxic properties of CTX. This B cell depletion provides a direct biological explanation for the substantially higher incidence of infections observed in the CTX group compared with the TCZ group. B cells play a central role in humoral immunity through antibody production and immune regulation. CTX-induced B cell depletion leads to decreased immunoglobulin levels, particularly IgG and IgM, thereby weakening host defense against bacterial and viral pathogens and increasing susceptibility to opportunistic infections such as urinary tract infections and herpes zoster. Thus, the increased infection risk associated with CTX in our study is not incidental but mechanistically linked to its profound suppressive effect on B cells. In contrast, IL-6 plays a pivotal role in TAK pathogenesis by mediating vascular wall inflammation, promoting acute-phase protein synthesis, and regulating Th17-cell activation and cytokine release [ 16 ], while having minimal direct impact on B cell survival. By selectively blocking IL-6 receptor signaling [ 17 ], TCZ effectively suppresses vascular inflammation without inducing B cells depletion, thereby controlling disease activity while preserving humoral immune defenses. This selective immunomodulatory mechanism confers a clear advantage in reducing infection risk while maintaining immune competence[ 14 ]. Additionally, menstrual disturbances were observed in the CTX group[ 18 ] but were absent in the TCZ group, highlighting a potential advantage of TCZ in women of reproductive age. Although liver function abnormalities occurred more frequently in the TCZ group, the difference did not reach statistical significance, indicating that hepatic monitoring remains necessary during TCZ therapy. Other adverse events—including drug allergy, bone marrow suppression, hepatitis B reactivation, new-onset malignancy, and miscellaneous events—did not differ significantly between the groups. Overall, TCZ demonstrated a narrower and more manage able adverse event profile. This safety advantage is mechanistically attributed to its selective IL-6 receptor blockade, which suppresses inhibits inflammatory signaling without broadly suppressing DNA synthesis or causing cytotoxicity in proliferating immune cells, unlike CTX[ 19 , 20 ]. Consequently, TCZ has a reduced impact on systemic immunity, lowering the risks of infection, bone marrow suppression, and reproductive toxicity[ 20 , 21 ]. IL-6-targeted therapy selectively modulates inflammatory responses while preserving baseline immune defenses, resulting in improved clinical tolerability and safety. TCZ not only effectively controls TAK activity but also demonstrates a favorable safety profile [ 6 ], particularly in patients at high risk of infection or with fertility concerns, providing critical insights for clinical therapeutic decision-making In this study, the effects of TCZ and CTX on lymphocyte subsets demonstrated significant differences. In the TCZ group, B lymphocyte (CD19+) and total lymphocyte counts remained largely unchanged before and after treatment, indicating that IL-6 pathway inhibition selectively modulates inflammation while preserving baseline immune function. In contrast, the CTX group exhibited a marked reduction in B lymphocyte counts post-treatment, reflecting the broad immunosuppressive effect of CTX. Aclear correlation exists between B cell depletion and increased infection risk. B cells play a pivotal role in humoral immunity through antibody production and regulation of immune responses against pathogens. CTX-induced B cell depletion results in decreased levels of antibodies, particularly IgG and IgM, thereby weakening humoral immunity and increasing susceptibility to opportunistic infections such as urinary tract infections and herpes zoster. In this study, the infection rate was 31% in the CTX group versus 10.9% in the TCZ group, indicating that B cell depletion is a key mechanism underlying CTX-associated infections. Moreover, TAK is not a B cell-driven disease; its pathophysiology primarily involves T cell-mediated granulomatous inflammation, with minimal direct involvement of B cells [ 16 ].Therefore, B cell depletion by CTX is not essential for disease control and may instead increase the risk of infections and other immune-related adverse events. Based on these immunological insights, the selective IL-6 inhibition by TCZ aligns more closely with the pathophysiology of TAK, effectively controlling vascular inflammation without inducing unnecessary systemic immunosuppression. CTX can effectively control inflammation in TAK; however, CTX-induced B cell depletion significantly contributes to the elevated risk of infections. In contrast, TCZ, maintains B lymphocyte counts while effectively controlling disease activity, offering a therapeutic approach that balances efficacy with preserved immune defense, thus providing a mechanistic rationale for its use as a safer and more targeted therapy. From an immunological perspective, TCZ selectively inhibits IL-6 signaling to suppress vascular inflammation without significantly affecting B lymphocyte survival or function, thereby preserving humoral immune competence and reducing the incidence of infections and other immune-related adverse events[ 22 ]. In contrast, CTX, as a broad-spectrum cytotoxic agent, induces profound B cell depletion and impairs antibody production, leading to compromised host defense and increased susceptibility to bacterial and viral infections[ 23 ]. Extensive evidence has demonstrated that B cells are essential for protective immunity against a wide range of pathogens through the production of pathogen-specific antibodies, antigen presentation, and modulation of T-cell responses. B cell deficiency or dysfunction is strongly associated with recurrent respiratory tract infections, herpesvirus reactivation, and opportunistic infections[ 24 , 25 ]. Furthermore, depletion of B cells has been shown to markedly impair long-term humoral immune memory, predisposing patients to both primary and recurrent infections[ 26 , 27 ]. Therefore, CTX-induced B cell loss represents not only a transient immunosuppressive effect but also a sustained disruption of host immune defense. Considering the pathophysiology of TAK—primarily a T cell-mediated granulomatous vasculitis with limited direct B cell involvement—B cell depletion is neither necessary for disease control nor justified therapeutically, and instead poses avoidable immunological risks. This further provides a strong mechanistic rationale for favoring targeted IL-6 inhibition in clinical decision-making: precise blockade of the IL-6 pathway achieves effective suppression of vascular inflammation while minimizing unnecessary destruction of humoral immunity. Finally, the study underscores the importance of individualized treatment strategies for TAK patients. For individuals exhibiting high disease activity or rapid progression, tocilizumab(TCZ) may be preferred as an induction agent, typically in combination with glucocorticoids to achieve prompt control of inflammation. This preference is supported by randomized trial data and real-world evidence demonstrating superior efficacy and steroid-sparing effects of TCZ compared to conventional immunosuppressants like CTX in refractory TAK[ 28 ]. In patients with a history of infections or in women of childbearing potential, TCZ offers distinct advantages by reducing infection risk and minimizing menstrual disturbances. Conversely, CTX should be used cautiously in clinically stable patients or those with impaired B cell function, with careful evaluation of the risk-benefit profile. Limitations This study has limitations. Its retrospective, single-center design may introduce selection bias and limit generalizability. Despite a relatively larger sample, it remains underpowered to detect rare adverse events or assess long-term outcomes. Mechanistic insights were inferred from peripheral blood and literature rather than direct functional assays. Prospective, multicenter studies are needed. Conclusion TCZ may provide a more favorable balance between efficacy and safety compared with CTX in patients with TAK. Its ability to control disease activity while preserving B-cell–mediated immunity may have important implications for reducing infection risk, particularly in patients requiring long-term immunosuppressive therapy. Abbreviations TAK= Takayasu arteritis CTX=Cyclophosphamide IL-6= interleukin-6 TCZ= Tocilizumab CRP= C-reactive protein ESR= erythrocyte sedimentation rate TNF-α= tumor necrosis factor-alpha C3= complement 3 C4= complement 4 NIH scores= National Institutes of Health Stroke Scale IgA= Immunoglobulin A IgG= Immunoglobulin G IgM= Immunoglobulin M NE= neutrophil count LYM= lymphocyte count Declarations Ethics Approval and Consent to Participate: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University [No. 2026060X]. Conflicts of Interest: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Consent to participate: Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the participants for their participation in this research. Funding: This work was supported by the National Natural Science Foundation of China (82270427). High-level Research Special Project of the National Clinical Research Center for Cardiovascular Diseases of Beijing Anzhen Hospital (2025AZD3001, 2025AZB6002). The fund providers played no role in the study design, data collection or analysis, decision to publish or the preparation of the manuscript. Author Contribution: Hua Liao conceived the study, performed the statistical analysis and prepared the first draft of the manuscript. Cao Wei performed the data collection and the statistical analysis. Lili Pan took part in the study design and revision of the manuscript. All authors read and approved the final submitted version of the manuscript. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author or the first author on reasonable request. References Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M et al. Takayasu arteritis. ANN INTERN MED. 1994;120(11):919 – 29. 'doi:'10.7326/0003-4819-120-11-199406010-00004. Somashekar A, Leung YT. Updates in the diagnosis and management of Takayasu's arteritis. POSTGRAD MED. 2023;135(sup1):14–21. 'doi:'10.1080/00325481.2022.2159723. Mruthyunjaya P, Misra R. Update on Takayasu arteritis: Year in review 2024. INT J RHEUM DIS. 2024;27(9):e15314. 'doi:'10.1111/1756-185X.15314. Dejaco C, Ramiro S, Bond M, Bosch P, Ponte C, Mackie SL et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update. ANN RHEUM DIS. 2024;83(6):741 – 51. 'doi:'10.1136/ard-2023-224543. Tian X, Zeng X. Chinese guideline for the diagnosis and treatment of Takayasu’s arteritis (2023). Rheumatology and Immunology Research. 2024;5(1):5–26. 'doi:'10.1515/rir-2024-0002. Liao H, Du J, Li T, Pan L. Tocilizumab for faster and safer remission of Takayasu's arteritis. THER ADV CHRONIC DIS. 2022;13:374180291. 'doi:'10.1177/20406223221131715. Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. ANN RHEUM DIS. 2020;79(1):19–30. 'doi:'10.1136/annrheumdis-2019-215672. Esatoglu SN, Hatemi G. Takayasu arteritis. CURR OPIN RHEUMATOL. 2022;34(1):18–24. 'doi:'10.1097/BOR.0000000000000852. Nakaoka Y, Isobe M, Tanaka Y, Ishii T, Ooka S, Niiro H et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study. RHEUMATOLOGY. 2020;59(9):2427-34. 'doi:'10.1093/rheumatology/kez630. Shuai Z, Zhang C, Shuai Z, Ge S. Efficacy and safety of biological agents in the treatment of patients with Takayasu arteritis: a systematic review and meta-analysis. EUR REV MED PHARMACO. 2021;25(1):250–62. 'doi:'10.26355/eurrev_202101_24391. Curtis JR, Perez-Gutthann S, Suissa S, Napalkov P, Singh N, Thompson L et al. Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. SEMIN ARTHRITIS RHEU. 2015;44(4):381-8. 'doi:'10.1016/j.semarthrit.2014.07.006. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129-34. 'doi:'10.1002/art.1780330811. Nakaoka Y, Isobe M, Tanaka Y, Ishii T, Ooka S, Niiro H et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study. RHEUMATOLOGY. 2020;59(9):2427-34. 'doi:'10.1093/rheumatology/kez630. Singh A, Danda D, Hussain S, Najmi AK, Mathew A, Goel R et al. Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials. MOD RHEUMATOL. 2021;31(1):197–204. 'doi:'10.1080/14397595.2020.1724671. Sun X, Li J, Duan X, Wang Y, Chen Y, Wang Y et al. Mycophenolate mofetil plus methotrexate versus cyclophosphamide with sequential azathioprine for treatment of Takayasu arteritis. ANN RHEUM DIS. 2025;84(10):1733-42. 'doi:'10.1016/j.ard.2025.07.018. Kong X, Sun Y, Ma L, Chen H, Wei L, Wu W, et al. The critical role of IL-6 in the pathogenesis of Takayasu arteritis. CLIN EXP RHEUMATOL. 2016;34(3 Suppl 97):S21–7. Yoshifuji H. Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy. MOD RHEUMATOL. 2019;29(2):287 – 93. 'doi:'10.1080/14397595.2018.1546358. Abdi M, Fadaee M, Jourabchi A, Karimzadeh H, Kazemi T. Cyclophosphamide-Induced Infertility and the Impact of Antioxidants. AM J REPROD IMMUNOL. 2024;92(6):e70014. 'doi:'10.1111/aji.70014. Misra DP, Singh K, Rathore U, Patro P, Tomelleri A, Campochiaro C et al. The effectiveness of tocilizumab and its comparison with tumor necrosis factor alpha inhibitors for Takayasu Arteritis: A systematic review and meta-analysis. AUTOIMMUN REV. 2023;22(3):103275. 'doi:'10.1016/j.autrev.2023.103275. Mekinian A, Biard L, Lorenzo D, Novikov PI, Salvarani C, Espitia O et al. Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study. RMD OPEN. 2023;9(2). 'doi:'10.1136/rmdopen-2022-002830. Yazici Y. Treatment of systemic vasculitis. CURR OPIN RHEUMATOL. 2025. 'doi:'10.1097/BOR.0000000000001129. Nakaoka Y, Isobe M, Takei S, Tanaka Y, Ishii T, Yokota S et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). ANN RHEUM DIS. 2018;77(3):348 – 54. 'doi:'10.1136/annrheumdis-2017-211878. Todd J, Thomas P, Nguyen S. Cyclophosphamide and prednisolone for chemotherapy naive B cell multicentric lymphoma in dogs: 32 cases (2017–2021). J SMALL ANIM PRACT. 2022;63(1):52 – 5. 'doi:'10.1111/jsap.13428. Efe O, Sauvage G, Chung J, Jeyabalan A, Al Jurdi A, Seethapathy HS et al. Protracted COVID-19 pneumonia in B-cell-depleted patients. Rheumatology (Oxford, England). 2025;64(4):2303-5. 'doi:'10.1093/rheumatology/keae703. Ogishi M, Kitaoka K, Good-Jacobson KL, Rinchai D, Zhang B, Wang J et al. Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling. IMMUNITY. 2024;57(12):2790 – 807. 'doi:'10.1016/j.immuni.2024.10.014. Peters J, Longbrake EE. Infection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease. MULT SCLER RELAT DIS. 2022;68:104400. 'doi:'10.1016/j.msard.2022.104400. Ahmed A, Lippner E, Khanolkar A. Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future. CELLS-BASEL. 2022;11(21):3353. 'doi:'10.3390/cells11213353. Mekinian A, Comarmond C, Resche-Rigon M, Mirault T, Kahn JE, Lambert M et al. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients.CIRCULATION. 2015;132(18):1693 – 700. 'doi:'10.1161/CIRCULATIONAHA.114.014321. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviews received at journal 28 Apr, 2026 Reviewers agreed at journal 17 Apr, 2026 Reviewers invited by journal 15 Apr, 2026 Editor invited by journal 13 Apr, 2026 Editor assigned by journal 10 Apr, 2026 Submission checks completed at journal 10 Apr, 2026 First submitted to journal 06 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9330968","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":626366605,"identity":"603bf575-d78d-4335-a6c6-c80e79972eeb","order_by":0,"name":"Hua Liao","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Liao","suffix":""},{"id":626366606,"identity":"03dd0370-3c70-406b-924f-940df9ce5c04","order_by":1,"name":"Wei Cao","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Cao","suffix":""},{"id":626366607,"identity":"4c477465-93f7-43cc-bcfd-f8ffc2d25bdd","order_by":2,"name":"Lili Pan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACPmbmBhib8QGDARFa2JgZ4VqYDYjTwoDQwiZBlMPY2BnbpAtq7tgbXDtjVvmj4I48A/vhoxsIOKxNesaxZ4kzZ+eY3eYxeGbYwJOWdoOgFh62wwn80kAtDAaHGRskeMyI0PLvsD0bUEvhD4PD9sRp4W07zNgP1MLAY3A4kRgtzdYz+w4D/ZJWLA3UktxGyC/8/IcP3i74dtje4Hbyxo8//hy27Wc/fAyvFiBgkUa1l4ByEGD+TISiUTAKRsEoGMkAAKQbQreu01DCAAAAAElFTkSuQmCC","orcid":"","institution":"Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Lili","middleName":"","lastName":"Pan","suffix":""}],"badges":[],"createdAt":"2026-04-06 07:24:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9330968/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9330968/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107619135,"identity":"3975809e-7a99-4cb7-8989-08c4ce297213","added_by":"auto","created_at":"2026-04-23 09:27:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1597605,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in inflammatory markers, immunoglobulins, complement levels, leukocyte counts, and lymphocyte subsets were evaluated at baseline and at 3, 6, and 12 months after treatment initiation. TCZ treatment was associated with significantly lower erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and NIH disease activity scores compared with CTX during follow-up. Serum IL-6 levels increased in the TCZ group at 3 months. Complement levels (C3 and C4) were lower in the TCZ group at several time points. Lymphocyte subset analysis showed that B-cell counts and B-cell percentages were significantly higher in the TCZ group at 6 and 12 months, whereas other lymphocyte subsets showed no significant differences between groups. Panels: (A) ESR; (B) CRP; (C) IL-6; (D) NIH score; (E) IgA; (F) IgG; (G) IgM; (H) C3; (I) C4; (J) neutrophil count; (K) lymphocyte count; (L) CD3⁺ T cells; (M) CD4⁺ T cells; (N) CD8⁺ T cells; (O) NK cells; (P) B-cell absolute counts; (Q) B-cell percentage.\u003c/p\u003e\n\u003cp\u003eData are shown as mean values. Red circles indicate TCZ and green squares indicate CTX. *P \u0026lt; 0.05, **P \u0026lt; 0.01, ***P \u0026lt; 0.001. TAK, Takayasu arteritis; CTX, Cyclophosphamide; TCZ, Tocilizumab; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IL-6, interleukin-6; NIH scores, National Institutes of Health Stroke Scale; IgA, Immunoglobulin A; IgG, Immunoglobulin G; IgM, Immunoglobulin M; C3, complement 3; C4, complement 4; NE, neutrophil count; LYM, lymphocyte count.\u003c/p\u003e","description":"","filename":"Fig1LC1.png","url":"https://assets-eu.researchsquare.com/files/rs-9330968/v1/2bccaf4975466935e7921121.png"},{"id":107619085,"identity":"32335b5f-a5a6-4173-a2b0-9b07551f089a","added_by":"auto","created_at":"2026-04-23 09:27:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1026539,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of adverse events between the TCZ and CTX groups. Forest plot showing the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events in patients with Takayasu arteritis treated with tocilizumab (TCZ) versus cyclophosphamide (CTX). The vertical dashed line represents an OR of 1. Values to the right of the line indicate a higher risk in the TCZ group, whereas values to the left indicate a higher risk in the CTX group. Adverse events analyzed included severe infection, other infections, abnormal liver function, hepatitis B activation, tumor occurrence, myelosuppression, allergy, menstrual disorders, total events, and infection.\u003c/p\u003e\n\u003cp\u003eAbbreviations: TCZ, tocilizumab; CTX, cyclophosphamide; OR, odds ratio; CI, confidence interval.\u003c/p\u003e","description":"","filename":"Fig2LC.png","url":"https://assets-eu.researchsquare.com/files/rs-9330968/v1/c049e525f427a0c520d2c1ff.png"},{"id":107619187,"identity":"dbda0feb-28b3-42b7-916e-d61c95ad082e","added_by":"auto","created_at":"2026-04-23 09:27:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3134947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9330968/v1/db00ec4a-af8e-4420-b736-98595cfd4f17.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Safety and Immunological Effects of Tocilizumab versus Cyclophosphamide in Takayasu Arteritis: A Retrospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTakayasu arteritis (TAK) is a rare chronic granulomatous vasculitis predominantly involving the aorta and its major branches, most frequently affecting women under the age of 40. The global incidence is estimated at approximately 1.2\u0026ndash;2.6 cases per million person-years[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Pathologically, TAK is characterized by transmural vascular inflammation with variable degrees of fibrosis, which may lead to stenosis, occlusion, and ischemic complications in affected organs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Clinical manifestations are diverse and may include pulselessness, refractory hypertension, and multi-organ dysfunction. Approximately half of the patients develop irreversible vascular damage within 5 years of diagnosis, indicating that the treatment window is very limited. Although advances in imaging techniques such as FDG-PET/CT have enhanced early detection [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], the etiology of TAK remains poorly understood. Current treatment strategies continue to rely on glucocorticoids and empiric immunosuppressive agents,, with limited individualization based on high-quality evidence.\u003c/p\u003e \u003cp\u003eWhile glucocorticoids combined with CTX have historically remained a common induction therapy for moderate-to-severe TAK in Chinese clinical practice. This approach is reflected in recent Chinese diagnostic and treatment guidelines and national expert consensus statements, as well as in clinical reviews summarizing experiences from Chinese cohorts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].CTX exerts immunosuppressive effects through non-selectively selective inhibition of DNA synthesis, targeting rapidly proliferating immune cells to promptly control inflammation and alleviate clinical symptoms. However, its broad cytotoxicity restrictsclinical use, with frequent adverse events including bone marrow suppression, infections, hepatotoxicity, nephrotoxicity, and gonadal toxicity. Long-term administration is associated with cumulative dose-dependent risks such as secondary malignancies. Studies indicate that approximately 30% of patients experience neutropenia and a significantly increased risk of severe infections, while nearly 40% develop disease relapses or suboptimal responses to treatment [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], highlighting the trade-off between efficacy and safety.\u003c/p\u003e \u003cp\u003eIn recent years, advances in understanding the immunopathogenesis of TAK have underscored the pivotal role of the interleukin-6 (IL-6) signaling pathway in mediating vascular inflammation[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Tocilizumab (TCZ), a humanized monoclonal antibody that targets the IL-6 receptor, inhibits IL-6\u0026ndash;mediated activation of the JAK/STAT signaling pathway, thereby suppressing Th17 cell differentiation and the production of acute-phase proteins, leading to attenuation of the inflammatory cascade. Emerging evidence suggests that TCZ can rapidly reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in refractory TAK, induce clinical remission[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and substantially reduce glucocorticoid requirements[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Nevertheless, its potential risk such as infections, hepatotoxicity warrant caution[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Due to a lack of high-quality comparative studies, it remains uncertain whether TCZ offers a more favorable risk-benefit profile compared to conventional immunosuppressants\u003c/p\u003e \u003cp\u003eIn this retrospective study, we included hospitalized TAK patients treated with either TCZ or CTX. We compared changes in laboratory parameters at 3, 6, and 12 months, the incidence of adverse events, and immunological profiles between the two treatment groups. Particular attention was paid to associations between infections, liver function abnormalities, myelosuppression, and alterations in B lymphocyte subsets. Our objective was to evaluate the comparative effectiveness and safety of these two therapeutic strategies, and to further elucidate the immunoregulatory role of the IL-6 pathway in TAK, thereby providing a clinical basis for future optimization of targeted therapies. This study provides real-world comparative evidence linking B-cell preservation to reduced infection risk in TAK.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Subjects\u003c/h2\u003e \u003cp\u003eThis retrospective study included 75 patients with TAK who were hospitalized at Beijing Anzhen Hospital from December 2012 to July 2024. The inclusion criteria were a confirmed diagnosis of TAK according to the 1990 American College of Rheumatology classification criteria[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and treatment with either TCZ or CTX. The exclusion criteria were: (1) the use of TCZ and CTX consecutively or simultaneously within 6 months; (2) presence of active infectious diseases such as hepatitis B or tuberculosis; (3) receipt of other biologic agents for TAK treatment. Ultimately, 46 patients were assigned to the TCZ group, and 29 patients to the CTX group. The retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University [No. 2026060X].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical Data Collection and Indicators\u003c/h3\u003e\n\u003cp\u003eIn this study, National Institutes of Health Stroke Scale (NIH scores) and associated indicators were utilized during the clinical data collection process to ensure data accuracy and reliability. baseline data collection encompassed patients' clinical manifestations and laboratory parameters. The NIH score[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] was employed as a quantitative tool to assess disease activity and clinical symptoms. During the treatment period, the research team systematically collected laboratory parameters at 3, 6, and 12 months to monitor therapeutic response and disease progression. The selected laboratory parameters included erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), complement 3 (C3), complement 4 (C4), C-reactive protein (CRP), and lymphocyte subset analysis, including absolute counts and percentages of B lymphocytes. All collected data went rigorous review to ensure completeness and consistency, providing a solid foundation for subsequent statistical analysis.\u003c/p\u003e\n\u003ch3\u003eRecording and Assessment of Adverse Events\u003c/h3\u003e\n\u003cp\u003eALL adverse events occurring in participants during the treatment period were systematically recorded and evaluated. All patients were required to attend regular follow up visits t to facilitate timely identification and documentation of treatment-related adverse events. At each visit, the research team conducted detailed inquiries regarding patient-reported symptoms and complaints, recording any potential treatment-associated side effects. Adverse events included various new-onset infections, manifestations of bone marrow suppression: leukopenia(WBC\u0026thinsp;\u0026lt;\u0026thinsp;3.5*10\u003csup\u003e9\u003c/sup\u003e/L, NE\u0026thinsp;\u0026lt;\u0026thinsp;1.5*10\u003csup\u003e9\u003c/sup\u003e/L), thrombocytopenia(PLT\u0026thinsp;\u0026lt;\u0026thinsp;100*10\u003csup\u003e9\u003c/sup\u003e/L), hepaticdysfunction(ALT\u0026gt;40U/L, AST\u0026gt;40U/L), renal dysfunction(Scr\u0026gt;80\u0026micro;mol/L), reactivation of hepatitis B(HBV-DNA positive), allergic reactions (drug allergy), menstrual disturbances (irregular menstruation or amenorrhea), newly diagnosed malignancies, or recurrence of pre-existing tumors.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS software version 26.0 (IBM Corp., Armonk, NY, USA). A two-tailed P-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Continuous variables were assessed for normality using the Shapiro\u0026ndash;Wilk test. Normally distributed data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared between groups using the independent-samples t-test. Non-normally distributed data were expressed as median with interquartile range (IQR) and were analyzed using the Mann\u0026ndash;Whitney U test (rank-sum test). Categorical variables were presented as frequencies and percentages, and intergroup comparisons were performed using the Chi-square test or Fisher\u0026rsquo;s exact test as appropriate. Kaplan\u0026ndash;Meier survival analysis was used to estimate event-free survival, and differences between groups were assessed using the log-rank test.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003e1.Baseline characteristics of patients\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 75 patients were enrolled in this study, and assigned to either the TCZ group or the CTX group. The TCZ group, comprised 4 male and 42 female patients, with a mean age of 41\u0026thinsp;\u0026plusmn;\u0026thinsp;15 years, and disease duration ranging from 1 to 300 months, and a median of 18 months. The CTX group, included 3 male patients and 26 female patients, with an average age of 44\u0026thinsp;\u0026plusmn;\u0026thinsp;10 years, and disease duration ranging from 1 to 360 months, and a median of 48 months. No significant differences were observed between the two groups in terms of gender distribution or age prior to treatment (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Other baseline characteristics, including disease duration, ESR, CRP and related parameters showed no statistically significant differences between groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparable baseline conditions at enrollment. With respect to concomitant medication use, the proportion of methotrexate(MTX) use was significantly higher in the TCZ group than in the CTX group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas usage rates of other agents, including mycophenolate mofetil (MMF), hydroxychloroquine (HCQ), glucocorticoids, azathioprine (AZA), and leflunomide (LEF) did not differ significantly between groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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 Comparison Between CTX and TCZ Groups\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\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003egeneral condition\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTCZ(n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCTX(n\u0026thinsp;=\u0026thinsp;29)\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 \u003ctr\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 \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.370\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex(female), n( %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(91.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26(89.66)\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\u003eCourse of disease(month)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(6,120)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48(3,126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset(age)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.478\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.57\u0026thinsp;\u0026plusmn;\u0026thinsp;3.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.565\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplication\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBP, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(34.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(21.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2DM, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(3.45)\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\u003eHyperlipidemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(23.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(6.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(12.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(10.34)\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\u003eCerebrovascular disease, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(12.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(6.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMenopause, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(18.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(34.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(11.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(10.34)\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\u003eDrinking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(5.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(3.45)\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\u003e\u003cb\u003eMedication history\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMTX,n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(84.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(27.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\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\u003eMMF,n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(34.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(20.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.298\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\u003e4(8.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(10.34)\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\u003eGlucocorticoid,n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(80.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26(89.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAZA,n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(4.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEF,n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(13.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory tests and disease activity\u003c/b\u003e\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\u003eWBC(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.38(5.68,8.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.58()\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.94(1.59,2.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.93(,1.69,2.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.986\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNE(10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.81\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.00(9.00,18.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.00(7.90,14.00)\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\u003eAST(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.96\u0026thinsp;\u0026plusmn;\u0026thinsp;8.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCr(\u0026micro;mol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.40(49.00,66.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.50(49.20,65.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR(mm/h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.50(7.00,39.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.00(12.00,62.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP(mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.00(1.47,15.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.90(2.31,57.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.221\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIH Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(2,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.075\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eHBP, hypertension; T2DM, type 2 diabetes; CAD, coronary artery disease; MTX, methotrexate; MMF, mycophenolate mofetil; HCQ, hydroxychloroquine; AZA, azathioprine; LEF, leflunomide; WBC, white blood cell; NE, neutrophil; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, creatinine; TG, triglyceride; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, there was no significant difference in immune indicators or lymphocyte subsets between the CTX group and the TCZ group prior to treatment, except for CD3+(%) levels, which were significantly higher in the TCZ group than in the CTX group (p\u0026thinsp;=\u0026thinsp;0.028), although values in both groups remained within the normal reference range. (see 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\u003eComparison of immune indicators and lymphocyte subsets between the CTX group and the TCZ group\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIL-6(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTCZ(n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCTX(n\u0026thinsp;=\u0026thinsp;29)\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 \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.70(4.70,20.34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.06(2.88,26.68)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNF-ɑ(pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.57(2.73,32.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.45(2.81,18.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgA(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.48(1.83,3.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.83(2.00,3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.19\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.55\u0026thinsp;\u0026plusmn;\u0026thinsp;3.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.164\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgM(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgE(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.80(2.60,42.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.20(10.00,107.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC4(g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.23(0.19,0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.23(0.18,0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD3+(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76.20(72.95,80.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72.95(69.03,75.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" 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\u003eCD4+(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.96\u0026thinsp;\u0026plusmn;\u0026thinsp;7.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44.92\u0026thinsp;\u0026plusmn;\u0026thinsp;6.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.982\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8+(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.54\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.355\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB lymphocyte(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.02\u0026thinsp;\u0026plusmn;\u0026thinsp;6.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.227\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNK(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.60(6.25,12.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.20(5.50,15.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.790\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4%/CD8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.75(1.23,2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.78(1.38,2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD3+(/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1289.00(1100.50,1767.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1484.50(1299.25,1772.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4+(/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e780.00(647.00,938.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e985.00(758.00,1188.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8+(/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e505.00(339.00,827.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e467.00(417.25,714.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB lymphocytes(/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e261.06\u0026thinsp;\u0026plusmn;\u0026thinsp;143.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e363.69\u0026thinsp;\u0026plusmn;\u0026thinsp;173.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNK(/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149.00(115.50,206.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e218.56()\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e2.Laboratory and Immunological Responses to Tocilizumab and Cyclophosphamide Therapy\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAt 3 months aftertreatment initiation, significant intergroup differences emerged. The TCZ group exhibited lower ESR (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and CRP (p\u0026thinsp;=\u0026thinsp;0.016) levels (Fig.\u0026nbsp;1A-Fig.\u0026nbsp;1B). The serum IL-6 level in the TCZ group was significantly higher than that in the CTX group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;1C). Additionally, C4 levels were significantly lower in the TCZ group (p\u0026thinsp;=\u0026thinsp;0.020) (Fig.\u0026nbsp;1I). By 6 months, the TCZ group continued to show reduced ESR (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), CRP (p\u0026thinsp;=\u0026thinsp;0.002), C3 (p\u0026thinsp;=\u0026thinsp;0.004), and C4 (p\u0026thinsp;=\u0026thinsp;0.001) levels relative to the CTX group. Notably, B lymphocyte counts (both percentage and absolute values) were significantly higher in the TCZ group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (Fig.\u0026nbsp;1). At 12 months post-treatment, the TCZ group maintained lower ESR (p\u0026thinsp;=\u0026thinsp;0.006) and C4 (p\u0026thinsp;=\u0026thinsp;0.025) levels. B lymphocyte counts remained elevated in the TCZ group compared with the CTX group (percentage: p\u0026thinsp;=\u0026thinsp;0.005; absolute count: p\u0026thinsp;=\u0026thinsp;0.008), suggesting sustained preservation of B cells. The total lymphocyte count was also higher in the TCZ group at 12 months (p\u0026thinsp;=\u0026thinsp;0.005) (Fig.\u0026nbsp;1). After 3 and 6 months of treatment, the TCZ group demonstrated significantly lower NIH scores than the CTX group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;1D).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eComparison of Adverse Event Probability\u003c/h2\u003e \u003cp\u003e All patients were followed up for a median of 6 months (range, 1\u0026ndash;12 months). During the follow-up period, adverse events were reported in 16 patients in the TCZ group and 13 patients in the CTX group. Data on adverse events were unavailable for 1 patient in the TCZ group and 2 patients in the CTX group due to loss to follow-up. No deaths occurred in either group during the observation period.\u003c/p\u003e \u003cp\u003eInfection was the most common adverse event, occurring in 5 patients (including 1 case of severe acute gastroenteritis) in the TCZ group and in 9 patients (including 2 severe cases\u0026mdash;1 pyelonephritis and 1 herpes zoster) in the CTX group. The overall infection rate was significantly lower in the TCZ group (p\u0026thinsp;=\u0026thinsp;0.021), whereas the incidence of severe infections did not differ significantly between the two groups.\u003c/p\u003e \u003cp\u003eAbnormal liver function was observed in 9 patients in the TCZ group and 1 patient in the CTX group (p\u0026thinsp;=\u0026thinsp;0.113). Reactivation of hepatitis B occurred in 1 patient in each group. Menstrual disorders were reported in 3 patients in the CTX group but none in the TCZ group (p\u0026thinsp;=\u0026thinsp;0.034). Other adverse events included 1 case of corneal and oral ulcers in the TCZ group and 1 case each of vaginal bleeding and gastrointestinal symptoms in the CTX group, with no significant difference (p\u0026thinsp;=\u0026thinsp;0.648) (Fig.\u0026nbsp;2).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort study, designed to compare the efficacy, safety, and immunological effects of TCZ and CTX in TAK, we found that TCZ was associated with both superior disease control and a more favorable safety profile over a 12-month treatment period. TCZ treatment resulted in significantly greater improvements in key indicators of disease activity, including lower NIH scores and more pronounced reductions in inflammatory markers such as ESR and CRP, compared with CTX. At the same time, TCZ was associated with a significantly lower incidence of infections and menstrual disorders. Our findings suggest that preservation of B-cell\u0026ndash;mediated humoral immunity may represent a key mechanism underlying the lower infection risk observed with IL-6 inhibition.\u003c/p\u003e \u003cp\u003eImportantly, these clinical advantages were accompanied by distinct immunological differences between the two therapies. Lymphocyte subset analysis demonstrated that TCZ preserved B lymphocyte (CD19⁺) counts throughout follow-up, whereas CTX induced marked B-cell depletion. This preservation of humoral immune components provides a biologically plausible explanation for the reduced infection risk observed in the TCZ group. Collectively, these findings suggest that TCZ offers a more favorable risk\u0026ndash;benefit profile than CTX by achieving superior control of disease activity while minimizing unnecessary immunosuppression, particularly in patients at increased risk of infection, while remaining an effective therapeutic option for the management of TAK. In this study, both the TCZ and CTX groups demonstrated significant improvement in inflammatory activity following treatment, as evidenced by marked reductions in CRP and ESR compared with baseline. These findings indicate that both conventional immunosuppressants and targeted biologic therapies can effectively control systemic inflammation in TAK. While, the therapeutic response was notably faster in the TCZ group, with a notable decline in inflammatory markers and improvement in NIH scores observed as early as 3 months after treatment initiation, whereas comparable improvements in the CTX group typically required more than 6 months of therapy. This discrepancy suggests that IL-6 signaling plays a critical role in the early inflammatory cascade of TAK, and its inhibition may rapidly suppress disease activity[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTocilizumab exerts its effects by selectively binding to IL-6 receptors and inhibiting downstream JAK/STAT signaling, thereby suppressing acute-phase protein synthesis (e.g., CRP) and Th17 cell activation. This mechanism, which directly targets a central pathway of inflammation, likely accounts for its more rapid onset of therapeutic effect compared to the nonspecific cytotoxic action of CTX, which inhibits DNA synthesis in proliferating immune cells. Consequently, CTX achieves inflammation control more slowly and may delay the restoration of immune homeostasis. In this study, TCZ-treated patients showed significantly lower ESR and CRP levels at 3 months compared with those treated with CTX, alongside parallel improvement in clinical symptoms such as fatigue, fever, and vascular bruits, confirming its rapid and stable anti-inflammatory effects. In summary, tocilizumab showed superior therapeutic efficiency and a faster onset of action during the induction phase, suggesting that IL-6 blockade represents a promising strategy for optimizing future treatment approaches in TAK[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eImportantly, our lymphocyte subset analysis revealed a key mechanistic distinction between the two agents. In the TCZ group, both total lymphocyte counts and B lymphocyte (CD19⁺) counts remained largely unchanged before and after treatment, indicating preservation of baseline immune competence. In contrast, the CTX group exhibited a marked reduction in both absolute B cell counts and B cell proportions following treatment, reflecting the broad immunosuppressive and cytotoxic properties of CTX. This B cell depletion provides a direct biological explanation for the substantially higher incidence of infections observed in the CTX group compared with the TCZ group.\u003c/p\u003e \u003cp\u003eB cells play a central role in humoral immunity through antibody production and immune regulation. CTX-induced B cell depletion leads to decreased immunoglobulin levels, particularly IgG and IgM, thereby weakening host defense against bacterial and viral pathogens and increasing susceptibility to opportunistic infections such as urinary tract infections and herpes zoster. Thus, the increased infection risk associated with CTX in our study is not incidental but mechanistically linked to its profound suppressive effect on B cells.\u003c/p\u003e \u003cp\u003eIn contrast, IL-6 plays a pivotal role in TAK pathogenesis by mediating vascular wall inflammation, promoting acute-phase protein synthesis, and regulating Th17-cell activation and cytokine release [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], while having minimal direct impact on B cell survival. By selectively blocking IL-6 receptor signaling [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], TCZ effectively suppresses vascular inflammation without inducing B cells depletion, thereby controlling disease activity while preserving humoral immune defenses. This selective immunomodulatory mechanism confers a clear advantage in reducing infection risk while maintaining immune competence[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, menstrual disturbances were observed in the CTX group[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] but were absent in the TCZ group, highlighting a potential advantage of TCZ in women of reproductive age. Although liver function abnormalities occurred more frequently in the TCZ group, the difference did not reach statistical significance, indicating that hepatic monitoring remains necessary during TCZ therapy.\u003c/p\u003e \u003cp\u003eOther adverse events\u0026mdash;including drug allergy, bone marrow suppression, hepatitis B reactivation, new-onset malignancy, and miscellaneous events\u0026mdash;did not differ significantly between the groups. Overall, TCZ demonstrated a narrower and more manage able adverse event profile. This safety advantage is mechanistically attributed to its selective IL-6 receptor blockade, which suppresses inhibits inflammatory signaling without broadly suppressing DNA synthesis or causing cytotoxicity in proliferating immune cells, unlike CTX[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Consequently, TCZ has a reduced impact on systemic immunity, lowering the risks of infection, bone marrow suppression, and reproductive toxicity[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. IL-6-targeted therapy selectively modulates inflammatory responses while preserving baseline immune defenses, resulting in improved clinical tolerability and safety.\u003c/p\u003e \u003cp\u003eTCZ not only effectively controls TAK activity but also demonstrates a favorable safety profile [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], particularly in patients at high risk of infection or with fertility concerns, providing critical insights for clinical therapeutic decision-making\u003c/p\u003e \u003cp\u003eIn this study, the effects of TCZ and CTX on lymphocyte subsets demonstrated significant differences. In the TCZ group, B lymphocyte (CD19+) and total lymphocyte counts remained largely unchanged before and after treatment, indicating that IL-6 pathway inhibition selectively modulates inflammation while preserving baseline immune function. In contrast, the CTX group exhibited a marked reduction in B lymphocyte counts post-treatment, reflecting the broad immunosuppressive effect of CTX. Aclear correlation exists between B cell depletion and increased infection risk. B cells play a pivotal role in humoral immunity through antibody production and regulation of immune responses against pathogens. CTX-induced B cell depletion results in decreased levels of antibodies, particularly IgG and IgM, thereby weakening humoral immunity and increasing susceptibility to opportunistic infections such as urinary tract infections and herpes zoster. In this study, the infection rate was 31% in the CTX group versus 10.9% in the TCZ group, indicating that B cell depletion is a key mechanism underlying CTX-associated infections.\u003c/p\u003e \u003cp\u003eMoreover, TAK is not a B cell-driven disease; its pathophysiology primarily involves T cell-mediated granulomatous inflammation, with minimal direct involvement of B cells [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].Therefore, B cell depletion by CTX is not essential for disease control and may instead increase the risk of infections and other immune-related adverse events. Based on these immunological insights, the selective IL-6 inhibition by TCZ aligns more closely with the pathophysiology of TAK, effectively controlling vascular inflammation without inducing unnecessary systemic immunosuppression.\u003c/p\u003e \u003cp\u003eCTX can effectively control inflammation in TAK; however, CTX-induced B cell depletion significantly contributes to the elevated risk of infections. In contrast, TCZ, maintains B lymphocyte counts while effectively controlling disease activity, offering a therapeutic approach that balances efficacy with preserved immune defense, thus providing a mechanistic rationale for its use as a safer and more targeted therapy. From an immunological perspective, TCZ selectively inhibits IL-6 signaling to suppress vascular inflammation without significantly affecting B lymphocyte survival or function, thereby preserving humoral immune competence and reducing the incidence of infections and other immune-related adverse events[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In contrast, CTX, as a broad-spectrum cytotoxic agent, induces profound B cell depletion and impairs antibody production, leading to compromised host defense and increased susceptibility to bacterial and viral infections[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExtensive evidence has demonstrated that B cells are essential for protective immunity against a wide range of pathogens through the production of pathogen-specific antibodies, antigen presentation, and modulation of T-cell responses. B cell deficiency or dysfunction is strongly associated with recurrent respiratory tract infections, herpesvirus reactivation, and opportunistic infections[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Furthermore, depletion of B cells has been shown to markedly impair long-term humoral immune memory, predisposing patients to both primary and recurrent infections[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, CTX-induced B cell loss represents not only a transient immunosuppressive effect but also a sustained disruption of host immune defense.\u003c/p\u003e \u003cp\u003eConsidering the pathophysiology of TAK\u0026mdash;primarily a T cell-mediated granulomatous vasculitis with limited direct B cell involvement\u0026mdash;B cell depletion is neither necessary for disease control nor justified therapeutically, and instead poses avoidable immunological risks. This further provides a strong mechanistic rationale for favoring targeted IL-6 inhibition in clinical decision-making: precise blockade of the IL-6 pathway achieves effective suppression of vascular inflammation while minimizing unnecessary destruction of humoral immunity.\u003c/p\u003e \u003cp\u003eFinally, the study underscores the importance of individualized treatment strategies for TAK patients. For individuals exhibiting high disease activity or rapid progression, tocilizumab(TCZ) may be preferred as an induction agent, typically in combination with glucocorticoids to achieve prompt control of inflammation. This preference is supported by randomized trial data and real-world evidence demonstrating superior efficacy and steroid-sparing effects of TCZ compared to conventional immunosuppressants like CTX in refractory TAK[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In patients with a history of infections or in women of childbearing potential, TCZ offers distinct advantages by reducing infection risk and minimizing menstrual disturbances. Conversely, CTX should be used cautiously in clinically stable patients or those with impaired B cell function, with careful evaluation of the risk-benefit profile.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study has limitations. Its retrospective, single-center design may introduce selection bias and limit generalizability. Despite a relatively larger sample, it remains underpowered to detect rare adverse events or assess long-term outcomes. Mechanistic insights were inferred from peripheral blood and literature rather than direct functional assays. Prospective, multicenter studies are needed.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTCZ may provide a more favorable balance between efficacy and safety compared with CTX in patients with TAK. Its ability to control disease activity while preserving B-cell\u0026ndash;mediated immunity may have important implications for reducing infection risk, particularly in patients requiring long-term immunosuppressive therapy.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eTAK= Takayasu arteritis\u003c/p\u003e\n\u003cp\u003eCTX=Cyclophosphamide\u003c/p\u003e\n\u003cp\u003eIL-6= interleukin-6\u003c/p\u003e\n\u003cp\u003eTCZ= Tocilizumab\u003c/p\u003e\n\u003cp\u003eCRP= C-reactive protein\u003c/p\u003e\n\u003cp\u003eESR= erythrocyte sedimentation rate\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha;= tumor necrosis factor-alpha\u003c/p\u003e\n\u003cp\u003eC3= complement 3\u003c/p\u003e\n\u003cp\u003eC4= complement 4\u003c/p\u003e\n\u003cp\u003eNIH scores= National Institutes of Health Stroke Scale\u003c/p\u003e\n\u003cp\u003eIgA= Immunoglobulin A\u003c/p\u003e\n\u003cp\u003eIgG= Immunoglobulin G\u003c/p\u003e\n\u003cp\u003eIgM= Immunoglobulin M\u003c/p\u003e\n\u003cp\u003eNE= neutrophil count\u003c/p\u003e\n\u003cp\u003eLYM= lymphocyte count\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics Approval and Consent to Participate:\u003c/h2\u003e \u003cp\u003e The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University [No. 2026060X].\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e \u003cp\u003eThe authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent to participate:\u003c/h2\u003e \u003cp\u003e Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the participants for their participation in this research.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by the National Natural Science Foundation of China (82270427). High-level Research Special Project of the National Clinical Research Center for Cardiovascular Diseases of Beijing Anzhen Hospital (2025AZD3001, 2025AZB6002). The fund providers played no role in the study design, data collection or analysis, decision to publish or the preparation of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution:\u003c/h2\u003e\u003cp\u003eHua Liao conceived the study, performed the statistical analysis and prepared the first draft of the manuscript. Cao Wei performed the data collection and the statistical analysis. Lili Pan took part in the study design and revision of the manuscript. All authors read and approved the final submitted version of the manuscript.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials:\u003c/h2\u003e \u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author or the first author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci AS, Rottem M et al. Takayasu arteritis. ANN INTERN MED. 1994;120(11):919\u0026thinsp;\u0026ndash;\u0026thinsp;29. 'doi:'10.7326/0003-4819-120-11-199406010-00004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSomashekar A, Leung YT. Updates in the diagnosis and management of Takayasu's arteritis. POSTGRAD MED. 2023;135(sup1):14\u0026ndash;21. 'doi:'10.1080/00325481.2022.2159723.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMruthyunjaya P, Misra R. Update on Takayasu arteritis: Year in review 2024. 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'doi:'10.1016/j.ard.2025.07.018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKong X, Sun Y, Ma L, Chen H, Wei L, Wu W, et al. The critical role of IL-6 in the pathogenesis of Takayasu arteritis. CLIN EXP RHEUMATOL. 2016;34(3 Suppl 97):S21\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshifuji H. Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy. MOD RHEUMATOL. 2019;29(2):287\u0026thinsp;\u0026ndash;\u0026thinsp;93. 'doi:'10.1080/14397595.2018.1546358.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdi M, Fadaee M, Jourabchi A, Karimzadeh H, Kazemi T. Cyclophosphamide-Induced Infertility and the Impact of Antioxidants. AM J REPROD IMMUNOL. 2024;92(6):e70014. 'doi:'10.1111/aji.70014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra DP, Singh K, Rathore U, Patro P, Tomelleri A, Campochiaro C et al. The effectiveness of tocilizumab and its comparison with tumor necrosis factor alpha inhibitors for Takayasu Arteritis: A systematic review and meta-analysis. AUTOIMMUN REV. 2023;22(3):103275. 'doi:'10.1016/j.autrev.2023.103275.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMekinian A, Biard L, Lorenzo D, Novikov PI, Salvarani C, Espitia O et al. Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study. RMD OPEN. 2023;9(2). 'doi:'10.1136/rmdopen-2022-002830.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYazici Y. Treatment of systemic vasculitis. CURR OPIN RHEUMATOL. 2025. 'doi:'10.1097/BOR.0000000000001129.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakaoka Y, Isobe M, Takei S, Tanaka Y, Ishii T, Yokota S et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). ANN RHEUM DIS. 2018;77(3):348\u0026thinsp;\u0026ndash;\u0026thinsp;54. 'doi:'10.1136/annrheumdis-2017-211878.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTodd J, Thomas P, Nguyen S. Cyclophosphamide and prednisolone for chemotherapy naive B cell multicentric lymphoma in dogs: 32 cases (2017\u0026ndash;2021). J SMALL ANIM PRACT. 2022;63(1):52\u0026thinsp;\u0026ndash;\u0026thinsp;5. 'doi:'10.1111/jsap.13428.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEfe O, Sauvage G, Chung J, Jeyabalan A, Al Jurdi A, Seethapathy HS et al. Protracted COVID-19 pneumonia in B-cell-depleted patients. Rheumatology (Oxford, England). 2025;64(4):2303-5. 'doi:'10.1093/rheumatology/keae703.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgishi M, Kitaoka K, Good-Jacobson KL, Rinchai D, Zhang B, Wang J et al. Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling. IMMUNITY. 2024;57(12):2790\u0026thinsp;\u0026ndash;\u0026thinsp;807. 'doi:'10.1016/j.immuni.2024.10.014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeters J, Longbrake EE. Infection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease. MULT SCLER RELAT DIS. 2022;68:104400. 'doi:'10.1016/j.msard.2022.104400.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed A, Lippner E, Khanolkar A. Clinical Aspects of B Cell Immunodeficiencies: The Past, the Present and the Future. CELLS-BASEL. 2022;11(21):3353. 'doi:'10.3390/cells11213353.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMekinian A, Comarmond C, Resche-Rigon M, Mirault T, Kahn JE, Lambert M et al. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients.CIRCULATION. 2015;132(18):1693\u0026thinsp;\u0026ndash;\u0026thinsp;700. 'doi:'10.1161/CIRCULATIONAHA.114.014321.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Takayasu arteritis, tocilizumab, B lymphocytes","lastPublishedDoi":"10.21203/rs.3.rs-9330968/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9330968/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTakayasu arteritis (TAK) requires long-term immunosuppression. Cyclophosphamide (CTX) is effective but toxic, whereas tocilizumab provides targeted IL-6 inhibition; however, comparative data on efficacy and safety remain limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo compare the efficacy, safety, and immunological effects of TCZ versus CTX in patients with TAK.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cohort study included 75 patients with TAK (TCZ, n = 46; CTX, n = 29). Disease activity NIH score, inflammatory markers, complement levels, and lymphocyte subsets were assessed at baseline and at 3, 6, and 12 months. Adverse events were systematically recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth treatments significantly reduced inflammatory markers and improved NIH scores over 12 months, with TCZ achieving faster disease activity control at 3 months. Lymphocyte subset analysis showed stable B-cell counts in the TCZ group, whereas CTX was associated with marked B-cell depletion. The TCZ group had a significantly lower incidence of infections than the CTX group (10.9% vs. 31.0%, p = 0.037) and fewer menstrual disorders (p = 0.026). Other adverse events were comparable between groups. No deaths occurred during follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTCZ demonstrated comparable or improved disease control with a more favorable safety profile than CTX. Preservation of B-cell–mediated immunity may be associated with the reduced infection risk observed with TCZ, highlighting a potential mechanism underlying its clinical advantage.\u003c/p\u003e","manuscriptTitle":"Comparative Safety and Immunological Effects of Tocilizumab versus Cyclophosphamide in Takayasu Arteritis: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:26:19","doi":"10.21203/rs.3.rs-9330968/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"41611950376115567490979991294264205566","date":"2026-05-14T21:01:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"284703584889845757380553454861875906532","date":"2026-05-13T05:31:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-28T14:23:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70461706855905460986074384683943422720","date":"2026-04-17T15:40:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-15T09:01:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-13T20:19:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-10T14:27:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-10T14:27:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Rheumatology","date":"2026-04-06T07:09:09+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":"8925fd2c-3a68-4761-9d59-1d96b000b2d7","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"41611950376115567490979991294264205566","date":"2026-05-14T21:01:18+00:00","index":45,"fulltext":""},{"type":"reviewerAgreed","content":"284703584889845757380553454861875906532","date":"2026-05-13T05:31:34+00:00","index":43,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:26:22+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:26:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9330968","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9330968","identity":"rs-9330968","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}