Comparative effectiveness of subcutaneous sarilumab 200 mg biweekly, subcutaneous Tocilizumab 162 mg biweekly, and intravenous Tocilizumab 8 mg/kg every 4 weeks in patients with rheumatoid arthritis: a prospective cohort study

Abstract

While targeting the interleukin-6 receptor (IL-6R) through the use of sarilumab (SAR) or tocilizumab (TCZ) has become a major therapeutic approach for rheumatoid arthritis (RA), direct comparisons between IL-6R inhibitors (IL-6Ris) for treating RA have not been conducted. We aimed to compare the effectiveness of subcutaneous sarilumab (SAR-SC), subcutaneous tocilizumab (TCZ-SC), and intravenous TCZ (TCZ-IV) against RA in a multicenter cohort study. Within the target trial emulation framework, an incident new-user and active-comparator cohort design was used. The source population was the entire cohort of a multicenter prospective study (the ANSWER cohort study) in Japan from 2009 to 2023. We consecutively included patients with IL-6Ri-naïve RA who initiated treatment with SAR-SC 200 mg biweekly, TCZ-SC 162 mg biweekly, or TCZ-IV 8 mg/kg every 4 weeks as the approved starting dose and dosing interval at baseline. The primary outcome of interest was the change in the clinical disease activity index (CDAI) at 24 weeks. In total, 1001 IL-6Ri-naïve patients were included (SAR-SC 200 mg biweekly, 201 patients; TCZ-SC 162 mg biweekly, 546; TCZ-IV 8 mg/kg every 4 week, 254). The improvement in CDAI at 24 weeks (primary outcome) was statistically significantly greater in the SAR-SC group than in the TCZ-SC group (-2.53, 95% confidence interval (CI): -4.38 to -0.69, p = 0.007), but that in TCZ-IV was not significantly different from that in TCZ-SC (1.00, 95% CI: -0.68 to 2.69, p = 0.243). Similar results were noted regarding the changes in CDAI at weeks 4, 12, and 48. The retention rates at 48 weeks in SAR-SC and TCZ-IV did not significantly differ from that in TCZ-SC. SAR-SC 200 mg biweekly initiation was associated with a statistically significantly greater decrease in disease activity than TCZ-SC 162 mg biweekly in IL-6Ri-naïve patients with RA. In contrast, no statistically significant differences were identified between TCZ-IV 8 mg/kg every 4 week and TCZ-SC 162 mg biweekly. However, the effect size of our findings should necessitate careful consideration of the cost difference between TCZ-SC 162 mg biweekly including its biosimilars and SAR-SC 200 mg biweekly.