Comparative effectiveness of rituximab and cladribine in relapsing-remitting multiple sclerosis: A target trial emulation.

BACKGROUND

Head-to-head comparisons of high-efficacy therapies for relapsing-remitting multiple sclerosis (RRMS) are lacking. We conducted a target trial emulation to compare the long-term effectiveness of rituximab and cladribine.

METHODS

We estimated the effect of initiating treatment with rituximab versus cladribine using observational data from the Norwegian MS Registry and Biobank at two university hospitals with different treatment strategies. Cumulative incidence and risk differences (RDs) were estimated using weighted Kaplan-Meier estimators, adjusting for baseline covariates. The primary outcome was magnetic resonance imaging (MRI) disease activity, with secondary outcomes including relapses and safety.

RESULTS

The study included 285 patients, 159 receiving rituximab and 126 cladribine, with a median follow-up of 4.5 years (interquartile range (IQR): 4.2-4.7). The 4-year risk of new MRI disease activity was 17% (95% confidence interval (CI): 11-23) for rituximab-treated patients and 57% (95% CI: 44-66) for cladribine-treated patients, yielding an RD of 40 percentage-points (95% CI: 28-50). The 4-year RD for relapse was 12 percentage-points (95% CI: 4-19). The incidence of hospitalizations related to potential adverse events was 6.0 per 100 person-years for rituximab and 4 per 100 person-years for cladribine.

CONCLUSION

These findings suggest that rituximab has superior effectiveness compared to cladribine during a median follow-up of 4.5 years.