Abstract
Background/Objectives Cladribine reduces the frequency of relapses by 57% and disability worsening by 33% compared to placebo in relapsing-remitting multiple sclerosis (RRMS). No head-to-head comparisons of cladribine to other potent immunotherapies are available.
Methods Patients with RRMS who were treated with cladribine, fingolimod, natalizumab, ocrelizumab or alemtuzumab from 01/2018 were identified in the global MSBase cohort study and 2 UK centres. Included patients were followed for >=6 months and had a minimum of 3 disability assessments. Patients were matched using propensity score. Four pairwise analyses compared annualised relapse rates (ARR), and disability outcomes. All subsequent events were analysed, regardless of changes in treatment status.
Results The eligible cohorts consisted of 853(fingolimod), 464(natalizumab), 1131(ocrelizumab), 123(alemtuzumab), or 493(cladribine) patients. Cladribine was associated with a lower ARR than fingolimod (ARR 0.07 vs 0.12,p=0.006), and a higher ARR than natalizumab (0.10 vs 0.06,p=0.03), ocrelizumab (0.09 vs 0.05,p=0.008), and alemtuzumab (0.17 vs 0.04,p<0.001). Compared to cladribine, the risk of disability worsening did not differ in patients treated with fingolimod (HR1.08, 95%CI 0.47–2.47) or alemtuzumab (0.73, 0.26–2.07), but was lower for patients treated with natalizumab (0.35, 0.13–0.94) and ocrelizumab (0.45, 0.26–0.78).
Conclusion Cladribine is an effective therapy, associated with low absolute ARR. While cladribine effectiveness on relapses is superior to fingolimod, alemtuzumab is superior to cladribine in reducing relapses. Natalizumab and ocrelizumab are superior to cladribine in reducing both relapses and disability accrual. Cladribine can thus be viewed as a step-up in effectiveness from fingolimod, but less effective than the most potent intravenous MS therapies.
