Abstract
Background: Clinical trial or real-world evidence supporting the effectiveness of cladribine tables (CladT) over other oral disease-modifying therapies (DMTs) is limited. The MSBase registry records demographics, DMT, Expanded Disability Status Scale (EDSS) scores and relapses in over 74,000 multiple sclerosis (MS) patients globally.
Objectives: Compare treatment patterns and clinical outcomes in relapsing MS patients newly initiating CladT vs fingolimod, dimethyl fumarate (DMF) and teriflunomide in the real-world.
Methods: Data were extracted on July 1, 2024, for adult patients (> 18 years old) who newly initiated CladT or oral comparators from January 2018. Propensity score matching (PSM, 1:1) for three pairwise comparisons (CladT vs oral DMTs) included age, sex, disease duration, baseline EDSS, pre-baseline relapses, prior DMT initiations, MS type and country. Outcomes included time-to-discontinuation (for CladT, switch to alternate DMT), annualized relapse rate (ARR) and time-to-first relapse. Time-to-event analyses used marginal Cox models with hazard ratio (HR) and 95% confidence intervals (CI). ARRs were compared with a weighted negative binomial model with a cluster term for matched patient sets.
Results: PSM cohorts were found to be well balanced on demographic and clinical characteristics. Median follow-up times were between 15-23 months. For CladT vs fingolimod (n = 1965/group), ARR was 0.11 vs 0.13 (p = 0.0013), HR for time-to-first relapse was 0.81 (0.70, 0.93, p = 0.004) and for time-to-discontinuation was 0.31 (0.27, 0.36, p < 0.001). For CladT vs DMF (n = 2064/group), ARR was 0.10 vs 0.13 (p < 0.001), HR for time-to-first relapse was 0.69 (0.59, 0.80, p < 0.001) and for time-to-discontinuation was 0.17 (0.15, 0.19, p < 0.001). For CladT vs teriflunomide (n = 2069/group), ARR was 0.09 vs 0.14 (p < 0.001), HR for time-to-first relapse was 0.59 (0.51, 0.68, p < 0.001) and for time-to-discontinuation was 0.22 (0.19, 0.25, p < 0.001).When limited to subgroups of patients with either relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) at baseline, CladT was associated with an 18% reduction in the rate of first relapse vs fingolimod (HR 0.82; 95% CI 0.70, 0.95; p = 0.008) and a 69% reduction in discontinuation rate (HR 0.31; 95% CI 0.26, 0.36; p < 0.001). Compared to DMF, CladT was associated with a 31% reduction in first relapse rate (HR 0.69; 95% CI 0.59, 0.80; p < 0.001) and an 83% reduction in discontinuation rate (HR 0.17; 95% CI 0.14, 0.19; p < 0.001). Compared to teriflunomide, CladT was associated with a 42% reduction in the rate of first relapse (HR 0.58; 95% CI 0.50, 0.68; p < 0.001) and a 78% reduction in discontinuation rate (HR 0.22; 95% CI 0.19, 0.26; p < 0.001).
Conclusions: For all three pairwise comparisons, relapse and discontinuation outcomes significantly favored CladT. Future analyses with longer follow-up comparing disability progression events are warranted.