Effects of High- and Low-Efficacy Therapy in Secondary Progressive Multiple Sclerosis

ObjectiveTo compare the clinical effectiveness of high- and low-efficacy treatments in patients with recently active and inactive secondary progressive multiple sclerosis (SPMS) after accounting for therapeutic lag.MethodsPatients treated with high-efficacy (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon beta, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and Observatoire Francais de la Sclerose en Plaques (OFSEP), 2 large observational cohorts. Therapeutic lag was estimated for each patient from their demographic and clinical characteristics. Propensity score was used to match patients treated with high- and low-efficacy therapies. Outcomes after the period of therapeutic lag was disregarded were compared in paired, pairwise-censored analyses.ResultsOne thousand patients were included in the primary analysis. Patients with active SPMS treated with high-efficacy therapy experienced less frequent relapses than those on low-efficacy therapy (hazard ratio [HR] 0.7, p = 0.006). In patients with inactive SPMS, there was no evidence for a difference in relapse frequency between groups (HR 0.8, p = 0.39). No evidence for a difference in the risk of disability progression was observed.ConclusionIn treated patients with SPMS, high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active but not those with inactive SPMS. However, more potent therapies do not offer an advantage in reducing disability progression in this patient group.Classification of EvidenceThis study provides Class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS, although we did not find a difference in disability progression between patients treated with high- and low-efficacy therapy.

Automated summary

High-efficacy therapy is more effective in reducing relapses in patients with active SPMS compared to low-efficacy therapy, but no difference was observed in relapse frequency between the two therapies in patients with inactive SPMS. There was no evidence for a difference in disability progression risk between high- and low-efficacy therapies in treated patients with SPMS.