Effects of high and low-efficacy therapy in secondary progressive multiple sclerosis

Objective: To 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.

Methods: Patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferon β, glatiramer acetate, teriflunomide) therapies after SPMS onset were selected from MSBase and OFSEP, two large observational cohorts. Therapeutic lag was estimated for each patient based on their demographic and clinical characteristics.  Propensity score was used to match patients treated with high and low-efficacy therapies.  Outcomes after disregarding the period of therapeutic lag were compared in paired, pairwise-censored analyses.

Results: 1000 patients, 510 with active and 490 with inactive SPMS, 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 number between groups (HR=0.8,p=0.39).  No difference in the risk of disability progression was observed.

Conclusion: In 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 Evidence: This study provides class III evidence that high-efficacy therapy is superior to low-efficacy therapy in reducing relapses in patients with active SPMS whilst disability progression is comparable between patients treated with high- and low-efficacy therapy.