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.