A non-parametric propensity score for estimating the effect of interferon-beta or glatiramer acetate on long-term outcomes of multiple sclerosis

Background: The few observational studies that investigated the long-term effects of interferon-beta and glatiramer acetate were usually focused on progression to irreversible disability and other outcomes such as number of relapses and transition to secondary-progressive multiple sclerosis (SPMS) have been rarely studied. The objective of this paper is to estimate the effect of interferon-beta/glatiramer acetate on progression to irreversible disability, transition from relapsing-remitting multiple sclerosis (RRMS) to SPMS and the rate of relapses over 10 years.

Methods: Analyses included 2498 patients with confirmed diagnosis of RRMS followed in Montréal from 1977 to 2016. Marginal structural models with propensity score for treatment and censoring were used to account for potential confounding and attrition. Specifically, we used pooled logistic regression for progression to irreversible disability and transition to SPMS, and Poisson models for the rate of relapses.

Results: 77% of subjects were female and the median age at RRMS diagnosis was 35 years. The hazard of progression to irreversible disability was lower among treated patients than untreated patients (HR=0.73, 95% CI [0.57-0.94]). We did not find evidence of an association between interferon-beta/glatiramer acetate and the rate of transition to SPMS either over the 3-month intervals or for the duration of treatment. Patients treated for >5 years had a lower rate of relapses compared to those untreated (HR=0.70, 95% CI [0.57-0.86]).

Conclusion: Treatment with interferon-beta/glatiramer acetate suggests a beneficial effect on progression to irreversible disability and rate of relapses, but not on transition to SPMS.