Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis
Authors: Diouf Ibrahima , Malpas Charles B. , Sharmin Sifat , Roos Izanne , Horakova Dana , Havrdova Eva Kubala , Patti Francesco , Shaygannejad Vahid , Ozakbas Serkan , Izquierdo Guillermo , Eichau Sara , Onofrj Marco , Lugaresi Alessandra , Alroughani Raed , Prat Alexandre , Girard Marc , Duquette Pierre , Terzi Murat , Boz Cavit , Grand'Maison Francois , Hamdy Sherif , Sola Patrizia , Ferraro Diana , Grammond Pierre , Turkoglu Recai , Buzzard Katherine , Skibina Olga , Yamout Bassem , Altintas Ayse , Gerlach Oliver , van Pesch Vincent , Blanco Yolanda , Maimone Davide , Lechner‐Scott Jeannette , Bergamaschi Roberto , Karabudak Rana , Iuliano Gerardo , McGuigan Chris , Cartechini Elisabetta , Barnett Michael , Hughes Stella , Sa Maria José , Solaro Claudio , Kappos Ludwig , Ramo‐Tello Cristina , Cristiano Edgardo , Hodgkinson Suzanne , Spitaleri Daniele , Soysal Aysun , Petersen Thor , Slee Mark , Butler Ernest , Granella Franco , de Gans Koen , McCombe Pamela , Ampapa Radek , Van Wijmeersch Bart , van der Walt Anneke , Butzkueven Helmut , Prevost Julie , Sinnige L. G. F. , Sanchez‐Menoyo Jose Luis , Vucic Steve , Laureys Guy , Van Hijfte Liesbeth , Khurana Dheeraj , Macdonell Richard , Gouider Riadh , Castillo‐Triviño Tamara , Gray Orla , Aguera‐Morales Eduardo , Al‐Asmi Abdullah , Shaw Cameron , Deri Norma , Al‐Harbi Talal , Fragoso Yara , Csepany Tunde , Perez Sempere Angel , Trevino‐Frenk Irene , Schepel Jan , Moore Fraser , Kalincik Tomas 
Published: January 2023

Background and purpose

This study assessed the effect of patient characteristics on the response to disease‐modifying therapy (DMT) in multiple sclerosis (MS).

Methods

We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow‐up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12‐month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.

Results

Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.

Conclusions

DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.