Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis
M. Hay, Fabien Rollot, Romain Casey, Anne Kerbrat, Gilles Edan, Guillaume Mathey, Pierre Labauge, de Sèze, Sandra Vukusic, David Laplaud, Caroline Papeix, Thibault Moreau, Éric Thouvenot, Gilles Defer, Christine Lebrun‐Frénay, Jonathan Ciron, Eric Berger, Bruno Stankoff, Pierre Clavelou, Élisabeth Maillart, Olivier Heinzlef, Hélène Zéphir, Aurélie Ruet, Olivier Casez, Solène Moulin, Abdullatif Al-Khedr, Bertrand Bourre, Jean Pelletier, Laurent Magy, Jean‐Philippe Neau, Jean‐Philippe Camdessanché, Inès Doghri, Abir Wahab, M. Tchikviladzé, Céline Labeyrie, Karolina Hankiewicz, Emmanuelle Le Page, Laure Michel, as the OFSEP Investigators
Abstract
BACKGROUND AND OBJECTIVES: Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort. METHODS: This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity. RESULTS: = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group. DISCUSSION: Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.