High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS
Authors: Jouvenot Guillaume , Courbon Guilhem , Lefort Mathilde , Rollot Fabien , Casey Romain , Le Page Emmanuelle , Michel Laure , Edan Gilles , de Seze Jérome , Kremer Laurent , Bigaut Kevin , Vukusic Sandra , Mathey Guillaume , Ciron Jonathan , Ruet Aurélie , Maillart Elisabeth , Labauge Pierre , Zephir Hélène , Papeix Caroline , Defer Gilles , Lebrun-Frenay Christine , Moreau Thibault , Laplaud David Axel , Berger Eric , Stankoff Bruno , Clavelou Pierre , Thouvenot Eric , Heinzlef Olivier , Pelletier Jean , Al-Khedr Abdullatif , Casez Olivier , Bourre Bertrand , Cabre Philippe , Wahab Abir , Magy Laurent , Camdessanché Jean-Philippe , Doghri Ines , Moulin Solène , Ben-Nasr Haifa , Labeyrie Céline , Hankiewicz Karolina , Neau Jean-Philippe , Pottier Corinne , Nifle Chantal , Collongues Nicolas , Kerbrat Anne ,   OFSEP Investigators, Cotton François , Douek Pascal , Guillememin Francis , Pachot Alexandre , Olaiz Javier , Rigaud-Bully Claire , Marignier Romain , Debouverie Marc , Lubetzki Catherine , Cohen Mikaël , Fromont Agnès , Wiertlewsky Sandrine , Audoin Bertrand , Giannesini Claire , Gout Olivier , Montcuquet Alexis , Bakchine Serge , Maurousset Aude , Maubeuge Nicolas 
Published: March 2024

Importance

A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity.

Objective

To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET.

Design, Setting, and Participants

This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022.

Exposures

Natalizumab, fingolimod, rituximab, and ocrelizumab.

Main Outcomes and Measures

Time to first relapse.

Results

Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P &amp;lt; .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy.

Conclusion and Relevance

As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.