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Observational Study
. 2024 May 1;81(5):490-498.
doi: 10.1001/jamaneurol.2024.0395.

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

Guillaume Jouvenot  1   2 , Guilhem Courbon  3 , Mathilde Lefort  4 , Fabien Rollot  5   6   7   8 , Romain Casey  5   6   7   8 , Emmanuelle Le Page  3   9 , Laure Michel  3   9 , Gilles Edan  3   9 , Jérome de Seze  1   2   10 , Laurent Kremer  2   10 , Kevin Bigaut  2   10 , Sandra Vukusic  5   6   7   8 , Guillaume Mathey  11   12 , Jonathan Ciron  13 , Aurélie Ruet  14 , Elisabeth Maillart  15 , Pierre Labauge  16 , Hélène Zephir  17 , Caroline Papeix  18 , Gilles Defer  19 , Christine Lebrun-Frenay  20 , Thibault Moreau  21 , David Axel Laplaud  22   23 , Eric Berger  24 , Bruno Stankoff  25 , Pierre Clavelou  26 , Eric Thouvenot  27 , Olivier Heinzlef  28 , Jean Pelletier  29 , Abdullatif Al-Khedr  30 , Olivier Casez  31 , Bertrand Bourre  32 , Philippe Cabre  33 , Abir Wahab  34 , Laurent Magy  35 , Jean-Philippe Camdessanché  36 , Ines Doghri  37 , Solène Moulin  38 , Haifa Ben-Nasr  39 , Céline Labeyrie  40 , Karolina Hankiewicz  41 , Jean-Philippe Neau  42 , Corinne Pottier  43 , Chantal Nifle  44 , Nicolas Collongues  1   2   10   45 , Anne Kerbrat  3   9   46 ; OFSEP Investigators
Collaborators, Affiliations
Observational Study

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

Guillaume Jouvenot et al. JAMA Neurol. .

Abstract

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 < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr de Seze reported personal fees from Roche, Biogen, Novartis, Sanofi, Merck, Alexion, Horizon/Amgen, Sandoz, UCB, LFB, and Argenx outside the submitted work. Dr Bigaut reported personal fees from Biogen, Novartis, Roche, and Sanofi outside the submitted work. Dr Vukusic reported grants from Biogen, Merck, Novartis, Roche, and Sanofi as well as fees paid to her institution from Bristol Myers Squibb/Celgene and Sandoz outside the submitted work. Dr Mathey reported grants from Novartis, Biogen, Roche, Bayer, Actelion, Alexion, Teva, and Sanofi Genzyme during the conduct of the study. Dr Ciron reported personal fees from Biogen, from Novartis, Merck, Sanofi, and Roche outside the submitted work. Dr Ruet reported grants from Biogen, Roche, Sanofi Genzyme, and Bristol Myers Squibb; personal fees from Biogen, Sanofi Genzyme, and Merck; and nonfinancial support from Biogen, Novartis, and Merck outside the submitted work. Dr Maillart reported grants from Biogen as well as personal fees from Biogen, Roche, Sanofi Genzyme, Teva, Novartis, Merck, and Janssen outside the submitted work. Dr Papeix reported personal fees from Biogen during the conduct of the study as well as personal fees from Alexion outside the submitted work. Dr Defer reported personal fees from Roche, Novartis, Genzyme, Biogen, Bristol Myers Squibb, and Merck Serono outside the submitted work. Dr Laplaud reported grants from Roche, Fondation Association pour la Recherche Contre la Sclérose en Plaques, Fondation European Database for Multiple Sclerosis, and Association Nationale pour la Recherche as well as personal fees from Alexion, Biogen, Merck, Sanofi, Novartis, Bristol Myers Squibb, and Merck Sharp & Dohme outside the submitted work. Dr Berger reported personal fees from Biogen Idec, Novartis, and Merck outside the submitted work. Dr Stankoff reported grants from Roche, Novartis, and Merck as well as personal fees from Janssen, Merck, and Novartis outside the submitted work. Dr Thouvenot reported grants from Biogen, Novartis, and Merck as well as personal fees from Merck, Biogen, Novartis, Janssen, Sanofi, Roche, and Bristol Myers Squibb outside the submitted work. Dr Casez reported personal fees from Biogen, Roche, Novartis, and Merck during the conduct of the study. Dr Bourre reported Alexion, Biogen, Merck, Novartis, Roche, Sanofi, Sandoz, Horizon, and Janssen outside the submitted work. Dr Wahab reported personal fees from Novartis, Merck, and Roche outside the submitted work. Dr Magy reported personal fees from Biogen, Novartis, Merck, Roche, and Sanofi outside the submitted work. Dr Doghri reported personal fees from Merck and Novartis as well as nonfinancial support from Merck, Sanofi, and Novartis outside the submitted work. Dr Collongues reported personal fees from Alexion, Biogen, Bristol Myers Squibb, Horizon Therapeutics, Merck, Novartis, Roche, and Sanofi outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
HET indicates high-efficacy therapy; OFSEP, Observatoire Français de la Sclérose en Plaques.
Figure 2.
Figure 2.. Time to First Relapse in the High-Efficacy Therapy (HET) Treatment Discontinuation vs HET Continuation Groups After Propensity Score Matching
Rituximab and ocrelizumab were grouped together as anti-CD20 therapies. The shaded area indicates 95% CIs.
Figure 3.
Figure 3.. Annualized Relapse Rate in the High-Efficacy Therapy Discontinuation Group by Type of Medication Stopped (Natalizumab, Fingolimod, or Anti-CD20 Therapy)
Rituximab and ocrelizumab were grouped together as anti-CD20 therapies. Error lines indicate 95% CIs.
Figure 4.
Figure 4.. Time to Confirm Disability Progression in the High-Efficacy Therapy (HET) Treatment Discontinuation vs HET Continuation Groups After Propensity Score Matching
Rituximab and ocrelizumab were grouped together as anti-CD20 therapies. The shaded area indicates 95% CIs.
See this image and copyright information in PMC

Comment in

  • Hochwirksame MS-Mittel nicht absetzen.
    Menge T. Menge T. MMW Fortschr Med. 2024 Nov;166(20):28-29. doi: 10.1007/s15006-024-4482-2. MMW Fortschr Med. 2024. PMID: 39576522 Review. German. No abstract available.

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