High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS - Université de Rennes
Article Dans Une Revue JAMA neurology Année : 2024

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

Guillaume Jouvenot (1) , Guilhem Courbon (2) , Mathilde Lefort (3, 4, 5, 6) , Fabien Rollot (7, 8, 9) , Romain Casey (7, 8, 9) , Emmanuelle Le Page (2, 10) , Laure Michel (2, 10) , Gilles Edan (2, 10) , Jérome de Seze (1, 11) , Laurent Kremer (11) , Kevin Bigaut (11) , Sandra Vukusic (7, 8, 9) , Guillaume Mathey (12, 13) , Jonathan Ciron (14) , Aurélie Ruet (15, 16) , Elisabeth Maillart (17) , Pierre Labauge (18) , Hélène Zephir (19) , Caroline Papeix (20) , Gilles Defer (21) , Christine Lebrun-Frenay (22) , Thibault Moreau (23) , David Axel Laplaud (24, 25, 26) , Eric Berger (27) , Bruno Stankoff (28) , Pierre Clavelou (29) , Eric Thouvenot (30) , Olivier Heinzlef (31) , Jean Pelletier (32) , Abdullatif Al-Khedr (33) , Olivier Casez (34) , Bertrand Bourre (35) , Philippe Cabre (36) , Abir Wahab (37) , Laurent Magy (38) , Jean-Philippe Camdessanché (39) , Ines Doghri (40) , Solène Moulin (41) , Haifa Ben-Nasr (42) , Céline Labeyrie (43) , Karolina Hankiewicz (44) , Jean-Philippe Neau (45) , Corinne Pottier (46) , Chantal Nifle (47) , Nicolas Collongues (1, 11) , Anne Kerbrat (48, 2, 10) , François Cotton (49) , Pascal Douek , Francis Guillememin (50) , Alexandre Pachot (49) , Javier Olaiz (51) , Claire Rigaud-Bully (7) , Romain Marignier (49) , Marc Debouverie (52) , Catherine Lubetzki (17) , Mikaël Cohen (53) , Agnès Fromont (54) , Sandrine Wiertlewsky (24) , Bertrand Audoin (55) , Claire Giannesini (17) , Olivier Gout (20) , Alexis Montcuquet (56) , Serge Bakchine (57) , Aude Maurousset (58) , Nicolas Maubeuge (59)
1 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
2 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
3 ARENES - Arènes: politique, santé publique, environnement, médias
4 RSMS - Recherche sur les services et le management en santé
5 EHESP - École des Hautes Études en Santé Publique [EHESP]
6 METIS - Département Méthodes quantitatives en santé publique
7 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
8 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
9 Fondation Eugène Devic EDMUS
10 CIC - Centre d'Investigation Clinique [Rennes]
11 Service de Neurologie [Strasbourg]
12 Service de neurologie [CHRU Nancy]
13 INSPIIRE - INterdisciplinarité en Santé Publique Interventions et Instruments de mesure complexes
14 CRC-SEP Toulouse - Centre Ressources et Compétences sclérose en plaques (CRC-SEP) [CHU Toulouse]
15 CIC Bordeaux
16 Service de neurologie [Bordeaux]
17 CHU Pitié-Salpêtrière [AP-HP]
18 CHU Montpellier
19 CRC-SEP Nord-Pas de Calais - Centre de Ressources et de Compétences sur la Sclérose en Plaques (CRC-SEP) [Lille]
20 Hôpital Fondation Adolphe de Rothschild = Adolphe de Rothschild Foundation Hospital
21 Service de Neurologie [CHU Caen]
22 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
23 Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon)
24 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
25 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
26 CIC Plurithématique de Nantes
27 Service de Neurologie [CHRU Besançon]
28 CHU Saint-Antoine [AP-HP]
29 Service Neurologie [CHU Clermont-Ferrand]
30 Pôle NIRR - Service de Neurologie [CHU Nimes]
31 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
32 TIMONE - Hôpital de la Timone [CHU - APHM]
33 Service de neurologie [Amiens]
34 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
35 Service de neurologie [Rouen]
36 Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
37 Hôpital Henri Mondor
38 Hôpital Dupuytren [CHU Limoges]
39 Service de Neurologie [CHU de Saint-Étienne]
40 Hôpital Bretonneau
41 Service de neurologie [Reims]
42 Centre Hospitalier Sud Francilien
43 Service de neurologie [Le Kremlin Bicêtre]
44 Centre Hospitalier de Saint-Denis [Ile-de-France]
45 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
46 Centre Hospitalier René Dubos [Pontoise]
47 CHV - Centre Hospitalier de Versailles André Mignot
48 EMPENN - Neuroimagerie: méthodes et applications
49 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
50 CIC - Centre d'investigation clinique [Nancy]
51 Lyon Ingénierie Projets
52 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
53 CHU Nice [Cimiez]
54 Service de neurochirurgie [CHU Dijon]
55 CRMBM - Centre de résonance magnétique biologique et médicale
56 CH Brive - Centre Hospitalier de Brive-la-Gaillarde
57 CHU Reims - Hôpital universitaire Robert Debré [Reims]
58 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
59 Service de Neurochirurgie [CHU de Poitiers]
Pierre Labauge
  • Fonction : Auteur
Abir Wahab
  • Fonction : Auteur
Ines Doghri
  • Fonction : Auteur
François Cotton
Pascal Douek
  • Fonction : Auteur
Mikaël Cohen
  • Fonction : Auteur

Résumé

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.

Domaines

Neurosciences

Dates et versions

hal-04529619 , version 1 (02-04-2024)

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Citer

Guillaume Jouvenot, Guilhem Courbon, Mathilde Lefort, Fabien Rollot, Romain Casey, et al.. High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS. JAMA neurology, 2024, pp.e240395. ⟨10.1001/jamaneurol.2024.0395⟩. ⟨hal-04529619⟩
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