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Article Dans Une Revue JAMA neurology Année : 2024

Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis

1 CHU Angers - Centre Hospitalier Universitaire d'Angers
2 CHU Nantes - Centre Hospitalier Universitaire de Nantes
3 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
4 CIC Plurithématique de Nantes
5 UCBL - Université Claude Bernard Lyon 1
6 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
7 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
8 OFSEP - Observatoire Français de la Sclérose En Plaques [Lyon]
9 Fondation Eugène Devic EDMUS
10 Service de neurologie [CHRU Nancy]
11 UL - Université de Lorraine
12 Service de Neurologie [Rennes] = Neurology [Rennes]
13 EMPENN - Neuroimagerie: méthodes et applications
14 HUS - Les Hôpitaux Universitaires de Strasbourg
15 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
18 CHU Bordeaux
19 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
20 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
21 CHU Pitié-Salpêtrière [AP-HP]
22 Hôpital Roger Salengro [Lille]
23 LilNCog - Lille Neurosciences & Cognition - U 1172
24 Service de neurologie [Hôpital Fondation Adolphe de Rothschild]
25 CHU Caen
26 CHU Nice - Centre Hospitalier Universitaire de Nice
27 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
28 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
29 Service de Neurologie [CHRU Besançon]
30 CHU Saint-Antoine [AP-HP]
31 CHU Clermont-Ferrand
32 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
33 TIMONE - Hôpital de la Timone [CHU - APHM]
34 CRMBM - Centre de résonance magnétique biologique et médicale
35 Pôle NIRR - Service de Neurologie [CHU Nimes]
36 IGF - Institut de Génomique Fonctionnelle
37 CHU Amiens-Picardie
38 CHU Rouen
39 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
40 CHU de la Martinique [Fort de France]
41 Hôpital Henri Mondor
42 CHU Limoges
Gilles Defer
  • Fonction : Auteur
Bertrand Bourre
  • Fonction : Auteur
Abir Wahab
  • Fonction : Auteur
Laurent Magy
  • Fonction : Auteur

Résumé

Importance: Moderately effective therapies (METs) have been the main treatment in pediatric-onset multiple sclerosis (POMS) for years. Despite the expanding use of highly effective therapies (HETs), treatment strategies for POMS still lack consensus. Objective: To assess the real-world association of HET as an index treatment compared with MET with disease activity. Design, setting, and participants: This was a retrospective cohort study conducted from January 1, 2010, to December 8, 2022, until the last recorded visit. The median follow-up was 5.8 years. A total of 36 French MS centers participated in the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Of the total participants in OFSEP, only treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least 1 follow-up clinical visit were included in the study. All eligible participants were included in the study, and none declined to participate. Exposure: HET or MET at treatment initiation. Main outcomes and measures: The primary outcome was the time to first relapse after treatment. Secondary outcomes were annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions. Results: Of the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean [SD] age, 16.0 [1.8] years; 364 female [68.7%]) were included in the study. In study patients, both treatment strategies were associated with a reduced risk of first relapse within the first 2 years. HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46; 95% CI, 0.31-0.67; P < .001) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34; 95% CI, 0.18-0.66; P = .001), and with a better tolerability pattern than MET. The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97; 95% CI, 2.92-12.20). The primary reasons for treatment discontinuation were lack of efficacy and intolerance. Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51; 95% CI, 0.24-1.10; P = .09). Conclusions and relevance: Results of this cohort study suggest that compared with MET, initial HET in POMS was associated with a reduction in the risk of first relapse with an optimal outcome within the first 2 years and was associated with a lower rate of treatment switching and a better midterm tolerance in children. These findings suggest prioritizing initial HET in POMS, although long-term safety studies are needed.

Dates et versions

hal-04458180 , version 1 (14-02-2024)

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Nail Benallegue, Fabien Rollot, Sandrine Wiertlewski, Romain Casey, Marc Debouverie, et al.. Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis. JAMA neurology, 2024, 81 (3), pp.273-282. ⟨10.1001/jamaneurol.2023.5566⟩. ⟨hal-04458180⟩
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