Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry.

Disease Progression Humans Multiple Sclerosis / drug therapy Multiple Sclerosis, Chronic Progressive / drug therapy Registries Wheelchairs
disease progression ocrelizumab primary progressive multiple sclerosis wheelchair

Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
04 2022
Historique:
revised: 19 02 2021
received: 03 12 2020
accepted: 11 03 2021
pubmed: 17 3 2021
medline: 5 4 2022
entrez: 16 3 2021
Statut: ppublish

Résumé

Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase. In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

Sections du résumé

BACKGROUND AND PURPOSE
Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662).
METHODS
Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase.
RESULTS
In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years.
CONCLUSIONS
Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

Identifiants

DOI: 10.1111/ene.14824 PMID: 33724638 PMC: PMC9292576
pubmed: 33724638
doi: 10.1111/ene.14824
pmc: PMC9292576
doi:

Banques de données

ClinicalTrials.gov
['NCT01194570']
ANZCTR
['ACTRN12605000455662']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1082-1090

Informations de copyright

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Références

Ann Neurol. 2005 Dec;58(6):840-6
pubmed: 16283615
Lancet Neurol. 2020 Dec;19(12):998-1009
pubmed: 33129442
PLoS One. 2014 Aug 25;9(8):e104604
pubmed: 25153835
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
J Immunol. 2008 Jan 1;180(1):361-71
pubmed: 18097037
Curr Med Res Opin. 2010 Jan;26(1):109-19
pubmed: 19916707
Int J MS Care. 2015 Mar-Apr;17(2):74-82
pubmed: 25892977
Control Clin Trials. 2003 Dec;24(6):682-701
pubmed: 14662274
MAbs. 2013 Jan-Feb;5(1):22-33
pubmed: 23211638
N Engl J Med. 2017 Jan 19;376(3):209-220
pubmed: 28002688
Mult Scler. 2017 Jul;23(8):1123-1136
pubmed: 28273775
Eur J Neurol. 2019 Feb;26(2):363-370
pubmed: 30298572
Lancet Neurol. 2007 Oct;6(10):903-12
pubmed: 17884680
Mult Scler. 2006 Dec;12(6):769-74
pubmed: 17263005

Auteurs

Helmut Butzkueven (H)

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
ORCID: 0000-0003-3940-8727

Tim Spelman (T)

Department of Medicine and Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.

Dana Horakova (D)

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Stella Hughes (S)

Department of Neurology, Craigavon Area Hospital, Craigavon, UK.
Belfast Health and Social Care Trust, Belfast, UK.

Claudio Solaro (C)

CRRF "Mons. Luigi Novarese", Moncrivello, (VC), Italy.

Guillermo Izquierdo (G)

Vithas Nisa Hospital, Seville, Spain.

Eva Kubala Havrdová (E)

Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University, Prague, Czech Republic.

Francois Grand'Maison (F)

Neuro Rive-Sud, Quebec City, Quebec, Canada.

Alexandre Prat (A)

CHUM and Universite de Montreal, Montreal, Quebec, Canada.

Marc Girard (M)

CHUM and Universite de Montreal, Montreal, Quebec, Canada.

Raymond Hupperts (R)

Zuyderland Ziekenhuis, Sittard, The Netherlands.

Marco Onofrj (M)

University G. d'Annunzio, Chieti, Italy.

Alessandra Lugaresi (A)

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOSI Riabilitazione Sclerosi Multipla, Bologna, Italy.
Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.

Bruce Taylor (B)

Royal Hobart Hospital, Hobart, Tasmania, Australia.

Gavin Giovannoni (G)

Queen Mary University of London, London, UK.

Ludwig Kappos (L)

Research Center for Clinical Neuroimmunology and Neuroscience and MS Center, University Hospital Basel and University of Basel, Basel, Switzerland.

Stephen L Hauser (SL)

University of California, San Francisco, California, USA.

Xavier Montalban (X)

Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Licinio Craveiro (L)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Rita Freitas (R)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Fabian Model (F)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

James Overell (J)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Erwan Muros-Le Rouzic (E)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Annette Sauter (A)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Qing Wang (Q)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

David Wormser (D)

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Jerry S Wolinsky (JS)

McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, Texas, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Risk of requiring a wheelchair in primary...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Risk of requiring a wheelchair in primary...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Risk of requiring a wheelchair in primary...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Sclérose en plaques chronique progressive › Risk of requiring a wheelchair in primary...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enregistrements › Risk of requiring a wheelchair in primary...
questionsmedicales.fr › Équipement et fournitures › Dispositifs d'assistance au mouvement › Fauteuils roulants › Risk of requiring a wheelchair in primary...