Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.

Multiple sclerosis Progression independent of relapse activity Relapse-associated worsening Secondary progression

Journal

Journal of neurology

ISSN: 1432-1459

Titre abrégé: J Neurol

Pays: Germany

ID NLM: 0423161

Informations de publication

Date de publication:
28 May 2024

Historique:

received: 25 03 2024

accepted: 14 05 2024

revised: 12 05 2024

medline: 28 5 2024

pubmed: 28 5 2024

entrez: 28 5 2024

Statut: aheadofprint

Résumé

We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS). Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively. Over 11.8 ± 5.4 years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003). In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase.

Identifiants

DOI: 10.1007/s00415-024-12448-4 PMID: 38805052

pubmed: 38805052

doi: 10.1007/s00415-024-12448-4

pii: 10.1007/s00415-024-12448-4

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

Références

Jakimovski D, Bittner S, Zivadinov R et al (2023) Multiple sclerosis. Lancet. https://doi.org/10.1016/S0140-6736(23)01473-3

doi: 10.1016/S0140-6736(23)01473-3 pubmed: 37949093

Lublin FD, Reingold SC, Cohen JA et al (2014) Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 83(3):278–286

doi: 10.1212/WNL.0000000000000560 pubmed: 24871874 pmcid: 4117366

Kappos L, Wolinsky JS, Giovannoni G et al (2020) Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol 77(9):1132–1140. https://doi.org/10.1001/jamaneurol.2020.1568

doi: 10.1001/jamaneurol.2020.1568 pubmed: 32511687

Lublin FD, Häring DA, Ganjgahi H et al (2022) How patients with multiple sclerosis acquire disability. Brain. https://doi.org/10.1093/brain/awac016

doi: 10.1093/brain/awac016 pubmed: 35104840 pmcid: 9536294

Cree BAC, Hollenbach JA, Bove R et al (2019) Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol 85(5):653–666. https://doi.org/10.1002/ana.25463

doi: 10.1002/ana.25463 pubmed: 30851128 pmcid: 6518998

Kappos L, Butzkueven H, Wiendl H et al (2018) Greater sensitivity to multiple sclerosis disability worsening and progression events using a roving versus a fixed reference value in a prospective cohort study. Mult Scler 24(7):963–973. https://doi.org/10.1177/1352458517709619

doi: 10.1177/1352458517709619 pubmed: 28554238

Portaccio E, Bellinvia A, Fonderico M et al (2022) Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study. Brain. https://doi.org/10.1093/brain/awac111

doi: 10.1093/brain/awac111 pubmed: 35325059

Tur C, Carbonell-Mirabent P, Cobo-Calvo Á et al (2023) Association of early progression independent of relapse activity with long-term disability after a first demyelinating event in multiple sclerosis. JAMA Neurol 80(2):151–160. https://doi.org/10.1001/jamaneurol.2022.4655

doi: 10.1001/jamaneurol.2022.4655 pubmed: 36534392

Trojano M, Bergamaschi R, Amato MP et al (2019) The Italian multiple sclerosis register. Neurol Sci 40(1):155–165. https://doi.org/10.1007/s10072-018-3610-0

doi: 10.1007/s10072-018-3610-0 pubmed: 30426289

Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33(11):1444–1452

doi: 10.1212/WNL.33.11.1444 pubmed: 6685237

Thompson AJ, Banwell BL, Barkhof F et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2):162–173. https://doi.org/10.1016/S1474-4422(17)30470-2

doi: 10.1016/S1474-4422(17)30470-2 pubmed: 29275977

Lorscheider J, Buzzard K, Jokubaitis V et al (2016) Defining secondary progressive multiple sclerosis. Brain 139(Pt 9):2395–2405. https://doi.org/10.1093/brain/aww173

doi: 10.1093/brain/aww173 pubmed: 27401521

Lizak N, Malpas CB, Sharmin S et al (2020) Association of sustained immunotherapy with disability outcomes in patients with active secondary progressive multiple sclerosis. JAMA Neurol 77(11):1398–1407. https://doi.org/10.1001/jamaneurol.2020.2453

doi: 10.1001/jamaneurol.2020.2453 pubmed: 32716480

Koch MW, Moral E, Brieva L et al (2023) Relapse recovery in relapsing-remitting multiple sclerosis: an analysis of the CombiRx dataset. Mult Scler. https://doi.org/10.1177/13524585231202320

doi: 10.1177/13524585231202320 pubmed: 37830451 pmcid: 10687796

Müller J, Cagol A, Lorscheider J et al (2023) Harmonizing definitions for progression independent of relapse activity in multiple sclerosis: a systematic review. JAMA Neurol 80(11):1232–1245. https://doi.org/10.1001/jamaneurol.2023.3331

doi: 10.1001/jamaneurol.2023.3331 pubmed: 37782515

Cree BAC, Arnold DL, Chataway J et al (2021) Secondary progressive multiple sclerosis: new insights. Neurology 97(8):378–388. https://doi.org/10.1212/WNL.0000000000012323

doi: 10.1212/WNL.0000000000012323 pubmed: 34088878 pmcid: 8397587

Confavreux C, Vukusic S (2006) Natural history of multiple sclerosis: a unifying concept. Brain 129(Pt 3):606–616. https://doi.org/10.1093/brain/awl007

doi: 10.1093/brain/awl007 pubmed: 16415308

Iaffaldano P, Portaccio E, Lucisano G et al (2023) Multiple sclerosis progression and relapse activity in children. JAMA Neurol 30(2):137–138. https://doi.org/10.1177/13524585231224667

doi: 10.1177/13524585231224667