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Original Investigation
July 27, 2020

Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis

Author Affiliations
  • 1Clinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  • 2Department of Medicine, The Alfred Hospital, Melbourne, Victoria, Australia
  • 3Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  • 4Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  • 5Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Seville, Spain
  • 6Istituto delle Scienze Neurologiche di Bologna, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Unita Operative Semplici d'Istituto (UOSI) Riabilitazione Sclerosi Multipla, Bologna, Italy
  • 7Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy
  • 8Department of Neurology, Hopital Notre Dame, Montreal, Quebec, Canada
  • 9Department of Medicine, Centre Hospitalier de l'Universite de Montreal, Universite de Montreal, Montreal, Quebec, Canada
  • 10Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
  • 11Neuro Rive-Sud, Quebec, Canada
  • 12Integrated Health and Social Services Centres (CISSS), Chaudiere-Appalaches, Levis, Quebec, Canada
  • 13Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy
  • 14Department of Neurology, Zuyderland Ziekenhuis, Sittard, the Netherlands
  • 15Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Mondino Foundation, Pavia, Italy
  • 16Medical Faculty, Farabi Hospital, Karadeniz Technical University, Trabzon, Turkey
  • 17Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium
  • 18Neurochemistry Unit, Institute of Neuroscience, Universite Catholique de Louvain, Louvain-la-Neuve, Belgium
  • 19Institute of Neurology, Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy
  • 20Medical Faculty, 19 Mayis University, Samsun, Turkey
JAMA Neurol. 2020;77(11):1398-1407. doi:10.1001/jamaneurol.2020.2453
Key Points

Question  Are clinical and demographic factors associated with the rate at which disability accumulates in secondary progressive multiple sclerosis, and is immunotherapy associated with a slower accumulation of disability among patients with active secondary progressive multiple sclerosis?

Findings  In this cohort study of 1621 patients with secondary progressive multiple sclerosis, relapses during the secondary progressive disease stage were associated with a faster rate of disability accumulation. Immunotherapies were associated with reductions in disability accumulation among patients who experienced superimposed relapses during the course of secondary progressive disease, and patients with active secondary progressive multiple sclerosis who were receiving sustained immunotherapy were less likely to become wheelchair-dependent than those who were not receiving immunotherapy.

Meaning  The study’s findings suggest that disease-modifying therapies are associated with a slower rate of disability accumulation in patients with active secondary progressive multiple sclerosis.


Importance  It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS).

Objective  To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation.

Design, Setting, and Participants  In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020.

Exposures  The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated.

Main Outcomes and Measures  Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models).

Results  Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent.

Conclusions and Relevance  In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study’s results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.

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