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Review
. 2022 Jan;28(1):16-28.
doi: 10.1177/13524585211059766. Epub 2021 Dec 1.

Charting a global research strategy for progressive MS-An international progressive MS Alliance proposal

Alan J Thompson  1 , William Carroll  2 , Olga Ciccarelli  1 , Giancarlo Comi  3 , Anne Cross  4 , Alexis Donnelly  5 , Anthony Feinstein  6 , Robert J Fox  7 , Anne Helme  8 , Reinhard Hohlfeld  9 , Robert Hyde  10 , Pamela Kanellis  11 , Douglas Landsman  12 , Catherine Lubetzki  13 , Ruth Ann Marrie  14 , Julia Morahan  15 , Xavier Montalban  16 , Bruno Musch  17 , Sarah Rawlings  18 , Marco Salvetti  19 , Finn Sellebjerg  20 , Caroline Sincock  21 , Kathryn E Smith  22 , Jon Strum  23 , Paola Zaratin  24 , Timothy Coetzee  12
Affiliations
Review

Charting a global research strategy for progressive MS-An international progressive MS Alliance proposal

Alan J Thompson et al. Mult Scler. 2022 Jan.

Abstract

Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management.

Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS.

Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms "progressive multiple sclerosis", "primary progressive multiple sclerosis", "secondary progressive MS". Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee.

Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS.

Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.

Keywords: Multiple sclerosis; progression; progressive; progressive multiple sclerosis.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Thompson et al Conflict of Interest Disclosures.

AJ Thompson reports personal fees paid to his institution from Eisai Ltd; is an editorial board member for The Lancet Neurology receiving a free subscription; is Editor-in-Chief for Multiple Sclerosis Journal receiving an honorarium from SAGE Publications; receives support for travel as Chair, Scientific Advisory Committee, International Progressive MS Alliance, and from the National MS Society (USA) as member, NMSS Research Programs Advisory Committee.

WM Carroll reports honoraria and travel assistance for participation in industry sponsored meetings from and has provided advice to Biogen, Novartis, Genzyme, Sanofi, Aventis, Merck, and Celgene and has received travel support from the International Progressive MS Alliance, PACTRIMS and the World Federation of Neurology.

O Ciccarelli is Deputy Editor for Neurology and has acted as a Consultant for Merck and Biogen.

RAM receives research funding from CIHR, the MS Society of Canada, Research Manitoba, the CMSC, National MS Society, US Department of Defense, and Crohn’s and Colitis Canada. She is supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on studies funded by Biogen Idec and Roche.

G. Comi has received compensation for consulting services for Bristol Myers Squibb, Janssen, Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, Roche, Almirall, Chugai, Receptos, and Forward Pharma and compensation for speaking activities for Novartis, Teva, Sanofi, Genzyme, Merck, Biogen, Excemed, and Roche.

A. Cross has done paid consulting for Biogen, Bristol Myers Squibb (Celgene), EMD Serono, Genentech/Roche, Greenwich Biosciences, Horizon Therapeutics, Janssen, Novartis, and TG Therapeutics and has contracted research funded by EMD Serono and Genentech.

A. Feinstein is on an Advisory Board for Akili Interactive and reports grants from the MS Society of Canada, book royalties from Johns Hopkins University Press, Cambridge University Press and Amadeus Press and speaker’s honoraria from Novartis, Biogen, Roche, and Sanofi-Genzyme.

C. Lubetzki reports grants from Biogen and personal fees for participation to advisory boards and/or symposia from Biogen, Merck Serono, Roche, Rewind, and Ipsen.

A Donnelly receives support for travel and subsistence as a member, Scientific Advisory Committee, International Progressive MS Alliance.

RJ Fox reports personal consulting fees from AB Science, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Immunic, Janssen, Novartis, Sanofi, and TG Therapeutics; has served on advisory committees for AB Science, Biogen, Genzyme, Immunic, Janssen, Novartis, Sanofi, and TG Therapeutics; and receives clinical trial contract and research grant funding from Biogen, Novartis, and Sanofi.

Anne Helme has no personal pecuniary interests to disclose, other than being an employee of the MS International Federation (MSIF), which receives income from a range of corporate sponsors, recently including: Biogen, Bristol Myers Squibb (formerly Celgene), Genzyme, Med-Day, Merck, Mylan, Novartis, Roche. MSIF is a managing member of the International Progressive MS Alliance.

P Kanellis is an employee of the Multiple Sclerosis Society of Canada, a member of the International Progressive MS Alliance

R Hohlfeld received consultancy fees from Novartis, Sanofi, Biogen, Merck, Janssen/Johnson&Johnson, and Roche.

R. Hyde is an employee of Biogen and co-chair of the International Progressive MS Alliance Industry Forum.

D Landsman is an employee of the National Multiple Sclerosis Society, a managing member of the International Progressive MS Alliance and has no conflict of interest.

X Montalban received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF, and NMSS.

JM Morahan is an employee of Multiple Sclerosis Australia, a managing member of the International Progressive MS Alliance.

B. Musch is an employee of Genentech, a subsidiary of Roche AG.

M. Salvetti reports speaking honoraria and research support from Merck, Sanofi, Novartis, Biogen, Roche, Bristol Myers Squibb.

S Rawlings is an employee of the MS Society UK, a managing member of the International Progressive MS Alliance.

C Sincock receives support for travel and subsistence as a member of the Scientific Advisory Committee, International Progressive MS Alliance.

K Smith receives consulting fees for project work from the International Progressive MS Alliance, and travel support from the Alliance as a member of the Scientific Steering Committee and the National MS Society as a member of their Scientific Advisory Committee.

F Sellebjerg has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche, and Sanofi Genzyme.

J Strum is the host of the RealTalk MS podcast. He has received podcast sponsorship fees from the National MS Society, EMD Serono, and Janssen Pharmaceuticals. As a speaker, he has received honoraria from Novartis, Auburn University, European MS Platform, and Can-Do MS. As co-lead investigator for caregiver research projects, he has received compensation from the Accelerated Cure Project for MS. He has also received support for travel to conferences and meetings from the National MS Society, the International Progressive MS Alliance, and the Accelerated Cure Project for MS.

P Zaratin is an employee of the Italian Multiple Sclerosis Society, a managing member of the International Progressive MS Alliance and has no conflict of interest.

T Coetzee is an employee of the National Multiple Sclerosis Society, a managing member of the International Progressive MS Alliance and has no conflict of interest.

Figures

Figure 1.
Figure 1.
Pathways influencing development of progressive MS: The accumulation of disability and development of progressive MS likely reflects a combination of factors including damage arising from inflammatory disease mechanisms, neurodegenerative mechanisms, and biological aging. These processes are likely attenuated by compensatory mechanisms and reserve during the early- to mid-stages of the disease, but over time these compensatory processes are depleted. Moderators such as sex, gender, socioeconomic status, and DMT utilization likely exert positive and negative influences on progression and the development of progressive MS.
Figure 2.
Figure 2.
Progressive MS treatments in clinical development. Active clinical trials evaluating agents in progressive MS and registered with ClinicalTrials.gov or World Health Organization International Clinical Trials Registry Platform as of April 2021 are illustrated. Trials are positioned based on their stage of development and agent or intervention profile (disease modification or symptom management/quality of life). Phase 0/I studies are in the outermost ring, with Phase II and III studies reflected in the inner rings. Phase I/II and II/III studies are placed on the borders of the respective rings.
Figure 3.
Figure 3.
Quality-of-life intervention targets. Potential targets for quality-of-life interventions in progressive MS span several inter-related domains. While some are directly associated with disease mechanisms (e.g. cognition, pain) others are associated with other disease indications (e.g. hypertension) or social support mechanisms (e.g. care providers, housing) that affect quality of life.
Figure 4.
Figure 4.
Stakeholders in the progressive MS agenda. Addressing the challenges of MS is a multi-stakeholder effort spanning patient organizations, clinical professionals, government, and industry.
See this image and copyright information in PMC

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