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Review
. 2014 Sep;20(10):1306-11.
doi: 10.1177/1352458513513207. Epub 2013 Nov 30.

Risk evaluation and monitoring in multiple sclerosis therapeutics

Michel C Clanet  1 , Jerry S Wolinsky  2 , Raymond J Ashton  3 , Hans-Peter Hartung  4 , Stephen C Reingold  5
Affiliations
Free PMC article
Review

Risk evaluation and monitoring in multiple sclerosis therapeutics

Michel C Clanet et al. Mult Scler. 2014 Sep.
Free PMC article

Abstract

Background: Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks.

Objectives: The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring.

Results: Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making.

Conclusions: It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions.

Keywords: Risk; benefit; disease-modifying therapy; multiple sclerosis; safety; surveillance.

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Conflict of interest statement

Conflicts of interest: Over the past 12 months MC had consulting agreements or received speaker honoraria from the following commercial entities, or its institution received research financial support from: Biogen Idec, Merck Serono, Teva Pharmaceuticals, Sanofi Genzyme, Novartis. Travel funds for this workshop that served as the basis of this manuscript were provided by the foundation ARSEP.

SCR has received consulting fees and/or travel funds in the past three years for data safety monitoring board and other advisory activities from Bayer HealthCare, Coronado Biosciences Inc, Cleveland Clinic Foundation, Eli Lilly & Company, Merck Serono, European Committee for Treatment and Research in Multiple Sclerosis, Genentech, F. Hoffmann-LaRoche, INC Research, Ironwood Pharmaceuticals Inc, Isis Pharmaceuticals Inc, MediciNova Inc, Medimmune, National Multiple Sclerosis Society, Novartis Pharmaceuticals Corporation, Observatoire Français de la Sclérose en Plaques, Opexa Therapeutics, Sanofi-Aventis, SK Biopharmaceuticals, Synthon Pharmaceuticals Inc, and Teva Pharmaceuticals Industries; travel funds for the meeting that served as the basis for this manuscript were provided by the Fondation pour l’aide à la Recheche sur La Sclérosis en Plaques.

Over the past 12 months, JSW has served on advisory boards or data monitoring committees, has had consulting agreements, or received speaker honoraria from the following commercial entities: Genzyme, advisory board, speakers bureau, Hoffman LaRoche (member steering committee), Janssen RND (consultant), Medscape CME (consultant), Novartis Pharmaceuticals Corporation (member steering committee and consultant), Sanofi (member steering committees), Serono Symposia International Foundation (speaker), Teva Neuroscience (consultant), Teva Pharmaceuticals (consultant), XenoPort (consultant). Royalties are received for out-licensed monoclonal antibodies through the University of Texas Health Science Center at Houston (UTHSCH) to Millipore (Chemicon International) Corporation since 1993. Grant or contractual support to the UTHSCH derives from the National Institutes of Health, 2 U01 NS045719-07 (principal investigator of the subcontract to UTHSCH for image analysis) and 2RO1-EB002095-06A1 (co-investigator), the National Multiple Sclerosis Society (RC-1019 A5), and Sanofi/Genzyme.

HPH has received speaking fees and honoraria for consulting from Bayer HealthCare, Biogen Idec, Genzyme, EMD Merck Serono, Novartis, Teva Pharmaceuticals, Sanofi Aventis and Hoffmann-La Roche.

RJA received compensation as medical writer to assist in preparation of the manuscript and was engaged by the co-authors independently of meeting sponsorship.

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