Long-term drug treatment in multiple sclerosis: safety success and concerns

ABSTRACT

Introduction

The portfolio of multiple sclerosis (MS) disease modifying treatments (DMTs) has significantly expanded over the past two decades. Given the lifelong use of MS pharmacotherapy, understanding their long-term safety profiles is essential in determining suitable and personalized treatment.

Areas covered

In this narrative review, we summarize the short-, mid-, and long-term safety profile of currently available MS DMTs categories. In addition to the initial trial findings, safety outcomes derived from long-term extension studies (≥5–20 years) and safety-based prescription programs have been reviewed. In order to better understand the risk-benefit ratio for each particular DMT group, a short description of the DMT-based efficacy outcomes has been included.

Expert opinion

Long-term extension trials, large observational studies and real-world databases allow detection of rare and potentially serious adverse events. Two-year-long trials are unable to fully capture the positive and negative effects of immune system modulation and reconstitution. DMT-based monitoring programs can provide greater insights regarding safe use of MS medications in different patient populations and clinical settings. During the process of shared DMT decision, both MS care providers and their patients should be aware of an ever-expanding number of drug-based adverse events and their influence on the risk-benefit analysis.

KEYWORDS:

• Adverse events
• disease modifying treatment
• efficacy
• extension trials
• long-term safety
• multiple sclerosis
• observational studies

Article highlights

• There is an increasing number of available diseases modifying treatments (DMT) for multiple sclerosis (MS).

• Compared to efficacy outcomes, commonly used 2-year Phase III trial periods are not sufficiently long enough for detecting long-term pharmacovigilance concerns.

• Open-label extension studies, observational studies and real-world databases are crucial in detecting rare but severe adverse events.

• Continuous development of strategies for derisking the DMT use are currently ongoing and highly warranted.

• Systematic DMT-specific risk-benefit analysis can better align the choice of medication with the patient preferences.

• Baseline screening for patient selection, continuous monitoring for serious adverse events and DMT modifications are essential steps that contribute towards better risk management.

This box summarizes key points contained in the article.

Acknowledgments

The Authors would like to thank Penny Pennington (Advancing Research in MS; ARMS) for editorial revision of the manuscript.

Declaration of interest

R Zivadinov received personal compensation from EMD Serono, Sanofi, Novartis, Bristol Myers Squibb for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Keystone heart, V-VAWE Medica, Boston Scientific and Protembo. B Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, EMD Serono, Genentech, Novartis, Mallinckrodt, Celgene, Abbvie. B Weinstock-Guttman received research funds from Biogen Idec, EMD Serono, Genentech, and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.