Sequencing of disease-modifying therapies for relapsing–remitting multiple sclerosis: a theoretical approach to optimizing treatment

Abstract

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing–remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit–risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Keywords:

• Multiple sclerosis
• relapsing multiple sclerosis
• relapsing–remitting multiple sclerosis
• disease-modifying therapy
• treatment start
• treatment sequencing
• treatment switch
• sub-optimal treatment

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Declaration of funding

Author contributions: All authors have reviewed the manuscript for intellectual content, provided guidance during manuscript development and approved the final version submitted for publication. The final responsibility for the content lies with the authors.

Declaration of financial/other relationships

F.G. has disclosed that he has received grant funding from Novartis, Chugai, Opexa, Serono, Biogen, Roche, Genzyme, Abbott and Actelion. M.Y. has disclosed that he has received consultation fees from EMD Serono, Genzyme and Novartis, and the Canadian Agency for Drugs and Technologies in Health (CADTH)/Health Canada, and research support from Biogen-Idec, Genzyme, Hoffmann-La Roche, Novartis, and Teva Canada Innovation. S.A.M. has disclosed that he has received honoraria for speaking, consulting and advisory board participation from Biogen Idec, EMD Serono, Genzyme, Novartis and Roche; she has acted as site principal investigator for clinical trials for Novartis, Genzyme and Roche; she has received investigator initiated trial funding from Genzyme. L.L. has disclosed that he has served on advisory boards, received honoraria, conducted clinical trials with and received research funding from Allergan, Biogen Canada, Serono Canada, Teva Neurosciences, Schering (Berlex), BioMS, Bayer Canada, Novartis Canada, Sanofi-Aventis, Genzyme Canada and Roche Canada. F.E. has disclosed that he has received honoraria as a speaker, consultant/advisor or received educational/CME grant or a research grant from Biogen Idec, EMD Serono, Genzyme, Novartis, Teva Innovation and Hoffman-La Roche. B.J.W. has disclosed that he received compensation from Novartis for work related to infectious complications of DMTs. P.L. has disclosed that he has served as a consultant in an advisory board related to fingolimod; he has received honoraria as a speaker on the immunological effects of DMTs in MS from Novartis and Sanofi; he has also received reimbursement of travel and lodging expenses to give presentations on the immunological effects of DMTs in MS from Novartis. R.S. has disclosed that she is an employee of Novartis Pharmaceuticals Canada Inc.

Acknowledgements

Avinash Thakur and Sreelatha Komatireddy (Novartis Healthcare Pvt Ltd) provided medical writing assistance.

Additional information

Funding

This manuscript was funded by Novartis Pharmaceuticals Canada Inc.