Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command

Abstract

Objective:

The therapies available today for multiple sclerosis (MS) reduce but do not fully control disease activity. The objective of this article is to review the definitions of and treatments for suboptimally controlled MS and highlight the challenges faced by clinicians to increase awareness of recognizing and managing patients with suboptimally controlled MS.

Methods:

Published literature describing treatment failure, treatment optimization paradigms or algorithms, clinical studies of therapies in patients with suboptimally controlled MS, or case reports of management of patients with suboptimally controlled MS were identified from searches of EMBASE and MEDLINE. This was supplemented with case reports and discussions from an expert panel meeting of MS specialists focused on the diagnosis and treatment of suboptimally controlled MS.

Results:

Several groups have created recommendations for evaluating suboptimal response to disease-modifying drugs (DMDs) in MS. Currently no robust evidence-based data exist to guide treatment decisions in patients who have suboptimal response to a particular therapy. In the absence of data, several treatment paradigms for suboptimally controlled MS have been proposed using a step therapy or platform therapy approach. Therapy modifications require consideration of disease- and patient-specific factors while accounting for the risk-benefit profile of the agent(s). Unapproved drugs and combination therapies should be reserved as agents of last resort because of the experimental nature of these treatments.

Conclusions:

In the absence of evidence-based data, identifying and treating MS patients with suboptimal response to the available platform therapies remains challenging. Developing algorithms able to quantify breakthrough disease activity and suboptimal response to DMDs in individual MS patients remains an important target for the MS community. Consideration should be given for all reasons why a particular DMD may not be working for a given patient and for the use of an individualized step therapy.

Key words: :

• Disease management
• Disease progression
• Drug therapy
• Relapsing-remitting multiple sclerosis
• Treatment failure

Transparency

Declaration of funding

Funding support for development of the manuscript was provided by EMD Serono, Inc., Rockland, MA, USA and Pfizer Inc, New York, NY, USA.

Declaration of financial/other relationships

All authors have disclosed that they had significant input to the content of, and revisions to, the manuscript and did not receive any financial compensation for their involvement. They have disclosed that they have received honoraria from EMD Serono and Pfizer for consulting activities. M.S.F. has disclosed that he has received honoraria for speaking on behalf of Pfizer, Bayer HealthCare, Biogen Idec, Teva Neuroscience, sanofi-aventis, and EMD Serono. He receives stipends for his role on steering or advisory committees from Bayer HealthCare, BioMS, Eli Lilly, Novartis, sanofi-aventis, and Merck Serono. B.C. has disclosed that he has received consulting fees, honoraria and/or educational program support from Bayer/Berlex, Biogen Idec, EMD Serono, Genentech, Novartis, Pfizer, and Teva Neuroscience. S.D.-J. has disclosed that he has received consulting fees and research grants from Teva, Bayer HealthCare, and EMD Serono. D.J. has disclosed that he has received honoraria and consulting fees from Bayer HealthCare, Biogen Idec, EMD Serono, Teva Neuroscience, GlaxoSmithKline, and Pfizer; and financial support for research from Bayer HealthCare, EMD Serono, and Teva Neuroscience. He has also received compensation for editorial review of a continuing medical education program sponsored by Bayer HealthCare. A.T.R. has disclosed that he has received consulting fees and honoraria from Aventis Pharma, Bayer HealthCare, Berlex Laboratories, BioMS, Biogen, Biogen/Idec, Caremark, Elan, Eli Lilly, Genentech, Genzyme, Medlink/Neurobase electronic journal, National MS Society, Neurocrine Biosciences, Novartis, Pfizer, EMD Serono, Schering, and Teva Neuroscience. M.S.-W. has disclosed that she has received consulting fees and honoraria from Bayer HealthCare, Biogen Idec, Genentech, Merck Serono, and sanofi-aventis; and is on the board of directors of Active Biotech. B.W.-G. has disclosed that she has received personal compensation from Biogen Idec, Teva Neuroscience, EMD Serono, and Novartis; and research support from Biogen Idec, Teva Neuroscience, EMD Serono, Acorda, Aspreva, and Cognition.

All peer reviewers receive honoraria from CMRO for their review work. Peer reviewer 1 has disclosed that he/she has a grant partially supported by Wyeth Consumer Healthcare for a subject unrelated to the topic of this paper, however Pfizer recently acquired Wyeth. Peer reviewer 2 has disclosed that he/she has grants from Genzyme, Genentech, and sanofi-aventis.

Acknowledgment

The authors acknowledge Alison Gagnon, PhD and Maryann Travaglini, PharmD of Complete Healthcare Communications, Inc., for editorial assistance with the manuscript.