Evaluating response to disease-modifying therapy in relapsing multiple sclerosis

Abstract

Despite the broadening range of available treatments, the response of multiple sclerosis patients to disease-modifying therapies remains quite heterogeneous, thus a scheme is required in order to flag individuals achieving a suboptimal treatment response, so that they may switch to a different, possibly more effective disease-modifying therapy. There are several treatment outcomes that can be defined as surrogate markers for continued treatment efficacy and can be used for optimizing disease-modifying therapy. As no single marker is validated, we must make use of all available potential surrogates to help predict the future course of the disease. Only by putting all of the outcome measures together can a true picture be derived that will indicate an optimal response to treatment.

Keywords:

• disease-modifying therapy
• disease progression
• multiple sclerosis
• optimization
• surrogate markers

Financial & competing interests disclosure

MS Freedman has received honoraria or consultancy fees from Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi-Aventis, Teva Canada Innovation. MS Freedman has also served on the advisory board of Bayer Healthcare, Biogen Idec, Hoffman La-Roche, Merck Serono, Novartis, Opexa, Sanofi-Aventis. MS Freedman has participated in a company sponsored speaker’s bureau for Genzyme. M Abdoli has received honoraria or consultancy fees from EMD Canada, Consortium of Multiple Sclerosis Centers. 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There is no single surrogate marker that could be used to guide treatment response.

• There are many proposals for schemes to optimize disease-modifying treatment.

• The prevention or delay of the progressive phase of the disease is the key therapeutic target in relapsing forms of multiple sclerosis.

• Early suppression of disabling relapses will prolong the time to long-term disability.

• There are features concerning disease progression, which are more strongly pointing to suboptimal treatment response.

• MRI activity in the first year of could be predictive of continued activity.

• The combination of relapse, progression, and MRI activity offers the best model for disease outcome prediction.