Combination therapy for multiple sclerosis

To improve the partial benefit of approved monotherapies in multiple sclerosis (MS), over 25 combined therapies have been tested in recent years, either as fixed-dose or sequential combination regimes. The main therapeutic targets for combination therapy in MS are the same as for monotherapy: the immune-mediated inflammatory cascade, oxidative toxicity and excitotoxicity. There are numerous reasons to consider combination therapy in MS, including to improve the benefit and/or tolerance in patients responding to approved treatments, stop frequent disabling relapses and/or rapid progression in patients who do not respond to approved therapies, and maintain the benefit of immunosuppressive treatments. Preliminary clinical trials suggest that combination therapy in MS does not increase the side-effects of approved monotherapy; its efficacy over monotherapy should therefore be tested. Statistically robust trials would need to involve many patients for each combination, so the first step in determining the efficacy of combination therapy should be to perform safety studies, followed by proof-of-concept efficacy studies.