Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis.

Immunomodulating agents have beneficial effects in the treatment of multiple sclerosis (MS), decreasing the frequency of relapses, the progression of disability, and MRI measures of disease activity. Despite the efficacy of these agents, many patients continue to show progression of disability, breakthrough relapses, and active disease on MRI. Therefore, clinicians have employed a variety of combinations of agents in an attempt to decrease disease activity in those with active disease despite standard immunomodulatory therapy. Although a variety of combination therapies have been used in clinical practice, there is a paucity of data available to guide clinical decision-making. A major pitfall in using combination therapy in the absence of data demonstrating safety is the possibility that the agent added to the primary therapy may have no effect or, worse, may antagonize the effect of the primary agent. The combination of mitoxantrone and interferon beta (IFNbeta) appears safe in short-term studies from a toxicity standpoint and is associated with a reduction in relapse rates, a decrease in the frequency of enhancing lesions, and a decrease in T2 lesion burden. Other combinations that appear safe in preliminary studies include IFNbeta-1a and methotrexate, IFNbeta-1a and azathioprine, and mitoxantrone plus methylprednisolone. The decision to use combination therapy in patients with a suboptimal response to monotherapy should be considered early and not be delayed until disability becomes advanced. This review discusses the available data regarding the combination of standard immunomodulatory therapy with immunosuppressive agents.