Combination therapy for the treatment of multiple sclerosis: challenges and opportunities.
OBJECTIVE
Multiple sclerosis (MS) is a complex, heterogeneous disease. Standard treatment of relapsing MS includes interferon beta (IFNbeta) and glatiramer acetate. These agents reduce relapse rates, and IFNbeta-1a is associated with a slowing of disease progression. Despite treatment, many patients experience disease progression, prompting neurologists to use combination therapies to delay this progression. Agents that may be considered for combination therapy are those with unique mechanisms of action that exert additive or synergistic efficacy. This article reviews combination treatment with immunosuppressive therapies and new agents for the management of MS.


METHODS
The Medline and EMBASE databases were searched for clinical trials using the following search terms: multiple sclerosis, interferon, Avonex, Betaseron, Rebif, glatiramer, copolymer 1, Copaxone, immunosuppressant, cytotoxic, corticosteroid, azathioprine, cyclophosphamide, methotrexate, mitoxantrone, natalizumab, combination therapy. The National MS Society website was searched for clinical trials of combination therapies.


RESULTS
Several small studies have analyzed the effects of immunosuppressive therapy added to IFNbeta treatment, and some encouraging results have been obtained. Few data are available on combination therapy with new drug classes; however, current data suggest that combination therapy with new agents is effective. Although the available data on combination regimens are promising, interpretation is limited by lack of controlled study design, small patient population, and short study duration.


CONCLUSIONS
Combination of standard therapies with immunosuppressive agents or with new therapies may provide synergistic effects that will likely benefit patients with MS. Larger, well-controlled trials need to be conducted.
Stuart
William H
WH
MS Center of Atlanta, Atlanta, GA 30327, USA. whstuart@aol.com
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D003603:Cytotoxins / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D008727:Methotrexate / Q000627:therapeutic use; D008942:Mitoxantrone / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D000700:Analgesics; D003603:Cytotoxins; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D003520:Cyclophosphamide; D008942:Mitoxantrone; D001379:Azathioprine; D008727:Methotrexate