Combination therapies for multiple sclerosis: scientific rationale, clinical trials, and clinical practice.
OBJECTIVE
To outline the scientific rationale for combination therapy in multiple sclerosis and to discuss the evidence for combination treatment strategies from animal models and clinical trials of multiple sclerosis.


RESULTS
Experiments conducted in experimental autoimmune encephalomyelitis have recently shown beneficial effects of numerous combination therapies. The combination of approved and experimental drugs and two or more experimental agents may positively impact clinical disease activity, inflammation within the central nervous system, and neurorepair. Clinical trials are currently underway to establish the therapeutic efficacy and safety of various combination therapies for multiple sclerosis patients.


CONCLUSIONS
More effective therapies are needed to treat multiple sclerosis. There are good scientific rationales for the use of combination therapy in multiple sclerosis, and the pharmacologic principles for evaluating and understanding their actions are available. The evaluation of specific combination therapies in the controlled setting of clinical trials should be a priority in clinical multiple sclerosis research.
Costello
Fiona
F
Departments of Medicine, The University of Ottawa, Ottawa, Ontario, Canada. fcostello@ottawahospital.on.ca
Stüve
Olaf
O
Weber
Martin S
MS
Zamvil
Scott S
SS
Frohman
Elliot
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002985:Clinical Protocols / Q000592:standards; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data / Q000639:trends*; D004359:Drug Therapy, Combination; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods / Q000639:trends*; D016899:Interferon-beta / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D010455:Peptides / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta