Alemtuzumab
Another major advance in MS therapy has been the development of more powerful parenteral biologic agents for the treatment of aggressive MS or for treatment failure on first-generation therapies. The CARE-MS I and II studies that were reported at the meeting and shortly thereafter provided further data on the efficacy and safety of alemtuzumab (Campath). CARE-MS I enrolled treatment-naive early relapsing-remitting MS patients into two different dosing regimens of alemtuzumab versus the active comparator interferon beta-1a. Alemtuzumab reduced the risk of relapse by greater than 50% after 2 years, but failed to show a greater reduction in the risk of SAD when compared with interferon-beta. (An earlier phase II trial of alemtuzumab had reported significant results for its efficacy.) The unexpectedly low rate of disability progression in the placebo group may have made this study underpowered for this second primary end point, similar to the situation seen in the BRAVO trial of laquinimod. Thyroid disorders (18.1% vs. 6.4%), infections (67% vs. 46%), and immune thrombocytopenic purpura (0.8% vs. 0.5%) all occurred more frequently with alemtuzumab than with interferon-beta.
The CARE-MS II study enrolled patients with ongoing disease activity on previous interferon-beta therapy and randomized patients to treatment with alemtuzumab or high-dose interferon beta-1a. This study did show a significant 49% reduction in ARR rate as well as a 42% reduction in SAD, compared with the active comparator. No new safety signals arose from either study.
Daclizumab
The SELECT study of daclizumab versus placebo also reported significant reductions in ARR at 1 year in the two daclizumab arms (54% and 50%) versus placebo. The phase II study also showed a significant reduction in the risk of SAD at 1 year in both daclizumab arms, which was somewhat surprising given the short duration of treatment. MRI showed significant reductions in new or active MRI lesions in both treatment arms versus placebo. Adverse events included cutaneous reactions – some of which were serious – and elevated liver enzymes.
This column, "Frontal Matter," regularly appears in Clinical Neurology News, an Elsevier publication. Dr. Carter is an associate professor of medicine at the Mayo Clinic in Scottsdale, Ariz., and has a clinical interest in multiple sclerosis, optic neuritis, transverse myelitis, and neuroimmunology. He is on the data safety monitoring board of an MS clinical trial for Ono Pharmaceuticals and receives research support from funds paid to the Mayo Clinic by Actelion, EMD Serono, Biogen Idec, Genzyme, and Sanofi-Aventis.