NEW YORK (Reuters Health) – As a treatment for early multiple sclerosis, alemtuzumab, an antibody that targets CD52 on lymphocytes and monocytes, is more effective than interferon beta-1a, but it may cause serious autoimmunity-related complications, new research shows.

In the study, reported in The New England Journal of Medicine for October 23, alemtuzumab was better than interferon at preventing disability and disease relapse and also reduced the lesion burden on MRI. However, autoimmune complications, including one fatal case of immune thrombocytopenic purpura, were more common with alemtuzumab.

The phase II trial featured 334 previously untreated early multiple sclerosis patients who enrolled in the study between December 2002 and July 2004. The subjects were randomized to receive subcutaneous interferon beta-1a (44 micrograms three times per week) or annual intravenous cycles of alemtuzumab (12 or 24 mg) in a 1:1:1 ratio for 36 months.

The alemtuzumab arm was stopped in September 2005 after three cases of ITP, one fatal, arose.

The rate of sustained accumulation of disability with alemtuzumab was 9.0%, significantly lower than the 26.2% rate seen with interferon, lead author Dr. Alasdair J. Coles, from Addenbrooke’s Hospital in Cambridge, UK, and colleagues note (p < 0.001). Patients treated with alemtuzumab had an improvement in disability scores, while those given interferon had worsening scores. Alemtuzumab was also associated with a lower annualized rate of relapse (0.10 vs. 0.36, p < 0.001) and with reduced lesion burden on T2-weighted MRI (p = 0.005). From 12 to 36 months, brain volume rose in the alemtuzumab group, but fell in the interferon group (p = 0.02). Other side effects included autoimmune thyroid disorders, which occurred in 23% of alemtuzumab-treated patients compared with just 3% of interferon-treated subjects. As noted, the ITP rate was also higher in the alemtuzumab group: 3% vs. 1%. Lastly, 66% of patients in the alemtuzumab group had an infectious complication compared with 47% of those in the interferon group. No difference in efficacy was noted between the 12 and 24 mg-doses of alemtuzumab, the report indicates. The findings support the concept that “early suppression of inflammation in multiple sclerosis inhibits the complex cascade of disease mechanisms responsible for long-term disability,” Dr. Cole’s group concludes. However, they also “raise the difficult issue of exposing young adults who have little disability to a drug having potentially serious adverse effects.” In a related editorial, Dr. Stephen L. Hauser, from the University of California, San Francisco, agrees that these study findings and others highlight “the value of very aggressive therapy instituted at the beginning of the disease process, a time when the majority of inflammatory damage is subclinical and disability is absent or mild in most patients.” Reference:
N Engl J Med 2008;359:1786-1801,1838-1841.