BOSTON – The efficacy of alemtuzumab was maintained at 4-year follow-up in patients who had active relapsing-remitting multiple sclerosis and relapsed on prior therapy, according to findings from the extension phase of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS II) study.
Response was maintained even though most of the 393 patients in the extension study had not received either alemtuzumab or any other disease modifying therapy during the 3 years after they received two courses of alemtuzumab as part of the core CARE-MS II study – a phase 3, randomized comparison of alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), Dr. Hans-Peter Hartung of Heinrich-Heine University, Dusseldorf, Germany and his colleagues reported in a poster at the joint Americas and European committees on Treatment and Research in MS conference.
In the core CARE-MS II trial, annual treatment with alemtuzumab – a humanized anti-CD52 monoclonal antibody – reduced the annualized relapse rate by 49% (from 0.52 to 0.26), and reduced the rate of sustained accumulation of disability by 42%, compared with SC IFNB-1a (Rebif) at 2 years. Alemtuzumab is not approved in the United States for MS, although it is approved for MS in more than 30 other countries. Alemtuzumab was withdrawn from the market by Genzyme in the form of brand name Campath, indicated for a type of leukemia, when it was being developed for MS.
In 393 patients who were in the alemtuzumab 12-mg arm of the core study and enrolled in the extension study (93% of the population), the annualized relapse rate was 0.22 at 3 years, and 0.23 at 4 years (mean of 0.24 for years 0-4). Disability, as assessed by change in the Expanded Disability Status Scale score, remained stable or improved from baseline; 69%, 66%, and 67% of patients improved or remained stable from years 0-3, 0-4, and 3-4, respectively, the researchers reported.
“At year 4, 71% and 76% of alemtuzumab-treated patients were sustained accumulation of disability-free by 3- and 6-month sustained disability criteria, respectively,” they wrote.
Over the 4 years of the extension study, 68% of the patients received only the initial two annual courses of alemtuzumab; 24% received one additional course, 7% received two additional courses, and 5% received another disease-modifying therapy.
In 146 patients who were in the SC IFNB-1a 44 mcg arm of the core study and enrolled in the extension study (83%), 143 crossed over to alemtuzumab, and 131 of them received 2 courses. The annualized relapse rate in those who received alemtuzumab decreased by 71% at 4 years (from 0.52 to 0.15), and the Expanded Disability Status Scale scores at 2 years either remained stable or improved in 69% of patients.
“Two years after switching to alemtuzumab, the proportion of patients experiencing 3-month sustained accumulation of disability or 6-month sustained accumulation of disability were 15% and 11%, respectively, compared with 23% and 21% during the 2 years of SC IFNB-1a in CARE-MS II,” the researchers reported.
No unexpected adverse events occurred in either group during the extension study, and the safety profile among those who switched from SC IFNB-1a was similar to that in patients who received alemtuzumab for all 4 years.
“These findings augment previously reported data in support of the durable efficacy and positive benefit-risk profile for alemtuzumab in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy,” the investigators concluded.