HealthDay New — Treatment with the anti-CD52 monoclonal antibody alemtuzumab as first-line therapy for relapsing-remitting multiple sclerosis (MS), or as first-line therapy for refractory relapsing-remitting MS correlates with reductions in both the relapse rate and in sustained accumulation of disability, study findings indicate.
Results of the two head-to-head phase-3 studies that compared once-yearly alemtuzumab to interferon beta-1a (Rebif), along with an editorial that called the outcomes “encouraging,” were published in Lancet.
Alemtuzumab (Campath), originally approved for B-cell chronic lymphocytic leukemia, significantly reduced relapse rates in patients who failed first-line MS therapies, as well as in treatment-naive patients, both trials showed.
In the study involving treatment-naive patients, called CARE MS-I, Jeffrey A. Cohen, MD, from the Cleveland Clinic, and colleagues randomly assigned a total of 386 patients with relapsing-remitting MS to alemtuzumab (12 mg by IV infusion, 5 days during the first course and 3 days during the second course one year later) and 195 to interferon beta 1a (44 mcg three times a week by subcutaneous injection).
At two year follow-up, the relapse rate was 40% in the interferon beta 1a group vs. 22% in the alemtuzumab group (rate ratio= 0.45), with 59% and 78% of patients, respectively, relapse-free at two years (OR=2.36; 95% CI: 1.62-3.43; P<0.0001).
Sustained accumulation of disability was observed in 11% and 8% percent of interferon beta 1a-treated and alemtuzumab-treated patients (HR= 0.70; P=0.22), respectively.
In the second study, CARE MS-II, Alasdair J. Coles, MD, from the University of Cambridge in the United Kingdom, and colleagues compared the efficacy and safety of almtuzumab vs interferon beta 1a among patients who had experienced at least one relapse on interferon beta or glatiramer.
Two of the study arms used the same dosing as in the first trial. The third arm involved a 24-mg daily IV dose of alemtuzumab, given for 5 days at baseline and 3 days a year later. Only safety data from the 24-mg group were included in the Lancet study.
The researchers assigned 202 patients to interferon, 426 to the 12-mg alemtuzumab group, and 170 to the 24-mg group.
Outcomes were similar to those observed in the CARE MS-I study. The relapse rate was 51% in the interferon beta 1a group compared with 35% in the alemtuzumab group (RR= 0.51). Relapse-free status at two-year follow-up was 47% and 65%, respectively. Sustained accumulation of disability was noted in 20% of the interferon beta 1a group and 13% of the alemtuzumab group (HR=0.58).
In both studies, brain atrophy was significantly slowed with alemtuzumab relative to the interferon group, but not stopped. More than 90% of patients assigned to alemtuzumab experienced adverse reactions such as headache, rash, fever or nausea immediately following the infusions.
Patients belonging to the alemtuzumab groups were also more likely to experience infections and thyroid disorder; however, serious adverse events were generally manageable and seldom led to withdrawal from the study, according to the researchers.