NEW ORLEANS—Compared with interferon beta-1a, alemtuzumab reduced the annualized relapse rate by 49% among patients with relapsing–remitting multiple sclerosis (MS) who had relapsed on previous therapy, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. Approximately 65% of patients taking alemtuzumab were relapse-free, compared with 47% of patients taking interferon beta-1a, per results from the phase III Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II (CARE-MS II) study.
In addition, patients with relapsing–remitting MS taking alemtuzumab had a 12.7% risk of sustained accumulation of disability, while patients taking interferon had a 21% risk, said Jeffrey A. Cohen, MD, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center. This reduction represents a hazard ratio of 0.58, or 42% treatment effect, he noted.
During a two-year period, the average Expanded Disability Status Scale (EDSS) score decreased by 0.17 steps among patients taking alemtuzumab, compared with an increase of 0.24 steps among patients taking interferon. The net difference of 0.41 EDSS steps between the two groups after two years was statistically significant, said Dr. Cohen, as were the differences between each group’s scores at baseline and at 12 months.
Patients receiving alemtuzumab also experienced a 29% chance of sustained reduction of disability. Patients receiving interferon, in contrast, experienced a 13% chance of this outcome.
Comparing the Same Drugs in a New Patient Population
The results of the study were consistent with those of a previous phase III trial—Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) (see sidebar). The two-year CARE-MS II trial, conducted by Dr. Cohen and colleagues, compared the effects of alemtuzumab and interferon beta-1a in patients who had relapsed on prior therapy. The study’s two primary efficacy end points were relapse rate and time to six-month sustained accumulation of disability. Additional end points included EDSS change from baseline and sustained reduction of disability, MRI lesion analyses, and normalized whole-brain volume, as measured by brain parenchymal fraction.
Eligible patients ages 18 to 55 were randomized to receive either 12 mg of alemtuzumab for five days at month 0 and for three days at month 12, or 44 µg of subcutaneous interferon beta-1a three times per week. To prevent side effects, the alemtuzumab patients received three days of IV methylprednisolone with each infusion course, and the same therapy was administered annually to the interferon patients. “Because of the distinct mode of administration and side-effect profiles, we felt that blinding of participants and treating clinicians was not feasible,” said Dr. Cohen.
The patients’ average EDSS score was 2.7, and participants had had an average of 1.5 relapses in the previous year. Approximately 80% of patients had previously received interferon therapy, 30% had received glatiramer acetate, and 20% had received both therapies.
Alemtuzumab Reduces the Number of T2 Lesions
Approximately 46% of patients receiving alemtuzumab had new or enlarging T2 lesions over two years, compared with 68% of patients receiving interferon. Although T2 lesion volume decreased in both patient groups, the difference was not statistically significant. Patients taking alemtuzumab experienced 23% less brain volume loss over two years, as measured by brain parenchymal fraction, compared with patients taking interferon beta-1a.
The overall incidence of adverse events was similar in both groups, as was the incidence of serious adverse events. Infections such as nasopharyngitis, sinusitis, and upper respiratory infection were somewhat more common among patients receiving alemtuzumab, as were serious infections such as pneumonia, appendicitis, and herpes zoster.
“This study showed superior efficacy of alemtuzumab, compared with interferon beta-1a, across multiple outcomes,” said Dr. Cohen. “This is now the third study demonstrating superior efficacy of alemtuzumab, and it’s important to note [that] all three of those studies were against an active comparator—subcutaneous interferon beta-1a—which itself is effective against relapses, disability, and MRI. The adverse event profile was consistent with [that of] previous studies, and a comprehensive monitoring program was successful in early detection, facilitating early treatment,” he concluded.
—Erik Greb
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