Major Finding: Significantly more patients who took 12 mg/day or 24 mg/day of alemtuzumab were clinically disease-free after 4 years, compared with patients who received subcutaneous interferon beta-1a (71% vs. 35%).
Data Source: A subset of patients from a phase II trial of 334 patients with relapsing-remitting MS.
Disclosures: The trial was sponsored by Genzyme. Dr. Khan has received research support and personal compensation from Teva Neuroscience, Biogen Idec, EMD Serono, and Bayer Healthcare. He also has received personal compensation from Novartis. Dr. Brinar has received research support from Genzyme.
TORONTO — Data further gleaned from a phase II study of low or high dose alemtuzumab indicate that the drug kept nearly three-fourths of multiple sclerosis patients clinically disease free for 4 years and was effective in halting disease activity even in patients who suffered autoimmune adverse events.
Dr. Omar Khan of Wayne State University, Detroit, and his colleagues reported 4-year follow-up results for a subset of patients in the CAMMS223 trial, an assessor-blinded study that randomized 334 patients to either 12 mg/day or 24 mg/day of alemtuzumab (Campath) against 44 mcg of subcutaneous interferon beta 1-a (IFN beta-1a, Rebif) 3 times a week.
Campath already is approved as a single agent for the treatment of B-cell chronic lymphocytic leukemia.
Data on follow-up at 4 years were available for 42 patients who received IFN beta-1a, 63 patients who received 12 mg/day of alemtuzumab, and 71 patients who received 24 mg/day of alemtuzumab. Treatment with alemtuzumab consisted of two to three cycles each year that each lasted 3–5 days. A total of 110 patients received only two cycles of alemtuzumab annually. The demographics of this subset of patients were similar to those in the original study group, Dr. Khan and his associates reported in a poster session at the annual meeting of the American Academy of Neurology.
After 4 years, no clinical disease activity had occurred in 71% of all patients treated with alemtuzumab and in 72% of those who received only two cycles of alemtuzumab. In comparison, significantly fewer patients in the IFN beta-1a group (35%) were free from clinical disease activity. Alemtuzumab-treated patients also had significantly higher rates of freedom from sustained accumulation of disability, compared with patients treated with IFN beta-1a (91% vs. 68%).
In addition, significantly more patients in the alemtuzumab groups (77%) were relapse-free than were those in the IFN beta-1a group (49%).
Comparisons between the IFN beta-1a group and each of the two alemtuzumab groups drew similar efficacy conclusions, Dr. Khan wrote.
Another analysis of the trial suggested that alemtuzumab may halt disease progression in the subset of MS patients who experienced autoimmune adverse events. In a poster at the meeting, Dr. Vesna Brinar of University Hospital Center in Zagreb, Croatia, and her colleagues reviewed 3-year follow-up data from 216 patients treated with alemtuzumab and 107 patients treated with IFN beta-1a in the phase II trial.
After 3 years, autoimmune adverse events had occurred in 47 patients who received alemtuzumab and in 3 patients who received IFN beta-1a. The most common events in alemtuzumab-treated patients included hyperthyroidism (21 patients), hypothyroidism (13 patients), and autoimmune thyroiditis (8 patients).
By 36 months, 12% of alemtuzumab-treated patients had experienced sustained accumulation of disability, compared with 26% of patients treated with IFN beta-1a.
The annualized relapse rate was significantly lower among the alemtuzumab-treated patients with autoimmune problems, compared with patients treated with IFN beta-1a (0.09 vs. 0.36), according to Dr. Brinar.
In addition, those who experienced autoimmune problems on alemtuzumab had a significant mean improvement on the Expanded Disability Status Scale of −0.44 points from baseline.
Ongoing phase III studies are in place to confirm and further expand the results, the researchers said.