Objectives: Compare the efficacy of alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a) on MS disease activity in a subset of patients with highly-active disease in the CARE-MS II study.
Methods: Active RRMS patients (≥2 relapses in previous 2 years; ≥1 relapse in prior year) who had relapsed on prior therapy were randomized to receive alemtuzumab 12 mg intravenously on 5 days at study start and on 3 days 1 year later or SC IFNB-1a 44µg 3-times weekly. Highly-active patients were defined as having ≥2 relapses in year before randomization and ≥1 baseline gadolinium-enhancing lesion. Expanded Disability Status Scale (EDSS) was assessed by blinded rater at baseline, quarterly, and for suspected relapses. 6-month SAD was defined as an increase of ≥1 EDSS point (≥1.5 point if baseline EDSS=0) sustained for 6 months. Magnetic resonance imaging with and without gadolinium occurred annually. MS disease activity-free was defined as no relapse, no SAD, no new gadolinium enhancing lesions or new/enlarging T2 hyperintense lesions.
Results: We compared highly-active patients receiving alemtuzumab 12 mg (n=101 [23.7%]) with those receiving SC IFNB-1a (n=42 [20.8%]). In the highly-active cohort, 33.3% of alemtuzumab-treated patients and 0% of IFNB-1a patients were MS disease activity-free after 1 year (P<0.0001); through the end of the study 24.2% of the highly-active group treated with alemtuzumab remained MS disease activity-free (P=0.0002). After 2 years, among highly-active patients receiving alemtuzumab and IFNB-1a, respectively: 35.8% and 60.0% had relapses; 7.4% and 17.5% had SAD; 22.1% and 52.5% had gadolinium-enhancing lesion activity, and 60.0% and 92.5% had T2 lesion activity.
Conclusions: In this cohort with highly-active disease despite prior therapy, alemtuzumab resulted in freedom from disease activity in 24% of patients, while IFNB-1a did not achieve this outcome in any patient. Alemtuzumab may therefore provide an important treatment option for this patient group.