Fewer Black Hole Conversions with Alemtuzumab Vs Subcutaneous Interferon Beta-1a in RRMS Patients Who Relapsed on Prior Therapy

Background: In the phase 3 Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II trial, alemtuzumab significantly reduced risk of relapse and sustained accumulation of disability, reduced formation of T2, gadolinium (Gd)-enhancing and T1-hypointense lesions, and slowed brain atrophy vs subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients who relapsed on prior therapy.

Objectives: To compare efficacy of alemtuzumab and SC IFNB-1a in preventing conversion of Gd-enhancing lesions (markers of active brain inflammation) to chronic T1-hypointense lesions or black holes (markers of permanent tissue destruction) on magnetic resonance imaging (MRI) in CARE-MS II patients.

Methods: CARE-MS II (NCT00548405) was a 2-year, randomized (2:1), rater-blinded trial comparing alemtuzumab and SC IFNB-1a in 798 RRMS patients who had relapsed while on disease-modifying therapy. Intravenous (IV) alemtuzumab 12 mg was administered on 5 days at study start and on 3 days 12 months later. SC IFNB-1a 44 mcg was administered 3 times weekly. T1-weighted MRI imaging, with/without IV Gd contrast, was obtained at baseline and Months 12 and 24 to assess conversions of Gd-enhancing lesions to chronic black holes (lesions with ≤85% signal hypointensity relative to surrounding normal-appearing white matter). T1-hypointense lesion numbers were assessed using negative binomial regressions. Odds ratios (ORs) and Pvalues for percentages of T1-hypointense conversions were calculated using logistic regression with generalized estimating equations.

Results: 426 and 202 patients treated with alemtuzumab and SC IFNB-1a, respectively, were eligible for this analysis. Baseline Gd-enhancing lesions evolved similarly in alemtuzumab- and SC IFNB-1a-treated patients (P=NS). Gd-enhancing lesions that formed on therapy, seen at Month 12, were significantly less likely to convert to black holes by Month 24 in alemtuzumab-treated than in SC IFNB-1a-treated patients (10.7% vs 27.3% [60.8% reduction]; OR 0.33; 95% confidence interval 0.15, 0.75; P=0.0078).

Conclusions: Compared with SC IFNB-1a, alemtuzumab significantly reduced the risk of conversion to chronic black holes for Gd-enhancing lesions that developed on therapy, suggesting that alemtuzumab reduces progression from active inflammation to irreversible tissue injury and axonal loss. Baseline Gd-enhancing lesions that developed before treatment did not benefit.