• Demyelinating Diseases
• Neuroimaging
• Neurology Clinical Trials
• Magnetic Resonance Imaging

• Demyelinating Diseases
• Neuroimaging
• Neurology Clinical Trials
• Neurology
• Magnetic Resonance Imaging

Subgroup analyses, entitled An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab [NCT00930553; Barkhof F et al. ACTRIMS/ECTRIMS 2014 (poster P075)], of an ongoing, open-label extension of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study Two [CARE-MS II; Coles AJ et al. Lancet. 2012], have confirmed the superiority of treatment of MS using the anti-CD52 humanized monoclonal antibody, alemtuzumab, over subcutaneous interferon beta-1a (SC IFN-β-1a) in magnetic resonance imaging (MRI) outcomes. The subgroup analyses were based on baseline demographics and disease characteristics, as well as prior use of SC IFN-β-1a. Alemtuzumab's superiority was, in most cases, a holdover from treatment received 2 years previously.

The latest findings from the subgroup analyses based on the phase 3, randomized, rater-blinded, active-controlled, head-to-head CARE-MS II study were presented by Frederik Barkhof, MD, VU University Medical Center, Amsterdam, the Netherlands.

CARE-MS II has established the significant superiority of alemtuzumab throughout 2 years compared with SC IFN-β-1a at reducing the risk of the development or enlargement of gadolinium-enhancing (Gd+) lesions and reducing brain volume loss [Coles AJ et al. Lancet. 2012], and in lessening the number of hypointense lesions [Arnold DL et al. ECTRIMS 2012). Eligible patients (n = 667) aged 18 to 55 years with active relapsing-remitting MS and a baseline Expanded Disability Status Scale (EDSS) score ≤ 5 (n = 667) were randomized 2:1 to receive alemtuzumab 12 mg/d intravenously for 5 consecutive days at baseline and 3 consecutive days 12 months later (n = 426), or to receive SC IFN-β-1a 44 μg 3 times a week on an ongoing basis (n = 202) [Coles AJ et al. Lancet. 2012]. The groups were similar at baseline concerning demographic and relevant clinical parameters.

The core phase ran for 2 years. In the subsequent extension phase, patients initially randomized to alemtuzumab could continue their treatment if they relapsed or presented with MRI signs of progression. This retreatment was unnecessary in 80% of cases.

The proportion of patients with new or enlarged Gd+, T2 lesions, and T1 lesions was significantly lower with alemtuzumab (≤ 20%) than IFN-β-1a in the core portion of the study (all P < .0001) [Coles AJ et al. Lancet. 2012], and the proportion in the extension phase in the 20% of patients who received alemtuzumab was comparable. Furthermore, the mean change in brain parenchymal fraction (BPF) from baseline through year 3 was significantly less in alemtuzumab-treated patients, with the year 2 value maintained at year 3, than in IFN-β-1a-treated patients (P = .012).

Subgroup analyses revealed that the risk of Gd+ lesions was significantly lower with alemtuzumab compared with IFN-β-1a (P < .05 for overall population) for most parameters, with only nonwhite race and Latin American geographic region being equivocal.

Other subgroup analyses based on the same parameters revealed that, compared with SC IFN-β-1a, alemtuzumab significantly lessened the risk of new or enlarging T2 lesions (P < .01) and new T1 lesions (P < .05) at year 2. Also, the subgroup analysis of the change from baseline in BPF consistently revealed the reduced loss in volume associated with alemtuzumab-treated patients. The difference in volume loss between the alemtuzumab and IFN-β-1a groups was significant for the parameters of patients aged < 34 years (P = .0126), white race (P = .0285), baseline EDSS score ≥ 2.5 (P = .0437), baseline BPF ≥ 0.816105 (P = .0359), baseline T2 lesion volume < 5.7135 cm³, disease duration < 3.8 years (P = .0142), and no prior SC IFN-β-1a use (P = .0076).

The latest findings strengthen support for the superiority of using alemtuzumab in the treatment of active relapsing-remitting MS in patients who have relapsed.

• © 2014 MD Conference Express®