• Demyelinating Diseases Clinical Trials

• Neurology
• Demyelinating Diseases
• Neurology Clinical Trials

Treatment with alemtuzumab is associated with durable improvements in magnetic resonance imaging (MRI) disease activity in patients with active relapsing-remitting multiple sclerosis, according to Douglas L. Arnold, MD, NeuroRX Research and Montreal Neurological Institute, McGill University, Montreal, Québec, Canada, who presented the 3-year results from An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab (ClinicalTrials.gov identifier: NCT00930553), an ongoing extension study of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) series of studies. The results showed that participants were free of gadolinium-enhancing, new or enlarging T₂ and new T lesions after 3 years of follow-up. Alemtuzumab also slowed the yearly rate of brain volume loss.

In 2 previous Phase 3 head-to-head trials with patients with active relapsing-remitting multiple sclerosis (CARE-MS I in treatment-naive patients and CARE-MS II in those who relapsed on prior therapy), 2 annual courses of alemtuzumab 12 mg proved superior to subcutaneous interferon-b1a (44 mg 3 times/wk) with respect to clinical efficacy and the reduction in MRI activity and brain volume loss over 2 years.

Patients treated with alemtuzumab in either of the CARE-MS studies continued uninterrupted follow-up in an extension study and were eligible for alemtuzumab retreatment (12 mg administered on 3 consecutive days ³12 months after their previous courses of therapy) on evidence of disease activity. MRI was performed at study entry and annually for each patient, and studies were centrally analyzed by experts masked to treatment group assignment. All patients underwent T₁-weighted pre- and post-Gd contrast, T₂-weighted and proton density precontrast, fluid-attenuated inversion recovery precontrast, and 3-dimensional gradient-echo postcontrast MRI sequences before the administration of methylprednisolone. Brain atrophy was measured by brain parenchymal fraction.

A total of 742 subjects entered the extension study (349 subjects from CARE-MS I and 393 from CARE-MS II). Durable effects on relapse rate and disability were reported at end of Year 1 of the extension study despite patients having been treated for only 2 years [Fox EJ et al. Neurology 2013].

The current report presents the results after 3 years of follow-up. In Year 3, 18% and 20% of the subjects in CARE-MS I and II, respectively, received retreatment with alemtuzumab; <3% of patients were treated with other disease-modifying therapies. The majority of alemtuzumab-treated patients were free of MRI activity (absence of both Gd-enhancing and new or enlarging T₂ hyperintense lesions) at both Year 2 and Year 3.

During the same period, alemtuzumab also slowed brain volume loss as measured by brain parenchymal fraction. The median yearly rate of brain atrophy decreased over time (Year 0 to 1, −0.59% and −0.48% for CARE-MS I and II, respectively; Year 1 to 2, −0.25% and −0.22%; Year 2 to 3, −0.19% and −0.10%).

These results support the efficacy of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis in both treatment-naive and previously treated patients and provide evidence of durability of benefit.

• © 2014 MD Conference Express®