Patients with Active RRMS and Inadequate Response to Therapy at Baseline Show Durable Disability Improvement over 5 Years with Alemtuzumab: Care-MS II

Background: Patients with active RRMS who had an inadequate response (≥1 relapse) to prior therapy at baseline had improved disability outcomes with alemtuzumab vs subcutaneous interferon beta-1a over 2 years in the CARE-MS II study (NCT00548405). Efficacy on disability endpoints was durable through 4 years.

Objectives: To examine 5-year disability outcomes in CARE-MS II patients who received alemtuzumab.

Methods: In the core study, alemtuzumab patients received 2 annual courses at Months 0 and 12. Patients could enter the extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse and/or MRI lesion activity, or other disease-modifying therapy (DMT) at investigator’s discretion. Disability endpoints included change in Expanded Disability Status Scale (EDSS) score from core study baseline, 6-month confirmed disability progression (≥1-point EDSS increase [≥1.5 point if baseline EDSS=0]); proportions with improved (≥1-point change) or stable (≤0.5-point) EDSS scores vs core study baseline; and sustained reduction in preexisting disability (SRD: ≥1-point EDSS decrease from baseline over 3, 6, or 12 months [patients with baseline EDSS ≥2.0]).

Results: 393 (93%) alemtuzumab-treated patients completing CARE-MS II enrolled in the extension. Through 5 years, 91% remained on study, 60% received no alemtuzumab since the initial 2 courses, and 92% received no other DMT. Mean change in EDSS score through Years 0–5 was +0.06, and 75% of patients were free from 6-month confirmed disability progression. Proportions of patients with 3-, 6-, and 12-month SRD through Years 0–5 were 48%, 43%, and 33%, respectively; 96% of patients who achieved 6-month SRD were also free from 6-month confirmed disability progression. At Year 5, 77% of patients had improved (25%) or stable (52%) EDSS scores vs core study baseline; improvement/stability was evident across all EDSS functional systems. Of 93 patients with improved EDSS scores from baseline to Year 2, most retained improvement in Years 3–5. Of 189 patients with stable EDSS scores from baseline to Year 2, 81% were improved (11%) or stable (70%) in Years 3–5.

Conclusions: Patients with inadequate response to prior therapy at baseline demonstrated durable improvements in disability outcomes over 5 years with alemtuzumab despite most not receiving treatment for 4 years. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continued treatment for RRMS patients.

Study supported by Genzyme, a Sanofi company, and Bayer Healthcare Pharmaceuticals.