Patients with Highly Active RRMS Despite Prior Therapy Show Durable Improvement with Alemtuzumab over 5 Years

Background: In CARE-MS II (NCT00548405), alemtuzumab significantly reduced disease activity versus subcutaneous interferon beta-1a (SC IFNB-1a) over 2 years in patients with highly active RRMS at baseline despite prior therapy. Improvements in clinical and MRI endpoints in this subgroup were durable over 4 years in an ongoing extension study (NCT00930553), despite most receiving no therapy since Month 12.

Objectives: To examine 5-year efficacy of alemtuzumab in the highly active subgroup, including those who received no additional treatment after the initial 2 alemtuzumab courses.

Methods: Highly active disease was defined as ≥2 relapses in the year before randomization and ≥1 gadolinium-enhancing lesion at baseline. Patients randomized to alemtuzumab in the core study received 2 annual courses at Months 0 and 12. In the extension, patients could receive alemtuzumab retreatment for relapse and/or MRI activity, or another disease-modifying therapy (DMT). No evidence of disease activity (NEDA) was defined as absence of clinical (relapse and 6-month confirmed disability progression) and MRI disease activity.

Results: The extension enrolled 92/103 (89%) alemtuzumab patients with highly active disease at core study baseline. Over 5 years, 57 patients (62%) had no alemtuzumab retreatment or other DMT. In the extension (Years 3–5), annualized relapse rate (ARR) was 0.18; 54% and 47% had no evidence of clinical and MRI disease activity, respectively. NEDA was observed in 54%, 52%, and 54% of patients in Years 3, 4, and 5, and 26% had sustained NEDA over Years 3–5. Six-month sustained reduction in disability (SRD) was achieved by 45% of patients over Years 0–5. Among patients with no retreatment or other DMT since the initial 2 alemtuzumab courses, ARR in the extension (Years 3–5) was 0.04, and 76% and 52% had no evidence of clinical and MRI disease activity, respectively. In this cohort, NEDA was observed in 71%, 63%, and 67% of patients in Years 3, 4, and 5, respectively, and 41% had NEDA sustained over Years 3–5. SRD was achieved by 53% over Years 0–5.

Conclusions: Efficacy of alemtuzumab in patients with highly active disease despite prior therapy was superior to that of SC IFNB-1a in the core study and was durable in the extension through Year 5 despite the majority not receiving treatment since Month 12. These results suggest that alemtuzumab may provide a unique treatment approach with durable efficacy in the absence of continued treatment for highly active RRMS.

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