Patients of African Descent with Active RRMS Demonstrate Clinical and Radiologic Benefits with Alemtuzumab over 5 Years

Friday, June 3, 2016: 2:00 PM
Maryland B
Annette Okai, MD , Multiple Sclerosis Treatment Center of Dallas, Dallas, TX
Keith R Edwards, MD , Multiple Sclerosis Center of Northeastern New York, Latham, NY
Brian Steingo, MD , Fort Lauderdale Multiple Sclerosis Center, Pompano Beach, FL
David H Margolin, MD, PhD , Genzyme, a Sanofi company, Cambridge, MA
Sourav Santra, PhD , Genzyme, a Sanofi company, Cambridge, MA
Mitzi J. Williams, MD , Multiple Sclerosis Center of Atlanta, Atlanta, GA

Background: African ancestry is a risk factor for progressive multiple sclerosis (MS) and may be associated with poor response to disease-modifying therapy (DMT). Patients with active RRMS who were treatment-naive (CARE-MS I; NCT00530348) or who had inadequate response (≥1 relapse) to prior therapy at baseline (CARE-MS II; NCT00548405) demonstrated improved efficacy over 2 years with alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a). Improvements in clinical and MRI endpoints were durable through 5 years.

Objectives: To evaluate the efficacy of alemtuzumab over 5 years in CARE-MS patients of African descent.

Methods: In CARE-MS core studies, patients were randomized to 2 annual courses of alemtuzumab 12 mg (Months 0 and 12) or SC IFNB-1a 44 µg for 2 years. In the extension (NCT00930553), patients could receive alemtuzumab retreatment for relapse and/or MRI activity, or another DMT at the investigator’s discretion. MRI scans were acquired at baseline and annually thereafter; brain volume (BV) loss was assessed by relative brain parenchymal fraction change.

Results: There were 46 patients of African descent in the core studies (alemtuzumab, n=35; SC IFNB-1a, n=11); 80% were from the USA and 76% were female. Of 32 alemtuzumab patients who entered the extension, 17 (53%) did not receive retreatment after Course 2 in Month 12, and 28 (88%) did not receive another DMT. Annualized relapse rates (ARRs) for core study Years 0–2 were 0.19 with alemtuzumab versus 0.62 with SC IFNB-1a; over Years 0–5, ARR with alemtuzumab was 0.16. Median annual BV changes for alemtuzumab for Years 1, 2, 3, 4, and 5 were -0.54%, -0.26%,
-0.03%, 0.02%, and -0.10%, respectively. No evidence of disease activity (NEDA) was achieved by 33% of alemtuzumab patients in Years 0–2 versus 13% with SC IFNB-1a; NEDA was observed in 45%, 42%, and 56% of patients in Years 3, 4, and 5, respectively; 25% had sustained NEDA over Years 3–5. There were no serious infusion-associated reactions, no serious thyroid adverse events, and no malignancies with alemtuzumab; serious infections (5.7%) occurred with similar incidence to that in the overall alemtuzumab study population.

Conclusions: Alemtuzumab improved clinical and radiologic outcomes in RRMS patients of African descent versus SC IFNB-1a, with durable efficacy over 5 years. Based on these findings, alemtuzumab may provide a unique treatment approach with durable efficacy in this higher-risk patient population.

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