Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study)

Annette F Okai; Lilyana Amezcua; Regina R Berkovich; Angel R Chinea; Keith R Edwards; Brian Steingo; Aljoeson Walker; Alan K Jacobs; Nadia Daizadeh; Mitzi J Williams; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators

doi:10.1007/s40120-019-00159-2

Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study)

Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25.

Affiliations

¹ Multiple Sclerosis Treatment Center of Dallas, Dallas, TX, USA. afokai@gmail.com.
² Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
³ , West Hollywood, CA, USA.
⁴ San Juan Multiple Sclerosis Center, Guaynabo, PR, USA.
⁵ MS Center of Northeastern New York, Latham, NY, USA.
⁶ Fort Lauderdale Multiple Sclerosis Center, Fort Lauderdale, FL, USA.
⁷ Medical University of South Carolina, Charleston, SC, USA.
⁸ Sanofi, Cambridge, MA, USA.
⁹ Multiple Sclerosis Center of Atlanta, Mableton, GA, USA.

Abstract

Introduction: Multiple sclerosis (MS) patients of African descent have increased risk for disease progression and may be less responsive to disease-modifying therapy.

Methods: Patients in the CARE-MS studies received alemtuzumab 12 mg/day [initial alemtuzumab treatment (IAT); baseline: 5 days; 12 months later: 3 days] or subcutaneous interferon beta-1a (SC IFNB-1a) 3 ×/week. Core study outcomes were compared between treatment groups. In the extension study CAMMS03409, SC IFNB-1a-treated patients switched to alemtuzumab [delayed alemtuzumab treatment (DAT)]. Data from IAT and DAT arms were pooled to assess outcomes through 6 years post alemtuzumab initiation; IAT patients had an additional 2 years of follow-up in TOPAZ.

Results: Of 1200 CARE-MS patients, 43 (4%) were of African descent (35 IAT; 8 DAT) and received alemtuzumab in the 2-year core and/or 6-year extension; 29 (67%) remained on study at the time of analysis (24 IAT patients completed year 8 post alemtuzumab; 5 DAT patients completed year 6 post alemtuzumab). In year 2, annualized relapse rate (ARR; 0.09 versus 0.42), percentage of patients with improved Expanded Disability Status Scale (EDSS; 18% versus 11%), 6-month confirmed disability improvement (CDI; 28% versus 13%), no evidence of disease activity (55% versus 13%), and cumulative brain volume loss (BVL; - 0.55% versus - 1.32%) favored alemtuzumab versus SC IFNB-1a. Alemtuzumab remained efficacious at year 6 (pooled IAT/DAT) and at year 8 (IAT only) post alemtuzumab (ARR: 0.15 and 0.30; improved EDSS: 17% and 25%; CDI: 47% and 55%; BVL: - 1.14% and - 0.70%, respectively). No safety signals were unique to this population.

Conclusions: Alemtuzumab was efficacious in a small cohort of relapsing-remitting MS patients of African descent over 8 years. Safety was consistent with the overall CARE-MS population, although the small sample size may have prevented the detection of known low-frequency adverse events. CLINICALTRIALS.

Gov registration numbers: CARE-MS I, II, extension, TOPAZ: NCT00530348, NCT00548405, NCT00930553, NCT02255656.

Funding: Sanofi (Cambridge, MA, USA) and Bayer HealthCare Pharmaceuticals (Leverkusen, Germany).

Keywords: African descent; Alemtuzumab; Disease-modifying therapy; Multiple sclerosis.

Associated data

ClinicalTrials.gov/NCT00530348
ClinicalTrials.gov/NCT00548405
ClinicalTrials.gov/NCT00930553
ClinicalTrials.gov/NCT02255656