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)

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.

Fig. 1

Schematic of IAT and DAT patient participation from the pooled CARE-MS I and II studies through the extension study and TOPAZ. SC IFNB-1a subcutaneous interferon beta-1a. ^aA total of 43 patients of African descent received alemtuzumab in either the core study and/or the extensions

Fig. 2

Efficacy outcomes over 8 years. Results are shown for alemtuzumab- and SC IFNB-1a-treated patients in the 2-year core studies (left panels) and pooled patients from years 1–8 after initiation of alemtuzumab (right panels). Year 7 and year 8 outcomes represent IAT patients only. a Yearly ARR. b Percentage of patients with improved, stable, and worsened EDSS scores from core study baseline to the specified time point. c Kaplan-Meier estimates of the percentages of patients free of 6-month CDW. d Kaplan-Meier estimates of the percentages of patients with 6-month CDI. ARR annualized relapse rate, CDI confirmed disability improvement, CDW confirmed disability worsening, EDSS Expanded Disability Status Scale, IAT initial alemtuzumab treatment, SC IFNB-1a subcutaneous interferon beta-1a, Y year. ^aCategories may not sum appropriately because of rounding

Fig. 3

Annual NEDA and freedom from MRI lesions over 8 years. Results are shown for alemtuzumab- and SC IFNB-1a-treated patients in the 2-year core studies (left panels) and pooled patients in years 2, 6, and 8 after initiation of alemtuzumab (right panels). Year 8 outcomes represent IAT patients only. a Percentage of patients achieving annual NEDA. b Percentage of patients free of new Gd-enhancing T1 lesions. c Percentage of patients free of new/enlarging T2 hyperintense lesions. d Percentage of patients free of new T1 hypointense lesions. CI confidence interval, Gd gadolinium, IAT initial alemtuzumab treatment, MRI magnetic resonance imaging, NEDA no evidence of disease activity, SC IFNB-1a subcutaneous interferon beta-1a, Y year. ^aAmong patients of African descent in the CARE-MS trials, 62% who received alemtuzumab and 36% who received SC IFNB-1a were free of Gd-enhancing T1 lesions at core study baseline

Fig. 4

Change in BPF over time in pooled patients. Results are shown for alemtuzumab- and SC IFNB-1a-treated patients in the 2-year core studies (left panel) and pooled patients from years 1–8 after initiation of alemtuzumab (right panel). Year 7 and year 8 outcomes represent IAT patients only. BPF brain parenchymal fraction, IAT initial alemtuzumab treatment, SC IFNB-1a subcutaneous interferon beta-1a, Y year