Improvements in Quality of Life Are Maintained in Alemtuzumab-Treated RRMS Patients Who Develop Autoimmune Adverse Events: Care-MS II

Background:  In the phase 3 CARE-MS II trial (NCT00548405), alemtuzumab demonstrated superior efficacy and quality of life (QoL) improvements over subcutaneous interferon beta-1a (SC IFNB-1a) in patients with relapsing-remitting multiple sclerosis (RRMS) and an inadequate efficacy response to prior therapy. Alemtuzumab’s consistent and manageable safety profile includes a risk of autoimmune disorders, predominantly thyroid disorders, less frequently, immune thrombocytopenia (ITP), and rarely nephropathies including anti-glomerular basement membrane disease.

Objectives:  To evaluate whether the occurrence of autoimmune adverse events (AEs) reduces QoL improvements seen in RRMS patients who received alemtuzumab 12 mg over 2 years in CARE-MS II.

Methods:  In CARE-MS II, patients with ≥1 relapse after ≥6 months of prior therapy were randomized to either 2 annual courses of alemtuzumab 12 mg/day or SC IFNB-1a 44 µg 3 times weekly. Stratified by the presence/absence of autoimmune AEs, QoL was assessed within the alemtuzumab group using the Short Form Health Survey (SF-36) physical component summary (PCS; scale 1–100), the Functional Assessment of Multiple Sclerosis (FAMS; scale 0–176), and the EuroQol 5-dimension scale (EQ-5D) Visual Analog Scale (VAS; scale 0–100). The SF-36 mental component summary was excluded from the analysis because there was no difference between alemtuzumab and SC IFNB-1a at Year 2. Monitoring for autoimmune AEs was performed at baseline and monthly (ITP; nephropathies) or quarterly (thyroid) through a comprehensive monitoring program.

Results:  Among alemtuzumab-treated patients, 17% (74 of 435) had autoimmune AEs during the 2-year controlled portion of CARE-MS II. At Year 2, mean changes in QoL scores were similar in alemtuzumab patients with or without autoimmune AEs: FAMS (with autoimmune AEs, 8.9 [SE=3.3]; no autoimmune AEs, 5.9 [1.2]), PCS (with autoimmune AEs, 2.7 [1.0]; no autoimmune AEs, 2.4 [0.4]), and EQ-5D VAS (with autoimmune AEs, 4.1 [2.0]; no autoimmune AEs, 3.7 [0.9]). In addition, mean (SE) changes in QoL scores from baseline in both subgroups were similar to the overall alemtuzumab cohort (FAMS, 6.7 [1.2]; PCS, 2.4 [0.4]; EQ-5D VAS, 3.6 [0.9]) and greater than the SC IFNB-a–treated group (FAMS, 1.8 [1.6]; PCS, 0.6 [0.6]; EQ-5D VAS, –0.9 [1.3]).

Conclusions:  QoL improvements were similar in alemtuzumab patients with or without autoimmune AEs; both subgroups had greater QoL improvements than patients treated with SC IFNB-1a.

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