Alemtuzumab improves visual outcomes in treatment-naïve patients with relapsing–/INS;remitting multiple sclerosis (RRMS): Analysis from the phase 3 CARE-MS I study

BACKGROUND: Alemtuzumab demonstrated clinical efficacy in the treatment of RRMS. Sloan low-contrast letter acuity can identify MS-related visual dysfunction. OBJECTIVE: Compare alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a) effects on visual outcomes in CARE-MS I. PATIENTS AND METHODS: Patients (N=581) were randomized to alemtuzumab 12mg/day IV on 5 consecutive days initially and 3 consecutive days 12months later or SC IFNB-1a 44μg 3×/INS;/week. MS Functional Composite (MSFC; disability composite) and binocular Sloan (letter acuity) assessments were performed twice yearly, with combined scores creating a normalized 4-dimensional composite (MSFC+Sloan) that incorporates visual impairments in the overall disability assessment. Worsened or improved visual function was /INS;defined as ≥7-point decreases or increases, respectively, from baseline in Sloan scores, and ≥0.5-point changes in MSFC+Sloan scores. RESULTS: Mean changes in low-contrast (2.5%) Sloan scores from baseline were smaller with alemtuzumab vs. SC IFNB-1a (significantly at 12months, p=0.0019; non-significantly /INS;at 24months, p=0.1205). When Sloan 2.5% was added to MSFC, treatment differences significantly favored alemtuzumab at 12 (p=0.0001) and 24months (p=0.009). Proportions of patients with worsened or improved Sloan 2.5% scores significantly favored alemtuzumab vs. SC IFNB-1a (worsened : 15.3% vs. 23.6%; improved : 18.5% vs. 13.4% at 12months; p=0.029). At 24months, results again numerically favored alemtuzumab in terms of the proportion who worsened or remained stable, although not significantly (p=0.2832). CONCLUSION: Low-contrast letter acuity by Sloan charts favored alemtuzumab. Use of a visual component measure is likely to augment ability to detect treatment effects across a variety of clinical dimensions in MS trials.