title: Alemtuzumab improves contrast sensitivity in patients with relapsing-remitting multiple sclerosis.
abstract: BACKGROUND
  Alemtuzumab is a monoclonal antibody directed against CD52 that depletes T and B lymphocytes.
  
  
  OBJECTIVE
  To evaluate the treatment effect of alemtuzumab on low-contrast vision in relapsing-remitting multiple sclerosis (RRMS) patients.
  
  
  METHODS
  This was a pre-defined exploratory analysis within a randomized, rater-blinded trial (CAMMS223) that was run at 49 academic medical centers in the US and in Europe. Patients with untreated, early, RRMS (McDonald, n = 334) were randomized 1:1:1 to subcutaneous interferon beta-1a (IFNB-1a), or alemtuzumab 12 mg or 24 mg. Visual contrast sensitivity was measured for each eye at baseline and quarterly, with Pelli-Robson charts.
  
  
  RESULTS
  The eyes of patients in the pooled alemtuzumab group (versus IFNB-1a) had a greater than 2-fold higher rate of both 3-month and 6-month sustained visual improvement, of at least 0.3 log units (2 triplets, 6 letters) (At 3 months the hazard ratio (HR) = 2.26; CI = 1.19 to 4.31; P = 0.013; and at 6 months the HR = 2.44; CI =1.16 to 5.15; P = 0.019), and they had a lower risk of 3- and 6-month sustained worsening of at least 0.15 log units (1 triplet, 3 letters) (At 3 months the HR = 0.58; CI = 0.38 to 0.89; P = 0.012; and at 6 months HR = 0.55; CI=0.35 to 0.87; P = 0.010). Over the 36-month study period, the eyes of patients in the pooled alemtuzumab group improved in mean contrast sensitivity to a greater extent than those in the IFNB-1a group (0.080 log units versus 0.038 log units; P = 0.0102).
  
  
  CONCLUSIONS
  Alemtuzumab was associated with a greater chance of improved contrast sensitivity in patients with RRMS and may delay the worsening of visual function. Contrast sensitivity testing was sensitive to treatment effects, even within an active comparator study design. These results support the validity of low-contrast vision testing as a clinical outcome in MS trials.
authors: University of Pennsylvania, Philadelphia, PA, USA. jennifer.graves@ucsf.edu
authors: Jennifer
authors: J
authors: Graves
authors: Steven L
authors: SL
authors: Galetta
authors: Jeffrey
authors: J
authors: Palmer
authors: David H
authors: DH
authors: Margolin
authors: Marco
authors: M
authors: Rizzo
authors: John
authors: J
authors: Bilbruck
authors: Laura J
authors: LJ
authors: Balcer
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D015350:Contrast Sensitivity / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy*; D016037:Single-Blind Method; D014786:Vision Disorders / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D016899:Interferon-beta; D000068556:Interferon beta-1a
keywords: Multiple sclerosis; alemtuzumab; contrast sensitivity; disease modifying therapy; interferon beta; outcome measurements; relapsing–remitting multiple sclerosis; visual function