title: Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial.
abstract: OBJECTIVE
  To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon β-1a (IFNβ-1a) through extended follow-up (up to 60 months from baseline).
  
  
  METHODS
  Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNβ-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months.
  
  
  RESULTS
  Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNβ-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNβ-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNβ-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNβ-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNβ-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFNβ-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab.
  
  
  CONCLUSIONS
  Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNβ-1a, with a safety profile consistent with previous reports.
  
  
  METHODS
  This study provides Class III evidence that alemtuzumab is more effective than interferon β-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period.
authors.affiliation: Department of Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge UK. ajc1020@medschl.cam.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Coles
authors.forename: E
authors.initials: E
authors.lastname: Fox
authors.forename: A
authors.initials: A
authors.lastname: Vladic
authors.forename: S K
authors.initials: SK
authors.lastname: Gazda
authors.forename: V
authors.initials: V
authors.lastname: Brinar
authors.forename: K W
authors.initials: KW
authors.lastname: Selmaj
authors.forename: A
authors.initials: A
authors.lastname: Skoromets
authors.forename: I
authors.initials: I
authors.lastname: Stolyarov
authors.forename: A
authors.initials: A
authors.lastname: Bass
authors.forename: H
authors.initials: H
authors.lastname: Sullivan
authors.forename: D H
authors.initials: DH
authors.lastname: Margolin
authors.forename: S L
authors.initials: SL
authors.lastname: Lake
authors.forename: S
authors.initials: S
authors.lastname: Moran
authors.forename: J
authors.initials: J
authors.lastname: Palmer
authors.forename: M S
authors.initials: MS
authors.lastname: Smith
authors.forename: D A S
authors.initials: DA
authors.lastname: Compston
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab; D016899:Interferon-beta; D000068556:Interferon beta-1a