title: Predictors of long-term outcome in multiple sclerosis patients treated with interferon β.
abstract: OBJECTIVE
  To identify early predictors of long-term outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFNβ-1a).
  
  
  METHODS
  A multicenter, observational, 15-year follow-up study of patients who completed ≥2 years in the pivotal trial of IM IFNβ-1a for RRMS was conducted. One hundred thirty-six patients participated in the 15-year follow-up (69 originally randomized to IM IFNβ-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: ≥2 gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 magnetic resonance imaging (MRI); ≥3 new T2 lesions on year 2 MRI compared to baseline; and ≥2 relapses over 2 years. Odds ratios were calculated for early disease activity predicting severe Expanded Disability Status Scale (EDSS) worsening (worst quartile of change, ≥4.5 EDSS points) during the 15-year interval.
  
  
  RESULTS
  The proportion of patients experiencing early disease activity was lower in patients on IM IFNβ-1a than placebo for all disease activity markers (range, 23.5-29.0% vs 41.0-45.5%). In the IM IFNβ-1a group, persistent disease activity predicted severe EDSS worsening: gadolinium-enhancing lesions (odds ratio [OR], 8.96; p < 0.001); relapses (OR, 4.44; p = 0.010); and new T2 lesions (OR, 2.90; p = 0.080). In placebo patients, early disease activity was not as strongly associated with long-term outcomes (OR range, 1.53-2.62; p = 0.069-0.408).
  
  
  CONCLUSIONS
  Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ-treated patients with MRI, and for changing therapy in patients with active disease.
authors: Neurological Institute, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, OH, USA. bermelr@ccf.org
authors: Robert A
authors: RA
authors: Bermel
authors: Xiaojun
authors: X
authors: You
authors: Pamela
authors: P
authors: Foulds
authors: Robert
authors: R
authors: Hyde
authors: Jack H
authors: JH
authors: Simon
authors: Elizabeth
authors: E
authors: Fisher
authors: Richard A
authors: RA
authors: Rudick
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016899:Interferon-beta; D000068556:Interferon beta-1a