title: Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis.
abstract: OBJECTIVE
  The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment.
  
  
  METHODS
  A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity.
  
  
  RESULTS
  A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001).
  
  
  CONCLUSIONS
  The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Prosperini
authors.forename: Chiara Rosa
authors.initials: CR
authors.lastname: Mancinelli
authors.forename: Laura
authors.initials: L
authors.lastname: De Giglio
authors.forename: Floriana
authors.initials: F
authors.lastname: De Angelis
authors.forename: Valeria
authors.initials: V
authors.lastname: Barletta
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D057216:Propensity Score; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta
keywords: Multiple sclerosis; breakthrough disease; interferon beta; observational study; propensity score; therapeutic algorithm