title: Efficacy of subcutaneous interferon β-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes.
abstract: OBJECTIVE
  The REbif FLEXible dosing in early MS (REFLEX) study compared several brain MRI outcomes in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis and treated with two dose-frequencies of subcutaneous interferon (IFN) β-1a or placebo.
  
  
  METHODS
  Patients were randomised (1:1:1) to IFN β-1a, 44 µg subcutaneously three times a week or once a week, or placebo three times a week for up to 24 months. MRI scans were performed every 3 months, or every 6 months if the patient developed clinically definite multiple sclerosis. End points analysed included: number of combined unique active lesions per patient per scan; numbers and volumes of new T2, T1 hypointense and gadolinium-enhancing (Gd+) lesions per patient per scan; and brain volume.
  
  
  RESULTS
  517 patients were randomised (intent-to-treat population: subcutaneous IFN β-1a three times a week, n=171; subcutaneous IFN β-1a once a week, n=175; placebo, n=171). Combined unique active lesions were lower in patients treated with subcutaneous IFN β-1a versus placebo (mean (SD) lesions per patient per scan: three times a week 0.6 (1.15); once a week 1.23 (4.26); placebo 2.70 (5.23); reduction versus placebo: three times a week 81%; once a week 63%; p<0.001) and with three times a week versus once a week (48% reduction; p=0.002). The mean numbers of new T2, T1 hypointense and Gd+ lesions were all significantly lower in the two active treatment arms compared with placebo (p≤0.004 for three times a week or once a week) and in the three times a week group compared with once a week (p≤0.012).
  
  
  CONCLUSIONS
  Both subcutaneous IFN β-1a 44 µg regimens improved MRI outcomes versus placebo, with the three times a week regimen having a more pronounced effect than once a week dosing.
  
  
  BACKGROUND
  clinicaltrial.gov identifier, NCT00404352.
authors.affiliation: Department of Neurological & Behavioral Sciences, University of Siena, , Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: Brian
authors.initials: B
authors.lastname: Hennessy
authors.forename: Florence
authors.initials: F
authors.lastname: Casset-Semanaz
authors.forename: Lorenz
authors.initials: L
authors.lastname: Lehr
authors.forename: Bettina
authors.initials: B
authors.lastname: Stubinski
authors.forename: Dominic L
authors.initials: DL
authors.lastname: Jack
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001921:Brain / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009929:Organ Size; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a
keywords: INTERFERON; MRI; Multiple Sclerosis; Randomised Trials