title: Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis: the EVIDENCE Study.
abstract: BACKGROUND
  The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-1a therapy with 44 microg 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 microg 1 time weekly (QW).
  
  
  OBJECTIVE
  To determine the effect of changing the dosage from 30 microg QW to 44 microg TIW in this extension of the EVIDENCE Study.
  
  
  METHODS
  Patients with relapsing MS originally randomized to interferon beta-1a, 30 microg QW, during the comparative phase of the study changed to 44 microg TIW, whereas patients originally randomized to 44 microg TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks.
  
  
  METHODS
  The within-patient pretransition to post-transition change in relapse rate.
  
  
  RESULTS
  At the transition visit, 223 (73%) of 306 patients receiving 30 microg QW converted to 44 microg TIW, and 272 (91%) of 299 receiving 44-microg TIW continued the same therapy. The post-transition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-microg TIW (P = .03). The change was greater in those increasing dose and frequency (P = .047). Patients converting to the 44-mug TIW regimen had fewer active lesions on T2-weighted MRI compared with before the transition (P = .02), whereas those continuing the 44-microg TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-1a therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy.
  
  
  CONCLUSIONS
  Patients receiving interferon beta-1a improved on clinical and MRI disease measures when they changed from 30 microg QW to 44 microg TIW.
authors.affiliation: Department of Neurology, University of Rochester, Rochester, NY 14642, USA. steven_schwid@urmc.rochester.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Schwid
authors.forename: John
authors.initials: J
authors.lastname: Thorpe
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharief
authors.forename: Magnhild
authors.initials: M
authors.lastname: Sandberg-Wollheim
authors.forename: Kottil
authors.initials: K
authors.lastname: Rammohan
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wendt
authors.forename: Hillel
authors.initials: H
authors.lastname: Panitch
authors.forename: Douglas
authors.initials: D
authors.lastname: Goodin
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.forename: Peter
authors.initials: P
authors.lastname: Chang
authors.forename: Gordon
authors.initials: G
authors.lastname: Francis
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a