title: Early MRI activity predicts treatment nonresponse with intramuscular interferon beta-1a in clinically isolated syndrome.
abstract: OBJECTIVE
  Determine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS) predicted progression to clinically definite multiple sclerosis (CDMS) over the subsequent 30 months in intramuscular interferon beta-1a (IM IFNβ-1a)-treated patients vs placebo-treated patients.
  
  
  METHODS
  CHAMPS patients were randomized to once-weekly IM IFNβ-1a 30 μg or placebo for up to 36 months. MRI was performed every 6 months until CDMS confirmation. Patient groups were defined based on new T2 and/or Gd+ lesions at 6 months.
  
  
  RESULTS
  Thirteen IM IFNβ-1a patients (6.7%) and 24 placebo patients (12.6%) developed CDMS prior to month 6 and did not undergo the 6-month MRI. At 6 months, 29.7% of IM IFNβ-1a-treated patients vs 40.9% of placebo-treated patients were defined as having high MRI activity levels (≥2 new T2 and/or ≥2 Gd+ lesions). In this subgroup, estimated cumulative probabilities of CDMS were similar between groups (HR=0.88 [0.44-1.77], p=0.7227). A significant treatment response was seen for patients with <2 new T2 and <2 Gd+ lesions at 6 months (HR=0.39 [0.19-0.82], p=0.0120).
  
  
  CONCLUSIONS
  MRI scans 6 months after IM IFNβ-1a initiation in CIS patients predict early treatment non-response. Standardized scanning and monitoring may facilitate early disease management.
authors.affiliation: Department of Neurosciences, University of California San Diego, 9500 Gilman Dr, MC 0662, La Jolla, CA 92093, USA. Electronic address: rkinkel@ucsd.edu.
authors.forename: R P
authors.initials: RP
authors.lastname: Kinkel
authors.affiliation: Portland VA Medical Center, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97239, USA. Electronic address: jacksimon1@me.com.
authors.forename: J H
authors.initials: JH
authors.lastname: Simon
authors.affiliation: Multiple Sclerosis Clinic, St. Michael׳s Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada. Electronic address: OCONNORP@smh.toronto.on.ca.
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: Robert.Hyde@biogenidec.com.
authors.forename: R
authors.initials: R
authors.lastname: Hyde
authors.affiliation: Biogen Idec Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: Amy.Pace@biogenidec.com.
authors.forename: A
authors.initials: A
authors.lastname: Pace
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D003287:Contrast Media; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005682:Gadolinium; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D003287:Contrast Media; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a
keywords: Clinically definite multiple sclerosis; Clinically isolated syndrome; Intramuscular interferon beta-1a; Magnetic resonance imaging; Multiple sclerosis; Treatment response