title: Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS.
abstract: OBJECTIVE
  To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy.
  
  
  METHODS
  Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center.
  
  
  RESULTS
  The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers.
  
  
  CONCLUSIONS
  This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.
authors.affiliation: Mellen Center U-10, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. cohenj@ccf.org
authors.forename: J A
authors.initials: JA
authors.lastname: Cohen
authors.forename: P B
authors.initials: PB
authors.lastname: Imrey
authors.forename: P A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: K R
authors.initials: KR
authors.lastname: Edwards
authors.forename: T
authors.initials: T
authors.lastname: Eickenhorst
authors.forename: W L
authors.initials: WL
authors.lastname: Felton
authors.forename: E
authors.initials: E
authors.lastname: Fisher
authors.forename: R J
authors.initials: RJ
authors.lastname: Fox
authors.forename: A D
authors.initials: AD
authors.lastname: Goodman
authors.forename: C
authors.initials: C
authors.lastname: Hara-Cleaver
authors.forename: G J
authors.initials: GJ
authors.lastname: Hutton
authors.forename: B F
authors.initials: BF
authors.lastname: Mandell
authors.forename: T F
authors.initials: TF
authors.lastname: Scott
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Apperson-Hansen
authors.forename: G J
authors.initials: GJ
authors.lastname: Beck
authors.forename: P L
authors.initials: PL
authors.lastname: Houghtaling
authors.forename: M T
authors.initials: MT
authors.lastname: Karafa
authors.forename: M
authors.initials: M
authors.lastname: Stadtler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D003299:Cooperative Behavior; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D018579:Patient Selection; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016899:Interferon-beta; D008775:Methylprednisolone; D000068556:Interferon beta-1a; D008727:Methotrexate