title: Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial.
abstract: BACKGROUND
  Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis.
  
  
  METHODS
  In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766.
  
  
  RESULTS
  341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group.
  
  
  CONCLUSIONS
  Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients.
  
  
  BACKGROUND
  Biogen Idec.
authors.affiliation: Danish Multiple Sclerosis Research Center, University of Copenhagen and Department of Neurology, Rigshospitalet, Copenhagen, Denmark. mravnborg@gmail.com
authors.forename: Mads
authors.initials: M
authors.lastname: Ravnborg
authors.forename: Per Soelberg
authors.initials: PS
authors.lastname: Sørensen
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Celius
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jongen
authors.forename: Irina
authors.initials: I
authors.lastname: Elovaara
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bartholomé
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.forename: Karsten
authors.initials: K
authors.lastname: Beer
authors.forename: Ellen
authors.initials: E
authors.lastname: Garde
authors.forename: Bjørn
authors.initials: B
authors.lastname: Sperling
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D018696:Neuroprotective Agents; D016899:Interferon-beta; D008775:Methylprednisolone; D000068556:Interferon beta-1a