title: Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
abstract: BACKGROUND
  Treatment options for patients with secondary progressive multiple sclerosis are few. Encouraging results in open-label studies prompted this randomised trial of mitoxantrone in such patients.
  
  
  METHODS
  194 patients with worsening relapsing-remitting or secondary progressive multiple sclerosis were assigned placebo or mitoxantrone (5 mg/m(2) [exploratory group] or 12 mg/m(2) intravenously) every 3 months for 24 months. Clinical assessments were made every 3 months for 24 months. The primary endpoint was a multivariate analysis of five clinical measures. Analyses of mitoxantrone 12 mg/m(2) versus placebo were based on patients who received at least one dose and returned for at least one assessment of efficacy.
  
  
  RESULTS
  Of 194 patients enrolled, 188 were able to be assessed at 24 months. There were no drug-related serious adverse events or evidence of clinically significant cardiac dysfunction. At 24 months, the mitoxantrone group experienced benefits compared with the placebo group for the primary outcome (difference 0.30 [95% CI 0.17-0.44]; p<0.0001) and the preplanned univariate analyses of those measures: change in expanded disability status scale (0.24 [0.04-0.44]; p=0.0194), change in ambulation index (0.21 [0.02-0.40]; p=0.0306), adjusted total number of treated relapses (0.38 [0.18-0.59]; p=0.0002), time to first treated relapse (0.44 [0.20-0.69]; p=0.0004), and change in standardised neurological status (0.23 [0.03-0.43]; p=0.0268).
  
  
  CONCLUSIONS
  Mitoxantrone 12 mg/m(2) was generally well tolerated and reduced progression of disability and clinical exacerbations. Further studies are needed to identify the patients with these forms of multiple sclerosis who are most likely to respond to therapy, the best treatment protocols, and the frequency of long-term drug-related side-effects.
authors.affiliation: Department of Neurology, Heinrich-Heine-Universität, Düsseldorf, Germany. hans-peter.hartung@uni-duesseldorf.de
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Richard
authors.initials: R
authors.lastname: Gonsette
authors.forename: Nikolaus
authors.initials: N
authors.lastname: König
authors.forename: Hubert
authors.initials: H
authors.lastname: Kwiecinski
authors.forename: Andreas
authors.initials: A
authors.lastname: Guseo
authors.forename: Sean P
authors.initials: SP
authors.lastname: Morrissey
authors.forename: Hilmar
authors.initials: H
authors.lastname: Krapf
authors.forename: Thomas
authors.initials: T
authors.lastname: Zwingers
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000145:classification / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D008942:Mitoxantrone