title: Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.
abstract: OBJECTIVE
  Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy.
  
  
  METHODS
  This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed.
  
  
  RESULTS
  One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo.
  
  
  CONCLUSIONS
  Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy.
authors: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: P S
authors: PS
authors: Sørensen
authors: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: F
authors: F
authors: Sellebjerg
authors: Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: J
authors: J
authors: Lycke
authors: Department of Neurology, University Central Hospital, Helsinki, Finland.
authors: M
authors: M
authors: Färkkilä
authors: Service de Neurologie, Hôpital Henri Mondor, Université Paris Est Créteil, Créteil, France.
authors: A
authors: A
authors: Créange
authors: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors: C G
authors: CG
authors: Lund
authors: Service de Neurologie, Département des Neurosciences Cliniques, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: M
authors: M
authors: Schluep
authors: Department of Neurology, Glostrup Esbjerg, Sonderborg, and Vejle, and University of Copenhagen, Copenhagen, Denmark.
authors: J L
authors: JL
authors: Frederiksen
authors: Department of Neurology, Esbjerg Hospital, Sonderborg Hospital, Vejle Hospital, Odense, Denmark.
authors: E
authors: E
authors: Stenager
authors: Department of Neurology, Aalborg Hospital, Aalborg, Denmark.
authors: C
authors: C
authors: Pfleger
authors: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors: E
authors: E
authors: Garde
authors: Department of Neurology, HUS Hyvinkään Hospital, Hyvinkää, Finland.
authors: E
authors: E
authors: Kinnunen
authors: Merck Serono Global Medical Affairs, Merck GmbH, Vienna, Austria.
authors: K
authors: K
authors: Marhardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline; D000068556:Interferon beta-1a
keywords: combination therapy; interferon β; minocycline; multiple sclerosis; randomized controlled trial