title: Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial.
abstract: OBJECTIVE
  To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing-remitting multiple sclerosis (RRMS) having breakthrough disease activity.
  
  
  METHODS
  Open-label, 7-month trial.
  
  
  METHODS
  Louisiana State University Health Sciences Center, Shreveport.
  
  
  METHODS
  Fifteen patients with RRMS taking interferon beta-1a with breakthrough disease activity took doxycycline for 4 months. Patients underwent monthly neurologic examination, magnetic resonance imaging of the brain using triple-dose gadolinium, and safety blood work.
  
  
  METHODS
  Ongoing treatment with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4 months.
  
  
  METHODS
  The primary end point was gadolinium-enhancing lesion number change, and the secondary end points were relapse rates, safety and tolerability of the combination of interferon beta-1a and doxycycline in patients with MS, Expanded Disability Status Scale score, serum matrix metalloproteinase-9 levels, and transendothelial migration of monocytes exposed to serum from patients with RRMS.
  
  
  RESULTS
  Combination of doxycycline and interferon beta-1a treatment resulted in reductions in contrast-enhancing lesion numbers and posttreatment Expanded Disability Status Scale values (P < .001 for both). Only 1 patient relapsed. Multivariate analyses indicated correlations between decreased serum matrix metalloproteinase-9 levels and enhancing lesion activity reduction. Transendothelial migration of monocytes incubated with serum from patients with RRMS undergoing combination therapy was suppressed. Adverse effects were mild; no adverse synergistic effects of combination therapy or unexpected adverse events were reported.
  
  
  CONCLUSIONS
  Combination of intramuscular interferon beta-1a and oral doxycycline treatment was effective, safe, and well tolerated. Controlled clinical trials in larger cohorts of patients with MS are needed to evaluate the efficacy and tolerability of this combination. Trial Registration clinicaltrials.gov Identifier: NCT00246324
authors: Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. aminag@lsuhsc.edu
authors: Alireza
authors: A
authors: Minagar
authors: J Steven
authors: JS
authors: Alexander
authors: Robert N
authors: RN
authors: Schwendimann
authors: Roger E
authors: RE
authors: Kelley
authors: Eduardo
authors: E
authors: Gonzalez-Toledo
authors: Joaquim J
authors: JJ
authors: Jimenez
authors: Lucia
authors: L
authors: Mauro
authors: Wenche
authors: W
authors: Jy
authors: Stacy J
authors: SJ
authors: Smith
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology*; D002465:Cell Movement; D003287:Contrast Media; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular; D005260:Female; D005682:Gadolinium; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009000:Monocytes; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D015999:Multivariate Analysis; D009460:Neurologic Examination; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000276:Adjuvants, Immunologic; D015415:Biomarkers; D003287:Contrast Media; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D005682:Gadolinium; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline; D000068556:Interferon beta-1a