Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial.
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
Minagar
Alireza
A
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. aminag@lsuhsc.edu
Alexander
J Steven
JS
Schwendimann
Robert N
RN
Kelley
Roger E
RE
Gonzalez-Toledo
Eduardo
E
Jimenez
Joaquim J
JJ
Mauro
Lucia
L
Jy
Wenche
W
Smith
Stacy J
SJ
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
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