Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis
An Open-Label Trial
Objective
To evaluate the efficacy, safety, and tolerabilityof combination therapy with intramuscular interferon beta-1aand oral doxycycline, a potent inhibitor of matrix metalloproteinases (a family of enzymes)in patients with relapsing-remitting multiple sclerosis (RRMS)having breakthrough disease activity.
Design
Open-label, 7-month trial.
Setting
Louisiana State University Health Sciences Center,Shreveport.
Patients
Fifteen patients with RRMS taking interferonbeta-1a with breakthrough disease activity took doxycyclinefor 4 months. Patients underwent monthly neurologic examination,magnetic resonance imaging of the brain using triple-dose gadolinium,and safety blood work.
Interventions
Ongoing treatment with intramuscular interferonbeta-1a plus oral doxycycline, 100 mg daily, for 4 months.
Main Outcome Measures
The primary end point was gadolinium-enhancinglesion number change, and the secondary end points were
o relapserates,
o safety and
o tolerability
of the combination of interferonbeta-1a and doxycycline in patients with MS, Expanded DisabilityStatus Scale score, serum matrix metalloproteinase-9 levels,and transendothelial migration of monocytes exposed to serumfrom patients with RRMS.
Results
Combination of doxycycline and interferon beta-1atreatment resulted in reductions in contrast-enhancing lesionnumbers and posttreatment Expanded Disability Status Scale values(P < .001 for both). Only 1 patient relapsed. Multivariateanalyses indicated correlations between decreased serum matrixmetalloproteinase-9 levels and enhancing lesion activity reduction.Transendothelial migration of monocytes incubated with serumfrom patients with RRMS undergoing combination therapy was suppressed.Adverse effects were mild; no adverse synergistic effects ofcombination therapy or unexpected adverse events were reported.
Conclusions
Combination of intramuscular interferon beta-1aand oral doxycycline treatment was effective, safe, and welltolerated. Controlled clinical trials in larger cohorts of patientswith MS are needed to evaluate the efficacy and tolerabilityof this combination.
Author Affiliations:
Departments of Neurology (Drs Minagar, Schwendimann, and Kelley and Ms Smith), Cellular and Molecular Physiology (Dr Alexander), and Radiology (Dr Gonzalez-Toledo), Louisiana State University Health Sciences Center, Shreveport; and Wallace H. Coulter Platelet Laboratory, Department of Medicine, University of Miami School of Medicine, Miami, Florida (Drs Jimenez and Jy and Ms Mauro).