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 (1),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 relapserates, safety and 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 post-treatment 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.