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Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis 10 December 2007
A preliminary study suggests that combining a medication currently used to treat multiple sclerosis with an antibiotic may slow the progress of the disease, according to an article posted online today that will appear in the February 2008 print issue of Archives of Neurology, one of the JAMA/Archives journals.
“Multiple sclerosis (MS) is an immune-mediated disorder that affects genetically susceptible individuals after exposure to certain, as yet unidentified environmental antigens,” or disease-causing agents, the authors write as background information in the article. The development of MS involves inflammation that destroys parts of the brain along with progressive degeneration of brain tissue. The most common type is relapsing remitting MS, in which patients experience attacks of symptoms such as muscle weakness and spasms followed by periods of symptom-free remission. Many patients with relapsing-remitting MS who take interferon, a medication that boosts the immune system and fights viruses, still experience relapses and may continue to develop new areas of damaged brain tissue (lesions) visible on magnetic resonance imaging (MRI).
Alireza Minagar, M.D., of Louisiana State University Health Sciences Center, Shreveport, and colleagues conducted a single-center trial involving 15 patients (average age 44.5) with relapsing-remitting MS who had been taking interferon for at least six months and were experiencing symptoms and developing new brain lesions. For four months, participants took 100 milligrams daily of the antibiotic doxycycline in addition to continuing interferon therapy. They underwent monthly neurological examinations, MRI to detect brain lesions and blood work to monitor safety.
After four months, the combination treatment resulted in fewer lesions visible on MRI—60 percent of the patients had more than a one-fourth reduction in the number of lesions from the beginning of the study. The patients also had reduced average scores on a scale designed to assess disability levels. Only one patient relapsed; adverse effects were mild and included only known effects of the two drugs individually rather than new effects associated with combining the medications.
Antibiotics in the tetracycline family, including doxycycline, may be effective against MS and other inflammatory diseases by inhibiting the action of enzymes that destroy certain nervous system cells, protecting the brain and increasing the effectiveness of the immune system, the authors note.
“There is growing interest in combination therapy in patients with MS to stabilize the clinical course, reduce the rate of clinical relapses and decelerate the progressive course of the underlying pathologic mechanism,” they write. “Overall, data from this cohort suggest that the treatment combination of oral doxycycline and interferon beta-1a may be safe and effective in some patients with MS; however, further controlled clinical trials are warranted to demonstrate safety and efficacy in a larger patient population.”
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.
Design: Open-label, 7-month trial.
Setting: Louisiana State University Health Sciences Center, Shreveport.
Patients: 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.
Interventions: Ongoing treatment with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4 months.
Main Outcome Measures: 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 contrastenhancing 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.
Source: Arch Neurol. 2008;65(2):(doi:10.1001/archneurol.2007.41) ©2008 American Medical Association. All rights reserved.(10/12/07)
Last edited by bromley on Mon Dec 10, 2007 5:11 am, edited 1 time in total.
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