Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis

An open-label trial

Alireza Minagar, J. Steven Alexander, Robert N. Schwendimann, Roger E. Kelley, Eduardo Gonzalez-Toledo, Joaquin J Jimenez, Lucia Mauro, Wenche Jy, Stacy J. Smith

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)199-204
Number of pages6
JournalArchives of Neurology
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2008

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Doxycycline
Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Transendothelial and Transepithelial Migration
Therapeutics
Matrix Metalloproteinase 9
Gadolinium
Serum
Monocytes
Blood Safety
Safety
Interferon beta-1a
Therapy
Matrix Metalloproteinase Inhibitors
Controlled Clinical Trials
Neurologic Examination
Multivariate Analysis
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
Recurrence

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Minagar, A., Alexander, J. S., Schwendimann, R. N., Kelley, R. E., Gonzalez-Toledo, E., Jimenez, J. J., ... Smith, S. J. (2008). Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: An open-label trial. Archives of Neurology, 65(2), 199-204. https://doi.org/10.1001/archneurol.2007.41

Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis : An open-label trial. / Minagar, Alireza; Alexander, J. Steven; Schwendimann, Robert N.; Kelley, Roger E.; Gonzalez-Toledo, Eduardo; Jimenez, Joaquin J; Mauro, Lucia; Jy, Wenche; Smith, Stacy J.

In: Archives of Neurology, Vol. 65, No. 2, 01.02.2008, p. 199-204.

Research output: Contribution to journalArticle

Minagar, A, Alexander, JS, Schwendimann, RN, Kelley, RE, Gonzalez-Toledo, E, Jimenez, JJ, Mauro, L, Jy, W & Smith, SJ 2008, 'Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: An open-label trial', Archives of Neurology, vol. 65, no. 2, pp. 199-204. https://doi.org/10.1001/archneurol.2007.41
Minagar, Alireza ; Alexander, J. Steven ; Schwendimann, Robert N. ; Kelley, Roger E. ; Gonzalez-Toledo, Eduardo ; Jimenez, Joaquin J ; Mauro, Lucia ; Jy, Wenche ; Smith, Stacy J. / Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis : An open-label trial. In: Archives of Neurology. 2008 ; Vol. 65, No. 2. pp. 199-204.
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