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Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial.
Arch Neurol 2008; 65(2):199-204AN

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. Trial Registration clinicaltrials.gov Identifier: NCT00246324

Authors+Show Affiliations

Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. aminag@lsuhsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18071030

Citation

Minagar, Alireza, et al. "Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis: an Open-label Trial." Archives of Neurology, vol. 65, no. 2, 2008, pp. 199-204.
Minagar A, Alexander JS, Schwendimann RN, et al. Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. Arch Neurol. 2008;65(2):199-204.
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), pp. 199-204.
Minagar A, et al. Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis: an Open-label Trial. Arch Neurol. 2008;65(2):199-204. PubMed PMID: 18071030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. AU - Minagar,Alireza, AU - Alexander,J Steven, AU - Schwendimann,Robert N, AU - Kelley,Roger E, AU - Gonzalez-Toledo,Eduardo, AU - Jimenez,Joaquim J, AU - Mauro,Lucia, AU - Jy,Wenche, AU - Smith,Stacy J, Y1 - 2007/12/10/ PY - 2007/12/12/pubmed PY - 2008/3/20/medline PY - 2007/12/12/entrez SP - 199 EP - 204 JF - Archives of neurology JO - Arch. Neurol. VL - 65 IS - 2 N2 - 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. Trial Registration clinicaltrials.gov Identifier: NCT00246324 SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/18071030/Combination_therapy_with_interferon_beta_1a_and_doxycycline_in_multiple_sclerosis:_an_open_label_trial_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2007.41 DB - PRIME DP - Unbound Medicine ER -