"We saw a great reduction in gadolinium-enhancing lesions over the period of 4 months after we introduced oral doxycycline to interferon treatment with Avonex," said investigator Rhonda Brooks, clinical research coordinator, Louisiana State University Medical Center, Baton Rouge, Louisiana, United States.

"We are hopeful that this combination treatment will prove to greatly reduce relapse rates among these patients, who are all relapsing-remitting patients," she said.

Doxycycline, a matrix metalloproteinase (MMP) inhibitor, has the potential to limit the transendothelial migration of activated leukocytes in MS, according to the researchers. "In addition," they wrote, "MMP-9, which proteolytically cleaves myelin basic protein, is also capable of cleaving interferon beta (IFNB), perhaps contributing to relapses despite therapy," they wrote in their abstract.

The purpose of the open-label, single-centre study was to determine the safety, tolerability, and efficacy of daily oral doxycycline 100 mg daily in combination with 30 mcg of weekly intramuscular Avonex for MS patients with breakthrough disease.

Patients aged 18 to 55 years with a diagnosis of RRMS were eligible for the study. Eligibility also included: Expanded Disability Status Scale (EDSS) score of 1.5 to 4.5, one or more Gd+ lesions on MRI, treatment with IFNB-1a continuously for a minimum of 6 months prior to enrollment, and a relapse within 60 days of the baseline clinical visit.

Eligible subjects were evaluated monthly for 3 months while on weekly Avonex monotherapy and before initiation of doxycycline. Then they are evaluated monthly for 4 months while receiving combination therapy. Assessments include MRIs and clinical examinations.

To date, 12 subjects have enrolled in the study, 6 have completed, and 5 are still active. At baseline, patients' mean age was 42 years, mean duration of disease was 6.2 years, and mean duration of treatment with Avonex was 3.8 years. Mean baseline EDSS score was 3.6.

During the combination treatment period, the mean number of Gd+ lesions (6.2) decreased significantly compared with the pretreatment monotherapy period (10.3, P = .001).

The combination of Avonex and oral doxycycline appeared to be safe and well tolerated, the researchers reported.

"A larger, randomised trial is needed to confirm these results," they concluded.

The research is supported by a grant from Biogen Idec, Inc.


[Presentation title: An Open-Label Trial of Combination Therapy With Intramuscular Interferon Beta-1a and Oral Doxycycline in Patients With Multiple Sclerosis. Poster 312]

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