Therapy - immunomodulation - Part IThursday, September 29, 2005, 15:30 - 17:00
An open-label trial of combination therapy with intramuscular interferon beta-1a and oral doxycycline in patients with multiple sclerosisA. Minagar, J.S. Alexander, R. Brooks, R.E. Kelley, E. Gonzalez-Toledo (Shreveport, USA)
The use of multiple therapeutic agents possessing distinctly different mechanisms of action represents a major advance in the management of multiple sclerosis (MS). Doxycycline, a potent matrix metalloproteinase (MMP) inhibitor, can potentially suppress destruction of the extracellular matrix and therefore limit the transendothelial migration of activated leukocytes in MS. In addition, MMP-9, which proteolytically cleaves myelin basic protein, is also capable of cleaving interferon-beta (IFNB) perhaps contributing to relapses despite therapy. The purpose of this open-label, single-center study was to determine the safety, tolerability, and efficacy of daily oral doxycycline 100 mg combined with weekly intramuscular (IM) IFNB-1a 30 mcg (Avonex) in MS patients who were experiencing breakthrough disease. Patients aged 18 to 55 years with a diagnosis of relapsing MS were eligible to participate. Eligible patients had an EDSS score of 1.5 to 4.5, one or more gadolinium-enhancing (Gd+) lesions on MRI, had been treated with IM IFNB-1a continuously for a minimum of 6 months, and had a relapse within 60 days of their baseline visit (month íV3). Patients underwent MRIs at months -3, -2, -1, 0, +1, +2, +3 and began drug therapy with doxycycline at month 0. Patients (n=12) had a mean age of 42▒13.3 years, a mean duration of disease of 6.2▒5.0 years at baseline, and a mean duration of treatment with IM IFNB-1a of 3.8+/-2.8 years at baseline. Mean baseline EDSS was 3.6+/-0.4 and mean number of Gd+ lesions was 3.9▒1.1. During pretreatment (months -3, -2, -1, and 0), the mean number of Gd+ lesions was 10.8▒7.2, which decreased to 7.0▒5.7 during combination therapy (p=0.0039). Pretreatment EDSS (n=9 patients) averaged 3.9▒0.4 and decreased to 1.4▒0.6 over the treatment period (p=0.0039). One patient had transiently elevated hepatic enzymes while being treated with combination therapy, but no other adverse events related to treatment were reported. To date, no patients have dropped out of the study. Based on the results of this study combination therapy with doxycycline 100 mg daily and IM IFNB-1a 30 mcg weekly appears to be safe and effective in patients with relapsing MS. Final results on MRI and clinical measures will be presented. A larger, randomized trial is needed to confirm these results.