BARCELONA—The tetracycline antibiotic minocycline reduces the relative risk of multiple sclerosis (MS) in patients experiencing their first clinical demyelinating event by 44.6%, according to the results of a phase III double-blind placebo-controlled Canadian multicenter clinical trial reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
“Current proven therapies for patients experiencing their first clinical demyelinating event show benefit the earlier they are introduced. However, payment coverage varies throughout the world, often delaying treatment until patients have demonstrated a second clinical attack,” said Luanne M. Metz, MD, Professor and Head of the Division of Neurology and Director of the MS Program at the University of Calgary in Canada, and her research colleagues. “Current oral therapies may not be ideal options because of safety concerns. Minocycline is an inexpensive oral antibiotic with a recognized safety profile. It is widely available, often in generic formulation. Preclinical and preliminary clinical studies suggest it may be a therapeutic option in MS as both monotherapy and as an add-on treatment.”
Dr. Metz and colleagues enrolled subjects between ages 18 and 60, with onset of their first demyelinating symptoms within the previous 180 days and at least two T2 hyperintense lesions on brain MRI. The study subjects were randomized to oral minocycline 100 mg bid or identical placebo. Treatment continued for 24 months or until MS diagnosis by 2005 McDonald criteria was confirmed. Follow-up visits were scheduled at one, three, six, nine, 12, 15, 18, 21, and 24 months. MRI scans were scheduled at screen, months three, six, 12, and 24 and at early end of study. The primary outcome was the proportion of participants who developed MS by six months. Risk estimates, absolute risk reductions, and relative risk reductions were calculated from actuarial life table analysis.
Starting in December 2008, 236 patients were screened at 12 Canadian sites; 143 were randomized. Intention to treat analysis included 142 subjects, as one subject was randomized in error; 72 received minocycline. Mean age was 35.8; 68.3% were women. Onset was monofocal in 76.8%, median Expanded Disability Status Scale score was 1.5, mean duration since onset of demyelinating symptoms was 84.5 days, 69% had more than eight T2 lesions, and 34.5% had enhancing lesions at screen. The risk of conversion to MS by six months was 61.4% in the placebo group and 34.0% in the minocycline group. The absolute risk reduction was 27.4%, the relative risk reduction was 44.6%, and the number needed to treat (NNT) was four. At 12 months, the absolute risk reduction was 25.1%, the relative risk reduction was 37.6%, and the NNT was four.
Based on their findings, the researchers concluded that minocycline 100 mg bid reduces conversion of the first clinical demyelinating event to MS. “Given its known safety and low cost, minocycline should be considered for initial treatment as well as for combination therapy trials.”