• Luanne M Metz, David K B Li, Anthony L Traboulsee, Pierre Duquette, Misha Eliasziw, Graziela Cerchiaro, Jamie Greenfield, Andrew Riddehough, Michael Yeung, Marcelo Kremenchutzky, Galina Vorobeychik, Mark S Freedman, Virender Bhan, Gregg Blevins, James J Marriott, Francois Grand'Maison, Liesly Lee, Manon Thibault, Michael D Hill, V Wee Yong, and Minocycline in MS Study Team.
• From the Cumming School of Medicine and the Hotchkiss Brain Institute, Calgary, AB (L.M.M., G.C., J.G., M.Y., M.D.H., V.W.Y.), the University of British Columbia, Vancouver (D.K.B.L., A.L.T., A.R.), the University of Montreal, Montreal (P.D.), Western University, London, ON (M.K.), Fraser Health MS Clinic, Burnaby, BC (G.V.), the University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (M.S.F.), Dalhousie University, Halifax, NS (V.B.), the University of Alberta, Edmonton (G.B.), the University of Manitoba, Winnipeg (J.J.M.), Clinique Neuro Rive-Sud, Greenfield Park, QC (F.G.), the University of Toronto, Toronto (L.L.), and CHA-Hôpital Enfant-Jésus, Quebec, QC (M.T.) - all in Canada; and Tufts University, Boston (M.E.).
• N. Engl. J. Med. 2017 Jun 1; 376 (22): 2122-2133.

BackgroundOn the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis.MethodsDuring the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T1-weighted MRI plus new and newly enlarged lesions on T2-weighted MRI]).ResultsA total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo.ConclusionsThe risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

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