Minocycline, a broad-spectrum tetracycline antibiotic, reduces risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS), according to a multicenter study from Canada reported in the New England Journal of Medicine.1 Compared with placebo, CIS conversion at 6 months was significantly reduced with 100 mg minocycline, although the effect was not fully sustained to 24 months.
For the Minocycline in Multiple Sclerosis (MS) Study, a total of 142 participants from 12 Canadian MS clinics (identified as having CIS) were randomly assigned to receive minocycline (n=72) or placebo (n=70). Mean age was 35.8 and two-thirds of participants (68.3%) were women. At the primary end point of 6 months, the unadjusted conversion rate for placebo was 61%, compared with 33.4% for minocycline, representing a difference of 27.6% (95% CI, range 11.4 to 43.9; P =.001).
“The adjusted rate reaching MS in our placebo group was 74.2%, which is about 10% lower than the rates in other trials: 85% in the Betaseron trial, 85.8% in the Rebif trial, over 85% in the Aubagio trial, and 87.1% in the oral cladribine trial,” study co-investigator Luanne Metz, MD, FRCPC, section chief, division of neurology at the University of Calgary, Alberta, Canada, told Neurology Advisor.
The main limitation of the trial was sample size. “We had very few patients by 24 months though, as all of these other trials started with 2.5-3 times as many patients per treatment arm [and] so still had enough patients at the end [of the study] to get a more precise estimate of the average outcome; our estimate was quite imprecise because there were fewer people left to include in the average,” Dr Metz said, referring to withdrawals from their study due to adverse events (AEs), which were higher in the minocycline group than in the placebo group (86.1% vs 61.4%, P =.001). Minor AEs were significantly more frequent in the minocycline group compared with the placebo group, including rash, affecting 15.3% vs 2.9%, (P =.01), dental discoloration (8.3% vs 0%, P =.01), and dizziness (13.9% vs 1.4%, P =.005).
Still, the study indicated a benefit to clinical use of minocycline in CIS. “There was a similar benefit to that seen with other treatments and the benefit was maintained at 12 months,” Dr Metz added. “There is no biological reason why [the] benefit would be lost and every patient is monitored to determine if the treatment they start is working and tolerable by them. If there were no monitoring it would be prudent to consider a therapy that works in a greater proportion of people or has evidence of longer effect, but nobody with MS in North America is likely to go more than a year without an MRI to see if their treatment is effective. Even if this drug is only used short term from the time CIS is confirmed until insurance approvals are made and another drug is started, it has value. It is so inexpensive that it can be prescribed immediately with no insurance issues and is affordable for many who have no insurance,” she said.
Metz LM, Traboulsee P, Duquette M, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376:2122-2133. doi:10.1056/NEJMoa1608889