BARCELONA — Minocycline, an inexpensive oral therapy with a proven safety record, may have a new role to treat patients with possible multiple sclerosis (MS), a new study suggests.

The antibiotic has been around for 40 years and is better known as a treatment for infections and severe acne, but a new study showed that after 6 months of treatment, minocycline reduced the absolute risk of developing MS by 27.4%, and the relative risk by 44.6%, compared with placebo in patients with clinically isolated syndrome.

"This is comparable with the efficacy of other approved therapies," said lead author, Luanne Metz, MD, professor and head, Division of Neuroscience, Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.

She added that this is the first phase 3 trial to demonstrate a benefit for an antibiotic in MS. Not only does minocycline require no safety monitoring, but giving it to patients involves "a simple prescription" that doesn't require "complex paperwork," she said.

The findings were presented here at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015.

Multiple Immune Effects

Although minocycline is an antibiotic, it has multiple immune-modulating effects, including preventing leukocytes from crossing the blood-brain barrier, and inhibition of microglia, a mechanism that might be important in MS, said Dr Metz.

Previous research suggested that minocycline might actually modulate disease activity in MS, as a monotherapy or as an add-on treatment.

The new study included adult patients at 12 centers across Canada who had their first clinical demyelinating event within the previous 180 days and had at least two T2 hyperintense lesions on brain MRI.

Researchers randomly assigned participants to placebo or to 100 mg of generic minocycline twice daily. According to Dr Metz, this is the standard dose used to treat an infection or for long-term acne therapy.

Participants continued receiving the assigned therapy for up to 24 months or until they had changes that indicated they had MS.

The two groups were similar at baseline except that more patients in the placebo group had a spinal cord site of onset (P = .04), which is a predictor of an earlier switch to MS, said Dr Metz. As well, more patients in the placebo group had two or more gadolinium-enhancing lesions. "That was one factor, along with spinal cord site, that could bias in favor of the drug."

Cranial MRI was done at baseline and at regular intervals for 24 months. Participants were contacted by phone throughout the study, "so we were in touch with patients at least every 3 months," said Dr Metz.

The MRI scans were interpreted by the same blinded independent reader at the University of British Columbia in Vancouver.

The primary outcome was the proportion of patients who had a relapse or MRI changes that would confirm they had definite MS (as determined by the McDonald criteria of 2005) at 6 months.

Of the 143 patients who were randomly assigned, 1 was assigned in error because the criteria were not met. At 6 months, 9 patients had withdrawn from the study in the minocycline group (3 because of drug intolerance) and 4 in the placebo group had withdrawn. By the end of 24 months, 18 had withdrawn in the minocycline group compared with 6 in placebo group.

At 6 months, 61.4% of the placebo group developed MS compared with 34.0% in the treatment group. The absolute risk reduction was 27.4% (95% confidence interval [CI], 11.0% - 43.7%). The relative risk reduction was 44.6% (95% CI, 21.0% - 61.0%; P = .001).

There were also significant group differences at 3 and 12 months. "We had very few patients at the 24-month outcome, which made confidence intervals extremely wide, so it becomes very difficult to interpret the 24-month data," commented Dr Metz.

A sensitivity analysis in which all dropouts were considered treatment failures still had statistical significance, she said. A regression analysis that included the variables of two or more G2 lesions and spinal cord onset also still had statistical significance, she reported. "In fact, the results were even more in favor of minocycline."

There was no preplanned subgroup analyses because of the relatively small sample size, but the researchers did evaluate several variables typically investigated in MS, including age, sex, and race. "Everything we looked at showed no interaction with the outcome," said Dr Metz.

There were no adverse effects outside of the common ones typically found in patients taking an antibiotic.

"Minocycline 100 mg twice daily is a safe, well-tolerated, inexpensive oral therapy that should be considered for the treatment of a first demyelinating event," concluded Dr Metz.

The cost of the dose used in the study is $500 to $600 (Canadian) per year.

It's not clear how the drug affects MS. "We don't know what the primary effect is because the drug has so many effects," said Dr Metz. "It may be that there's no real primary effect; it may operate in many ways."

She noted that minocycline is not recommended for pregnant women or for children. Some literature suggests waiting until age 18 years to prescribe it because it can discolor patients' teeth.

Minocycline may help fill a void in the field of MS. "One of the treatment gaps is getting people on therapy very early," said Dr Metz. "When you look at any of our current therapies, they're all very expensive and potentially complex, for example, patients might have to learn to do injections. We can't just see a patient and prescribe a medication; we have to go through the insurance process, and there are often delays of several months."

And in some areas of the world, for example, India, a sizable number of people don't have access to MS drugs at all, she said. In such countries, using minocycline should have "some impact."

Session co-chair Wolfgang Brück, MD, professor, neuropathology, University of Gottingen, Germany, called the study results exciting. "The data seem to suggest that minocycline is comparable to approved drugs that are used for conversion to clinically definite MS," he told Medscape Medical News.

Dr Brück agreed that the drug is safe, "but we still don't know exactly what the mechanism of action is" in MS.

ECTRIMS president Xavier Montalban, MD, PhD, director, MS Center of Catalonia, Barcelona, Spain, was also optimistic. Although he said he would have to look at the data carefully to say anything substantial, "it looks very promising."

The study was funded by MS Society of Canada. None of authors or sponsors holds any patent related to minocycline, and none will gain any financial benefit from this trial.

Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2015. Parallel session 13, #227. Presented October 10, 2015.


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