An inexpensive antibiotic used to fight acne appears to delay the development of multiple sclerosis (MS) in people in the earliest stage of the crippling disease, according to a Canadian study.
Reuters Health reports that treatment with the generic tetracycline drug minocycline produced fewer cases of MS after six months compared to people given a placebo. The drug was tested in 142 patients who had shown some early symptoms, but the disease had not been confirmed.
The benefit was also seen after one year of therapy, but not after two years, said chief author Dr Luanne Metz of the University of Calgary’s Hotchkiss Brain Institute. “We did not have enough patients at 24 months to know whether the drug was still doing anything or not,” she is quoted as saying. Further tests would be ideal but paying for them will be difficult because no pharmaceutical company stands to make a lot of money from this use for the generic drug.
Generally, two out of three patients with the early signs of multiple sclerosis, known as clinically isolated syndrome, go on to develop MS within six months. The disease attacks the insulation protecting the body’s nerves.
In the new study, the six-month risk of conversion to MS was 33.4% with 100 mg of minocycline twice daily versus 61.0% in the placebo group. When the researchers adjusted for the results of MRI scans, the odds rose to 43.0% with minocycline but stayed the same with placebo. Yet after two years, the unadjusted risk was comparable in the two groups, raising the possibility that the benefit may not last.
The treatment costs about C$600 ($444) per year in Canada versus C$20,000 to C$40,000 for conventional MS therapy, the researchers said. The price tag is about three times higher in the US. In addition, minocycline therapy can be started rapidly. In Canada, conventional MS therapy can take months to get approved.
“It’s a very inexpensive medication – less than C$2 per day – that can be initiated immediately,” co-author Wee Yong said in the report. “We know that time matters in MS. With the passage of time, the immune insults on the brain continue. I see this as potentially a game-changer in terms of overcoming the challenges of time against MS.” In addition, the drug could help patients in areas of the world that don’t have access to the more expensive drugs for multiple sclerosis, he said.
“Overall, the findings from this trial suggest a potential clinical benefit of minocycline in early multiple sclerosis, with an effect size similar to that of existing disease-modifying treatments,” said Drs Zongqi Xia of the Pittsburgh Institute of Neurodegenerative Diseases and Robert Friedlander of the University of Pittsburgh School of Medicine in an editorial.
Despite some limitations, including the small size of the study, the findings “make a compelling case for the further study of the effect of minocycline in multiple sclerosis,” they said. “However, use of minocycline in multiple sclerosis is not supported until its benefit can be confirmed in larger long-term clinical trials.”
According to the National Multiple Sclerosis Society, people who experience neurologic symptoms for at least 24 hours and those symptoms are caused by an inflammation or a loss of myelin in the central nervous system may – but not always – progress to MS. The odds are about 60% to 80% when MRI detects MS-like brain lesions; about 20% when they’re not seen.
In the new test, done at 12 Canadian MS clinics, all volunteers had at least two brains lesions larger than 3 millimetres. The study team used minocycline because it has anti-inflammatory properties and, unlike most drugs, it crosses the blood-brain barrier.
Among the minocycline side effects: dizziness (seen 10 times more often than in the placebo group), rash (which was 5 times more common) and dental discoloration (seen in 6 of 72 patients but none in the 70-member placebo group).
Six people in the minocycline group withdrew from the test because of side effects versus one person in the placebo group. “Most people stay on it and tolerate it very well,” Metz said. Side effects usually fade over time to the point where “it’s tolerated much like taking a vitamin pill.”
Background: On 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.
Methods: During 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]).
Results: A 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.
Conclusions: The 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.)
Luanne M Metz, David KB 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