Minocycline potential option for multiple sclerosis
Minocycline, a common acne medication, may delay the progress from a first demyelinating event to multiple sclerosis (MS), suggests a recent study.
At 6 months, the risk of conversion from a first demyelinating event (or clinically isolated syndrome) to MS was lower in participants treated with minocycline than with placebo (unadjusted risk, 33.4 percent vs 61.0 percent, percentage point difference: 27.6; p=0.001). [N Engl J Med 2017;376:2122-2133]
“This trial met a prespecified outcome of an absolute difference of 25 percentage points in the risk of conversion to MS in the unadjusted analysis,” observed the researchers.
The multicentre double-blind trial randomized 142 participants (mean age 35.8 years, 68.3 percent women), who had a first demyelinating event within the past 6 months, to receive oral minocycline 100 mg twice daily or placebo for 24 months or until diagnosis of definitive MS, whichever came first.
Nonetheless, there were significantly more participants with symptom onset in the spinal cord (p=0.04) and ≥1 enhancing lesion of MRI at baseline (p=0.04) in the placebo group.
After adjusting for the imbalance in enhancing lesions at baseline, the risk of conversion to MS remained significantly lower with minocycline at 6 months (percentage point difference: 18.5; p=0.01).
The risk was not significantly different between the two groups at 24 months.
Adverse events occurred more frequently in the minocycline than the placebo groups (86.1 percent vs 61.4 percent; p=0.001), including rash (15.3 percent vs 2.9 percent; p=0.01), dizziness (13.9 percent vs 1.4 percent; p=0.005), and dental discolouration (8.3 percent vs 0 percent; p=0.01).
“Patients will now have yet another treatment option, one that does not require injections, monitoring lab work, or special authorization by their insurance company; provided they have adequate coverage to begin with. These processes can delay treatment initiation for three to four months whereas minocycline can be started immediately,” said lead author Dr Luanne Metz from the Cumming School of Medicine and the Hotchkiss Brain Institute in Calgary, Canada.
Minocycline is a “relatively safe and inexpensive” tetracycline antibiotic that crosses the blood-brain barrier, according to the researchers.
“Given the safety profile and low cost of minocycline, these … [are] compelling results but too early to tell,” commented Drs Xia Zongqi and Robert Friedlander of University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania, US, in an accompanying editorial. [N Engl J Med 2017;376:2191-2193]
“The 6-month period for the primary outcome was shorter than that in many other trials of disease-modifying treatments for MS, and given that MS is a chronic disease, the finding for the primary outcome has limited applicability in clinical practice,” they wrote.
Other limitations such as the small sample size could have led to the nonsignificant outcome at 24 months, while the adverse effects with minocycline (eg, rash and dental discoloration) might mitigate the blinding of the trial, noted Xia and Friedlander.
“Use of minocycline in MS is not supported until its benefit can be confirmed in larger long-term clinical trials,” they added.