medwireNews: In girls with pediatric-onset multiple sclerosis (MS), menarche may represent a time for increased disease activity, with MS onset tending to occur in the 2–3 years after menarche, and the risk for relapse increased during and following menarche, suggests research.
Jennifer Graves (University of California San Diego, La Jolla, USA) and colleagues write in Neurology that “[t]he increase in relapse rate at the menarche transition and the high frequency of MS onset in the years after menarche suggest that hormonal and associated immunologic changes occurring at puberty may play a role in onset of MS and relapses.”
They also note that disease-modifying therapy (DMT) had a strong protective association with the risk for relapse, with significant reductions during use of oral and infusion DMT.
The US Network of Pediatric MS Centers analyzed data on 736 girls with pediatric MS collected from 12 specialist centers in the USA between 2011 and 2022. The researchers note that patients who tested positive for myelin oligodendrocyte glycoprotein antibody were excluded to rule out the potential for an alternative demyelinating disease, although 46% of participants were not tested.
The mean age at MS onset was 14.4 years and the mean age at menarche was 11.6 years. The median follow-up time was 4.1 years, during which most (86%) of the girls received DMT. Perimenarche was considered the period from 1 year before to 1 year after the estimated menarche date based on menarche integer age.
In all, 74 participants had premenarche onset of MS, 112 perimenarche onset, and 551 postmenarche onset of MS. The median time for onset of MS was 2.8 years after menarche.
Adjusting for race, first available report of BMI, and DMT use, the estimated annualized relapse rate (ARR) during perimenarche was 0.65, which was significantly higher than during premenarche, and postmenarche, at an ARR of 0.43 for each. This translated to an estimated 1.52-fold higher relapse rate in the perimenarche, compared with the postmenarche, period.
In Cox regression analyses that adjusted for time-varying use of DMT, the risk for relapse was significantly higher during perimenarche and postmenarche compared with premenarche, at 78% and 67%, respectively
The findings were sustained in sensitivity analyses that included only those participants who had data spanning at least two of the three defined menarche periods, the researchers report.
Commenting on this finding in an associated editorial, J Nicholas Brenton (University of Virginia, Charlottesville, USA) says that this suggests “that the elevated risk of relapse in the perimenarche and postmenarche epoch is true within participants in addition to between groups.”
There was a strong association between DMT use and risk for relapse. During periods when the participants were receiving oral and particularly infusion DMT, the risk for relapse was significantly lower compared with when there was no DMT use. The hazard ratios were a significant 0.47 for oral DMT (dimethyl fumarate, fingolimod, teriflunomide) and 0.24 for infusion DMT (natalizumab, rituximab, ocrelizumab, alemtuzumab).
“[T]his research supports consideration of a therapeutic change before menarche for those children previously started on low-efficacy DMTs,” writes Brenton.
The researchers conclude that their study “is one of association and further work is needed to confirm the mechanisms that may contribute to the change in relapse rates across the pubertal transition in female individuals.”
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