The disease-modifying therapy fingolimod can slow the rate of brain atrophy in children with MS in the same way as it does in adults, an MRI study has shown.
A follow up to the PARADIGMS randomised controlled trial involving 215 people aged 10-18 with paediatric-onset multiple sclerosis (PoMS) has shown that fingolimod significantly reduced the accrual of lesions on MRI compared to interferon beta-1a.
The international multicentre phase 3 study found that over a two year treatment period fingolimod reduced the annual rate of brain atrophy (ARBA) by 40% versus interferon beta-1a treatment, with an absolute difference of 0.32% per year.
Children in the trial were randomised to once-daily oral fingolimod (n=107) or once-weekly intramuscular IFN β-1a (n=108) with MRI performed at baseline and every 6 months for up to 2 years.
The results, published in Journal of Neurology, Neurosurgery and Psychiatry showed that at two years fingolimod treatment reduced the annualised rate of formation of new/newly enlarging T2 lesions by 52.6% (p<0.001) compared to IFN β-1a. It also reduced the number of Gd+ T1 lesions per scan (66.0%, p<0.001), annualised rate of new T1 hypointense lesions (62.8%, p<0.001) and combined unique active (CUA) lesions per scan (60.7%, p<0.001).
The percent increases from baseline in T2 (18.4% vs 32.4%, p<0.001) and Gd+ T1 (–72.3% vs 4.9%, p=0.001) lesion volumes and ARBA (–0.48% vs −0.80%, p=0.014) were lower with fingolimod versus IFN β-1a, the latter partially due to accelerated atrophy in the IFN β-1a group.
The study authors, led by Dr Douglas Arnold of the Montreal Neurological Institute, said the effect on MRI disease activity was similar in both male and female, and in patients who were DMT-naïve or DMT-experienced at baseline, “confirming the efficacy of fingolimod treatment in children regardless of sex or prior treatment experience.”
However they also noted that a large part of the benefit on brain volume loss occurred in the first 6 months of treatment, and may have reflected the accelerated atrophy known to occur after starting treatment with IFN β-1a. Subsequent differences between groups in brain volume were smaller, and not significantly in favour of fingolimod.
Nevertheless, they said the study had shown that in addition to its previously demonstarted 82% reduction in relapse rates, children with MS benefit from fingolimod treatment due to a direct anti-inflammatory effect on MRI disease activity and a possible secondary effect on brain atrophy.
“These findings have important practical implications on the timing of treatments to slow the brain damage in children,” an accompanying commentary stated.
The findings would also establish fingolimod as the active comparator benchmark to test future therapies in paediatric MS, wrote Professor Arman Eshaghi of the UCL Institute of Neurology, University College London.