Lower Risk of Relapse Seen Among UK Children With RRMS Receiving Newer DMTs

Maggie L. Shaw

Compared with their peers receiving injectable treatments for their relapsing-remitting multiple sclerosis (RRMS), children who received newer disease-modifying therapies (DMTs) had improved scores on several measures of disease progression.

Annualized relapse rate (ARR), time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score showed greater improvements among children in the United Kingdom with relapsing-remitting multiple sclerosis (RRMS) who received newer disease-modifying therapies (DMTs) vs injectables, reports a study published in Neurology Neuroimmunology & Neuroinflammation.

Part of the UK Childhood Inflammatory Demyelination Network, the investigators gauged outcomes among 103 children (89 started treatment with injectables and 14, newer DMTs). Most of the patients (61%) were on 1 DMT, followed by 36% on 2 DMTs, and 3% on 3 or more DMTs. All were receiving treatment at 1 of 7 pediatric neuroscience centers throughout England. Their overall median (interquartile range [IQR]) age at symptom onset was 14 (12.0-14.8) years, and those in the DMT group were slightly older at treatment initiation, at a median (IQR) age of 14.3 (12.9-15.1) years compared with 13.9 (11.9-14.6) years in the injectables group.

“Current treatment strategies in pediatric MS are largely center specific and reliant on adult protocols,” the authors wrote. “There is a clear need to balance the risk of undertreating children causing poor disease control or overtreating them, exposing the child to unnecessary toxic effects.”

Their principal outcomes of concern were ARRs before and on treatment, time to relapse, time to new MRI lesions, and change in EDSS score.

The results overwhelmingly place the newer DMTs ahead of injectables in terms of positive improvements in the disease course:

  • 15% of the DMT group vs 59.5% of the injectables groups had relapses on treatment.
  • The overall ARR dropped from 1.6 to 0.3 (P = .002) in the DMT group vs 1.9 to 1.1 among the injectables group (P <.001).
  • The ARR for newer DMTs dropped from 1.7 to 0.4 when used as first medication (P = .02) and from 1.6 to 0.2 when used as a second- or third-line treatment (P = .003).
  • Among patients who switched groups, the ARR fell from 1.7 to 0.2 (P = .0001).
  • 47% of the DMT group exhibited new MRI lesions vs 86.5% of the injectables group (P = .0001).
  • Patients in the DMT group had a longer time to relapse, switching treatment, and new radiologic activity vs the injectable group (log rank P <.01).
  • There was a 12-fold greater risk of clinical relapse in the injectables group (adjusted HR [aHR], 12.12; 95% CI, 1.64-89.87; P = .015).
  • There was an approximately 2-fold greater risk of new radiologic activity in the injectables group (aHR, 2.78; 95% CI, 1.08-7.13; P = .034).
  • Close to half as many adverse effects were seen in the DMT group vs the injectables group: 33% vs 61.8%.

Despite these findings, less time occurred between initial presentation and starting injectables treatment compared with initiating DMT treatment: 1.0 (IQR, 0.6-1.9) vs 1.8 (IQR, 1.4-2.5) years, respectively.

Overall, just 37% of patients “had MRI activity in the absence of clinical relapse,” the authors noted, and no changes in EDSS score were seen over the average 3.8-year follow-up from first clinical presentation.

“Our study adds weight to the argument for an imminent shift in practice toward the use of newer, more efficacious DMTs in the first instance,” the authors concluded. “This study provides Class IV evidence that newer DMTs (oral or infusions) are superior to injectables (interferon beta/glatiramer acetate) in reducing both clinical relapses and radiologic activity in children with RRMS.”

Reference

Abdel-Mannan OA, Manchoon C, Rossor T, et al. Use of disease-modifying therapies in pediatric relapsing-remitting multiple sclerosis in the United Kingdom. Neurol Neuroimmunol Neuroinflamm. Published online May 21, 2021. doi:10.1212/NXI.0000000000001008