Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom

Abstract

ObjectivesTo compare the real-world effectiveness of newer disease-modifying therapies (DMTs) vs injectables in children with relapsing-remitting multiple sclerosis (RRMS).MethodsIn this retrospective, multicenter study, from the UK Childhood Inflammatory Demyelination Network, we identified children with RRMS receiving DMTs from January 2012 to December 2018. Clinical and paraclinical data were retrieved from the medical records. Annualized relapse rates (ARRs) before and on treatment, time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score were calculated.ResultsOf 103 children treated with DMTs, followed up for 3.8 years, relapses on treatment were recorded in 53/89 (59.5%) on injectables vs 8/54 (15%) on newer DMTs. The ARR was reduced from 1.9 to 1.1 on injectables (p < 0.001) vs 1.6 to 0.3 on newer DMTs (p = 0.002). New MRI lesions occurred in 77/89 (86.5%) of patients on injectables vs 26/54 (47%) on newer DMTs (p = 0.0001). Children on newer DMTs showed longer time to relapse, time to switch treatment, and time to new radiologic activity than patients on injectables (log-rank p < 0.01). After adjustment for potential confounders, multivariable analysis showed that injectables were associated with 12-fold increased risk of clinical relapse (adjusted hazard ratio [HR] = 12.12, 95% CI = 1.64–89.87, p = 0.015) and a 2-fold increased risk of new radiologic activity (adjusted HR = 2.78, 95% CI = 1.08–7.13, p = 0.034) compared with newer DMTs. At 2 years from treatment initiation, 38/103 (37%) patients had MRI activity in the absence of clinical relapses. The EDSS score did not change during the follow-up, and only 2 patients had cognitive impairment.ConclusionNewer DMTs were associated with a lower risk of clinical and radiologic relapses in patients compared with injectables. 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.Classification of EvidenceThis 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.

Analysis of the Group of Pediatric Patients With Relapsing-Remitting Multiple Sclerosis: Data From the Czech National Registry

“…In addition, out of 98 patients who started on first line drug treatment, 27 (27.55%) patients switched to the second line drug treatment within 24 months. Similar findings were confirmed by a UK study ( 12 ).…”

“…However, it should be noted that a number of phase II and III trials are currently underway to evaluate the efficacy and safety of unapproved molecules in pediatric MS patients ( 1 , 9 – 11 ). The treatment of pediatric patients is strictly indicated in specialized centers and is mostly based on recommended treatment protocols for adult patients ( 12 ).…”

Current international trends in the treatment of multiple sclerosis in children—Impact of the COVID-19 pandemic

“…Our results indicate an attitude which is in line with recent studies of children with MS or clinically isolated syndrome, where newer DMTs were increasingly used in more recent years( Krysko et al, 2018 ) and where initial treatment with newer DMTs led to better disease activity control compared to injectables. ( Abdel-Mannan et al, 2021 ; Krysko et al, 2020 ) Two recent reviews also propose that highly effective DMTs should be used during the first years post-onset, a time with a high relapse rate and rapid loss of brain tissue. ( Hacohen et al, 2020 ; McGinley and Rossman, 2017 )…”

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021

“…114 Therefore, due to the limited number of reported cases, it is difficult to assess a causal relationship between the use of immunosuppressive or immunomodulatory treatments and the development of infections. 115 Four main issues arise when trying to evaluate such a relationship. First, there is no consensus on the correct dosage to be used in terms of efficacy and safety.…”

“…114 Therefore, due to the limited number of reported cases, it is difficult to assess a causal relationship between the use of immunosuppressive or immunomodulatory treatments and the development of infections. 115…”