An estimated 3%-10% of MS patients are diagnosed during childhood. These patients experience a higher relapse rate and have higher magnetic resonance imaging (MRI) activity than do adult-onset patients. They have a slower rate of progression, but they reach irreversible disability milestones at an early age, with more than 50% having secondary progressive disease by age 30.
Studies in adults suggest that use of high-efficacy DMTs is most effective when initiated during the early active phase of MS, but little is known about children. “Early recognition of predictors of faster disability in children is crucial for clinicians to make the treatment decisions at the earliest possible time,” Sifat Sharmin, PhD, said during her presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Dr. Sharmin is a statistician and research fellow at the University of Melbourne.
‘Reassuring’ data
“I think the most important observation that was made here is the protective factor of use of high efficacy disease modifying therapies,” said Bruce Cree, MD, PhD, who was asked to comment on the study.
That result wasn’t unexpected, but it should provide reassurance. “For parents of children who are hesitant about use of high efficacy therapies, this study provides supporting evidence for use of these high efficacy therapies early on, to try and prevent irreversible disability from occurring,” said Dr. Cree, professor of clinical neurology and the George A. Zimmermann Endowed Professor in Multiple Sclerosis at the University of California at San Francisco UCSF Weill Institute for Neurosciences.
The study provides real-world data to back up findings from a phase 3 clinical trial that showed fewer relapses and fewer new lesions in pediatric patients with MS who were taking fingolimod versus interferon beta-1a.
“Given a large randomized, controlled trial, and now with this additional real-world data set showing the same thing, the only conclusion to reach is that if you’ve got a kid with MS, they should be treated with fingolimod,” said Dr. Cree. He noted that other DMTs such as natalizumab may also benefit pediatric patients, but fingolimod is the only drug that has been studied in randomized, controlled trials in children.
Real-world data
The researchers analyzed data from 672 patients drawn from the international MSBase Neuroimmunology Registry, who had undergone neurological assessment within 1 year of symptom onset and had at least two annual visits where the Expanded Disability Status Scale (EDSS) was recorded. They sought to identify predictors of Multiple Sclerosis Severity Score (MSSS). A secondary analysis looked at predictors of EDSS sustained worsening at 6 months, defined as an increase of 1.5 if EDSS baseline was 0, 1.0 or more if baseline EDSS was 1.0-5.5, or 0.5 if baseline EDSS was over 5.5.
The researchers also conducted a sensitivity analysis that looked at relapse phenotypes and relapse frequency in the first year, as well as a subgroup analysis of patients with available MRI data from the first year. The researchers adjusted for time on high-efficacy DMTs at each visit.
Among the study participants, 70% were female. The median age of onset was 16 years. The median EDSS score was 1.5 at inclusion, and the median score was 1.0 at follow-up of 3 years. At 6 months, 82 worsening events occurred in 57 patients.
A total of 76% of the patients were treated with DMTs. The most commonly prescribed DMTs were interferon beta (40.63%), natalizumab (8.48%), and fingolimod (6.40%). Seventy-eight percent of those who received DMTs started treatment before age 18. Twenty-seven percent received high-efficacy DMTs.
The analysis showed associations between disability and older age at onset [exp(beta), 1.09; 95% confidence interval, 1.03-1.16], maximum EDSS score during the first year of disease [exp(beta), 1.25; 95% CI, 1.13-1.36], or first-year pyramidal symptoms [exp(beta), 1.34; 95% CI, 1.13-1.58], visual symptoms [exp(beta), 1.28; 95% CI, 1.10-1.48], or cerebellum symptoms [exp(beta), 1.17; 95% CI, 1.00-1.39]. A greater amount of time on high-efficacy DMTs was associated with a lower probability of disability [exp(beta), 0.96; 95% CI, 0.93-0.99].
A complete recovery from the first relapse was associated with a lower probability of relapse, though this association did not reach statistical significance [exp(beta), 0.83; 95% CI, 0.68-1.03].
The secondary analyses found that the only predictor of 6-month EDSS worsening [exp(beta), 1.32; 95% CI, 1.21-1.45] was having a maximum EDSS score in the first year. Sensitivity analyses of complete and incomplete recovery from relapses found that a higher MSSS was associated incomplete recovery [exp(beta), 1.16; 95% CI, 1.02-1.32], and confirmed the primary finding that recovery from first relapse was associated with a lower probability of disability [exp(beta), 0.78; 95% CI, 0.63-0.96].
Among patients with MRI data, a new MRI lesion in year 1 was associated with a lower future MSSS score [exp(beta), 0.81; 95% CI, 0.66-0.99].
The study was funded by the National Health and Medical Research Council of Australia. The study authors disclosed ties with a wide range of pharmaceutical companies, including Biogen and Novartis. Dr. Cree has consulted for Biogen, Novartis, and other pharmaceutical companies.