Worsening Disability in Children With MS Predicted By Clinico-Demographic Characteristics

Sifat Sharmin, PhD, MS, BSc

Data recently presented at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 13-15, showed that for patients with pediatric-onset multiple sclerosis (POMS), the presentation of symptoms later in childhood, frequent relapses, and higher disability during the first year predicted significant worsening of the disease. 

Investigators, led by Sifat Sharmin, PhD, MS, BSc, postdoctoral research fellow and the University of Melbourne, Australia, included a total of 672 patients from 30 countries. All participants were under the age of 18 years, logging a total of 9357 visits in the global MSBase registry. Sharmin and colleagues utilized the Multiple Sclerosis Severity Score (MSSS) to evaluate disability rank, normalized for disease duration in the primary analysis. Potential predictors included the impact of age of symptom onset, complete recovery following the first relapse, Expanded Disability Status Scale (EDSS) score, as well as phenotypes and frequency of relapse during the first 12 months. 

A higher future MSSS was associated with older age at symptom onset (ß = 1.09 [95% CI, 1.03-1.14]), a higher EDSS score (ß = 1.25 [95% CI, 1.13-1.36]), and more frequent relapses within 12 months post-diagnosis (ß = 1.04 [95% CI, 0.96-1.13). Lower future MSSS was associated with a full recovery from the first relapse (ß = 0.83 [95% CI, 0.68-1.03]), as well as having a brainstem relapse (ß = 0.90 [95% CI, 0.77-1.04]).

When evaluating the effect of disease modifying therapies (DMTs), as MSSS was reduced by 4% per each unit increase in proportion of time taking high-efficacy DMTs (ß = 0.96 [95% CI, 0.93-0.99]), indicating a protective factor. In the study cohort, beta interferons were the most common DMT (n = 361; 53.72%), following by fingolimod (Gilenya; Novartis) (n = 143; 21.28%), and natalizumab (Tysabri; Biogen) (n = 117; 17.41%) at the start of treatment. 

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“Clinical characteristics and MRI activity have been identified as predictors of relapse and disability…studies have reported that high-efficacy disease-modifying therapies reduce relapse rate and disease progression in children,” Sharmin said during her presentations at the ECTRIMS virtual conference. “Evidence from the adult-onset MS research suggest that these high-efficacy DMTs are most effective in preventing long-term disability when started in the early active phase of the disease. Early recognition of predictors of possible disability in children is crucial for the clinicians to make the treatment decisions at the earliest possible time.” 

“In this study, we aimed to identify predictors of disability worsening as early as [the] first year since symptoms onset, considering the potential for commencing high-efficacy disease-modifying therapies,” she added.

A secondary analysis was conducted using confirmed worsening of EDSS score as the outcome of interest, concluding that EDSS score in the first year of diagnosis is a predictor of the score worsening at 6 months. Sensitivity analyses evaluated relapses in the first year, as well as a subset of patients who had brain MRI data was also performed. Investigators found that a greater number of relapses, as well as incomplete recovery from relapse was associated with a higher MSSS and presence of a new MRI lesion in year 1 was associated with a lower future MSSS score. 

“Of note, 91% of the patients with at least 1 new MRI lesion in year 1 were treated with disease-modifying therapies, compared to 77% from those without a new MRI lesion in year 1,” Sharmin said during her presentation. 

Patients, 70% of whom were female, had a median age of 16 years (standard deviation, 15-17) at symptom onset and had their first neurological assessment with 12 months following. Patients were required to have annual visits, 2 of which required EDSS score to be recorded. Exclusion criteria were a diagnosis of progressive MS at the onset of symptoms and participation in randomized clinical trials.

For more coverage of ECTRIMS 2021, click here.

REFERENCE

Sharmin S, Malpas C, Roos I, et al. Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national cohort. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Poster 187.