Citations

ABSTRACT Objective Little is known about shifting from pediatric to adult‐focused multiple sclerosis (MS) care. This study aims to explore transition of care and follow‐up in the US pediatric‐onset MS (POMS) population. Methods Surveys were distributed to 10 sites in the US Network of Pediatric MS Centers (US NPMSC) about transition‐of‐care practices. A cohort of POMS/clinically isolated syndrome (CIS) at 12 US NPMSC sites was analyzed. The primary comparison was between < 18 and ≥ 18‐years of age. The primary outcome was 1‐ and 2‐year lapse in last follow‐up visit, measured from last recorded database visit to data lock date or, if ≥ 18 years of age, up to 1 year after a patient reached their site's typical transition age, if earlier. Secondary outcomes were baseline factors associated with follow‐up lapse. The model was adjusted for preidentified confounders. Results Compared with < 18 years, age ≥ 18 was associated with greater hazard of 1‐ and 2‐year follow‐up lapse. In POMS/CIS, the estimated hazard was 1.61 for 1‐year lapse (95% confidence interval [CI] 1.32–1.97, p < 0.001) and 1.40 for 2‐year lapse (95% CI 1.11–1.76, p = 0.004). In POMS‐only, the estimated hazard was 1.70 for 1‐year lapse (95% CI 1.33–2.18, p < 0.001) and 1.49 for 2‐year lapse (95% CI 1.11–1.99, p = 0.007). Platform injectable disease‐modifying therapy was associated with greater and intravenous with lesser hazard of lapse in follow‐up, while MS was associated with lower hazard than CIS. Conclusion Variable transition‐of‐care practices and barriers were reported by major US POMS centers. Before typical transition age, age ≥ 18 was associated with greater hazard of 1‐ and 2‐year follow‐up lapse than < 18. Developing standardized, targeted transition‐of‐care practices in POMS may be important.

Background Increased chronological age correlates with reduced relapse rates and increased disability in multiple sclerosis (MS). Biological age may better capture ageing’s impact on MS and might accelerate due to MS itself. Establishing accelerated biological ageing in adults is complicated by normal ageing and comorbidities. Telomere length, a well-recognised biological ageing marker, is shortened in adults with MS and associated with disability. Demonstrating accelerated biological ageing in paediatric-onset MS (POMS) would strengthen the hypothesis that MS drives premature biological ageing. This study aimed to determine if telomere length differs in POMS compared to age-similar healthy controls. Methods We performed a cross-sectional case-control study of whole blood samples and clinical data from The US Network of Pediatric MS Centers. Real-time quantitative PCR measured telomere length, expressed as a telomere to somatic DNA ratio (T/S ratio). T/S ratio was compared between cases and age-similar healthy controls using multivariate regression analysis adjusting for chronological age, sex, race, ethnicity, tobacco exposure, socioeconomic status and body mass index. Results We analysed 300 POMS cases and 200 controls. The unadjusted mean T/S ratios were 1.66 (SD 0.32) for cases and 1.71 (SD 0.29) for controls (mean difference –0.05, 95% CI –0.10 to 0.01, p=0.08). After adjusting for key covariables with face validity, POMS participants had a mean 0.086 shorter T/S ratio than controls (95% CI 0.015 to 0.157, p=0.018). Conclusions POMS participants demonstrated shorter telomeres than age-similar controls in a multivariable model adjusting for sociodemographic variables, suggesting that MS may contribute to accelerated biological ageing.

Background: Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. Objectives: To determine the correlation between DNAm and TL aging markers. Methods: We conducted a cross-sectional case–control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. Results: We analyzed biological ages in 270 participants (125 POMS, mean 15.7 years; 145 controls, mean 15.3 years). There were moderate correlations among the different DNAm clocks, but no correlations between DNAm clocks and TL in pooled analyses. In a stratified analysis, only the control group showed a modest correlation between TL and PhenoAge clock ( r = 0.2, p = 0.06). Conclusions: DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.