Puberty onset and pediatric multiple sclerosis activity in boys

Objectives: To determine the association of age of onset and puberty with relapse rate in boys with pediatric multiple sclerosis (MS). Background: While sex steroid hormones have been shown to have immune effects, it is not known how age or puberty influence disease course in boys with MS. We have previously shown an association in girls with menarche and risk of relapse. Methods: Patients from the UCSF Regional Pediatric MS Center were included in this retrospective study. Age of disease onset was used to stratify patients into three groups approximating pubertal stage: age less than 11 years, between 11-14 years, and greater than 14 years, corresponding to pre-, peri-, and post-puberty, respectively. Negative binomial regression was used to determine the association between pubertal status at disease onset with relapse rate. Results: 58 male pediatric patients with onset of relapsing-remitting MS before 18 years of age participated to the analyses (<11 onset, n = 21; 11-14 onset, n = 21; >14 onset, n = 16). 60% of patients identified as White, and 43% as Hispanic. Median follow-up was 3.17 years (IQR 1.42-5.35). Univariate negative binomial regression models demonstrated a 2.4 fold increased relapse rate for boys with disease onset in the peri-puberty age group compared to the post-puberty age group (IRR = 2.43, 95% CI 1.33-4.47, p = 0.004). Adjustments for race, ethnicity, and use of disease-modifying therapy did not change these results (IRR = 2.39, 95% CI 1.20-4.79, p = 0.014). No differences in relapse rate between the pre-pubertal onset group and post-pubertal onset group were found. Conclusions: Pubertal onset of MS may be associated with increased relapses in boys. Further investigation is indicated to understand the intersection of pubertal effects and MS pathophysiology.