Long-Term Risk of Rheumatoid Arthritis in Individuals With Autism Spectrum Disorder: A Population-Based Matched Cohort Study.

Abstract

To investigate the long-term risk of rheumatoid arthritis (RA) among individuals with autism spectrum disorder (ASD), addressing potential immune comorbidity in ASD populations. A population-based matched cohort was assembled using Swedish registers, including 46,164 individuals diagnosed with ASD between 1987 and 2017, matched to 4,634,895 controls by sex and birth year. Cohort members were followed from age 18 until RA diagnosis, death, emigration, or end of follow-up, providing up to 30 years of observation into adulthood. Cox proportional hazards models estimated hazard ratios (HR) for RA, with sensitivity analyses adjusting for parental autoimmune, psychiatric history, and socioeconomic status. RA diagnosis rates were similar between individuals with ASD (n = 58, 0.13%) and controls (n = 5484, 0.12%), with no increased risk: overall HR = 1.06 (95% CI 0.82-1.37), seropositive HR = 1.00 (0.67-1.48), and seronegative HR = 1.12 (0.79-1.57). Complementary analyses adjusting for parental psychiatric history, autoimmune conditions, and socioeconomic factors yielded consistent null findings (HR = 1.34, 95% CI 0.97-1.84). Sensitivity analyses, including accelerated failure time models and alternative RA subtype definitions, confirmed these results. This large-scale population study does not suggest an increased RA risk in individuals with ASD. Despite suggested immune dysfunction in ASD and shared genetic pathways with autoimmune conditions, we did not observe evidence that ASD is associated with elevated RA risk during adulthood; In conclusion, these findings inform understanding of autoimmune comorbidity patterns in autism and may guide evidence-based clinical monitoring for autistic adults.