(1348) The Association Between Comorbid Insomnia and Sleep Apnea (COMISA) and Autoimmune Diseases: A Database Study

Introduction: To investigate the 5-year longitudinal risk of a broad spectrum of autoimmune diseases in patients with comorbid insomnia and obstructive sleep apnea (COMISA) relative to those with obstructive sleep apnea (OSA) alone.

Methods: Utilizing the TriNetX US Collaborative Network, we identified an incident cohort of adults with OSA. Participants, consisting patients within the period of 2010 to 2023, were stratified into COMISA (insomnia diagnosed within 90 days post-OSA) or OSA-alone groups. After 1:1 propensity score matching (PSM) for demographics, physical comorbidities, and medications, the risk of 10 distinct autoimmune categories was evaluated using Cox proportional hazards regression. Subgroup analyses were conducted to examine potential effect modification (interaction) by sex, CPAP initiation, and sedative (benzodiazepine/Z-drug) exposure. Sensitivity analyses were performed by expanding diagnostic windows and liberalizing treatment criteria to evaluate the robustness of the findings.

Results: COMISA was associated with a significantly elevated 5-year risk for 9 out of 10 investigated autoimmune categories. The risk was most prominent for Sjögren’s syndrome (HR 1.451, 95% CI: 1.312–1.605) and systemic sclerosis/MCTD/IIM (HR 1.362, 95% CI: 1.169–1.586). Rheumatoid arthritis exhibited the highest cumulative burden (HR 1.28, 95% CI: 1.206–1.36; 5-year NNH = 328), followed by Sjögren’s syndrome (NNH = 591) and hematologic/neurologic autoimmune diseases (NNH = 630). Notably, CPAP use significantly mitigated the risk of seronegative spondyloarthropathy in COMISA patients (P interaction = 0.004), whereas sedative exposure (BZD/Z-drugs) exacerbated the risk of psoriasis (P interaction = 0.013). Autoimmune liver/biliary disease showed no significant association.

Conclusions: COMISA is a critical risk indicator for various autoimmune diseases. The observed interactions with CPAP and sedatives suggest that the relationship between sleep disorders and immune dysregulation is influenced by clinical management and medication status.