Ocular Inflammation as a Risk Factor for Antiadalimumab Antibodies in Patients with Autoimmune Diseases Treated with Adalimumab

PURPOSE: To investigate the potential impact of ocular inflammation on development of antiadalimumab antibodies (AAAs) in patients with systemic autoimmune diseases treated with adalimumab. DESIGN: Retrospective case-control study. PARTICIPANTS: Patients who were treated with adalimumab for various autoimmune conditions for at least 6 months and were tested for adalimumab levels, AAA, or both from June 2005 through May 2024. METHODS: The Stanford Research Repository database, a clinical data warehouse that aggregates electronic health records from Stanford Health Care, Stanford Children's Health, and affiliated clinics, was used to identify eligible participants. Demographic data, systemic diagnoses, ocular involvement, and prior and concurrent treatment also were collected. Subsequently, univariable and multivariable logistic regression analyses were conducted to identify factors associated with AAA development. MAIN OUTCOME MEASURES: The correlation of AAAs with ocular inflammation and the proportion of patients with positive AAA findings in the study cohort. RESULTS: Among 704 patients, 151 patients (21.5%) demonstrated AAAs. The group was predominantly female compared with the AAA-negative group (60.9% vs. 47.0%; adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.07-2.85; P = 0.024). On multivariable analysis, ocular inflammation (aOR, 2.19; 95% CI, 1.19-4.02; P = 0.011), female sex (aOR, 1.75; 95% CI, 1.08-2.85; P = 0.024), and adalimumab interruption (aOR, 1.74; 95% CI, 1.03-2.94; P = 0.038) remained independent risk factors for AAA formation. Prior biologic therapy other than tumor necrosis factor (TNF)-α inhibitors was protective (aOR, 0.27; 95% CI, 0.08-0.98; P = 0.046), although prior TNF-α inhibitor exposure remained a risk factor (aOR, 2.11; 95% CI, 1.25-3.55; P = 0.005). CONCLUSION: Ocular inflammation in patients with autoimmune disorders is associated with an increased risk of AAA formation, prospective studies are needed to determine whether this reflects a mechanistic relationship and whether therapeutic drug monitoring in this subgroup improves clinical outcomes. Notably, more than one-fifth of patients receiving adalimumab in this cohort demonstrated AAAs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.