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

Osama Elaraby; Dalia El-Feky; Jia-Horung Hung; Amir Akhavanrezayat; Abdelaziz Abdelaal; Negin Yavari; Ishaan Iyer; David Ni Xu; Zheng-Xian Thng; Anadi Khatri; Gunay Uludag Kirimli; Mohammad Bagher Rajabi; Vahid Bazojoo; Cigdem Yasar; Irmak Karaca; Gunjan Awatramani; Azadeh Mobasserian; David Chanthan; Ngoc Trong Tuong Than; Christopher Or; Diana Do; Quan Dong Nguyen

doi:10.1016/j.ophtha.2026.05.028

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

Ophthalmology. 2026 May 26:S0161-6420(26)00376-3. doi: 10.1016/j.ophtha.2026.05.028. Online ahead of print.

Authors

Osama Elaraby¹, Dalia El-Feky², Jia-Horung Hung¹, Amir Akhavanrezayat¹, Abdelaziz Abdelaal³, Negin Yavari¹, Ishaan Iyer¹, David Ni Xu¹, Zheng-Xian Thng⁴, Anadi Khatri⁵, Gunay Uludag Kirimli¹, Mohammad Bagher Rajabi¹, Vahid Bazojoo⁶, Cigdem Yasar¹, Irmak Karaca⁷, Gunjan Awatramani¹, Azadeh Mobasserian¹, David Chanthan⁸, Ngoc Trong Tuong Than¹, Christopher Or¹, Diana Do¹, Quan Dong Nguyen⁹

Affiliations

¹ Byers Eye Institute, Stanford University School of Medicine, California.
² Byers Eye Institute, Stanford University School of Medicine, California; Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta, Egypt.
³ Department of Postgraduate Medical Education, Harvard Medical School, Boston, Massachusetts.
⁴ Byers Eye Institute, Stanford University School of Medicine, California; Department of Ophthalmology, National Health Group Eye Institute, Tan Tock Seng Hospital, Singapore, Republic of Singapore.
⁵ Gautam Buddha Eye Care Centre, Lumbini, Nepal; Kathamandu University, Kathmandu, Nepal.
⁶ Department of Radiology, Weill Cornell Medicine, New York, New York.
⁷ Byers Eye Institute, Stanford University School of Medicine, California; Department of Ophthalmology, Irving Medical Center, Columbia University, New York, New York.
⁸ Byers Eye Institute, Stanford University School of Medicine, California; Department of Ophthalmology, Khmer-Soviet Friendship Hospital, Phnom Penh, Cambodia.
⁹ Byers Eye Institute, Stanford University School of Medicine, California. Electronic address: ndquan@stanford.edu.

PMID: 42203133
DOI: 10.1016/j.ophtha.2026.05.028

Abstract

Purpose: To investigate the potential impact of ocular inflammation on development of 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, antiadalimumab antibodies (AAAs), 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 TDM 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.

Keywords: Adalimumab; Antiadalimumab antibodies; Antidrug antibodies; Ocular inflammation; Uveitis.