The prevalence and potential associations of anti-drug antibodies against adalimumab in patients with non-infectious uveitis: a cross-sectional study

Adalimumab is effective in treating non-infectious uveitis (NIU), but some patients develop anti-drug antibodies against adalimumab (ADA-A), which can reduce its effectiveness, resulting in active inflammation and vision loss. We sought to determine the prevalence of ADA-A in adults receiving adalimumab for NIU, and investigate factors associated with the presence of ADA-A. In this cross-sectional study, eighty-one (46 female) consecutive adult patients receiving adalimumab for NIU at The Royal Victorian Eye and Ear Hospital, and Eye Surgery Associates in Melbourne, Australia were recruited from March 2023 to February 2024 inclusive. The median age of patients was 45 years (range 18, 87) with median disease duration of 5.3 years (range 0.4, 25.3), and median duration of adalimumab therapy of 2.3 years (range 0.2, 13.1). Panuveitis (N = 27, 33%) was the commonest anatomical form of uveitis treated, and most patients had bilateral uveitis (N = 73, 90%). The most common diagnoses were presumed idiopathic uveitis (N = 27, 33%) and sarcoidosis (N = 13, 16%). Most patients (N = 50, 62%) were concurrently treated with conventional immunosuppression, most commonly using methotrexate (N = 32, 40%). ADA-A were present in 5/81 patients (6.2%, 95%CI 2.7, 13.6), and their presence was associated with higher Body Mass Index [median 34.9 kg/m2 (IQR 32.5, 38.0) vs. 28.4 kg/m2 (IQR 24.4, 31.9), p = 0.010], higher C-reactive protein [median 7.4 mg/L (IQR 5.5, 7.9) vs. 2.0 mg/L (IQR 0.0, 6.0), p = 0.030], lower patient-reported health [median 5/10 (IQR 5, 6) vs. 8/10 (IQR 6, 8), p = 0.024], and lower serum adalimumab levels [median 0.0 µg/mL (IQR 0.0, 0.0) vs. 5.0 µg/mL (IQR 2.8, 7.8), p = 0.002]. There was no association between ADA-A and the duration of adalimumab therapy, use of concurrent conventional immunosuppression, presence of systemic inflammatory disease, uveitis activity, visual acuity or adverse effects to adalimumab. ADA-A were uncommon, and their presence may be associated with obesity, increased C-reactive protein, and poorer patient-reported health. Within the limitations of our statistical power, the presence of ADA-A was not associated with systemic inflammatory disease, uveitis activity, nor adalimumab monotherapy.