Adalimumab Dose Adjustment for Pediatric uveitis Treatment (ADAPT) Trial

About This Grant

PROJECT SUMMARY Juvenile idiopathic arthritis (JIA) is the most common rheumatologic condition in children, and 12-38% of patients with JIA develop chronic asymptomatic anterior uveitis, typically within 4 to 7 years of arthritis onset. JIA- associated uveitis can cause significant morbidity, with as many as 1/3 of all patients developing substantial visual impairment and up to 15% becoming legally blind. The anti-tumor necrosis factor (TNF) human monoclonal antibody adalimumab has shown efficacy in treating JIA-associated uveitis but is associated with a risk of serious adverse events, including opportunistic infections and malignancy. Furthermore, long-term treatment with adalimumab is expensive and causes a significant financial burden for the patient and healthcare system. The Adalimumab in Juvenile Idiopathic Arthritis (JIA)-associated Uveitis Stopping Trial (ADJUST), an NEI-funded, double-masked, randomized controlled trial recently conducted by our team, revealed 64% cumulative failure among patients with previously stable JIA-associated uveitis at 24 weeks after stopping adalimumab. The rate of recurrence of inflammation when stopping adalimumab was high, even when over 70% of the patients had over two years of controlled uveitis. Encouragingly, all patients who relapsed regained control upon restarting treatment. Collectively, these reasons contribute to a growing interest in developing evidence-based guidelines for reduction in adalimumab dose frequency once control of inflammation has been achieved. We propose to conduct a multicenter, parallel-treatment, observer-masked, randomized trial to generate an adalimumab regimen-response curve with rates of treatment failure in patients with controlled JIA-associated uveitis across a range of adalimumab injection frequencies. (Aim 1). 160 patients across eighteen clinical centers will be randomized to one of four regimens: 1) injections administered every 2 weeks (standard of care) 2) injections administered every 4 weeks 3) injections administered every 8 weeks 4) injections administered every 12 weeks. Additionally, we aim to identify the optimal range of drug exposure for adalimumab that maintains JIA-associated uveitis disease remission. (Aim 2). A comprehensive investigation of the clinical pharmacology of adalimumab will enhance our understanding of the association between drug levels and optimal immunosuppression and provide more effective but convenient dosing strategies for long- term disease control. Results from this clinical trial can be used to guide the counseling of patients and families who want to optimize treatment. Therefore, reduced-frequency dosing strategies for adalimumab may be a promising alternative strategy to stopping adalimumab.