Adalimumab dose adjustment for pediatric uveitis treatment (adapt) trial

The National Institutes of Health National Eye Institute awarded the Regents of the University of California, San Francisco a $3.382 million cooperative agreement on May 1, 2026, under the Vision Research program (CFDA 93.867) to conduct the Adalimumab Dose Adjustment for Pediatric Uveitis Treatment (ADAPT) Trial.

The trial is a multicenter, observer-masked, randomized controlled study designed to generate an adalimumab regimen-response curve and establish evidence-based guidelines for reducing adalimumab dose frequency in patients with controlled juvenile idiopathic arthritis (JIA)-associated uveitis. The study will randomize 160 patients across eighteen clinical centers to one of four adalimumab injection frequency regimens, measuring rates of treatment failure across the range of dosing schedules. This work builds on prior NEI-funded research (the ADJUST trial) showing 64% cumulative failure at 24 weeks after stopping adalimumab in previously stable patients, but full inflammation control upon restarting treatment.

Work is performed in San Francisco, California, with a period of performance from May 1, 2026, through April 30, 2030. The underlying clinical need addresses the high cost and serious adverse event risk associated with long-term adalimumab therapy—opportunistic infections, malignancy, and substantial financial burden—while balancing the high recurrence of uveitis inflammation when treatment is discontinued entirely.

Abstract

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.