The monoclonal antibody adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. However, data has been scarce regarding the effects of discontinuing adalimumab after control of the disease has been achieved. Patients and families are motivated to discontinue treatment because of the high cost of treatment, the burden of taking an injectable drug and risk of adverse events.
In a study published last January in The Lancet, UCSF researchers sought to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis by conducting a multicenter, randomized-controlled trial at twenty ophthalmology and rheumatology clinics across the U.S., the United Kingdom, and Australia.
The researchers found that discontinuing adalimumab led to higher rates of recurrence of uveitis, arthritis, or both in patients with previously controlled juvenile idiopathic arthritis-associated uveitis. However, all patients who had recurrence of inflammation successfully regained control of inflammation by the end of the 48-week study period after restarting adalimumab.
“Results from this clinical trial can be used to guide counselling of patients and families who are considering discontinuing adalimumab for juvenile idiopathic arthritis-associated uveitis,” said trial principal investigator Nisha R. Acharya, MD, MS, professor of Ophthalmology and director of the UCSF Uveitis and Ocular Inflammatory Disease Service. “If an attempt is made to withdraw therapy, patients should be closely monitored for recurrence, especially during the first 6 months, given the high risk of recurrence. However, it is reassuring that disease control can be regained after restarting treatment.”
The ADJUST trial (Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial), was an NIH-funded, double-masked, randomized, placebo-controlled trial of 87 patients who were least 2 years old and had controlled arthritis and uveitis for at least 1 year on adalimumab. The patients were randomly assigned in a 1:1 ratio to receive adalimumab or placebo, administered subcutaneously every 2 weeks until the 48-week visit or treatment failure.
The primary outcome was the time to treatment failure, defined by recurrence of uveitis or arthritis. Unmasking occurred at treatment failure, or at the 48-week visit if treatment failure did not occur. All ophthalmology and rheumatology assessments were performed before unmasking. Patients who experienced treatment failure were offered open-label adalimumab.
“Close monitoring of patients for relapse and prompt restarting of adalimumab following treatment failure probably contributed to preventing vision loss,” said Acharya.
The researchers suggest that recommendations from the American College of Rheumatology and the Single Hub and Access Point for Pediatric Rheumatology in Europe that withdrawal of treatment can be attempted after two years of control, should be considered with caution.
In future analyses, the research team plans to investigate whether clinical characteristics or laboratory biomarkers can be used to predict successful discontinuation of adalimumab.
Additional Authors: Athimalaipet V. Ramanan FMedSci, Alison B. Coyne, MPH, Kathryn L. Dudum, MPH, Elia M. Rubio, MAS, Sydney M. Woods, BS, Catherine M. Guly, MBChB, Elena Moraitis, PhD, Harry J.D. Petrushkin, FRCOphth, Kate Armon, DM, Narman Puvanachandra, FRCOphth, Jessy T. Choi FRCOphth, Daniel P. Hawley, BMBS, and Benjamin F. Arnold, PhD.
Funding: US National Institutes of Health (National Eye Institute).
About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is a top-ranked specialty hospital, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland; Langley Porter Psychiatric Hospital; UCSF Benioff Children’s Physicians; and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit http://www.ucsfhealth.org/. Follow UCSF Health on Facebook, Threads or LinkedIn.
