The Canadian Rheumatology Association (CRA) released guidelines for the screening, monitoring, and treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. The full report has been published in The Journal of Rheumatology.1
Studies evaluating systemic treatments in JIA-associated uveitis are limited despite a consistent treatment approach and regulatory body approval for new therapies. The American College of Rheumatology (ACR)/Arthritis Foundation (AF) guidelines provide opportunities for education and lobbying to local, provincial, and federal regulatory agencies and payers to better access breakthrough therapies. The availability of expert consensus standards for monitoring and managing JIA-associated uveitis in Canada will help in standardizing the highest standard of care across the country.
A working group including pediatric rheumatologists, ophthalmologists skilled in the care of uveitis, and parent/patient participation developed the guidelines using the Grading of Recommendations Assessment and Development and Evaluation (GRADE)-ADOLOPMENT methodology2 while considering Canadian contextual variations, such as patient preferences, cost/resource considerations, and the feasibility of implementation.
The ADOLOPMENT approach offers a practical framework for building on prior work and minimizing duplication. Following the adoption, adaptation, or de novo implementation of recommendations, the formulation of evidence-to-decision tables for each recommendation offers a transparent procedure for evaluating the available evidence and context-specific considerations.
According to the authors, this is first set of Canadian guidelines for JIA-associated uveitis and the first CRA guidelines to use the GRADE-ADOLOPMENT system.
The population, intervention, comparison, and outcomes (PICO) format was used to formulate clinical questions. Systematic literature reviews were conducted to address each PICO question, and the quality of evidence was graded as high, moderate, low, or very low. The quality of evidence was low for all PICO questions. Consensus on both the strong and conditional recommendations was achieved by an 80% level of agreement. However, all adapted and de novo recommendations had a 100% level of agreement.
Recommendations for Screening, Monitoring, and Treatment of JIA-Associated Uveitis
Adapted recommendation for children and adolescents with JIA at high risk of developing uveitis, including those with oligoarthritis, polyarthritis (rheumatoid factor-negative), psoriatic arthritis, or undifferentiated arthritis with antinuclear antibody (ANA) positivity, younger than 7 years at JIA onset, and have a JIA duration of 4 years or fewer:
- The panel conditionally recommended that high-risk individuals undergo ophthalmic screening at least once every 3 months during the first 4 years of the disease.
- Following diagnosis, patients should be screened as early as possible (within the first 1-3 months if asymptomatic).
Adopted recommendations forchildren and adolescents with JIA and controlled uveitis:
- For patients undergoing tapering or discontinuation of glucocorticoids, the panel strongly recommended ophthalmic monitoring within a month after each topical glucocorticoid change vs monitoring less frequently.
- For patients receiving stable therapy, ophthalmic monitoring at least every 3 months was strongly recommended vs monitoring less frequently.
- For patients undergoing tapering or discontinuation of systemic therapy, ophthalmic monitoring was strongly recommended within 2 months of changing systemic therapy vs monitoring less frequently.
Adopted recommendations forchildren and adolescents with JIA and active chronic anterior uveitis (CAU):
- The panel conditionally recommended the use of prednisolone acetate 1% topical drops vs difluprednate topical drops.
- The panel also conditionally recommended the addition or increase of topical glucocorticoids for short-term control vs adding systemic glucocorticoids.
Adopted recommendations for children and adolescents with JIA who develop new CAU activity (no prior uveitis or loss of control of previously controlled uveitis) despite stable systemic therapy:
- The panel conditionally recommended the use of topical glucocorticoids prior to changing/escalating systemic therapy vs immediately changing/escalating systemic therapy.
Adapted recommendations for children and adolescents with JIA and CAU requiring more than 2 drops/day of prednisolone acetate 1% for uveitis control:
- For patients not receiving systemic therapy, the addition of systemic therapy for tapering topical glucocorticoids was conditionally recommended vs not adding systemic therapy and maintaining topical glucocorticoids only.
- The panel conditionally recommended to change or escalate systemic therapy vs maintaining current systemic therapy among patients receiving systemic therapy and requiring more than 2 drops/day of prednisolone acetate 1% (or equivalent) for at least 3 months.
Disease-Modifying Antirheumatic Drugs (DMARDs) and Biologics
De novo recommendations for children and adolescents with JIA and active CAU:
- Methotrexate was conditionally recommended as a first-line DMARD for patients in whom systemic treatment has been initiated for uveitis.
Adopted recommendations for children and adolescents with JIA and active CAU:
- The panel conditionally recommended tumor necrosis factor inhibitors (TNFis) vs etanercept in patients in whom monoclonal antibody therapy or a TNFi has been initiated.
- Switching to a new monoclonal antibody TNFi was conditionally recommended vs to a biologic in a different class in patients who with an inadequate response to the first monoclonal antibody TNFi at above a standard dose and/or frequency.
Adapted recommendations for children and adolescents with JIA and active CAU:
- The panel conditionally recommended the optimization of the dose and/or frequency of TNFi vs switching to another monoclonal antibody TNFi in patients with an inadequate response to 1 monoclonal antibody TNFi.
- The panel also conditionally recommended to use abatacept or tocilizumab as a biologic DMARD vs a nonbiologic DMARD (mycophenolate, leflunomide, or cyclosporine) in patients with an inadequate response to methotrexate and 2 monoclonal antibody TNFis at an optimized dose.
Education About the Treatment of Acute Anterior Uveitis (AAU)
Adopted recommendations for children and adolescents with spondyloarthritis:
- To decrease treatment delays, symptom duration, or uveitis complications, the panel strongly recommended education regarding the warning signs of AAU.
- The panel conditionally recommended against switching of systemic immunosuppressive therapy immediately in favor of treatment with topical glucocorticoids in patients with well-controlled disease receiving systemic immunosuppressive therapy who develop an isolated short-lived episode of AAU.
Taper Therapy for Uveitis
Adopted recommendations for children and adolescents with JIA and CAU that is controlled with systemic therapy but continue to receive 1 to 2 drops/day of prednisolone acetate 1% (or equivalent):
- The panel strongly recommended the tapering of topical glucocorticoids first vs tapering of systemic therapy.
Adopted recommendations for children and adolescents with JIA and uveitis that is well-controlled with DMARD and biologic systemic therapy only:
- The panel conditionally recommended at least 2 years of well-controlled disease before tapering therapy is initiated.
Overall, the authors of the paper concluded, “[W]e recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines with all supporting materials that were developed using a transparent process is available. The CRA JIA-associated CAU guidelines provide Canadian contextual considerations for optimal shared uveitis care, supporting equitable access to care and treatment.”
- Berard R, Ng HY, Human A, et al. Canadian Rheumatology Association recommendations for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. J Rheumatol. 2023;50(3):390-399. doi:10.3899/jrheum.220261
- Schünemann HJ, Wiercioch W, Brozek J, et al. GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT. J Clin Epidemiol. 2017;81:101-110. doi:10.1016/j.jclinepi.2016.09.009