The American College of Rheumatology (ACR) recently released updated guidelines for the pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on the treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome (MAS). The full report has been published in Arthritis & Rheumatology.1 

Overall, the updated guidelines included the treatment of active oligoarthritis, active TMJ arthritis, and systemic JIA with and without MAS with nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs), including biologic DMARDs (bDMARDs) and conventional synthetic DMARDs (csDMARDs). Recommendations for tapering and discontinuing treatment for inactive JIA were also included.

The current guideline complements the 2019 ACR JIA and uveitis guidelines for polyarthritis, sacroiliitis, enthesitis, and uveitis.2,3


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The patient/population, intervention, comparison, and outcomes (PICO) format was used to formulate clinical questions. Systematic literature reviews were conducted to address each PICO question. Using the Grading of Recommendations Assessment and Development and Evaluation (GRADE) methodology, recommendations were developed based on the best available evidence for commonly encountered clinical scenarios. Before final voting, a panel of young adults with JIA and caregivers of children with JIA reviewed the evidence report. Consensus on both the strong and conditional recommendations was achieved by a 70% level of agreement by the voting panel.

A total of 25 recommendations were developed, of which 9 were for oligoarthritis, 7 for TMJ arthritis, 6 for systemic JIA without MAS, and 3 for systemic JIA without MAS. Two recommendations on tapering medications were developed for inactive systemic JIA with or without MAS.

The majority of the recommendations were supported by very low-quality evidence.

Active Oligoarthritis

Strong Recommendations
1. As part of initial therapy, intra-articular glucocorticoids (IAGCs) are recommended.2. Triamcinolone hexacetonide is recommended as the preferred medication.3. For an inadequate response to scheduled NSAIDs and/or IAGC, csDMARDs are recommended.4. For an inadequate response to or intolerance of NSAIDs and/or IAGCs and at least 1 csDMARD, bDMARDs are recommended. No specific bDMARD is preferred.
Conditional Recommendations
1.     As part of initial therapy, a trial of scheduled NSAIDs are recommended.2.     Oral glucocorticoids are not recommended as part of initial therapy.3. Methotrexate (MTX) is recommended as a preferred medication over leflunomide, sulfasalazine, and hydroxychloroquine, in the same order.4.     Treatment decisions must be guided by considering the risk factors for poor outcomes, such as involvement of ankle, wrist, hip, sacroiliac joint, and/or TMJ, presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, symmetric disease.5.     Treatment decisions must be guided by using validated disease activity measures, especially for treat-to-target approaches.

Active TMJ Arthritis

Strong Recommendation
1.     For an inadequate response to or intolerance of NSAIDs and/or IAGCs, csDMARDs are recommended.
Conditional Recommendations
1.     As part of initial therapy, a trial of scheduled NSAIDs are recommended.2.     As part of initial therapy, IAGCs are recommended. No specific IAGC is preferred.3.     Oral glucocorticoids are not recommended as part of initial therapy.4.     Methotrexate (MTX) is recommended over leflunomide.5.     For an inadequate response to or intolerance of NSAIDs and/or IAGCs and at least 1 csDMARD, bDMARDs are recommended. No specific bDMARD is preferred.6.     Treatment decisions must be guided by considering poor prognostic features, such as involvement of ankle, wrist, hip, sacroiliac joint, and/or TMJ, presence of erosive disease or enthesitis, delay in diagnosis, elevated levels of inflammation markers, and symmetric disease.

Systemic JIA Without MAS

Strong Recommendations
1.     csDMARDs are not recommended for initial monotherapy.2. For an inadequate response to or intolerance of NSAIDs and/or glucocorticoids, bDMARDs (interleukin [IL]-1 and IL-6 inhibitors) are recommended over a single or combination of csDMARDs.3. For residual arthritis and incomplete response to IL-1 and/or IL-6 inhibitors, bDMARDs or csDMARDs are recommended over long-term glucocorticoids. No specific bDMARD/csDMARDs are preferred.
Conditional Recommendations
1. NSAIDs are recommended for initial monotherapy.2.     Oral glucocorticoids are not recommended for initial monotherapy.3. bDMARDs (IL-1 and IL-6 inhibitors) are recommended for initial monotherapy. No specific bDMARD is preferred.

Systemic JIA With MAS

Strong Recommendation
1.     For residual arthritis and incomplete response to IL-1 and/or IL-6 inhibitors, bDMARDs or csDMARDs are recommended over long-term glucocorticoids. No specific bDMARD/csDMARD is preferred.
Conditional Recommendations
1. To achieve inactive disease and resolution of MAS, IL-1 and IL-6 inhibitors are recommended over calcineurin inhibitors.2. As part of initial therapy, glucocorticoids are recommended. No specific glucocorticoid is preferred.

Systemic JIA With Inactive Disease

Strong Recommendation
1.     After inactive disease has been achieved, it is recommended to taper and discontinue glucocorticoid use.
Conditional Recommendation
1.     After inactive disease has been achieved, it is recommended to taper and discontinue bDMARD use.

Overall, the authors concluded, “[These guidelines serve] as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline.”

References

1.     Onel KB, Horton DB, Lovell DJ, et al. 2021 American College of Rheumatology Guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2022;74(4):521-537. doi:10.1002/art.42037

2.     Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Rheumatol. 2019;71(6):846-863. doi:10.1002/art.40884

3.     Angeles-Han ST, Ringold S, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Rheumatol. 2019;71(6):864-877. doi:10.1002/art.40885