What is the initial treatment for juvenile rheumatoid arthritis (JRA)?

Initial Treatment for Juvenile Rheumatoid Arthritis (JRA)

The initial treatment for JRA depends on the subtype: for oligoarticular JIA, start with scheduled NSAIDs and/or intraarticular glucocorticoid injections (IAGCs); for polyarticular JIA, initiate DMARD therapy (methotrexate) strongly preferred over NSAID monotherapy; for systemic JIA without macrophage activation syndrome, NSAIDs are conditionally recommended as initial monotherapy. 1, 2

Treatment Algorithm by JIA Subtype

Oligoarticular JIA (≤4 joints in first 6 months)

• First-line therapy: A trial of scheduled NSAIDs is conditionally recommended as part of initial therapy 1, 2
• Intraarticular glucocorticoid injections (IAGCs) are strongly recommended as part of initial therapy 1, 2
• Oral glucocorticoids are conditionally recommended against as part of initial therapy 1, 2
• If inadequate response to NSAIDs and/or IAGCs, conventional synthetic DMARDs (csDMARDs) are strongly recommended, with methotrexate conditionally recommended as the preferred agent 1, 2
• Biologic DMARDs are strongly recommended if there is inadequate response to or intolerance of NSAIDs and/or IAGCs and at least one csDMARD 1, 2

Polyarticular JIA (≥5 joints)

• Initial therapy with a DMARD is strongly recommended over NSAID monotherapy 1, 2
• Methotrexate monotherapy is conditionally recommended as initial therapy over triple DMARD therapy 1, 2
• Subcutaneous methotrexate is conditionally recommended over oral methotrexate 2
• NSAIDs may be added as adjunctive therapy for symptom control 2, 3

Risk stratification for polyarticular JIA:

• Patients WITHOUT risk factors (negative RF, negative anti-CCP, no joint damage): Initial therapy with a DMARD is conditionally recommended over a biologic 1, 2
• Patients WITH risk factors (positive RF, positive anti-CCP, or joint damage): Initial therapy with a DMARD is conditionally recommended over a biologic, though initial biologic therapy may be considered for patients with high-risk joint involvement (cervical spine, wrist, hip), high disease activity, or those at high risk of disabling joint damage 1, 2

Systemic JIA (without Macrophage Activation Syndrome)

• NSAIDs are conditionally recommended as initial monotherapy 1, 2
• Oral glucocorticoids are conditionally recommended against as initial monotherapy 1, 2
• Conventional synthetic DMARDs are strongly recommended against as initial monotherapy 1, 2
• IL-1 and IL-6 inhibitors are strongly recommended over conventional synthetic DMARDs for inadequate response to or intolerance of NSAIDs and/or glucocorticoids 1, 2

NSAID Selection and Dosing

• Naproxen and ibuprofen are the most commonly prescribed NSAIDs for JIA, having largely supplanted salicylates 4, 5
• Recent evidence suggests ibuprofen has a better safety profile than naproxen (no adverse events vs. 12 adverse events requiring discontinuation, p=0.004), though efficacy is similar 4
• Treatment duration >28 days is associated with significantly higher odds for complete response (p=0.021) 4
• NSAIDs should be recognized as bridging therapy until more definitive treatment (IAGCs or DMARDs) is achieved 4

Methotrexate Dosing (FDA-Approved)

For polyarticular-course JRA:

• Recommended starting dose is 10 mg/m² given once weekly 6
• Dosages may be adjusted gradually to achieve optimal response 6
• Limited experience shows significant increase in serious toxic reactions at doses >20 mg/week in adults 6
• Children receiving 20-30 mg/m²/week may have better absorption and fewer GI side effects if administered intramuscularly or subcutaneously 6
• An adequate trial of methotrexate is 3 months, though changing or adding therapy may be appropriate if no or minimal response after 6-8 weeks 1, 2
• Therapeutic response usually begins within 3-6 weeks, with continued improvement for another 12 weeks or more 6

Critical Pitfalls to Avoid

• Never use chronic low-dose oral glucocorticoids regardless of disease activity, due to growth suppression and osteoporosis 2, 3
• Do not delay DMARD initiation in polyarticular disease, as early aggressive treatment prevents permanent joint damage 2, 3
• Do not dismiss insidious onset joint pain as simple overuse without ruling out inflammatory arthritis, as early DMARD therapy is crucial to prevent permanent joint damage 7
• Prolonged oral glucocorticoids should not be used as monotherapy; they are only for short-term bridging (<3 months) 1, 7
• Do not use preserved formulations of methotrexate for intrathecal or high-dose therapy due to benzyl alcohol content 6

Adjunctive Therapies

• Physical therapy and/or occupational therapy are conditionally recommended for children with JIA and polyarthritis who have or are at risk of functional limitations 1, 2, 3
• Intraarticular triamcinolone hexacetonide is strongly preferred over triamcinolone acetonide for accessible joints 2, 3
• Shared decision-making with patients and caregivers regarding treatment choices is essential throughout the disease course 1, 2, 3

Monitoring and Treatment Targets

• Use validated disease activity measures (cJADAS-10) to guide a treat-to-target approach 2, 3
• Target low disease activity (cJADAS-10 ≤2.5) or inactive disease 2, 3
• Assessment of hematologic, hepatic, renal, and pulmonary function should be made before beginning, periodically during, and before reinstituting methotrexate therapy 6
• Early treatment initiation is critical to improve long-term outcomes and prevent permanent joint damage 2