What is the treatment for juvenile idiopathic arthritis?

Treatment of Juvenile Idiopathic Arthritis

Initial Treatment Strategy

The treatment of juvenile idiopathic arthritis depends critically on the subtype, with methotrexate as the cornerstone DMARD for polyarticular and oligoarticular disease, while systemic JIA requires IL-1 or IL-6 inhibitors as first-line biologic therapy. 1

Oligoarticular JIA (≤4 joints)

Initial therapy should combine scheduled NSAIDs with intraarticular glucocorticoid injections (IAGCs), reserving methotrexate for inadequate response. 1, 2

• A trial of scheduled NSAIDs is conditionally recommended as part of initial therapy (very low evidence). 1, 2
• IAGCs are strongly recommended as part of initial therapy (very low evidence). 1, 2
• Triamcinolone hexacetonide is strongly recommended over triamcinolone acetonide for intraarticular injections (moderate evidence). 1
• Oral glucocorticoids are conditionally recommended against as initial therapy (very low evidence). 1, 2

Escalation pathway for oligoarticular JIA:

• If inadequate response to NSAIDs and/or IAGCs after 8 weeks, conventional synthetic DMARDs are strongly recommended. 1, 2
• Methotrexate is conditionally recommended as the preferred agent over leflunomide, sulfasalazine, and hydroxychloroquine (low to very low evidence). 1, 2
• Biologic DMARDs are strongly recommended only after inadequate response to NSAIDs/IAGCs AND at least one conventional synthetic DMARD (very low evidence). 1, 2

Polyarticular JIA (≥5 joints)

Initial therapy with a DMARD is strongly recommended over NSAID monotherapy, with methotrexate as the preferred first-line agent. 1

Initial treatment approach:

• DMARD therapy is strongly recommended over NSAID monotherapy (moderate evidence). 1
• Methotrexate monotherapy is conditionally recommended over triple DMARD therapy (low evidence). 1
• Subcutaneous methotrexate is conditionally recommended over oral methotrexate for better bioavailability (very low evidence). 1, 2
• NSAIDs are conditionally recommended as adjunct therapy only (very low evidence). 1

Risk stratification determines initial biologic use:

• Without risk factors (RF negative, anti-CCP negative, no joint damage): Initial DMARD therapy is conditionally recommended over a biologic (low evidence). 1
• With risk factors (RF positive, anti-CCP positive, or joint damage): Initial DMARD therapy is still conditionally recommended, but initial biologic therapy may be preferred for patients with high-risk joint involvement (cervical spine, wrist, hip), high disease activity (cJADAS-10 >2.5), or high risk of disabling joint damage (low evidence). 1, 2

Escalation for moderate/high disease activity (cJADAS-10 >2.5):

• If inadequate response to methotrexate after 3 months (or 6-8 weeks if minimal response), adding a biologic to the original DMARD is conditionally recommended over changing to a second DMARD (low evidence). 1
• Combination therapy with a biologic (etanercept, adalimumab, golimumab, abatacept, or tocilizumab) plus DMARD is conditionally recommended over biologic monotherapy (very low to moderate evidence). 1
• Combination therapy with a DMARD is strongly recommended for infliximab (low evidence). 1

After first TNF inhibitor failure:

• Switching to a non-TNF biologic (tocilizumab or abatacept) is conditionally recommended over switching to a second TNF inhibitor (very low evidence). 1
• A second TNF inhibitor may be appropriate for patients with good initial response who develop secondary failure. 1

Even with low disease activity (cJADAS-10 ≤2.5 with ≥1 active joint):

• Escalating therapy is conditionally recommended over no escalation, including optimization of DMARD dose, trial of methotrexate if not done, or adding/changing biologic (very low evidence). 1

Systemic JIA

IL-1 or IL-6 inhibitors are strongly recommended over conventional synthetic DMARDs for inadequate response to NSAIDs and/or glucocorticoids, with conventional synthetic DMARDs strongly recommended against as initial monotherapy. 1, 2

Initial approach:

• NSAIDs are conditionally recommended as initial monotherapy (no preferred agent). 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

For inadequate response to NSAIDs/glucocorticoids:

• IL-1 inhibitors (anakinra, canakinumab) or IL-6 inhibitors (tocilizumab) are strongly recommended (no preferred agent between IL-1 and IL-6 inhibitors). 1, 2

For residual arthritis despite IL-1/IL-6 inhibitor therapy:

• Add conventional synthetic DMARD or switch to different biologic DMARD (no preferred agent). 1, 2
• Biologic DMARDs or conventional synthetic DMARDs are strongly recommended over long-term glucocorticoids. 1, 2

Enthesitis-Related Arthritis (ERA) and Sacroiliitis

NSAIDs are strongly recommended as first-line therapy, with TNF inhibitors for inadequate response, and sulfasalazine specifically recommended for ERA over methotrexate. 1, 3

For active enthesitis:

• NSAID treatment is strongly recommended over no NSAID treatment (very low evidence). 1, 3
• For inadequate response to NSAIDs, TNF inhibitors are conditionally recommended over methotrexate or sulfasalazine (very low evidence). 1, 3
• Sulfasalazine is specifically recommended for enthesitis-related arthritis following adequate NSAID trial in patients with moderate or high disease activity (moderate evidence). 3
• Methotrexate monotherapy is strongly recommended against for enthesitis (very low evidence). 1

For active sacroiliitis:

• NSAID treatment is strongly recommended over no NSAID treatment (very low evidence). 1
• For inadequate response to NSAIDs, adding TNF inhibitor is strongly recommended over continued NSAID monotherapy (low evidence). 1
• Sulfasalazine is conditionally recommended for patients with contraindications to or failure of TNF inhibitor (low evidence). 1

Glucocorticoid Use

Bridging therapy with limited oral glucocorticoids (<3 months) is conditionally recommended during initiation/escalation in moderate/high disease activity, but chronic low-dose glucocorticoids are strongly recommended against. 1

• Bridging oral glucocorticoids (<3 months) during initiation or escalation of therapy in patients with high or moderate disease activity is conditionally recommended (very low evidence). 1
• Bridging oral glucocorticoids in patients with low disease activity is conditionally recommended against (very low evidence). 1
• Chronic low-dose glucocorticoids are strongly recommended against, irrespective of risk factors or disease activity. 1, 3

Adjunctive Therapies

Physical therapy and/or occupational therapy are conditionally recommended for patients who have or are at risk of functional limitations. 1

• Physical therapy is conditionally recommended for patients with polyarthritis, sacroiliitis, or enthesitis who have or are at risk of functional limitations (low to very low evidence). 1, 2
• Occupational therapy is conditionally recommended for patients with polyarthritis who have or are at risk of functional limitations (very low evidence). 1, 2

Disease Activity Monitoring and Treat-to-Target

Use validated disease activity measures (cJADAS-10) to facilitate treat-to-target approaches, with low disease activity defined as cJADAS-10 ≤2.5 with ≥1 active joint. 1, 2, 4

• The clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10) should be used to define disease activity. 1, 2
• Low disease activity: cJADAS-10 ≤2.5 with ≥1 active joint. 1, 2
• Moderate/high disease activity: cJADAS-10 >2.5. 1, 2
• An adequate trial of methotrexate is 3 months, but changing or adding therapy may be appropriate after 6-8 weeks if minimal response. 1, 2

FDA-Approved Biologic Dosing

Adalimumab (Humira) is FDA-approved for polyarticular JIA in patients ≥2 years, with weight-based dosing. 5

• 10 kg to <15 kg: 10 mg every other week. 5
• 15 kg to <30 kg: 20 mg every other week. 5
• ≥30 kg: 40 mg every other week. 5
• Can be used alone or in combination with methotrexate. 5

Critical Pitfalls to Avoid

• Do not use NSAID monotherapy as initial therapy for polyarticular JIA—DMARD therapy is strongly recommended (moderate evidence). 1
• Do not delay DMARD initiation while waiting for NSAID response in polyarticular disease—early aggressive treatment prevents permanent joint damage. 2, 4
• Do not use methotrexate as automatic first-line in enthesitis-related arthritis—sulfasalazine has specific evidence for this subtype. 3
• Do not use conventional synthetic DMARDs as initial monotherapy for systemic JIA—they are strongly recommended against. 1, 2
• Do not continue NSAID monotherapy beyond 2 months in patients with active arthritis. 3
• Do not use chronic low-dose oral glucocorticoids—they are strongly recommended against irrespective of disease activity. 1, 3
• Do not dismiss insidious onset joint pain as simple overuse without ruling out inflammatory arthritis—early DMARD therapy is crucial to prevent permanent joint damage. 4
• Do not use oral glucocorticoids as initial therapy for oligoarticular JIA—they are conditionally recommended against. 1, 2, 4