Treatment Recommendations for Juvenile Idiopathic Arthritis (JIA)

Initial Treatment Approach

• The American College of Rheumatology recommends initial therapy with NSAIDs and/or intraarticular glucocorticoid injections (IAGCs), followed by methotrexate as first-line DMARD therapy, with biologic DMARDs reserved for inadequate response to conventional therapy 1, 2
• For children with oligoarticular JIA, a trial of scheduled NSAIDs is conditionally recommended as part of initial therapy, with intraarticular glucocorticoid injections (IAGCs) strongly recommended as part of initial therapy 1
• Oral glucocorticoids are conditionally recommended against as part of initial therapy for children with oligoarticular JIA 1
• Conventional synthetic DMARDs (csDMARDs) are strongly recommended if there is inadequate response to NSAIDs and/or IAGCs for children with oligoarticular JIA, with methotrexate conditionally recommended as the preferred agent 1
• Biologic DMARDs are strongly recommended if there is inadequate response to or intolerance of NSAIDs and/or IAGCs and at least one csDMARD for children with oligoarticular JIA 1
• For children with polyarticular JIA, initial therapy with a DMARD is strongly recommended over NSAID monotherapy, with methotrexate monotherapy conditionally recommended as initial therapy 2
• For patients with polyarticular JIA without risk factors, initial therapy with a DMARD is conditionally recommended over a biologic 2
• For patients with polyarticular JIA with risk factors, initial therapy with a DMARD is conditionally recommended over a biologic, though initial biologic therapy may be considered for patients with high-risk joints involvement, high disease activity, or at high risk of disabling joint damage 2
• Subcutaneous methotrexate is conditionally recommended over oral methotrexate for children with polyarticular JIA 3
• For children with systemic JIA without macrophage activation syndrome (MAS), NSAIDs are conditionally recommended as initial monotherapy, with oral glucocorticoids conditionally recommended against as initial monotherapy 4
• Conventional synthetic DMARDs are strongly recommended against as initial monotherapy for children with systemic JIA without MAS, with IL-1 and IL-6 inhibitors strongly recommended over conventional synthetic DMARDs for inadequate response to or intolerance of NSAIDs and/or glucocorticoids 4

Subsequent Treatment Recommendations

• For children with oligoarticular JIA and inadequate response to NSAIDs and/or IAGCs, methotrexate is conditionally recommended as the preferred csDMARD, with biologic DMARDs strongly recommended if there is inadequate response to at least one csDMARD 1
• For children with polyarticular JIA and low disease activity, escalating therapy is conditionally recommended over no escalation, with options including intraarticular glucocorticoid injections, optimization of DMARD dose, trial of methotrexate, and adding or changing biologic 2
• For children with polyarticular JIA and moderate/high disease activity, adding a biologic to original DMARD is conditionally recommended over changing to a second DMARD or triple DMARD therapy, with switching to a non-TNF biologic conditionally recommended over switching to a second TNF inhibitor 2
• For children with systemic JIA and residual arthritis and incomplete response to IL-1 and/or IL-6 inhibitors, biologic DMARDs or csDMARDs are strongly recommended over long-term glucocorticoids 4

Monitoring and Treatment Targets

• The use of validated disease activity measures is conditionally recommended to guide treatment decisions, especially to facilitate treat-to-target approaches, with consideration of risk factors for poor outcome to guide treatment decisions 1
• An adequate trial of methotrexate is considered to be 3 months, with changing or adding therapy appropriate if no or minimal response is observed after 6-8 weeks 2
• Early treatment initiation is critical to improve long-term outcomes and prevent permanent joint damage 5

Continuation of Inflectra for Juvenile Idiopathic Arthritis

Treatment Rationale

• For patients with JIA and low disease activity (cJADAS10 ≤ 2.5), continuation of effective therapy is conditionally recommended to maintain disease control, as recommended by the American College of Rheumatology 6
• The patient has a cJADAS 10 score of 1, indicating low disease activity that is well-controlled on the current regimen, supporting the continuation of therapy 6

Methotrexate Considerations

• The patient stopped methotrexate in 2020 due to persistent liver function test elevation, which is a valid contraindication, according to the American College of Rheumatology 7
• While combination therapy with methotrexate is often recommended to reduce the formation of neutralizing antibodies to infliximab, monotherapy can be appropriate when methotrexate is contraindicated, as supported by the American College of Rheumatology 7

Tocilizumab Use in Polyarticular Juvenile Idiopathic Arthritis

Guideline Recommendations

• The American College of Rheumatology strongly supports the use of tocilizumab in patients with polyarticular juvenile idiopathic arthritis who have had an inadequate response to methotrexate or are unable to tolerate methotrexate, with biologic DMARDs conditionally recommended in combination with a DMARD (low quality evidence for tocilizumab specifically) 8, 9
• The American College of Rheumatology conditionally recommends adding a biologic to the original DMARD for patients with moderate/high disease activity receiving DMARD monotherapy, over changing to a second DMARD (low quality evidence) 10

Treatment Considerations

• For patients failing their first biologic, the American College of Rheumatology conditionally recommends switching to a non-TNF biologic (tocilizumab or abatacept) over switching to a second TNF inhibitor (very low quality evidence) 10
• The American College of Rheumatology recognizes that escalation of therapy may include optimization of DMARD dose, trial of methotrexate if not done, and adding or changing biologic 10

Patient Selection

• The American College of Rheumatology recommends tocilizumab for patients with polyarticular juvenile idiopathic arthritis who have active disease with involvement of multiple joints, and who have had an inadequate response to methotrexate or are unable to tolerate methotrexate 8, 11
• The American College of Rheumatology conditionally recommends tocilizumab for patients with chronic prednisone use, indicating failure to achieve adequate disease control with glucocorticoids alone 8, 9

Treatment of Juvenile Idiopathic Arthritis

Initial Treatment Strategy

• The American College of Rheumatology recommends 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 12, 13

Oligoarticular JIA

• Triamcinolone hexacetonide is strongly recommended over triamcinolone acetonide for intraarticular injections in patients with oligoarticular JIA (moderate evidence) 12, 13

Polyarticular JIA

• The American College of Rheumatology strongly recommends DMARD therapy over NSAID monotherapy, with methotrexate as the preferred first-line agent for patients with polyarticular JIA (moderate evidence) 12, 14
• Methotrexate monotherapy is conditionally recommended over triple DMARD therapy for patients with polyarticular JIA (low evidence) 12, 14
• Combination therapy with a biologic plus DMARD is conditionally recommended over biologic monotherapy for patients with polyarticular JIA (very low to moderate evidence) 12, 15

Systemic JIA

• IL-1 inhibitors or IL-6 inhibitors are strongly recommended over conventional synthetic DMARDs for inadequate response to NSAIDs and/or glucocorticoids in patients with systemic JIA (no preferred agent between IL-1 and IL-6 inhibitors) 13

Glucocorticoid Use

• 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) 12, 15
• Chronic low-dose glucocorticoids are strongly recommended against, irrespective of risk factors or disease activity 12, 15

Adjunctive Therapies

• Physical therapy and/or occupational therapy are conditionally recommended for patients who have or are at risk of functional limitations (low to very low evidence) 12, 16

Disease Activity Monitoring and Treat-to-Target

• The clinical Juvenile Arthritis Disease Activity Score based on 10 joints (cJADAS-10) should be used to define disease activity, with low disease activity defined as cJADAS-10 ≤2.5 with ≥1 active joint 12, 14
• Moderate/high disease activity is defined as cJADAS-10 >2.5 12, 14

Critical Pitfalls to Avoid

• Do not use NSAID monotherapy as initial therapy for polyarticular JIA—DMARD therapy is strongly recommended (moderate evidence) 12, 14
• Do not use conventional synthetic DMARDs as initial monotherapy for systemic JIA—they are strongly recommended against 13
• Do not use chronic low-dose oral glucocorticoids—they are strongly recommended against irrespective of disease activity 12, 15