What are the initial and subsequent treatment recommendations for Juvenile Idiopathic Arthritis (JIA)?

Treatment Recommendations for Juvenile Idiopathic Arthritis (JIA)

For children with JIA, initial therapy should include 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

Initial Treatment Approach by JIA Subtype

Oligoarticular JIA

• A trial of scheduled NSAIDs is conditionally recommended as part of initial therapy 1
• Intraarticular glucocorticoid injections (IAGCs) are strongly recommended as part of initial therapy, with triamcinolone hexacetonide as the preferred agent 1
• Oral glucocorticoids are conditionally recommended against as part of initial therapy 1
• Conventional synthetic DMARDs (csDMARDs) are strongly recommended if there is inadequate response to NSAIDs and/or IAGCs, with methotrexate conditionally recommended as the preferred agent over leflunomide, sulfasalazine, and hydroxychloroquine 1
• Biologic DMARDs are strongly recommended if there is inadequate response to or intolerance of NSAIDs and/or IAGCs and at least one csDMARD 1

Polyarticular JIA

• Initial therapy with a DMARD is strongly recommended over NSAID monotherapy 1
• Methotrexate monotherapy is conditionally recommended as initial therapy over triple DMARD therapy 1
• For patients without risk factors (negative RF, negative anti-CCP, no joint damage), initial therapy with a DMARD is conditionally recommended over a biologic 1
• For patients 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 1
• Subcutaneous methotrexate is conditionally recommended over oral methotrexate 1

Systemic JIA without Macrophage Activation Syndrome (MAS)

• NSAIDs are conditionally recommended as initial monotherapy 1
• Oral glucocorticoids are conditionally recommended against as initial monotherapy 1
• Conventional synthetic DMARDs are strongly recommended against as initial monotherapy 1
• 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

Sacroiliitis

• Treatment with an NSAID is strongly recommended over no treatment 1
• For active sacroiliitis despite NSAID treatment, adding a TNF inhibitor is strongly recommended over continued NSAID monotherapy 1
• Methotrexate monotherapy is strongly recommended against 1

Subsequent Treatment Recommendations

For Inadequate Response to Initial Therapy

Oligoarticular JIA

• If inadequate response to NSAIDs and/or IAGCs, add methotrexate as the preferred csDMARD 1
• If inadequate response to at least one csDMARD, biologic DMARDs are strongly recommended 1

Polyarticular JIA

• For low disease activity (cJADAS-10 ≤2.5 and ≥1 active joint), escalating therapy is conditionally recommended over no escalation 1

• Escalation options include: intraarticular glucocorticoid injections, optimization of DMARD dose, trial of methotrexate if not done, and adding or changing biologic 1

• For moderate/high disease activity (cJADAS-10 >2.5):

  • If on DMARD monotherapy: adding a biologic to original DMARD is conditionally recommended over changing to a second DMARD or triple DMARD therapy 1
  • If on first TNF inhibitor (± DMARD): switching to a non-TNF biologic (tocilizumab or abatacept) is conditionally recommended over switching to a second TNF inhibitor 1
  • A second TNF inhibitor may be appropriate for patients with good initial response to their first TNF inhibitor (secondary failure) 1
  • If on second biologic: using TNF inhibitor, abatacept, or tocilizumab (depending on prior biologics received) is conditionally recommended over rituximab 1

Systemic JIA

• For residual arthritis and incomplete response to IL-1 and/or IL-6 inhibitors, biologic DMARDs or csDMARDs are strongly recommended over long-term glucocorticoids 1

Medication Dosing

Biologics for JIA

• Adalimumab (for patients 2 years and older with polyarticular JIA):

  • 10-15 kg: 10 mg every other week
  • 15-30 kg: 20 mg every other week
  • ≥30 kg: 40 mg every other week 2

• Etanercept (for polyarticular JIA):

  • 0.4 mg/kg (maximum 25 mg per dose) subcutaneously twice weekly 3

Adjunctive Therapies

• Intraarticular glucocorticoids are conditionally recommended as adjunct therapy 1
• Triamcinolone hexacetonide is strongly recommended over triamcinolone acetonide for intraarticular glucocorticoid injections 1
• Bridging therapy with a limited course of oral glucocorticoid (<3 months) during initiation or escalation of therapy is conditionally recommended in patients with high or moderate disease activity 1
• Chronic low-dose glucocorticoid therapy is strongly recommended against, irrespective of risk factors or disease activity 1
• Physical therapy and occupational therapy are conditionally recommended for patients who have or are at risk of functional limitations 1

Monitoring and Treatment Targets

• Use of validated disease activity measures is conditionally recommended to guide treatment decisions, especially to facilitate treat-to-target approaches 1
• Consider risk factors for poor outcome (e.g., involvement of ankle, wrist, hip, sacroiliac joint, and/or TMJ, presence of erosive disease or enthesitis, delay in diagnosis, elevated inflammation markers, symmetric disease) to guide treatment decisions 1
• An adequate trial of methotrexate is considered to be 3 months. If no or minimal response is observed after 6-8 weeks, changing or adding therapy may be appropriate 1

Common Pitfalls and Caveats

• NSAIDs alone are effective only for a minority of patients, mainly those with oligoarthritis 4
• Methotrexate is less effective for systemic arthritis compared to other JIA subtypes 4
• There is still a lack of evidence for optimal treatment of systemic and enthesitis-related arthritis 4
• Despite advances in treatment, sustained remission off medication remains elusive for most patients with JIA 5
• Early treatment initiation (window of opportunity) is critical to improve long-term outcomes and prevent permanent joint damage 1, 5