What is the treatment for systemic joint inflammation?

Treatment for Systemic Joint Inflammation

For systemic juvenile idiopathic arthritis (JIA) without macrophage activation syndrome (MAS), IL-1 and IL-6 inhibitors are strongly recommended over conventional synthetic DMARDs for patients with inadequate response to NSAIDs and/or glucocorticoids, as these biologics achieve resolution of systemic features and enable glucocorticoid discontinuation. 1

Initial Therapy for Systemic JIA Without MAS

First-Line Approach

• NSAIDs are conditionally recommended as initial monotherapy for a small proportion of patients who may respond, though many experts prefer avoiding NSAIDs altogether for systemic JIA 1
• If clinical response is not rapid and complete, rapid escalation of therapy is strongly recommended 1
• Oral glucocorticoids are conditionally recommended against as initial monotherapy, and if used, should be limited to the lowest effective dosage for the shortest duration possible 1
• Conventional synthetic DMARDs (methotrexate, leflunomide, sulfasalazine) are strongly recommended against as initial monotherapy due to documented lack of efficacy at controlling systemic features, leading to continued need for glucocorticoids 1

Critical Caveat

The recommendation against glucocorticoids is conditional because biologic DMARDs may not always be immediately available, and glucocorticoids may help control systemic and joint manifestations until IL-1 or IL-6 inhibitors can be started 1

Subsequent Therapy for Inadequate Response

Biologic DMARD Escalation

• IL-1 inhibitors (anakinra, canakinumab) and IL-6 inhibitors (tocilizumab) are strongly recommended over single or combination conventional synthetic DMARDs for inadequate response to or intolerance of NSAIDs and/or glucocorticoids 1
• There is no preferred agent between IL-1 and IL-6 inhibitors 1
• This strong recommendation is based on trials documenting resolution of systemic signs and ability to discontinue glucocorticoids 1

Managing Residual Arthritis

• Biologic DMARDs or conventional synthetic DMARDs are strongly recommended over long-term glucocorticoids for residual arthritis and incomplete response to IL-1 and/or IL-6 inhibitors 1
• Multiple options exist including adding methotrexate, switching to abatacept, or switching to a TNF inhibitor 1
• Conventional synthetic DMARDs in combination with biologic DMARDs can be considered for children with prominent arthritis 1

Treatment for Systemic JIA With MAS

Infection Screening

• All persons with MAS must be evaluated for infection concurrently with or prior to initiation of therapy, as infections can trigger MAS 1

Initial Therapy Algorithm

• IL-1 or IL-6 inhibitors are conditionally recommended over calcineurin inhibitors alone to achieve inactive disease and resolution of MAS 1
• There is no preferred agent between IL-1 and IL-6 inhibitors 1
• Glucocorticoids are conditionally recommended as part of initial treatment of systemic JIA with MAS, as benefits often outweigh risks even in infection-triggered MAS 1

Important Consideration for Severe Disease

Monotherapy may not be sufficient for severely ill patients—biologic DMARDs combined with glucocorticoids and calcineurin inhibitors may be necessary to control MAS 1

Common Pitfalls to Avoid

Undertreatment Risks

• Voting panelists were motivated by the extent of morbidity from undertreated systemic JIA and glucocorticoid-associated toxicities before the biologic DMARD era 1
• Conventional synthetic DMARDs as monotherapy lead to continued glucocorticoid dependence and fail to control systemic features 1

Emerging Safety Concern

• Systemic JIA-associated lung disease has been observed in some children treated with biologic DMARDs, with risk factors including younger age with MAS, history of reactions to tocilizumab, and trisomy 21 1
• Affected children often present with acute digital clubbing, which should raise immediate concern 1
• However, the need to balance effectiveness and relative safety of biologic DMARDs with the rarity of this serious outcome remains paramount 1

Duration of NSAID Trial

Voting panelists could not agree on the appropriate duration of initial NSAID use before escalating therapy, reflecting the preference of many panelists to avoid NSAIDs altogether for systemic JIA 1