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Treatment of systemic juvenile idiopathic arthritis

Abstract

Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory disease with hallmarks of severe systemic inflammation, which can be accompanied by arthritis. Contemporary scientific insights set this paediatric disorder on a continuum with its counterpart, adult-onset Still disease (AOSD). Patients with sJIA are prone to complications, including life-threatening hyperinflammation (macrophage activation syndrome (sJIA-MAS)) and sJIA-associated lung disease (sJIA-LD). Meanwhile, the treatment arsenal in sJIA has expanded markedly. State-of-the-art therapeutic approaches include biologic agents that target the IL-1 and IL-6 pathways. Beyond these, a range of novel agents are on the horizon, some of them already being used on a compassionate use basis, including JAK inhibitors and biologic agents that target IL-18, IFNγ, or IL-1β and IL-18 simultaneously. However, sJIA, sJIA-MAS and sJIA-LD still pose challenging conundrums to rheumatologists treating paediatric and adult patients worldwide. Although national and international consensus treatment plans exist for the treatment of ‘classic’ sJIA, the treatment approaches for early sJIA without arthritis, and for refractory or complicated sJIA, are not well defined. Therefore, in this Review we outline current approaches for the treatment of sJIA and provide an outlook on knowledge gaps.

Key points

  • Treatment of systemic juvenile idiopathic arthritis (sJIA) has evolved markedly over the past two decades, and most patients can be effectively treated using drugs that target the IL-1 or the IL-6 pathways.

  • Early diagnosis is very important so that effective, targeted therapy can be started as soon as possible, which might positively influence the long-term disease course (window of opportunity).

  • Many patients do not have arthritis at disease onset but nevertheless might benefit substantially from targeted therapies, thus preventing, rather than treating, arthritis.

  • Treat-to-target is an attractive strategy in sJIA, fusing both individualization and standardization of treatment.

  • Novel biomarkers, including calgranulins, IL-18 and CXCL9, might enable early diagnosis, prompt treatment and prediction of complications.

  • There is a substantial gap in knowledge and effective treatment options for patients with complicated sJIA, including patients with recurrent macrophage activation syndrome, sJIA-associated lung disease, and chronic, destructive arthritis.

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Fig. 1: Concepts of sJIA and their relationship to therapeutic strategies.
Fig. 2: sJIA disease phenotypes over time.
Fig. 3: Treatment algorithm for sJIA.
Fig. 4: Biomarkers to support treatment decisions including withdrawal.

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Correspondence to Dirk Foell.

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C.H.H. has received travel support from Pfizer. D.F. has received speaker fees/honoraria from Chugai-Roche, Novartis and Swedish Orphan Biovitrum (SOBI), as well as research support from Novartis, Pfizer and SOBI, and the German Research Foundation (DFG, grant number FO 354/14-1). C.K. has received consulting fees from Novartis and SOBI, research support from Novartis, and support from the German Research Foundation (grant number KE 2026 1/3).

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Hinze, C.H., Foell, D. & Kessel, C. Treatment of systemic juvenile idiopathic arthritis. Nat Rev Rheumatol 19, 778–789 (2023). https://doi.org/10.1038/s41584-023-01042-z

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