RARE DISEASE
Systemic-onset juvenile idiopathic arthritis
Systemic-onset juvenile idiopathic arthritis
Systemic-onset juvenile idiopathic arthritis
Synonyms: Still disease, Systemic-onset JIA
Synonyms: Still disease, Systemic-onset JIA
Synonyms: Still disease, Systemic-onset JIA
Drug discovery
4
drugs
With orphan designations
Overview
Systemic-onset juvenile idiopathic arthritis (sJIA) is a rare autoinflammatory disease characterized by arthritis, daily spiking fevers, evanescent rash, lymphadenopathy, and systemic inflammation. Diagnosed by ILAR criteria after excluding infections/malignancies, it carries risks of macrophage activation syndrome (20% mortality) and chronic polyarthritis [1][7][12]. Treatment focuses on interleukin-1/6 blockade (anakinra, tocilizumab) to control cytokine storms, with early biologic use reducing steroid dependence [11][13][14].
Categories: rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
389 drug discovery papers about Systemic-onset juvenile idiopathic arthritis, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
389 drug discovery papers about Systemic-onset juvenile idiopathic arthritis, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-02 | Clinical Features and Outcome Measures Across Still Disease (Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still Disease) Cohorts Worldwide: A Systematic Literature Review.
J Rheumatol 2026; doi: 10.3899/jrheum.2025-0822 The following text should be added to the acknowledgment: "The contributions of the National Institutes of Health (NIH) authors are considered works of the US government. The findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services." This correction applies to the December 1 2025 First Release and February 2026 print issue. The online version has been corrected.
2026-06-20 | Predictive Factors for Relapse in Still's Disease: A Retrospective Cohort Study of Clinical and Laboratory Biomarkers.
This retrospective cohort study aimed to identify clinical and laboratory predictors of relapse in patients with Still's disease. A total of 94 patients diagnosed by Yamaguchi or Fautrel criteria across two rheumatology centers between 2012 and 2024 were evaluated, of whom 87 were eligible for analysis. Thirty-one patients (35%) experienced relapses during follow-up. Relapse was associated with higher baseline C-reactive protein (CRP > 100 mg/L), elevated neutrophil counts, and lower albumin levels. Composite ratios such as ferritin/albumin, CRP/albumin, and neutrophil/albumin were also significantly higher in the relapse group. Clinically, a joint-dominant disease phenotype and initial use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were more common among patients who relapsed. In multivariate logistic regression, high CRP levels, joint-dominant phenotype, and csDMARD use emerged as independent predictors of relapse. These findings highlight the predictive value of widely available biomarkers and baseline clinical presentation in stratifying relapse risk in Still Disease. Early recognition of high-risk patients using these factors may guide more targeted treatment approaches, support earlier initiation of biologic therapies, and ultimately improve long-term disease outcomes.
2026-05-26 | Early intensification versus step-up biologic strategies in systemic juvenile idiopathic arthritis: a Bayesian network meta-analysis of remission and safety outcomes.
To compare the relative effects of different treatment strategies for Systemic Juvenile Idiopathic Arthritis (sJIA) on clinical inactivity (CID)/remission and safety using a Bayesian network meta-analysis and to rank the treatment options. PubMed, Embase, Web of Science, the Cochrane Library, and Scopus were systematically searched from inception to October 2025 according to PRISMA 2020 and PRISMA-NMA specifications. Randomized controlled trials (RCTs), prospective cohorts, and retrospective/registry studies were included. The primary outcome was the CID/remission rate, and the secondary outcome was the incidence of adverse events (AEs) (normalized per patient-year). Random-effects and Bayesian hierarchical network models were used. Risk of bias was assessed using ROB-2 and NOS, and the certainty of evidence was assessed using GRADE. A total of 2,408 records were retrieved. After deduplication, 1,088 records were screened for titles/abstracts, and 200 were reviewed in full text. Fifteen studies (total sample size 1,548) were ultimately included. A pooled analysis showed that approximately two-thirds of patients achieved CID/remission during follow-up (random-effects model). Stratification suggested that an early IL-1/IL-6 strategy had a more favorable response rate. A network meta-ranking analysis (SUCRA) showed that early IL-1/IL-6 blockade ranked first, followed by anakinra and canakinumab; tocilizumab was in the middle; and conventional care and mixed biologic strategies ranked last. The overall AE rate was low and consistent across studies; IL-1/IL-6 targeted drugs had a favorable safety profile. Multiple sensitivity analyses and cumulative evidence analysis supported the robustness of the conclusions. In sJIA, immediate intensive IL-1/IL-6 therapy at diagnosis is more effective than a step-up approach in achieving and maintaining CID/remission, while also having an acceptable safety profile, supporting the initial "target-to-treat (T2T)" strategy. Future prospective studies and biomarker-stratified validation of each strategy are needed.
2026-05-01 | Early C-reactive protein and ferritin kinetics after tocilizumab initiation predict macrophage activation syndrome in Still disease: a single-centre retrospective cohort study
Objectives This study aimed to evaluate the safety and effectiveness of tocilizumab (TCZ) as induction therapy in Still disease and identify early dynamic biomarkers, including C-reactive protein (CRP) and ferritin changes, for macrophage activation syndrome (MAS) risk stratification. Methods This single-centre retrospective cohort study included patients with Still disease treated from 2004 to 2024. Patients were classified by induction therapy (TCZ vs non-TCZ). MAS was defined using the 2016 European Alliance of Associations for Rheumatology/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation criteria. Early biomarker changes after prednisolone initiation were evaluated. Primary outcomes were week-4 CRP normalisation and clinically inactive disease (CID) at month 3. Associations with induction therapy were analysed using Firth's penalised logistic regression. In TCZ-treated patients, receiver operating characteristic analyses assessed laboratory biomarkers for MAS prediction. Results Among 54 patients, 12 received TCZ as initial induction therapy and 7 for relapse (19 episodes). MAS occurred in 5 episodes (26.3%). No significant differences were observed in week-4 CRP normalisation (75.0% vs 51.2%, P = .193) or month-3 CID (40.0% vs 14.6%, P = .090). After adjusting for the higher initial prednisolone dose, early TCZ exposure was independently associated with month-3 CID (odds ratio: 9.73, 95% CI: 1.25-77.50, P = .030). Week-1/baseline CRP ratio and ferritin ratios predicted MAS after TCZ induction; the week-1/baseline ferritin ratio showed the highest area under the curve (0.914), followed by the CRP ratio (0.877). Conclusions Early TCZ exposure was independently associated with CID at month 3. Insufficient early suppression of inflammatory markers, particularly higher ferritin and CRP ratios, may identify patients at higher risk of subsequent MAS.
2026-04-04 | Effectiveness of Canakinumab for First-Line Steroid-Free Treatment in Systemic-Onset Juvenile Idiopathic Arthritis and Juvenile Still Disease.
This prospective study assesses the response to canakinumab monotherapy administered as three monthly subcutaneous injections in glucocorticoid-naïve patients with newly diagnosed systemic juvenile idiopathic arthritis (sJIA) and Still disease and evaluates the durability of drug-free inactive disease for up to nine months after canakinumab cessation. In a multicenter, two-phase open-label study of newly diagnosed sJIA or Still disease, canakinumab was administered at 4 mg/kg subcutaneously every 4 weeks for 12 weeks. Thereafter, patients were followed for an additional 40 weeks. Routine care was provided to nonresponders. In total, 21 patients were recruited, and 1 was excluded due to protocol violations. Fever resolved immediately in 17/19 patients. Two nonresponders (n = 2) were managed with different strategies: one received steroids alone, and the other received steroids plus canakinumab as part of routine care. By week 12, 14 patients achieved inactive disease. Thereafter, two flares occurred at weeks 24 and 36. Macrophage activation syndrome (MAS) was diagnosed in a third patient at week 19 and responded to treatment with glucocorticoids and cyclosporine A. By week 52, 11 patients had reached drug-free inactive disease and 3 had minimal disease activity. A total of 97 adverse events were reported; four were serious (one MAS, two disease flares, and one viral infection), but none were attributed to the study drug. Canakinumab steroid-free first-line therapy in newly diagnosed sJIA induces long-lasting, drug-free inactive disease in a substantial proportion of patients. Discontinuation of canakinumab was associated with disease flares in a minority of patients.
2026-07-02 | Clinical Features and Outcome Measures Across Still Disease (Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still Disease) Cohorts Worldwide: A Systematic Literature Review.
J Rheumatol 2026; doi: 10.3899/jrheum.2025-0822 The following text should be added to the acknowledgment: "The contributions of the National Institutes of Health (NIH) authors are considered works of the US government. The findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the US Department of Health and Human Services." This correction applies to the December 1 2025 First Release and February 2026 print issue. The online version has been corrected.
2026-06-20 | Predictive Factors for Relapse in Still's Disease: A Retrospective Cohort Study of Clinical and Laboratory Biomarkers.
This retrospective cohort study aimed to identify clinical and laboratory predictors of relapse in patients with Still's disease. A total of 94 patients diagnosed by Yamaguchi or Fautrel criteria across two rheumatology centers between 2012 and 2024 were evaluated, of whom 87 were eligible for analysis. Thirty-one patients (35%) experienced relapses during follow-up. Relapse was associated with higher baseline C-reactive protein (CRP > 100 mg/L), elevated neutrophil counts, and lower albumin levels. Composite ratios such as ferritin/albumin, CRP/albumin, and neutrophil/albumin were also significantly higher in the relapse group. Clinically, a joint-dominant disease phenotype and initial use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were more common among patients who relapsed. In multivariate logistic regression, high CRP levels, joint-dominant phenotype, and csDMARD use emerged as independent predictors of relapse. These findings highlight the predictive value of widely available biomarkers and baseline clinical presentation in stratifying relapse risk in Still Disease. Early recognition of high-risk patients using these factors may guide more targeted treatment approaches, support earlier initiation of biologic therapies, and ultimately improve long-term disease outcomes.
2026-05-26 | Early intensification versus step-up biologic strategies in systemic juvenile idiopathic arthritis: a Bayesian network meta-analysis of remission and safety outcomes.
To compare the relative effects of different treatment strategies for Systemic Juvenile Idiopathic Arthritis (sJIA) on clinical inactivity (CID)/remission and safety using a Bayesian network meta-analysis and to rank the treatment options. PubMed, Embase, Web of Science, the Cochrane Library, and Scopus were systematically searched from inception to October 2025 according to PRISMA 2020 and PRISMA-NMA specifications. Randomized controlled trials (RCTs), prospective cohorts, and retrospective/registry studies were included. The primary outcome was the CID/remission rate, and the secondary outcome was the incidence of adverse events (AEs) (normalized per patient-year). Random-effects and Bayesian hierarchical network models were used. Risk of bias was assessed using ROB-2 and NOS, and the certainty of evidence was assessed using GRADE. A total of 2,408 records were retrieved. After deduplication, 1,088 records were screened for titles/abstracts, and 200 were reviewed in full text. Fifteen studies (total sample size 1,548) were ultimately included. A pooled analysis showed that approximately two-thirds of patients achieved CID/remission during follow-up (random-effects model). Stratification suggested that an early IL-1/IL-6 strategy had a more favorable response rate. A network meta-ranking analysis (SUCRA) showed that early IL-1/IL-6 blockade ranked first, followed by anakinra and canakinumab; tocilizumab was in the middle; and conventional care and mixed biologic strategies ranked last. The overall AE rate was low and consistent across studies; IL-1/IL-6 targeted drugs had a favorable safety profile. Multiple sensitivity analyses and cumulative evidence analysis supported the robustness of the conclusions. In sJIA, immediate intensive IL-1/IL-6 therapy at diagnosis is more effective than a step-up approach in achieving and maintaining CID/remission, while also having an acceptable safety profile, supporting the initial "target-to-treat (T2T)" strategy. Future prospective studies and biomarker-stratified validation of each strategy are needed.
2026-05-01 | Early C-reactive protein and ferritin kinetics after tocilizumab initiation predict macrophage activation syndrome in Still disease: a single-centre retrospective cohort study
Objectives This study aimed to evaluate the safety and effectiveness of tocilizumab (TCZ) as induction therapy in Still disease and identify early dynamic biomarkers, including C-reactive protein (CRP) and ferritin changes, for macrophage activation syndrome (MAS) risk stratification. Methods This single-centre retrospective cohort study included patients with Still disease treated from 2004 to 2024. Patients were classified by induction therapy (TCZ vs non-TCZ). MAS was defined using the 2016 European Alliance of Associations for Rheumatology/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation criteria. Early biomarker changes after prednisolone initiation were evaluated. Primary outcomes were week-4 CRP normalisation and clinically inactive disease (CID) at month 3. Associations with induction therapy were analysed using Firth's penalised logistic regression. In TCZ-treated patients, receiver operating characteristic analyses assessed laboratory biomarkers for MAS prediction. Results Among 54 patients, 12 received TCZ as initial induction therapy and 7 for relapse (19 episodes). MAS occurred in 5 episodes (26.3%). No significant differences were observed in week-4 CRP normalisation (75.0% vs 51.2%, P = .193) or month-3 CID (40.0% vs 14.6%, P = .090). After adjusting for the higher initial prednisolone dose, early TCZ exposure was independently associated with month-3 CID (odds ratio: 9.73, 95% CI: 1.25-77.50, P = .030). Week-1/baseline CRP ratio and ferritin ratios predicted MAS after TCZ induction; the week-1/baseline ferritin ratio showed the highest area under the curve (0.914), followed by the CRP ratio (0.877). Conclusions Early TCZ exposure was independently associated with CID at month 3. Insufficient early suppression of inflammatory markers, particularly higher ferritin and CRP ratios, may identify patients at higher risk of subsequent MAS.
2026-04-04 | Effectiveness of Canakinumab for First-Line Steroid-Free Treatment in Systemic-Onset Juvenile Idiopathic Arthritis and Juvenile Still Disease.
This prospective study assesses the response to canakinumab monotherapy administered as three monthly subcutaneous injections in glucocorticoid-naïve patients with newly diagnosed systemic juvenile idiopathic arthritis (sJIA) and Still disease and evaluates the durability of drug-free inactive disease for up to nine months after canakinumab cessation. In a multicenter, two-phase open-label study of newly diagnosed sJIA or Still disease, canakinumab was administered at 4 mg/kg subcutaneously every 4 weeks for 12 weeks. Thereafter, patients were followed for an additional 40 weeks. Routine care was provided to nonresponders. In total, 21 patients were recruited, and 1 was excluded due to protocol violations. Fever resolved immediately in 17/19 patients. Two nonresponders (n = 2) were managed with different strategies: one received steroids alone, and the other received steroids plus canakinumab as part of routine care. By week 12, 14 patients achieved inactive disease. Thereafter, two flares occurred at weeks 24 and 36. Macrophage activation syndrome (MAS) was diagnosed in a third patient at week 19 and responded to treatment with glucocorticoids and cyclosporine A. By week 52, 11 patients had reached drug-free inactive disease and 3 had minimal disease activity. A total of 97 adverse events were reported; four were serious (one MAS, two disease flares, and one viral infection), but none were attributed to the study drug. Canakinumab steroid-free first-line therapy in newly diagnosed sJIA induces long-lasting, drug-free inactive disease in a substantial proportion of patients. Discontinuation of canakinumab was associated with disease flares in a minority of patients.
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Drug Discovery Landscape
4 orphan drug designations for Systemic-onset juvenile idiopathic arthritis.
4 orphan drug designations for Systemic-onset juvenile idiopathic arthritis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
upadacitinib | small molecules | FDA | 2017-08-16 | — | AbbVie, Inc. |
interleukin-1 receptor antagonist anakinra | proteins | FDA | 2015-09-15 | — | Swedish Orphan Biovitrum AB |
Canakinumab [Ilaris] | antibodies | EMA | 2008-02-04 | — | Novartis Europharm Limited |
Interleukin-1 Trap | proteins | FDA | 2005-04-04 | — | Regeneron Pharmaceuticals, Inc. |
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