RARE DISEASE
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Synonyms: Juvenile chronic arthritis, Juvenile rheumatoid arthritis
Synonyms: Juvenile chronic arthritis, Juvenile rheumatoid arthritis
Synonyms: Juvenile chronic arthritis, Juvenile rheumatoid arthritis
Drug discovery
21
drugs
With orphan designations
Overview
Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by persistent joint inflammation (≥6 weeks) in children <16 years, with subtypes classified by clinical features. Diagnosis requires exclusion of alternative causes and may involve elevated inflammatory markers (ESR/CRP) or imaging. Early aggressive therapy with DMARDs/biologics improves remission rates, while untreated cases risk joint damage, growth impairment, and uveitis (15-30% risk) [1][6][11][17]. Management requires multidisciplinary care to address physical, ocular, and psychosocial impacts [1][16].
Population
Burden
25% of adults with JIA require biologics; 44% use glucocorticoids long-term [10][14]
Systemic JIA caregivers lose 25 workdays/year; patients miss 12% of school yearly [4][9]
31% with JIA have concurrent anxiety/depression; 19-20% higher risk of sustained high disease activity with comorbid joint hypermobility [12][15]
Therapies
First-line: Methotrexate ± intra-articular steroids (65% remission in oligoarticular JIA) [8][18]
Biologic escalation: Anti-IL1 (anakinra) or anti-IL6 (tocilizumab) for systemic JIA; TNF inhibitors for polyarticular forms [3][6][13]
Treat-to-target protocols achieve clinical inactivity in 66% within 12 months when initiated early [3][18]
Categories: rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
2,879 drug discovery papers about Juvenile idiopathic arthritis, with 4 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,879 drug discovery papers about Juvenile idiopathic arthritis, with 4 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-26 | Management strategies for articular flares during biologic therapy in non-systemic polyarticular JIA: a multicentre study.
Biologic disease-modifying antirheumatic drugs (bDMARDs) are the cornerstone of treatment for juvenile idiopathic arthritis (JIA), yet the optimal management of flares during ongoing biologic therapy remains unclear. We aimed to compare flare-management strategies and identify risk factors for treatment failure in non-systemic polyarticular JIA. We conducted a multicentre retrospective cohort study across four tertiary paediatric centres in Israel (01/2008-12/2024). We included children with non-systemic polyarticular JIA phenotypes who achieved clinically inactive disease (CID) on a bDMARD and subsequently experienced an articular flare. Treatment success (TS) was defined as achieving CID within 3 months following intervention and maintaining it for ≥3 months. Multivariable logistic regression and Cox proportional hazards models were used to identify predictors of success and time to remission. Among 65 patients and 116 flares, five strategies were compared: NSAIDs alone (2.6%), intra-articular corticosteroid injection (IACI; 28.4%), biologic dose optimization (43.1%), IACI plus dose optimization (13.8%), and switching biologics (12.1%). Overall, 71.6% of flares achieved TS. Success rates were highest for IACI (81.8%) and dose optimization (76.0%), and lowest for biologic switching (35.7%). Multivariable analysis identified biologic switching as an independent predictor of lower CID achievement (adjusted OR 0.27; p = 0.036) and significantly delayed remission (HR 0.40; p = 0.006). In non-systemic polyarticular JIA, local and incremental strategies like IACI and dose optimization result in higher and faster remission rates compared to immediate biologic switching. A stepwise algorithm prioritizing treatment optimization may prevent unnecessary cycling of biologics.
2026-09-23 | Shared pathogenic genes and therapeutic targets in periodontitis and systemic juvenile idiopathic arthritis: An integrative bioinformatics and machine learning study.
Periodontitis (PD) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases with potential clinical links, yet their shared molecular mechanisms remain unclear-patients with JIA face elevated periodontal risk, the temporomandibular joint affected in JIA shares inflammatory pathways with PD, Th17 cells drive both conditions, and glucocorticoid therapy may exacerbate periodontal vulnerability. This study aimed to explore the shared mechanisms and potential therapeutic targets of PD and sJIA using genetic expression data from the GEO database and performed comprehensive bioinformatics analyses, including differential expression gene analysis, weighted gene co‑expression network analysis (WGCNA), functional enrichment analysis, protein‑protein interaction network construction, and machine learning across 175 predictive models with the Ridge + AdaBoost ensemble identified as the best‑performing combination, followed by SHapley Additive exPlanations (SHAP) for model interpretability, CIBERSORT for immune infiltration assessment, and molecular docking with 100‑ns molecular dynamics simulations for therapeutic target validation. We identified 37 shared candidate genes between PD and sJIA, which were significantly enriched in IL‑17, NF‑κB, rheumatoid arthritis, and lipid atherosclerosis pathways, and machine learning screening further selected six core diagnostic genes (FAM46C, CXCL1, SELP, LGALSL, ELOVL4, VCAN), with SELP demonstrating the most robust cross‑model, cross‑dataset diagnostic value (AUC > 0.8); SHAP analysis confirmed SELP as a stable risk‑driving predictor across all models, while CXCL1 consistently showed protective effects. Immune infiltration revealed shared neutrophil elevation and CD8 ⁺ T‑cell reduction, with conserved CXCL1 and SELP correlations with neutrophils and resting mast cells, and FAM46C with plasma cells.Drug‑target network analysis identified IL1B, MMP1, and ITGAM as core targets, and molecular docking yielded strong binding affinities for deoxycholic acid-MMP1 (-7.6 kcal/mol), kaempferol-IL1B (-7.2 kcal/mol), kaempferol-ITGAM (-6.9 kcal/mol), with MD simulations confirming stable and specific binding. Collectively, this study explores shared genetic and immunological characteristics between PD and sJIA, suggests that SELP may serve as a critical cross‑disease diagnostic biomarker, and offers novel insights into their pathogenesis and potential therapeutic targets that warrant further experimental validation.
2026-09-19 | Towards personalized treatment in juvenile idiopathic arthritis: moving beyond the trial-and-error strategy.
The progressive elucidation of juvenile idiopathic arthritis (JIA) pathogenesis has led to growing interest in biomarkers to support diagnosis, subset classification, detection of subclinical inflammation, and/or prediction of disease course and therapeutic response (theragnostic biomarkers). JIA management in clinical practice currently follows a 'trial and error strategy', in which the treatment with the highest response chances is selected mainly based on the clinical phenotype. However, this strategy poses significant challenges, as a substantial proportion of patients fail to achieve sustained remission or experience disease flares. Here, we discuss key determinants of personalized medicine in non-systemic JIA, including ultrasound imaging, synovial fluid and tissue analysis, and circulating biomarkers. In the future, integrating multidimensional data may offer a unique opportunity to identify distinct disease endotypes, anticipate disease trajectory, and, once prospectively validated, inform targeted therapeutic strategies.
2026-09-06 | The role of ferroptosis in juvenile idiopathic arthritis: Causal inference and mediation by immune phenotypes.
This study employed a bidirectional 2-step, two-sample Mendelian randomization approach to investigate the causal relationships between ferroptosis-related genes and juvenile idiopathic arthritis (JIA) and to explore the mediating role of immune cells. Ferroptosis genes were identified from the deCODE database and matched with protein quantitative trait locus data as exposures to evaluate their causal effects on JIA, while immune cell traits were similarly assessed. For genes showing positive Mendelian randomization results, further analyses were conducted to determine whether immune cells mediated the effects on JIA, with mediation analysis performed only in the presence of causal associations. Data were sourced from the GWAS, FerrDb, and other public repositories. Nine ferroptosis-related genes were found to have causal links with JIA: HSPB1, DECR1, LIFR, and CTSB increased JIA risk, whereas PIEZO1, DPP4, BID, and others were protective. Forty immune cell traits were also causally associated with JIA. Mediation analysis revealed that several immune cells, including CD127- CD8+ T cells, partially mediated the genetic effects, with mediation proportions reaching up to 18.6%. Collectively, these results point to a ferroptosis-immune-JIA axis, suggesting that ferroptosis-related genes contribute to JIA pathogenesis through immune cell mediation and offering new mechanistic insights and potential therapeutic targets.
2026-09-04 | Janus kinase inhibitors for the treatment of Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of inflammatory arthritides encompassing at least six different categories, each with distinct clinical and biological characteristics. Despite significant advancements in the treatment of JIA, many cases of arthritis and/ or associated comorbidities such as chronic uveitis and interstitial lung disease (ILD) are refractory to current therapies. Janus kinase (JAK) inhibitors (JAKi) are small molecules or target–specific Disease Modifying Anti Rheumatic Drugs (tsDMARDs) that selectively inhibit janus kinases (JAKs) and block the JAK – Signal Transducers and Activators (STAT) pathway and the down steam proinflammatory effects associated with its activation. Herein, we review JAKi approved for the treatment of JIA and comment on JAKi currently with off- label use, with special considerations for their use in JIA-associated extraarticular manifestations and complications.
proteins
2026-02-13 | Model-Informed Abatacept Dose Recommendation in Pediatric Patients With Acute Graft Versus Host Disease.
This study uses a population pharmacokinetic (PPK) approach to provide abatacept dosing recommendations in pediatric patients 2 to < 6 years of age receiving unrelated donor hematopoietic stem cell transplantation (HSCT) due to hematologic malignancies (HMs), for the prophylaxis of acute graft-versus-host disease (aGVHD). An intermediate PPK model was developed and refined to include data from 904 patients aged 2-17 years with juvenile idiopathic arthritis administered with subcutaneous abatacept. Then, PK simulations were performed using the final PPK model for virtual pediatric patients aged 2 to < 6 years administered with either intravenous abatacept, fixed abatacept doses, or loading doses followed by maintenance dosing. The final model characterized abatacept exposure well using a linear, two-compartment model including absorption parameters (KA and F1), and generated parameter estimates comparable to previously published models. Further simulations of abatacept exposure in 10,000 virtual patients aged 2 to <6 years revealed that a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses achieved exposure levels similar to adults at risk of aGVHD, and therefore was selected for these patients. Additionally, an exposure-response (E-R) safety analysis in patients aged ≥6 years with HMs undergoing HSCT showed no significant relationship between abatacept exposure and occurrence of infection, confirming the safety of abatacept in these patients. The recommended dosing regimen for pediatric patients aged 2 to <6 years at risk of aGVHD is a 15-mg/kg loading dose on Day -1, followed by 12 mg/kg for the remaining doses on Days 5, 14, and 28.
2025-12-24 | Not Just Sjögren's: A Rare Life-Threatening Manifestation in a Pediatric Patient.
Macrophage activation syndrome (MAS), a severe hyperinflammatory state within the spectrum of hemophagocytic lymphohistiocytosis (HLH), is a life-threatening complication most commonly associated with rheumatologic disorders such as systemic juvenile idiopathic arthritis. Pediatric Sjögren's disease, however, is a rare and underrecognized etiology. We present the case of an eight-year-old female patient with no prior medical history who developed MAS in the setting of newly diagnosed Sjögren's disease, notably without classical sicca symptoms. Her course was marked by progressive systemic inflammation, multiorgan involvement, and laboratory findings suggestive of HLH/MAS. Diagnosis was confirmed through bone marrow biopsy and rheumatologic evaluation, and she responded favorably to immunosuppressive therapy with anakinra and corticosteroids. This case highlights the diagnostic challenges of MAS in atypical pediatric presentations and underscores the need for broader clinical suspicion in cytokine storm syndromes, particularly when established classification criteria are lacking.
2025-11-21 | Ameliorative effects of chitosan nanoparticles containing a scorpion-derived potassium channel inhibitory peptide (alpha-KTx 3.13) in a juvenile model of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a prevalent autoimmune disorder affecting millions of individuals worldwide, leading to chronic joint inflammation, progressive tissue damage, and substantial impairment of quality of life. In this study, we explored the therapeutic potential of chitosan nanoparticles encapsulating MeuKTx, a potassium channel inhibitory peptide targeting Kv1.3, in modulating articular tissue alterations in a neonatal rat model of RA. The peptide, alpha-KTx 3.13, was synthesized using solid-phase peptide synthesis, followed by purification and characterization through high-performance liquid chromatography (HPLC) and mass spectrometry to ensure its quality and bioactivity. Neonatal Wistar rats were assigned to various experimental groups, including a healthy control, an untreated RA model, and groups treated with methotrexate or peptide-based formulations delivered via chitosan nanoparticles. The treatment groups demonstrated significant reductions in serum malondialdehyde and rheumatoid factor (RF) levels, indicating a decrease in oxidative stress and systemic autoimmune activity. At the molecular level, expression of pro-inflammatory mediators, including transforming growth factor-beta (TGF-β) and monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as Caspase-8 protein levels, were markedly decreased in peptide-treated groups, correlating with improved histopathological outcomes in joint tissues. Notably, the chitosan nanoparticle formulation enhanced the bioavailability and therapeutic efficacy of MeuKTx, suggesting that targeted delivery to Kv1.3 channels can modulate immune and inflammatory responses more effectively than free peptide administration. Collectively, these findings highlight the potential of MeuKTx-loaded chitosan nanoparticles as a novel therapeutic strategy for RA, offering a promising approach to reduce joint inflammation, oxidative stress, and immune dysregulation while potentially minimizing reliance on conventional chemical drugs. This study provides a foundation for further exploration of peptide-based nanotherapies in autoimmune and inflammatory diseases.
2025-10-22 | Long-term safety of canakinumab in patients with systemic juvenile idiopathic arthritis: 5-year results from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.
Systemic juvenile idiopathic arthritis (SJIA) is a severe form of juvenile idiopathic arthritis characterized by fever, rash, chronic arthritis, and systemic inflammation. The introduction of biologics has improved the treatment options for SJIA. Canakinumab selectively inhibits interleukin-1β and is approved for SJIA treatment. In this study that utilized the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, long-term safety data available from patients with SJIA who started either canakinumab treatment or an alternative therapy were assessed. This long-term, prospective, non-interventional study was conducted from August 2015 to June 2022 using data from the CARRA Registry. Data for serious adverse events (SAEs) and pre-specified events of special interest (ESIs) were collected from patients with SJIA aged between ≥ 2 and < 18 years at the time of treatment initiation and followed for a minimum of 5 years. Data were summarized descriptively, and no hypothesis testing was performed. The final analysis included 177 patients: 90 in the overall canakinumab group (incident users [N = 39] and prevalent users [N = 51]) and 87 in the alternative treatment group. Median patient age at treatment initiation was 8.0 years in the overall canakinumab group. The incidence rates of SAEs per 100 patient-years were 3.62 (overall canakinumab group) and 3.39 (canakinumab incident users group). Of the predefined ESIs, macrophage activation syndrome (n = 5) and infections treated with intravenous anti-infectives (n = 1) were observed in the overall canakinumab group. The majority of patients (72.2%) treated with canakinumab received on-label dosing at some point during the first 5 years of the study. Overall, no changes were observed in the safety profile with long-term use of canakinumab in pediatric patients with SJIA. Particularly, no change in the frequency or severity of known ESIs occurred, and no new risks were identified. The findings suggest that canakinumab is effective in SJIA management and has a favorable safety profile with long-term use over a period of 5 years in real-world settings.
2025-05-30 | Semaphorin 5A as a Novel Diagnostic Biomarker of Juvenile Idiopathic Arthritis.
Although juvenile idiopathic arthritis (JIA) is the most common form of autoimmune-driven arthritis in pediatric population, due to the lack of universal diagnostic markers and heterogeneity of the disease, many patients face a significant delay when establishing the diagnosis. As the hallmark of JIA is the inflammation of synovial membrane with pathological angiogenesis, this study aimed to compare the concentrations of semaphorin 5A (SEMA5A), protein involved in both angiogenesis and immune response, between new-onset JIA and healthy controls. Thirty-five JIA patients and 35 sex-and-age matched healthy controls were enrolled in this study. Serum concentrations of SEMA5A and vascular endothelial growth factor A (VEGF-A) were established using the enzyme-linked immunosorbent assay (ELISA) method. The serum concentration of SEMA5A was elevated in JIA patients in comparison to healthy controls with the median value of 2.04 (interquartile range [IQR]: 12.41) in JIA patients and 1.34 (IQR: 1.79) in healthy controls (p = 0.002). The difference was particularly prominent in oligoarticular JIA, where median SEMA5A concentration equaled 1.76 ng/mL (IQR: 1.56) in comparison to 0.33 ng/mL (IQR: 1.34) in sex-and-age-matched healthy controls (p = 0.001). SEMA5A concentration correlated strongly with VEGF-A concentration (r = 0.807, p < 0.001) and differed significantly in subgroups of different synovial membrane power-Doppler ultrasound (PDUS) inflammatory activities (p = 0.018). Although our findings need to be repeated on larger groups of JIA patients, SEMA5A is a promising marker of JIA, linked to pathological angiogenesis of synovial membrane in this entity. Moreover, it may be useful as a target of innovative treatment strategies in the nearest future.
cell therapies
2026-06-13 | Systemic mesenchymal stem cell therapy for reduction of inflammatory burden in a patient with juvenile-onset rheumatoid arthritis and dialysis-dependent renal failure.
Chronic systemic inflammation is a key driver of disease progression in rheumatoid arthritis and chronic kidney disease (CKD), particularly in patients undergoing long-term hemodialysis. Persistent elevation of proinflammatory cytokines contributes to pain, anemia, endothelial dysfunction, and increased cardiovascular risk, while therapeutic options are often limited by comorbidities and drug intolerance. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may offer an alternative strategy for systemic inflammatory control. We report on the case of a 56-year-old woman with juvenile-onset rheumatoid arthritis and dialysis-dependent CKD who received three consecutive systemic administrations of MSCs. Baseline evaluation demonstrated elevated inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Following treatment, inflammatory parameters were consistently reduced, which was accompanied by improvement in hemoglobin levels and favorable trends in renal function markers. Additionally, pain assessment scores (Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Visual Analogue Scale) showed clinically significant improvement. The patient also reported significant subjective pain relief and improved overall well-being. Although limited by its single-case design, this report supports the biological plausibility of systemic MSC therapy as a potential immunomodulatory approach in patients with overlapping autoimmune and uremia-associated chronic inflammation. Further controlled studies are warranted.
2026-04-30 | Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes.
Human breast milk (HBM) is an ideal nutritional source for the growth and development of infants. In addition, HBM contains hormones, growth factors, microRNAs and exosomes that perform various physiological functions. This study investigates the immunomodulatory effects of HBM-derived exosomes on myeloid cells and chondrocytes, and implications for juvenile idiopathic arthritis. HBM-derived exosomes were isolated and characterized using nanoparticle track analyzer and Western blotting. The HBM-derived exosomes treatment decreased the expression of inflammatory mediators and proinflammatory cytokines in mouse peritoneal macrophages upon lipopolysaccharide stimulation. Flow cytometry analysis of bone marrow-derived macrophages indicated that exosomes promoted M2 polarization, as evidenced by a decrease in cells expressing CD80 (M1 marker) and a concurrent increase in cells expressing M2 marker CD206. In addition, exosome treatment attenuated the mitogen-activated protein kinase signaling pathway by reducing the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and IκB-α, thereby reducing the expression of inducible nitric oxide synthase, cyclooxygenase-2, metalloprotease (MMP)-1, MMP-3, and MMP-13 in SW1353 chondrocytes following IL-1β stimulation. These findings suggest that HBM-derived exosomes promote macrophage polarization toward an anti-inflammatory M2 phenotype and exert significant immunomodulatory effects.
2026-04-08 | Chimeric antigen receptor macrophage (CAR-M) immunotherapy in autoimmune inflammatory rheumatic diseases.
Chronic autoimmune inflammatory rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, systemic sclerosis (SSc), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are characterized by the dysregulation of the immune system and that of the neuroendocrine immune networks, leading to chronic inflammation and tissue damage. Perturbations of T, B, and macrophage cells result in uncontrolled inflammation. Traditional therapeutic approaches have focused on immunosuppressive drugs but more recently the use of biologics targeting specific cytokines or receptors on immune cells, and intracellular JAK pathways has been employed. However, these therapies often have limited efficacy and significant side effects. Moreover, they are not globally accessible due to high drug costs especially in poor as well as low- to middle-income countries. Cell immunotherapy, such as CAR-T and CAR-M cell therapy based on chimeric antigen receptor (CAR) technology, is opening up novel potential avenues for a precision approach to managing AIRD. This area is still experimental and in the research phase. This paper reviews the potential of CAR-M immunotherapy in AIRDs, highlighting its mechanisms of action and therapeutic applications.
2025-09-01 | Allogeneic haematopoietic stem cell transplantation for severe Still's disease: a retrospective report of three paediatric patients.
Severe forms of systemic JIA (sJIA), also called paediatric-onset Still's disease are associated with two major life-threatening complications: macrophage activation syndrome (MAS) and severe lung disease. Patients are usually resistant to conventional synthetic (cs) DMARDs, biologic (b) DMARDs, and targeted synthetic (ts) DMARDs. Recently, allogeneic haematopoietic stem cell transplantation (HSCT) has been performed in a small number of patients with refractory and life-threatening disease. We aimed to report outcomes and complications of allogeneic HSCT in patients with severe, refractory sJIA treated at our centre. We conducted a retrospective, observational, single-centre study in a tertiary paediatric immunology care centre (Necker Hospital, Paris, France). We report three sJIA patients who underwent allogeneic HSCT at a median age of 3.5 years. All had recurrent MAS; two had lung disease and the HLA-DRB1*15 haplotype, associated with severe delayed hypersensitivity to IL-1/IL-6 inhibitors. Donors were matched sibling donors for the first and third patient, and matched unrelated donor for the second patient. They presented multiple post-graft complications: graft-vs-host disease, infections, thrombotic microangiopathy and severe inflammatory complications on previously affected organs, such as skin and lungs. At a median follow-up of 22 months (20-33) after transplantation, they were all in remission with full-donor chimerism and were off immunosuppressive treatment. Allogeneic HSCT can be an effective salvage therapy in patients with refractory sJIA. However, the risk of post-transplant endothelial complications and severe inflammation in previously affected organs, such as joints, skin and lungs deserves particular attention.
2025-03-03 | The joint accumulation model of arthritis.
Most inflammatory arthritides are systemic diseases. In an individual patient, however, disease flares are more common in joints affected previously, a phenomenon termed joint-specific memory. A key driver of localized recurrence is the accumulation of CD8+ T resident memory (TRM) cells in inflamed synovial tissues. These cells remain during remission and initiate recurrent disease when activated by arthritogenic antigens. The joint accumulation model is a paradigm that recognizes the contribution of local as well as systemic immune mechanisms to arthritis chronicity, highlighting new targets for disease intervention, including but not limited to TRM cells. The joint accumulation model underscores the importance of preventing extension of arthritis to new joints, even in established disease, translating into a rolling window of opportunity for optimal long-term arthritis management.
antibodies
2026-09-26 | Effectiveness and Safety of Rituximab in Patients with Refractory Juvenile Idiopathic Arthritis: A Tertiary Center Experience.
Introduction: Despite the growing spectrum of modern drugs for the treatment of juvenile idiopathic arthritis (JIA), patients with a refractory, progressive course of the disease remain a clinical challenge. B-cell-depleting therapy has demonstrated efficacy in adult rheumatoid arthritis and several pediatric rheumatic diseases, encouraging us to evaluate rituximab (RTX) for children with refractory JIA. Objective: This study aimed to assess the long-term efficacy and safety of rituximab therapy in children with refractory juvenile idiopathic arthritis. Methods: This retrospective, single-center, observational study included 106 patients with JIA who had failed previous therapy. The efficacy and safety of the therapy were evaluated at baseline and at 3, 6, 12, 24, 36, and 48 months post-initial rituximab infusion using the American College of Rheumatology Pediatric Criteria (ACRpedi 30/50/70/90), C. Wallace criteria for inactive disease/remission, and the JADAS71 activity index until patient completion or withdrawal from the study. The primary endpoint was achieving an ACRpedi50 response by 3 months, and the secondary endpoint was achieving inactive disease status according to C. Wallace criteria by 6 months of follow-up. Results: An ACRpedi50 response was achieved in 78/100 (78%) patients by month 3 of rituximab therapy, and inactive disease status was reached in 48/93 (52%) patients by month 6. More than half of the patients demonstrate inactive disease or remission at each observation point. During rituximab therapy, oral glucocorticoids were discontinued in 18/57 (32%) patients, and 28/57 (49%) patients were able to halve their corticosteroid dose (p = 0.03). Rituximab demonstrated an acceptable safety profile, with a total of 351 adverse events (non-serious AEs: 304/351, 87%) and a serious AE rate of 0.8 per 100 patient-years. Conclusions: Rituximab can reduce disease activity and lower the dose of oral glucocorticoids in patients with refractory JIA, serving as a viable therapeutic option with an acceptable safety profile.
2026-08-27 | Real-World Evolution of Prescribing Patterns and Safety Profiles of Biologic and Targeted Synthetic Therapies in Inflammatory Rheumatic Diseases: A Comparative Study Between 2018-2019 and 2023-2024.
Background/Objectives: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) have expanded treatment options for inflammatory rheumatic diseases, highlighting the need for continuous pharmacovigilance. This study evaluated changes in prescribing patterns and safety profiles of b/tsDMARDs between 2018-2019 and 2023-2024 in routine clinical practice. Methods: A retrospective observational study was conducted in patients with rheumatoid arthritis (AR), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or juvenile idiopathic arthritis (JIA) treated at a rheumatology outpatient clinic in Southern Italy. Demographic and clinical characteristics, prescribed therapies, treatment switches/swaps, therapeutic failures, and adverse events (AEs) were collected through a structured pharmacovigilance program. Prescribing trends between the two study periods were compared using chi-square analysis. Results: A total of 342 patients were included (202 in 2018-2019 and 140 in 2023-2024). Prescribing patterns changed significantly over time (χ2 = 83.24, p < 0.0001), with increased use of newer therapeutic classes and biosimilars, while tumor necrosis factor (TNF) inhibitors remained the most frequently prescribed drugs. The proportion of biologic-naïve patients increased from 52.0% to 66.4%, whereas AEs decreased from 31.7% to 15.0%, with no serious adverse events (SAEs) reported. Conclusions: Prescribing strategies for inflammatory rheumatic diseases evolved substantially between 2018 and 2024, reflecting the availability of new therapeutic options and a more personalized treatment approach. b/tsDMARDs showed a favorable real-world safety profile, supporting the importance of ongoing pharmacovigilance.
2026-08-21 | Mortality and associated factors of JIA in hospitalized Thai children: a nationwide data analysis 2015-2023.
To characterize in-hospital mortality, respiratory failure requiring endotracheal intubation and associated comorbidities among hospitalized children with JIA using nationwide data from Thailand. This was a retrospective study using administrative inpatient data from Thailand's National database from January 2015 to December 2023. All hospital admissions for patients younger than 18 years with JIA were included. Primary outcomes were in-hospital mortality and respiratory failure, defined by endotracheal intubation. Demographics, JIA subtypes, hospital level, healthcare utilization and comorbidities were analysed. Multivariable logistic regression identified comorbidities independently associated with intubation, reported as adjusted odds ratios (aORs) with 95% confidence intervals. Among 3754 JIA admissions, 52.7% of patients were female, with a median age of 10 years (interquartile range 6-13). Endotracheal intubation occurred in 39 admissions (1.0%), and 17 patients died, yielding an in-hospital mortality rate of 0.5%; mortality among intubated patients was 33.3%. Length of stay and costs were substantially higher among intubated patients and non-survivors. Pneumonia was common in both groups. Myocarditis showed the strongest association with intubation (aOR 294.74), followed by pulmonary haemorrhage, acute kidney injury and septic shock. Macrophage activation syndrome was identified in 43 admissions (1.2%) and was more frequent among non-survivors (23.5% vs 1.0%; P < 0.001). Although overall mortality and intubation rates were low, respiratory failure identified a small, high-risk subgroup with substantial mortality and healthcare burden. Severe outcomes were driven by acute multi-organ complications, underscoring early recognition and aggressive management of high-risk comorbidities.
2026-08-11 | The Asia-Pacific League of Associations for Rheumatology Consensus Recommendations on the Management of Systemic Juvenile Idiopathic Arthritis (Juvenile Still's Disease).
The unique characteristics of the Asia Pacific called for the development of pragmatic and viable guidelines for the management of juvenile idiopathic arthritis (JIA). These consensus recommendations represent the second part of the guideline intending to offer an updated and regionally relevant framework for the management of systemic JIA (sJIA)/juvenile Still's disease. A multidisciplinary task force of 35 members from 14 countries, including pediatric and adult rheumatologists as well as patient representatives, was convened. The guideline development followed the GRADE, ADAPTE, and AGREE II frameworks. Relevant international guidelines were critically appraised, and a systematic literature review was performed to address 10 PICO questions. Draft statements were discussed and voted upon using a modified Delphi process, with consensus defined as ≥ 80% agreement. Four overarching principles and eighteen statements, including five statements addressing macrophage activation syndrome (MAS) were formulated. The recommendations align with international guidelines, advocating early use of IL-1/IL-6 inhibitors, avoidance of glucocorticoid monotherapy in sJIA without MAS, promoting tapering of glucocorticoids once inactive disease is achieved, alongside class switching for biologic refractory cases and a treat-to-target approach akin to EULAR/PReS guideline. Additional features include recommending conventional synthetic DMARD when biologics are unavailable and listing the options, acknowledging regional health system heterogeneity in the Asia Pacific, mentioning tapering strategy, discouraging NSAIDs as initial monotherapy, highlighting non-biologic salvage options, and placing less emphasis on sJIA-associated lung diseases. These recommendations provide direction for practitioners caring for sJIA patients in limited resource areas to avoid treatment delay, hence improve overall outcomes. A shared decision approach and treat-to-targets are emphasized.
2026-08-02 | Canakinumab for systemic-onset juvenile idiopathic arthritis/Still's disease-effectiveness and safety data from the BiKeR registry.
In Germany, canakinumab is approved for the treatment of refractory systemic juvenile idiopathic arthritis (sJIA)/Still's disease. This study assesses the experience of sJIA/Still's disease patients treated with canakinumab in clinical practice. Data of 79 sJIA/Still's disease patients extracted from the BiKeR registry included patients' and disease characteristics. Three subgroups with disease durations before canakinumab initiation of ≤3 months, >3 to ≤12 months, and >12 months were compared, and 2 with canakinumab as first- and second- or more-line treatment. Disease duration was ≤3 months before canakinumab initiation for 26 patients, >3 to ≤12 months for 24 patients, and >12 months for 29 patients. Thirty-nine patients received canakinumab as first-line treatment and 40 as second- or more-line treatment. Disease severity as assessed by the systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS10) was highest for patients with a disease duration <3 months before canakinumab initiation. In the total cohort, after 3, 6, 12, 18, and 24 months, 86%, 81%, 81%, 75%, and 87% of patients reached inactive disease, respectively. Numerically, more patients reached the treatment goal of inactive disease when the disease duration was shorter before initiation of canakinumab. Minimal disease activity (sJADAS10 ≤6.0) did not differ among subgroups. Compared with second-line, more patients with first-line treatment reached inactive disease at months 6, 12, and 24 after canakinumab initiation. sJADAS10 at 12 months correlated significantly with disease duration before treatment. Canakinumab treatment led to high improvement rates and achievement of inactive disease state, particularly if they are administered early. Data from clinical practice confirm clinical study data.
other
2026-09-27 | Combined Infliximab and Tofacitinib Therapy for Severe Refractory Juvenile Idiopathic Arthritis Associated Panuveitis: A Challenge, Dechallenge, Rechallenge Case Report.
To report a child with severe treatment-resistant juvenile idiopathic arthritis-associated uveitis (JIAU), characterized by panuveitis, diffuse retinal vascular leakage, and refractory cystoid macular edema. We describe the clinical course, treatment response, and challenge, dechallenge, and rechallenge sequence in a child with severe refractory JIAU treated with combined infliximab and tofacitinib therapy. The patient showed marked improvement in ocular inflammation, macular edema, and visual acuity following addition of tofacitinib to ongoing infliximab therapy. Inflammation recurred after holding infliximab despite continuation of tofacitinib and improved again following reintroduction of infliximab. This challenge, dechallenge, and rechallenge sequence is consistent with a possible complementary effect of infliximab and tofacitinib in this patient. However, causality and pharmacologic synergy cannot be established from a single case. Combined tumor necrosis factor alpha and Janus kinase inhibition may represent an exceptional rescue approach for carefully selected patients with severe refractory JIAU, although its efficacy and long-term safety require further evaluation.
2026-09-26 | Association of 9-Valent HPV Vaccination with Risk of Juvenile Idiopathic Arthritis: A Sex-Stratified Real-World Study.
To evaluate the association between 9-valent human papillomavirus (HPV9) vaccination and the risk of new-onset juvenile idiopathic arthritis (JIA), with particular attention to sex-specific differences, including the relative lack of evidence in males and the potential impact of the COVID-19 pandemic. Using the TriNetX U.S. Collaborative Network (2016-2023), children aged 9-13 years who received HPV9 vaccination were compared with unvaccinated controls in prepandemic and pandemic periods. Incident JIA was assessed using matched cohort analyses and time-to-event methods. Similar sex-specific patterns were observed across both periods. HPV9 vaccination was associated with a lower risk of JIA among girls (HR = 0.45 95% CI = 0.22-0.95 in prepandemic and HR = 0.36 95% CI = 0.17-0.74 during pandemic period), while no increased risk was observed among boys (HR = 1.57 95% CI = 0.67-4.05 in prepandemic and HR = 1.14 95% CI = 0.56-2.34 during pandemic period). Among unvaccinated individuals, girls consistently exhibited a higher incidence of JIA than boys. The COVID-19 pandemic did not alter these associations. HPV9 vaccination was not associated with an increased risk of JIA in either sex. A consistent sex-specific pattern was observed across both study periods, with a lower risk of JIA among vaccinated girls but not boys. This finding suggests a potential sex difference in the association between HPV9 vaccination and JIA and warrants further investigation. However, residual confounding, including healthy-vaccinee bias and differences in healthcare utilization, cannot be fully excluded.
2026-08-11 | Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.
Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.
2026-03-13 | Highlights on the Contribution of Gut Microbiota to Immune-Mediated Diseases in Childhood.
The gut microbiota, a vast community of symbiotic microorganisms inhabiting our gut, has been recognized as a key-lever for human health, shaping immune system resilience and being essential for immunological homeostasis throughout the life course. Gut microbiota composition may influence both initiation and/or perpetuation of intestinal inflammation, but recent research has highlighted its contribution to both rising and progression of protean non-intestinal inflammatory diseases: indeed, a perturbation of host-associated microbiota during critical developmental stages like early childhood can directly condition many cellular dynamics and impact long-term health. This narrative review explores the interactions among gut microbiota, physiologic healthy equilibrium, dysbiosis, and immune-mediated non-intestinal inflammatory diseases occurring in childhood, such as inflammasome-based disorders, juvenile idiopathic arthritis, Kawasaki disease, and IgA vasculitis, focusing on how microbial changes may alter disease outcomes and suggesting potentially novel therapeutic approaches. Additionally, this review examines the evolution of immune recognition mechanisms and their role in maintaining the gut microbiota-host mutualism as a result of millennia of human co-evolution with the microbial counterpart.
2026-01-12 | Impaired Generation of High-Affinity Memory B Cells and Neutralizing Antibodies Against SARS-CoV-2 in Adolescents and Young Adults With Juvenile Idiopathic Arthritis Treated With Tumor Necrosis Factor Inhibitors.
We evaluated the immunogenicity of SARS-CoV-2 mRNA vaccines in patients with juvenile idiopathic arthritis (JIA), focusing on the generation of spike-specific memory B cells (MBCs) and of neutralizing antibodies, and assessed the impact of disease-modifying antirheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi). This study enrolled 35 adolescent and young adult patients with JIA. Data concerning disease characteristics and SARS-CoV-2 vaccination and infection were collected. We analyzed the frequency of low-affinity spike-specific and high-affinity spike-specific MBCs by flow cytometry. We measured total anti-spike antibodies levels using a chemiluminescence microparticle immunoassay and assessed neutralizing antibody titers with a microneutralization assay. Patients with JIA showed a reduced frequency of high-affinity MBCs compared to controls, with a notably poorer response among those receiving TNFi treatment. Additionally, their ability to bind the Omicron variant was significantly lower, particularly among TNFi-treated patients. SARS-CoV-2 infection alone was not able to generate high-affinity MBCs and neutralizing antibodies in patients with JIA. After receiving three vaccine doses, 43% of patients with JIA exhibited a reduced frequency of high-affinity MBCs and neutralizing antibodies. Patients with JIA undergoing treatment with TNFi demonstrated a diminished immunogenic response to SARS-CoV-2 vaccination, with lower frequencies of high-affinity MBCs and decreased neutralizing antibody titers. These findings underscore the need for customized vaccination protocols, including the potential use of booster doses, to enhance immunoprotection in this group. Additionally, the development of reliable biomarkers to distinguish between patients with and without adequate protective immunity is imperative to refine therapeutic interventions and ensure optimal patient outcomes.
small molecules
2026-09-26 | Management strategies for articular flares during biologic therapy in non-systemic polyarticular JIA: a multicentre study.
Biologic disease-modifying antirheumatic drugs (bDMARDs) are the cornerstone of treatment for juvenile idiopathic arthritis (JIA), yet the optimal management of flares during ongoing biologic therapy remains unclear. We aimed to compare flare-management strategies and identify risk factors for treatment failure in non-systemic polyarticular JIA. We conducted a multicentre retrospective cohort study across four tertiary paediatric centres in Israel (01/2008-12/2024). We included children with non-systemic polyarticular JIA phenotypes who achieved clinically inactive disease (CID) on a bDMARD and subsequently experienced an articular flare. Treatment success (TS) was defined as achieving CID within 3 months following intervention and maintaining it for ≥3 months. Multivariable logistic regression and Cox proportional hazards models were used to identify predictors of success and time to remission. Among 65 patients and 116 flares, five strategies were compared: NSAIDs alone (2.6%), intra-articular corticosteroid injection (IACI; 28.4%), biologic dose optimization (43.1%), IACI plus dose optimization (13.8%), and switching biologics (12.1%). Overall, 71.6% of flares achieved TS. Success rates were highest for IACI (81.8%) and dose optimization (76.0%), and lowest for biologic switching (35.7%). Multivariable analysis identified biologic switching as an independent predictor of lower CID achievement (adjusted OR 0.27; p = 0.036) and significantly delayed remission (HR 0.40; p = 0.006). In non-systemic polyarticular JIA, local and incremental strategies like IACI and dose optimization result in higher and faster remission rates compared to immediate biologic switching. A stepwise algorithm prioritizing treatment optimization may prevent unnecessary cycling of biologics.
2026-09-23 | Shared pathogenic genes and therapeutic targets in periodontitis and systemic juvenile idiopathic arthritis: An integrative bioinformatics and machine learning study.
Periodontitis (PD) and systemic juvenile idiopathic arthritis (sJIA) are chronic inflammatory diseases with potential clinical links, yet their shared molecular mechanisms remain unclear-patients with JIA face elevated periodontal risk, the temporomandibular joint affected in JIA shares inflammatory pathways with PD, Th17 cells drive both conditions, and glucocorticoid therapy may exacerbate periodontal vulnerability. This study aimed to explore the shared mechanisms and potential therapeutic targets of PD and sJIA using genetic expression data from the GEO database and performed comprehensive bioinformatics analyses, including differential expression gene analysis, weighted gene co‑expression network analysis (WGCNA), functional enrichment analysis, protein‑protein interaction network construction, and machine learning across 175 predictive models with the Ridge + AdaBoost ensemble identified as the best‑performing combination, followed by SHapley Additive exPlanations (SHAP) for model interpretability, CIBERSORT for immune infiltration assessment, and molecular docking with 100‑ns molecular dynamics simulations for therapeutic target validation. We identified 37 shared candidate genes between PD and sJIA, which were significantly enriched in IL‑17, NF‑κB, rheumatoid arthritis, and lipid atherosclerosis pathways, and machine learning screening further selected six core diagnostic genes (FAM46C, CXCL1, SELP, LGALSL, ELOVL4, VCAN), with SELP demonstrating the most robust cross‑model, cross‑dataset diagnostic value (AUC > 0.8); SHAP analysis confirmed SELP as a stable risk‑driving predictor across all models, while CXCL1 consistently showed protective effects. Immune infiltration revealed shared neutrophil elevation and CD8 ⁺ T‑cell reduction, with conserved CXCL1 and SELP correlations with neutrophils and resting mast cells, and FAM46C with plasma cells.Drug‑target network analysis identified IL1B, MMP1, and ITGAM as core targets, and molecular docking yielded strong binding affinities for deoxycholic acid-MMP1 (-7.6 kcal/mol), kaempferol-IL1B (-7.2 kcal/mol), kaempferol-ITGAM (-6.9 kcal/mol), with MD simulations confirming stable and specific binding. Collectively, this study explores shared genetic and immunological characteristics between PD and sJIA, suggests that SELP may serve as a critical cross‑disease diagnostic biomarker, and offers novel insights into their pathogenesis and potential therapeutic targets that warrant further experimental validation.
2026-09-19 | Towards personalized treatment in juvenile idiopathic arthritis: moving beyond the trial-and-error strategy.
The progressive elucidation of juvenile idiopathic arthritis (JIA) pathogenesis has led to growing interest in biomarkers to support diagnosis, subset classification, detection of subclinical inflammation, and/or prediction of disease course and therapeutic response (theragnostic biomarkers). JIA management in clinical practice currently follows a 'trial and error strategy', in which the treatment with the highest response chances is selected mainly based on the clinical phenotype. However, this strategy poses significant challenges, as a substantial proportion of patients fail to achieve sustained remission or experience disease flares. Here, we discuss key determinants of personalized medicine in non-systemic JIA, including ultrasound imaging, synovial fluid and tissue analysis, and circulating biomarkers. In the future, integrating multidimensional data may offer a unique opportunity to identify distinct disease endotypes, anticipate disease trajectory, and, once prospectively validated, inform targeted therapeutic strategies.
2026-09-06 | The role of ferroptosis in juvenile idiopathic arthritis: Causal inference and mediation by immune phenotypes.
This study employed a bidirectional 2-step, two-sample Mendelian randomization approach to investigate the causal relationships between ferroptosis-related genes and juvenile idiopathic arthritis (JIA) and to explore the mediating role of immune cells. Ferroptosis genes were identified from the deCODE database and matched with protein quantitative trait locus data as exposures to evaluate their causal effects on JIA, while immune cell traits were similarly assessed. For genes showing positive Mendelian randomization results, further analyses were conducted to determine whether immune cells mediated the effects on JIA, with mediation analysis performed only in the presence of causal associations. Data were sourced from the GWAS, FerrDb, and other public repositories. Nine ferroptosis-related genes were found to have causal links with JIA: HSPB1, DECR1, LIFR, and CTSB increased JIA risk, whereas PIEZO1, DPP4, BID, and others were protective. Forty immune cell traits were also causally associated with JIA. Mediation analysis revealed that several immune cells, including CD127- CD8+ T cells, partially mediated the genetic effects, with mediation proportions reaching up to 18.6%. Collectively, these results point to a ferroptosis-immune-JIA axis, suggesting that ferroptosis-related genes contribute to JIA pathogenesis through immune cell mediation and offering new mechanistic insights and potential therapeutic targets.
2026-09-04 | Janus kinase inhibitors for the treatment of Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of inflammatory arthritides encompassing at least six different categories, each with distinct clinical and biological characteristics. Despite significant advancements in the treatment of JIA, many cases of arthritis and/ or associated comorbidities such as chronic uveitis and interstitial lung disease (ILD) are refractory to current therapies. Janus kinase (JAK) inhibitors (JAKi) are small molecules or target–specific Disease Modifying Anti Rheumatic Drugs (tsDMARDs) that selectively inhibit janus kinases (JAKs) and block the JAK – Signal Transducers and Activators (STAT) pathway and the down steam proinflammatory effects associated with its activation. Herein, we review JAKi approved for the treatment of JIA and comment on JAKi currently with off- label use, with special considerations for their use in JIA-associated extraarticular manifestations and complications.
proteins
2026-02-13 | Model-Informed Abatacept Dose Recommendation in Pediatric Patients With Acute Graft Versus Host Disease.
This study uses a population pharmacokinetic (PPK) approach to provide abatacept dosing recommendations in pediatric patients 2 to < 6 years of age receiving unrelated donor hematopoietic stem cell transplantation (HSCT) due to hematologic malignancies (HMs), for the prophylaxis of acute graft-versus-host disease (aGVHD). An intermediate PPK model was developed and refined to include data from 904 patients aged 2-17 years with juvenile idiopathic arthritis administered with subcutaneous abatacept. Then, PK simulations were performed using the final PPK model for virtual pediatric patients aged 2 to < 6 years administered with either intravenous abatacept, fixed abatacept doses, or loading doses followed by maintenance dosing. The final model characterized abatacept exposure well using a linear, two-compartment model including absorption parameters (KA and F1), and generated parameter estimates comparable to previously published models. Further simulations of abatacept exposure in 10,000 virtual patients aged 2 to <6 years revealed that a 15-mg/kg loading dose followed by 12-mg/kg maintenance doses achieved exposure levels similar to adults at risk of aGVHD, and therefore was selected for these patients. Additionally, an exposure-response (E-R) safety analysis in patients aged ≥6 years with HMs undergoing HSCT showed no significant relationship between abatacept exposure and occurrence of infection, confirming the safety of abatacept in these patients. The recommended dosing regimen for pediatric patients aged 2 to <6 years at risk of aGVHD is a 15-mg/kg loading dose on Day -1, followed by 12 mg/kg for the remaining doses on Days 5, 14, and 28.
2025-12-24 | Not Just Sjögren's: A Rare Life-Threatening Manifestation in a Pediatric Patient.
Macrophage activation syndrome (MAS), a severe hyperinflammatory state within the spectrum of hemophagocytic lymphohistiocytosis (HLH), is a life-threatening complication most commonly associated with rheumatologic disorders such as systemic juvenile idiopathic arthritis. Pediatric Sjögren's disease, however, is a rare and underrecognized etiology. We present the case of an eight-year-old female patient with no prior medical history who developed MAS in the setting of newly diagnosed Sjögren's disease, notably without classical sicca symptoms. Her course was marked by progressive systemic inflammation, multiorgan involvement, and laboratory findings suggestive of HLH/MAS. Diagnosis was confirmed through bone marrow biopsy and rheumatologic evaluation, and she responded favorably to immunosuppressive therapy with anakinra and corticosteroids. This case highlights the diagnostic challenges of MAS in atypical pediatric presentations and underscores the need for broader clinical suspicion in cytokine storm syndromes, particularly when established classification criteria are lacking.
2025-11-21 | Ameliorative effects of chitosan nanoparticles containing a scorpion-derived potassium channel inhibitory peptide (alpha-KTx 3.13) in a juvenile model of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a prevalent autoimmune disorder affecting millions of individuals worldwide, leading to chronic joint inflammation, progressive tissue damage, and substantial impairment of quality of life. In this study, we explored the therapeutic potential of chitosan nanoparticles encapsulating MeuKTx, a potassium channel inhibitory peptide targeting Kv1.3, in modulating articular tissue alterations in a neonatal rat model of RA. The peptide, alpha-KTx 3.13, was synthesized using solid-phase peptide synthesis, followed by purification and characterization through high-performance liquid chromatography (HPLC) and mass spectrometry to ensure its quality and bioactivity. Neonatal Wistar rats were assigned to various experimental groups, including a healthy control, an untreated RA model, and groups treated with methotrexate or peptide-based formulations delivered via chitosan nanoparticles. The treatment groups demonstrated significant reductions in serum malondialdehyde and rheumatoid factor (RF) levels, indicating a decrease in oxidative stress and systemic autoimmune activity. At the molecular level, expression of pro-inflammatory mediators, including transforming growth factor-beta (TGF-β) and monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as Caspase-8 protein levels, were markedly decreased in peptide-treated groups, correlating with improved histopathological outcomes in joint tissues. Notably, the chitosan nanoparticle formulation enhanced the bioavailability and therapeutic efficacy of MeuKTx, suggesting that targeted delivery to Kv1.3 channels can modulate immune and inflammatory responses more effectively than free peptide administration. Collectively, these findings highlight the potential of MeuKTx-loaded chitosan nanoparticles as a novel therapeutic strategy for RA, offering a promising approach to reduce joint inflammation, oxidative stress, and immune dysregulation while potentially minimizing reliance on conventional chemical drugs. This study provides a foundation for further exploration of peptide-based nanotherapies in autoimmune and inflammatory diseases.
2025-10-22 | Long-term safety of canakinumab in patients with systemic juvenile idiopathic arthritis: 5-year results from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.
Systemic juvenile idiopathic arthritis (SJIA) is a severe form of juvenile idiopathic arthritis characterized by fever, rash, chronic arthritis, and systemic inflammation. The introduction of biologics has improved the treatment options for SJIA. Canakinumab selectively inhibits interleukin-1β and is approved for SJIA treatment. In this study that utilized the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, long-term safety data available from patients with SJIA who started either canakinumab treatment or an alternative therapy were assessed. This long-term, prospective, non-interventional study was conducted from August 2015 to June 2022 using data from the CARRA Registry. Data for serious adverse events (SAEs) and pre-specified events of special interest (ESIs) were collected from patients with SJIA aged between ≥ 2 and < 18 years at the time of treatment initiation and followed for a minimum of 5 years. Data were summarized descriptively, and no hypothesis testing was performed. The final analysis included 177 patients: 90 in the overall canakinumab group (incident users [N = 39] and prevalent users [N = 51]) and 87 in the alternative treatment group. Median patient age at treatment initiation was 8.0 years in the overall canakinumab group. The incidence rates of SAEs per 100 patient-years were 3.62 (overall canakinumab group) and 3.39 (canakinumab incident users group). Of the predefined ESIs, macrophage activation syndrome (n = 5) and infections treated with intravenous anti-infectives (n = 1) were observed in the overall canakinumab group. The majority of patients (72.2%) treated with canakinumab received on-label dosing at some point during the first 5 years of the study. Overall, no changes were observed in the safety profile with long-term use of canakinumab in pediatric patients with SJIA. Particularly, no change in the frequency or severity of known ESIs occurred, and no new risks were identified. The findings suggest that canakinumab is effective in SJIA management and has a favorable safety profile with long-term use over a period of 5 years in real-world settings.
2025-05-30 | Semaphorin 5A as a Novel Diagnostic Biomarker of Juvenile Idiopathic Arthritis.
Although juvenile idiopathic arthritis (JIA) is the most common form of autoimmune-driven arthritis in pediatric population, due to the lack of universal diagnostic markers and heterogeneity of the disease, many patients face a significant delay when establishing the diagnosis. As the hallmark of JIA is the inflammation of synovial membrane with pathological angiogenesis, this study aimed to compare the concentrations of semaphorin 5A (SEMA5A), protein involved in both angiogenesis and immune response, between new-onset JIA and healthy controls. Thirty-five JIA patients and 35 sex-and-age matched healthy controls were enrolled in this study. Serum concentrations of SEMA5A and vascular endothelial growth factor A (VEGF-A) were established using the enzyme-linked immunosorbent assay (ELISA) method. The serum concentration of SEMA5A was elevated in JIA patients in comparison to healthy controls with the median value of 2.04 (interquartile range [IQR]: 12.41) in JIA patients and 1.34 (IQR: 1.79) in healthy controls (p = 0.002). The difference was particularly prominent in oligoarticular JIA, where median SEMA5A concentration equaled 1.76 ng/mL (IQR: 1.56) in comparison to 0.33 ng/mL (IQR: 1.34) in sex-and-age-matched healthy controls (p = 0.001). SEMA5A concentration correlated strongly with VEGF-A concentration (r = 0.807, p < 0.001) and differed significantly in subgroups of different synovial membrane power-Doppler ultrasound (PDUS) inflammatory activities (p = 0.018). Although our findings need to be repeated on larger groups of JIA patients, SEMA5A is a promising marker of JIA, linked to pathological angiogenesis of synovial membrane in this entity. Moreover, it may be useful as a target of innovative treatment strategies in the nearest future.
cell therapies
2026-06-13 | Systemic mesenchymal stem cell therapy for reduction of inflammatory burden in a patient with juvenile-onset rheumatoid arthritis and dialysis-dependent renal failure.
Chronic systemic inflammation is a key driver of disease progression in rheumatoid arthritis and chronic kidney disease (CKD), particularly in patients undergoing long-term hemodialysis. Persistent elevation of proinflammatory cytokines contributes to pain, anemia, endothelial dysfunction, and increased cardiovascular risk, while therapeutic options are often limited by comorbidities and drug intolerance. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that may offer an alternative strategy for systemic inflammatory control. We report on the case of a 56-year-old woman with juvenile-onset rheumatoid arthritis and dialysis-dependent CKD who received three consecutive systemic administrations of MSCs. Baseline evaluation demonstrated elevated inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Following treatment, inflammatory parameters were consistently reduced, which was accompanied by improvement in hemoglobin levels and favorable trends in renal function markers. Additionally, pain assessment scores (Western Ontario and McMaster Universities Arthritis Index, Knee Injury and Osteoarthritis Outcome Score, Visual Analogue Scale) showed clinically significant improvement. The patient also reported significant subjective pain relief and improved overall well-being. Although limited by its single-case design, this report supports the biological plausibility of systemic MSC therapy as a potential immunomodulatory approach in patients with overlapping autoimmune and uremia-associated chronic inflammation. Further controlled studies are warranted.
2026-04-30 | Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes.
Human breast milk (HBM) is an ideal nutritional source for the growth and development of infants. In addition, HBM contains hormones, growth factors, microRNAs and exosomes that perform various physiological functions. This study investigates the immunomodulatory effects of HBM-derived exosomes on myeloid cells and chondrocytes, and implications for juvenile idiopathic arthritis. HBM-derived exosomes were isolated and characterized using nanoparticle track analyzer and Western blotting. The HBM-derived exosomes treatment decreased the expression of inflammatory mediators and proinflammatory cytokines in mouse peritoneal macrophages upon lipopolysaccharide stimulation. Flow cytometry analysis of bone marrow-derived macrophages indicated that exosomes promoted M2 polarization, as evidenced by a decrease in cells expressing CD80 (M1 marker) and a concurrent increase in cells expressing M2 marker CD206. In addition, exosome treatment attenuated the mitogen-activated protein kinase signaling pathway by reducing the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and IκB-α, thereby reducing the expression of inducible nitric oxide synthase, cyclooxygenase-2, metalloprotease (MMP)-1, MMP-3, and MMP-13 in SW1353 chondrocytes following IL-1β stimulation. These findings suggest that HBM-derived exosomes promote macrophage polarization toward an anti-inflammatory M2 phenotype and exert significant immunomodulatory effects.
2026-04-08 | Chimeric antigen receptor macrophage (CAR-M) immunotherapy in autoimmune inflammatory rheumatic diseases.
Chronic autoimmune inflammatory rheumatic diseases (AIRD), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis, systemic sclerosis (SSc), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are characterized by the dysregulation of the immune system and that of the neuroendocrine immune networks, leading to chronic inflammation and tissue damage. Perturbations of T, B, and macrophage cells result in uncontrolled inflammation. Traditional therapeutic approaches have focused on immunosuppressive drugs but more recently the use of biologics targeting specific cytokines or receptors on immune cells, and intracellular JAK pathways has been employed. However, these therapies often have limited efficacy and significant side effects. Moreover, they are not globally accessible due to high drug costs especially in poor as well as low- to middle-income countries. Cell immunotherapy, such as CAR-T and CAR-M cell therapy based on chimeric antigen receptor (CAR) technology, is opening up novel potential avenues for a precision approach to managing AIRD. This area is still experimental and in the research phase. This paper reviews the potential of CAR-M immunotherapy in AIRDs, highlighting its mechanisms of action and therapeutic applications.
2025-09-01 | Allogeneic haematopoietic stem cell transplantation for severe Still's disease: a retrospective report of three paediatric patients.
Severe forms of systemic JIA (sJIA), also called paediatric-onset Still's disease are associated with two major life-threatening complications: macrophage activation syndrome (MAS) and severe lung disease. Patients are usually resistant to conventional synthetic (cs) DMARDs, biologic (b) DMARDs, and targeted synthetic (ts) DMARDs. Recently, allogeneic haematopoietic stem cell transplantation (HSCT) has been performed in a small number of patients with refractory and life-threatening disease. We aimed to report outcomes and complications of allogeneic HSCT in patients with severe, refractory sJIA treated at our centre. We conducted a retrospective, observational, single-centre study in a tertiary paediatric immunology care centre (Necker Hospital, Paris, France). We report three sJIA patients who underwent allogeneic HSCT at a median age of 3.5 years. All had recurrent MAS; two had lung disease and the HLA-DRB1*15 haplotype, associated with severe delayed hypersensitivity to IL-1/IL-6 inhibitors. Donors were matched sibling donors for the first and third patient, and matched unrelated donor for the second patient. They presented multiple post-graft complications: graft-vs-host disease, infections, thrombotic microangiopathy and severe inflammatory complications on previously affected organs, such as skin and lungs. At a median follow-up of 22 months (20-33) after transplantation, they were all in remission with full-donor chimerism and were off immunosuppressive treatment. Allogeneic HSCT can be an effective salvage therapy in patients with refractory sJIA. However, the risk of post-transplant endothelial complications and severe inflammation in previously affected organs, such as joints, skin and lungs deserves particular attention.
2025-03-03 | The joint accumulation model of arthritis.
Most inflammatory arthritides are systemic diseases. In an individual patient, however, disease flares are more common in joints affected previously, a phenomenon termed joint-specific memory. A key driver of localized recurrence is the accumulation of CD8+ T resident memory (TRM) cells in inflamed synovial tissues. These cells remain during remission and initiate recurrent disease when activated by arthritogenic antigens. The joint accumulation model is a paradigm that recognizes the contribution of local as well as systemic immune mechanisms to arthritis chronicity, highlighting new targets for disease intervention, including but not limited to TRM cells. The joint accumulation model underscores the importance of preventing extension of arthritis to new joints, even in established disease, translating into a rolling window of opportunity for optimal long-term arthritis management.
antibodies
2026-09-26 | Effectiveness and Safety of Rituximab in Patients with Refractory Juvenile Idiopathic Arthritis: A Tertiary Center Experience.
Introduction: Despite the growing spectrum of modern drugs for the treatment of juvenile idiopathic arthritis (JIA), patients with a refractory, progressive course of the disease remain a clinical challenge. B-cell-depleting therapy has demonstrated efficacy in adult rheumatoid arthritis and several pediatric rheumatic diseases, encouraging us to evaluate rituximab (RTX) for children with refractory JIA. Objective: This study aimed to assess the long-term efficacy and safety of rituximab therapy in children with refractory juvenile idiopathic arthritis. Methods: This retrospective, single-center, observational study included 106 patients with JIA who had failed previous therapy. The efficacy and safety of the therapy were evaluated at baseline and at 3, 6, 12, 24, 36, and 48 months post-initial rituximab infusion using the American College of Rheumatology Pediatric Criteria (ACRpedi 30/50/70/90), C. Wallace criteria for inactive disease/remission, and the JADAS71 activity index until patient completion or withdrawal from the study. The primary endpoint was achieving an ACRpedi50 response by 3 months, and the secondary endpoint was achieving inactive disease status according to C. Wallace criteria by 6 months of follow-up. Results: An ACRpedi50 response was achieved in 78/100 (78%) patients by month 3 of rituximab therapy, and inactive disease status was reached in 48/93 (52%) patients by month 6. More than half of the patients demonstrate inactive disease or remission at each observation point. During rituximab therapy, oral glucocorticoids were discontinued in 18/57 (32%) patients, and 28/57 (49%) patients were able to halve their corticosteroid dose (p = 0.03). Rituximab demonstrated an acceptable safety profile, with a total of 351 adverse events (non-serious AEs: 304/351, 87%) and a serious AE rate of 0.8 per 100 patient-years. Conclusions: Rituximab can reduce disease activity and lower the dose of oral glucocorticoids in patients with refractory JIA, serving as a viable therapeutic option with an acceptable safety profile.
2026-08-27 | Real-World Evolution of Prescribing Patterns and Safety Profiles of Biologic and Targeted Synthetic Therapies in Inflammatory Rheumatic Diseases: A Comparative Study Between 2018-2019 and 2023-2024.
Background/Objectives: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) have expanded treatment options for inflammatory rheumatic diseases, highlighting the need for continuous pharmacovigilance. This study evaluated changes in prescribing patterns and safety profiles of b/tsDMARDs between 2018-2019 and 2023-2024 in routine clinical practice. Methods: A retrospective observational study was conducted in patients with rheumatoid arthritis (AR), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or juvenile idiopathic arthritis (JIA) treated at a rheumatology outpatient clinic in Southern Italy. Demographic and clinical characteristics, prescribed therapies, treatment switches/swaps, therapeutic failures, and adverse events (AEs) were collected through a structured pharmacovigilance program. Prescribing trends between the two study periods were compared using chi-square analysis. Results: A total of 342 patients were included (202 in 2018-2019 and 140 in 2023-2024). Prescribing patterns changed significantly over time (χ2 = 83.24, p < 0.0001), with increased use of newer therapeutic classes and biosimilars, while tumor necrosis factor (TNF) inhibitors remained the most frequently prescribed drugs. The proportion of biologic-naïve patients increased from 52.0% to 66.4%, whereas AEs decreased from 31.7% to 15.0%, with no serious adverse events (SAEs) reported. Conclusions: Prescribing strategies for inflammatory rheumatic diseases evolved substantially between 2018 and 2024, reflecting the availability of new therapeutic options and a more personalized treatment approach. b/tsDMARDs showed a favorable real-world safety profile, supporting the importance of ongoing pharmacovigilance.
2026-08-21 | Mortality and associated factors of JIA in hospitalized Thai children: a nationwide data analysis 2015-2023.
To characterize in-hospital mortality, respiratory failure requiring endotracheal intubation and associated comorbidities among hospitalized children with JIA using nationwide data from Thailand. This was a retrospective study using administrative inpatient data from Thailand's National database from January 2015 to December 2023. All hospital admissions for patients younger than 18 years with JIA were included. Primary outcomes were in-hospital mortality and respiratory failure, defined by endotracheal intubation. Demographics, JIA subtypes, hospital level, healthcare utilization and comorbidities were analysed. Multivariable logistic regression identified comorbidities independently associated with intubation, reported as adjusted odds ratios (aORs) with 95% confidence intervals. Among 3754 JIA admissions, 52.7% of patients were female, with a median age of 10 years (interquartile range 6-13). Endotracheal intubation occurred in 39 admissions (1.0%), and 17 patients died, yielding an in-hospital mortality rate of 0.5%; mortality among intubated patients was 33.3%. Length of stay and costs were substantially higher among intubated patients and non-survivors. Pneumonia was common in both groups. Myocarditis showed the strongest association with intubation (aOR 294.74), followed by pulmonary haemorrhage, acute kidney injury and septic shock. Macrophage activation syndrome was identified in 43 admissions (1.2%) and was more frequent among non-survivors (23.5% vs 1.0%; P < 0.001). Although overall mortality and intubation rates were low, respiratory failure identified a small, high-risk subgroup with substantial mortality and healthcare burden. Severe outcomes were driven by acute multi-organ complications, underscoring early recognition and aggressive management of high-risk comorbidities.
2026-08-11 | The Asia-Pacific League of Associations for Rheumatology Consensus Recommendations on the Management of Systemic Juvenile Idiopathic Arthritis (Juvenile Still's Disease).
The unique characteristics of the Asia Pacific called for the development of pragmatic and viable guidelines for the management of juvenile idiopathic arthritis (JIA). These consensus recommendations represent the second part of the guideline intending to offer an updated and regionally relevant framework for the management of systemic JIA (sJIA)/juvenile Still's disease. A multidisciplinary task force of 35 members from 14 countries, including pediatric and adult rheumatologists as well as patient representatives, was convened. The guideline development followed the GRADE, ADAPTE, and AGREE II frameworks. Relevant international guidelines were critically appraised, and a systematic literature review was performed to address 10 PICO questions. Draft statements were discussed and voted upon using a modified Delphi process, with consensus defined as ≥ 80% agreement. Four overarching principles and eighteen statements, including five statements addressing macrophage activation syndrome (MAS) were formulated. The recommendations align with international guidelines, advocating early use of IL-1/IL-6 inhibitors, avoidance of glucocorticoid monotherapy in sJIA without MAS, promoting tapering of glucocorticoids once inactive disease is achieved, alongside class switching for biologic refractory cases and a treat-to-target approach akin to EULAR/PReS guideline. Additional features include recommending conventional synthetic DMARD when biologics are unavailable and listing the options, acknowledging regional health system heterogeneity in the Asia Pacific, mentioning tapering strategy, discouraging NSAIDs as initial monotherapy, highlighting non-biologic salvage options, and placing less emphasis on sJIA-associated lung diseases. These recommendations provide direction for practitioners caring for sJIA patients in limited resource areas to avoid treatment delay, hence improve overall outcomes. A shared decision approach and treat-to-targets are emphasized.
2026-08-02 | Canakinumab for systemic-onset juvenile idiopathic arthritis/Still's disease-effectiveness and safety data from the BiKeR registry.
In Germany, canakinumab is approved for the treatment of refractory systemic juvenile idiopathic arthritis (sJIA)/Still's disease. This study assesses the experience of sJIA/Still's disease patients treated with canakinumab in clinical practice. Data of 79 sJIA/Still's disease patients extracted from the BiKeR registry included patients' and disease characteristics. Three subgroups with disease durations before canakinumab initiation of ≤3 months, >3 to ≤12 months, and >12 months were compared, and 2 with canakinumab as first- and second- or more-line treatment. Disease duration was ≤3 months before canakinumab initiation for 26 patients, >3 to ≤12 months for 24 patients, and >12 months for 29 patients. Thirty-nine patients received canakinumab as first-line treatment and 40 as second- or more-line treatment. Disease severity as assessed by the systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS10) was highest for patients with a disease duration <3 months before canakinumab initiation. In the total cohort, after 3, 6, 12, 18, and 24 months, 86%, 81%, 81%, 75%, and 87% of patients reached inactive disease, respectively. Numerically, more patients reached the treatment goal of inactive disease when the disease duration was shorter before initiation of canakinumab. Minimal disease activity (sJADAS10 ≤6.0) did not differ among subgroups. Compared with second-line, more patients with first-line treatment reached inactive disease at months 6, 12, and 24 after canakinumab initiation. sJADAS10 at 12 months correlated significantly with disease duration before treatment. Canakinumab treatment led to high improvement rates and achievement of inactive disease state, particularly if they are administered early. Data from clinical practice confirm clinical study data.
other
2026-09-27 | Combined Infliximab and Tofacitinib Therapy for Severe Refractory Juvenile Idiopathic Arthritis Associated Panuveitis: A Challenge, Dechallenge, Rechallenge Case Report.
To report a child with severe treatment-resistant juvenile idiopathic arthritis-associated uveitis (JIAU), characterized by panuveitis, diffuse retinal vascular leakage, and refractory cystoid macular edema. We describe the clinical course, treatment response, and challenge, dechallenge, and rechallenge sequence in a child with severe refractory JIAU treated with combined infliximab and tofacitinib therapy. The patient showed marked improvement in ocular inflammation, macular edema, and visual acuity following addition of tofacitinib to ongoing infliximab therapy. Inflammation recurred after holding infliximab despite continuation of tofacitinib and improved again following reintroduction of infliximab. This challenge, dechallenge, and rechallenge sequence is consistent with a possible complementary effect of infliximab and tofacitinib in this patient. However, causality and pharmacologic synergy cannot be established from a single case. Combined tumor necrosis factor alpha and Janus kinase inhibition may represent an exceptional rescue approach for carefully selected patients with severe refractory JIAU, although its efficacy and long-term safety require further evaluation.
2026-09-26 | Association of 9-Valent HPV Vaccination with Risk of Juvenile Idiopathic Arthritis: A Sex-Stratified Real-World Study.
To evaluate the association between 9-valent human papillomavirus (HPV9) vaccination and the risk of new-onset juvenile idiopathic arthritis (JIA), with particular attention to sex-specific differences, including the relative lack of evidence in males and the potential impact of the COVID-19 pandemic. Using the TriNetX U.S. Collaborative Network (2016-2023), children aged 9-13 years who received HPV9 vaccination were compared with unvaccinated controls in prepandemic and pandemic periods. Incident JIA was assessed using matched cohort analyses and time-to-event methods. Similar sex-specific patterns were observed across both periods. HPV9 vaccination was associated with a lower risk of JIA among girls (HR = 0.45 95% CI = 0.22-0.95 in prepandemic and HR = 0.36 95% CI = 0.17-0.74 during pandemic period), while no increased risk was observed among boys (HR = 1.57 95% CI = 0.67-4.05 in prepandemic and HR = 1.14 95% CI = 0.56-2.34 during pandemic period). Among unvaccinated individuals, girls consistently exhibited a higher incidence of JIA than boys. The COVID-19 pandemic did not alter these associations. HPV9 vaccination was not associated with an increased risk of JIA in either sex. A consistent sex-specific pattern was observed across both study periods, with a lower risk of JIA among vaccinated girls but not boys. This finding suggests a potential sex difference in the association between HPV9 vaccination and JIA and warrants further investigation. However, residual confounding, including healthy-vaccinee bias and differences in healthcare utilization, cannot be fully excluded.
2026-08-11 | Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.
Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.
2026-03-13 | Highlights on the Contribution of Gut Microbiota to Immune-Mediated Diseases in Childhood.
The gut microbiota, a vast community of symbiotic microorganisms inhabiting our gut, has been recognized as a key-lever for human health, shaping immune system resilience and being essential for immunological homeostasis throughout the life course. Gut microbiota composition may influence both initiation and/or perpetuation of intestinal inflammation, but recent research has highlighted its contribution to both rising and progression of protean non-intestinal inflammatory diseases: indeed, a perturbation of host-associated microbiota during critical developmental stages like early childhood can directly condition many cellular dynamics and impact long-term health. This narrative review explores the interactions among gut microbiota, physiologic healthy equilibrium, dysbiosis, and immune-mediated non-intestinal inflammatory diseases occurring in childhood, such as inflammasome-based disorders, juvenile idiopathic arthritis, Kawasaki disease, and IgA vasculitis, focusing on how microbial changes may alter disease outcomes and suggesting potentially novel therapeutic approaches. Additionally, this review examines the evolution of immune recognition mechanisms and their role in maintaining the gut microbiota-host mutualism as a result of millennia of human co-evolution with the microbial counterpart.
2026-01-12 | Impaired Generation of High-Affinity Memory B Cells and Neutralizing Antibodies Against SARS-CoV-2 in Adolescents and Young Adults With Juvenile Idiopathic Arthritis Treated With Tumor Necrosis Factor Inhibitors.
We evaluated the immunogenicity of SARS-CoV-2 mRNA vaccines in patients with juvenile idiopathic arthritis (JIA), focusing on the generation of spike-specific memory B cells (MBCs) and of neutralizing antibodies, and assessed the impact of disease-modifying antirheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi). This study enrolled 35 adolescent and young adult patients with JIA. Data concerning disease characteristics and SARS-CoV-2 vaccination and infection were collected. We analyzed the frequency of low-affinity spike-specific and high-affinity spike-specific MBCs by flow cytometry. We measured total anti-spike antibodies levels using a chemiluminescence microparticle immunoassay and assessed neutralizing antibody titers with a microneutralization assay. Patients with JIA showed a reduced frequency of high-affinity MBCs compared to controls, with a notably poorer response among those receiving TNFi treatment. Additionally, their ability to bind the Omicron variant was significantly lower, particularly among TNFi-treated patients. SARS-CoV-2 infection alone was not able to generate high-affinity MBCs and neutralizing antibodies in patients with JIA. After receiving three vaccine doses, 43% of patients with JIA exhibited a reduced frequency of high-affinity MBCs and neutralizing antibodies. Patients with JIA undergoing treatment with TNFi demonstrated a diminished immunogenic response to SARS-CoV-2 vaccination, with lower frequencies of high-affinity MBCs and decreased neutralizing antibody titers. These findings underscore the need for customized vaccination protocols, including the potential use of booster doses, to enhance immunoprotection in this group. Additionally, the development of reliable biomarkers to distinguish between patients with and without adequate protective immunity is imperative to refine therapeutic interventions and ensure optimal patient outcomes.
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Drug Discovery Landscape
21 orphan drug designations for Juvenile idiopathic arthritis, including 5 approved therapies.
21 orphan drug designations for Juvenile idiopathic arthritis, including 5 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
sirukumab | antibodies | FDA | — | Janssen Research & Development, LLC |
protoplasmic protein matrix, omega-3 fatty oils, vitamins, minerals and trace elements, cell membrane matrix phospholipid, entracellular matrix, lipids, medium chain triglycerides, longer chain triglycerides, carbohydrates, probiotic, and phytonutrients | other | FDA | — | Leonard S. Girsh, MD |
Celecoxib oral liquid suspension | small molecules | FDA | — | NuBioPharma, LLC |
deflazacort | small molecules | FDA | — | PTC Therapeutics, Inc. |
upadacitinib [Rinvoq] | small molecules | FDA | Approved | AbbVie, Inc. |
Kre-Celazine | small molecules | FDA | — | All American Pharmaceutical & Natural Foods Corpor |
Givinostat | small molecules | EMA | Italfarmaco S.p.A. | |
canakinumab [ILARIS] | antibodies | FDA | Approved | Novartis Pharmaceuticals Corporation |
nabumetone | small molecules | FDA | — | Cook Pharma |
adalimumab [Humira] | antibodies | FDA | Approved | AbbVie Inc. |
rofecoxib | small molecules | FDA | — | MERCK & Co., Inc. |
meloxicam [Mobic] | small molecules | FDA | Approved | Avondale Pharmaceuticals |
infliximab | antibodies | FDA | Centocor, Inc. | |
human gammaglobulin | antibodies | FDA | — | Latona Life Sciences, Inc. |
etanercept [Enbrel] | proteins | FDA | Approved | Immunex Corporation |
interferon Beta-1a | proteins | FDA | — | Biogen, Inc. |
Purified type II collagen | proteins | FDA | — | AutoImmune, Inc. |
Gammalinolenic acid | small molecules | FDA | — | Zurier, Robert B. M.D. |
methotrexate | small molecules | FDA | Wyeth-Ayerst Laboratories | |
Immune globulin intravenous (human) | antibodies | FDA | — | Immuno Clinical Research Corp. |
Interleukin-1 receptor antagonist, human recombinant | proteins | FDA | Swedish Orphan Biovitrum AB (publ) (SOBI) |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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