RARE DISEASE
Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis
Synonyms: Juvenile polyarthritis, Juvenile polyarticular arthritis, Polyarticular JIA
Synonyms: Juvenile polyarthritis, Juvenile polyarticular arthritis, Polyarticular JIA
Synonyms: Juvenile polyarthritis, Juvenile polyarticular arthritis, Polyarticular JIA
Drug discovery
3
drugs
With orphan designations
Overview
Polyarticular juvenile idiopathic arthritis (pJIA) is a chronic inflammatory arthritis affecting ≥5 joints within the first 6 months of disease onset in children <16 years, characterized by persistent synovitis, joint damage risk, and potential extra-articular complications such as uveitis [1][9][16]. It is subdivided into rheumatoid factor (RF)-positive and RF-negative subtypes, with the former demonstrating similarities to adult rheumatoid arthritis [1][9]. Early diagnosis and aggressive treatment are critical to prevent irreversible joint destruction and disability [3][15].
Population
Therapies
First-line: Methotrexate (subcutaneous preferred) ± intra-articular corticosteroids [3][15]
Biologic escalation: TNF-α inhibitors (etanercept, infliximab) or IL-6 inhibitors for inadequate response [3][7][11]
Early aggressive therapy: Combination DMARD/biologic regimens improve remission rates (40-70% inactive disease at 12-24 months) [3][15]
Categories: rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
699 drug discovery papers about Polyarticular juvenile idiopathic arthritis, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
699 drug discovery papers about Polyarticular juvenile idiopathic arthritis, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-31 | Comprehensive Rehabilitation in Polyarticular Juvenile Idiopathic Arthritis: Functional Recovery in an Adolescent: A Case Report
Background: During a crucial stage of development, juvenile idiopathic arthritis (JIA) can result in chronic pain, stiffness, decreased mobility, and participation restrictions. When pharmaceutical treatment is not enough to restore function, rehabilitation is required. Case Presentation: A 15-year-old kid with rheumatoid factor-positive polyarticular JIA complained of pain and restricted movement in his right ankle, left knee, and both hands. The patient had stopped going to school, needed help with several everyday tasks, and had trouble walking. VAS discomfort of 6/10, CHAQ of 2/3, Barthel Index of 80/100, PedsQL problem score of 59/100, and a 6-minute walk test distance of 228 m were among the initial findings. Rehabilitation Intervention: The four-month multidisciplinary program consists of low-impact endurance exercises, range-of-motion exercises within pain limits, progressive strengthening, occupational therapy for hand function and self-care, paraffin baths, low-level laser therapy, joint protection education, and a home exercise regimen overseen by a carer. Outcome: VAS decreased from 6 to 0–2, CHAQ decreased from 2 to 0.125, and the 6-minute walk test distance increased from 228 to 448 meters at serial evaluations conducted at weeks 4, 9, 14, and 18. The BMI rose from 17.1 to 19.7 kg/m². The patient was able to walk, take care of themselves, and participate in school activities on their own once more. There were no negative effects linked to the treatment. Conclusion: Adolescents with polyarticular JIA who get individual rehabilitation in addition to continued medical therapy report significant clinical improvements in pain, disability, endurance, and participation.
2026-07-10 | Therapeutic efficacy of upadacitinib in refractory juvenile idiopathic arthritis: a case report
Background Juvenile idiopathic arthritis (JIA) remains a clinical challenge when conventional and biological therapies fail. Case presentation This report describes a case of highly refractory JIA and evaluates the efficacy of the Janus kinase (JAK) inhibitor upadacitinib, providing a potential therapeutic reference for difficult-to-treat pediatric autoimmune diseases. A 16-year-old female presented with a 3-year history of polyarticular swelling and pain that worsened over 1 month. Physical examination revealed extensive tenderness in the small joints of the hands, feet, and knees. Functional impairment was noted in the shoulder joints (restricted abduction and lifting) and wrist joints (limited flexion and extension). Laboratory results showed an erythrocyte sedimentation rate of 26 mm/h and a C-reactive protein level of 18.39 mg/L. Musculoskeletal ultrasound indicated grade 1 synovitis with effusion in the bilateral metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, as well as both wrist joints. Effusion was also observed in the suprapatellar bursae of both knees. The patient's condition was classified as refractory, with prior failure of multiple lines of therapy, including conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), various biologic DMARDs (bDMARDs) (such as TNF, IL-6, and IL-1 inhibitors), and targeted synthetic DMARDs, such as tofacitinib. Following initiation of upadacitinib, the patient achieved marked clinical remission and improved joint mobility. Conclusions Upadacitinib demonstrated potent efficacy in a pediatric patient with JIA who was nonresponsive to multiple bDMARDs and tofacitinib. These findings suggest that upadacitinib may be a viable salvage therapy for refractory JIA.
2026-04-01 | Management of Polyarticular Course Juvenile Idiopathic Arthritis and Temporomandibular Joint Arthritis: A Systematic Literature Review and Meta‐Analysis Informing the APLAR Consensus Recommendations
INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases and requires coordinated and targeted treatment strategies to avoid long-term disability. Existing guidelines from Western countries may not address region-specific factors, including genetic heterogeneity, limited treatment availability, and limitations in healthcare infrastructure, in the Asia Pacific region. The aim of this systematic literature review (SLR) and meta-analysis was to provide up-to-date evidence for the Asia Pacific League of Associations for Rheumatology (APLAR) recommendations for managing polyarticular course JIA (pcJIA) and temporomandibular joint (TMJ) arthritis. METHODS: This systematic review followed PRISMA guidelines, with searches conducted on MEDLINE, Embase, Web of Science, Scopus, and CENTRAL through January 2025. Included studies addressed pharmacologic or non-pharmacologic treatments for pcJIA and TMJ involvement. Studies were limited to publications not already covered in existing guidelines. The Cochrane Rob2 tool and GRADE approach were used to assess quality and evidence certainty. Meta-analyses were performed where applicable. RESULTS: Of the initial 9424 records, 86 studies were included in the qualitative analysis. Methotrexate remains the csDMARD of choice, and subcutaneous administration may be more advantageous. Biological DMARDs, particularly abatacept and tocilizumab, have evidence for good efficacy and acceptable safety profiles. Emerging evidence supports the use of JAK inhibitors. Biosimilars were reported to have efficacy and safety comparable to those of originator biologics in observational studies. Limited evidence suggests that gradual medication tapering after achieving inactive disease status reduces the risk of flares. Evidence for physiotherapy, occupational therapy, and complementary medicine was of very low certainty due to methodological heterogeneity. CONCLUSION: This SLR offers new evidence to support region-specific clinical practice in JIA. While many findings support global recommendations, important evidence gaps remain, particularly in tapering, biosimilar use, TMJ management, and non-pharmacological therapies. These insights will directly inform APLAR's upcoming clinical practice guideline for pcJIA and TMJ arthritis.
2026-03-26 | A Case of Refractory Polyarticular Juvenile Idiopathic Arthritis Post-hematopoietic Stem Cell Transplantation Successfully Treated With Ruxolitinib.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may trigger secondary autoimmune diseases, with autoimmune arthritis representing a rare yet challenging complication. Here, we report a six-year-old male who developed polyarticular juvenile idiopathic arthritis (JIA) three years after allo-HSCT for lymphoma. Despite resistance to multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs), including adalimumab and tocilizumab, treatment with the Janus kinase 1/2 inhibitor ruxolitinib achieved clinical remission sustained for over two years without significant adverse events or lymphoma relapse. Ruxolitinib may represent a viable therapeutic option for refractory secondary JIA post-allo-HSCT, particularly when conventional bDMARDs fail.
2026-03-01 | Juvenile Idiopathic Arthritis: A Deep Dive into Pediatric Autoimmune Arthritis
Arthritis is an autoimmune disease that causes inflammation of the joints, with seven major types identified.One of these is Juvenile Idiopathic Arthritis (JIA), which begins before the age of 16 years.JIA is further classified into six subtypes based on clinical and laboratory findings: systemic, oligoarticular, polyarticular with or without rheumatoid factor, enthesitis-related arthritis (ERA), psoriatic arthritis, and undifferentiated arthritis.Among these, polyarticular JIA is the most common type seen in children.Although the exact cause of JIA remains unknown, it cannot be completely prevented; however, adopting a healthy lifestyle, preventing infections, early diagnosis, and proper management can help reduce its severity and complications.Diagnosis varies depending on the subtype, for example, anti-CCP antibodies are used for polyarticular JIA, while HLA-B27 testing and MRI of joints aid in diagnosing ERA.Management strategies have evolved significantly: initially, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids were the primary treatments, but the introduction of biologic medications has greatly improved outcomes.Agents such as abatacept and tocilizumab have shown particular benefit in polyarticular JIA, while methotrexate, TNF inhibitors, and abatacept are effective in treating JIA-related uveitis.Looking ahead, the future of JIA treatment is moving towards more targeted, personalized, and less toxic therapies, including JAK inhibitors, IL-17/23 blockers, stem cell therapy, microbiome-based interventions, and nanomedicine.Early diagnosis and comprehensive management are crucial for preventing joint damage and improving long-term outcomes and adopting a healthy lifestyle, preventing infections, early diagnosis, and proper management can help reduce its severity and complications.Continued research on immunogenetics and novel biologics holds promise for personalized and more effective therapies in the future.
proteins
2025-06-04 | Inflammation-induced leg length discrepancy in children: from molecular mechanisms to clinical implications.
Leg length discrepancy (LLD) refers to a condition where the lower limbs are of unequal length, which can result from various underlying causes. Inflammatory conditions in children, such as monoarticular, pauciarticular or polyarticular juvenile idiopathic arthritis (JIA), can lead to the development of LLD when predominantly affecting one leg. To date, no review has addressed inflammation-induced LLD. Depending on the localization of the inflammation and age of onset, bone growth can be either locally retarded or accelerated in the affected leg. The resulting LLD can range from mild forms, where treatment is not necessary, to severe forms, leading to premature growth plate fusion and/or an LLD of 5 cm or more. The overall aim of this review is to provide an overview of inflammation-induced LLD and to discuss the possible underlying mechanisms at the growth plate level. In addition, this review offers guidance regarding the natural course of the disease and explores potential new treatment strategies for patients with inflammation-induced LLD.
2025-05-20 | Table 1_Inflammation-induced leg length discrepancy in children: from molecular mechanisms to clinical implications.docx
Leg length discrepancy (LLD) refers to a condition where the lower limbs are of unequal length, which can result from various underlying causes. Inflammatory conditions in children, such as monoarticular, pauciarticular or polyarticular juvenile idiopathic arthritis (JIA), can lead to the development of LLD when predominantly affecting one leg. To date, no review has addressed inflammation-induced LLD. Depending on the localization of the inflammation and age of onset, bone growth can be either locally retarded or accelerated in the affected leg. The resulting LLD can range from mild forms, where treatment is not necessary, to severe forms, leading to premature growth plate fusion and/or an LLD of 5 cm or more. The overall aim of this review is to provide an overview of inflammation-induced LLD and to discuss the possible underlying mechanisms at the growth plate level. In addition, this review offers guidance regarding the natural course of the disease and explores potential new treatment strategies for patients with inflammation-induced LLD.
2024-06-26 | S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25-5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48-9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03-8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02-5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57-5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23-5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46-9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76-7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07-3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10-4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15-8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.
2023-12-01 | GH therapy in children with juvenile idiopathic arthritis: a four-decade review
Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.
2021-03-12 | Growth and puberty in children with juvenile idiopathic arthritis
Abstract Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2–20 cases per 100,000 and a prevalence of 16–150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function . Although new therapeutic options are available to control inflammation, there are still 10–20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient’s bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients . Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
antibodies
2026-08-12 | Case Report: Telitacicept in the treatment of refractory juvenile idiopathic arthritis: clinical experience from three cases.
Refractory juvenile idiopathic arthritis (JIA) remains difficult to manage, particularly in patients with persistent disease activity despite multiple conventional synthetic disease-modifying antirheumatic drugs and biologic agents. Telitacicept is a dual inhibitor of B-cell activating factor and a proliferation-inducing ligand, but its use in JIA has not been well described. We report three pediatric patients with refractory JIA treated with telitacicept. Case 1 was a 6-year-old girl with extended oligoarticular JIA who presented with recurrent swelling, pain, and limited motion of multiple joints, and elevated inflammatory markers after previous treatment with methotrexate, leflunomide, adalimumab, and intra-articular glucocorticoids. After switching to telitacicept combined with tofacitinib and methotrexate, joint symptoms and inflammatory markers improved, and an ACR70 response was achieved; clinical improvement was maintained during 12 months of follow-up. Case 2 was a 17-year-old boy with RF-positive polyarticular JIA and long-standing active disease involving the wrists and small joints of the hands. After telitacicept was added to background therapy, joint swelling resolved, inflammatory markers normalized, and ACR90 response was achieved during 9 months of follow-up. Case 3 was an 11-year-old boy with systemic JIA whose systemic manifestations had been controlled but who continued to have predominant polyarticular involvement. After telitacicept initiation, wrist swelling and inflammatory markers improved during the first 2 months, and an early ACR90 response was observed; however, relapse occurred at month 3 with recurrence of systemic symptoms, leading to discontinuation of telitacicept. No serious adverse events were observed. One patient developed a mild upper respiratory tract infection that resolved with symptomatic treatment. These cases provide preliminary clinical observations on telitacicept use in refractory JIA. BAFF/APRIL inhibition may warrant further investigation in selected patients with refractory JIA, particularly those with persistent articular involvement; however, prospective controlled studies are needed to evaluate efficacy and safety.
2026-04-14 | [Clinical characteristics and outcomes of children with rheu-matoid factor-positive polyarticular juvenile idiopathic arthritis].
To compare the clinical characteristics and outcomes between patients with rheumatoid factor (RF)-positive and RF-negative polyarticular juvenile idiopathic arthritis (pJIA). A retrospective analysis was conducted on clinical data of 131 children diagnosed with pJIA at the Children's Hospital, Zhejiang University School of Medicine from January 2019 to January 2025. Patients were divided into an RF-positive group (n=59) and an RF-negative group (n=72) based on serum RF status. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27). All patients were followed for at least 6 months, with a maximum follow-up duration of 6 years. Clinical features, laboratory findings, and outcomes were compared between the two groups. Among the 131 pJIA patients, 122 (93.1%) had high disease activity at baseline. Compared with the RF-negative group, the RF-positive group had a higher proportion of females (58.3% vs. 84.7%, P<0.01), an older age at onset (7.14±3.98 years vs. 8.86±4.02 years, P<0.05), and a higher prevalence of interstitial lung disease (4.2% vs. 23.7%, P<0.01). The most frequently affected joints were the wrist in the RF-positive group, and the knee joints in the RF-negative group. At baseline, serum levels of IL-2, IL-6, IL-10, and tumor necrosis factor-α were significantly higher in the RF-positive group than those in the RF-negative group (all P<0.05). A total of 101 patients (77.1%) received biologic-targeted therapies, 46 (78.0%) in RF-positive group, and 55 (76.4%) in RF-negative group. Among them, 23 RF-positive patients (50.0%) and 12 RF-negative patients (21.8%) required two or more biologic-targeted drugs. RF positivity was identified as an independent risk factor for the use of two or more biologic-targeted drugs (OR=3.232, 95%CI: 1.109-9.421, P<0.05). Both groups showed significant reductions in JADAS-27 scores at 3, 6, 12, 24, 36, 48, 60, 72 months after treatment initiation compared with baseline (all P<0.01), with no significant differences in JADAS-27 scores or remission rates between the two groups at any follow-up time point (all P>0.05). The median time to achieve first clinical remission after treatment was 24 months in both groups (P>0.05). No significant differences were observed in remission rates or the proportion of patients requiring two or more biologic-targeted drugs among different types of biologic-targeted drugs (all P>0.05). Children with RF-positive pJIA showed higher baseline inflammatory status and a higher incidence of pulmonary involvement, yet they achieved comparable remission rates to those with RF-negative pJIA. Biologic-targeted therapies may contribute to improved remission rates and outcomes, but RF-positive patients may require switching or combination therapy with different targets to achieve clinical remission.
2026-03-07 | Soluble factors released from fibroblast-like synoviocytes of JIA patients with future extended course can condition persistent JIA synovial fibroblasts for increased IL-6 production
BACKGROUND: Juvenile Idiopathic Arthritis (JIA) includes a subset of oligoarticular patients who later extend to a polyarticular course (extended-to-be, ETB), resulting in worse outcomes. Predictors of extension remain poorly defined. We investigated whether interleukin-6 (IL-6) and fibroblast-like synoviocytes (FLS) contribute to this progression. METHODS: Synovial fluid samples from persistent oligoarticular patients who remained persistent (≤ 4 joints involved) throughout their disease course and ETB patients were analyzed using protein antibody arrays and ELISA. Importantly, ETB samples were collected prior to clinical extension, and persistent samples were from patients who never extended during the course of their disease. FLS were isolated from synovial fluid and cultured to assess IL-6 secretion. Conditioned media experiments were performed to evaluate whether factors secreted by ETB FLS could influence IL-6 expression in persistent FLS. RESULTS: MANOVA revealed that (Wilks’ λ = 0.5446, F(9, 31) = 2.88, p = 0.0136) IL-6 and multiple IL-6–related cytokines were significantly elevated in synovial fluid from ETB patients compared to persistent patients. Quantitative ELISA confirmed higher IL-6 concentrations in ETB samples (1.46-fold increase, p = 0.047). FLS isolated from ETB patients prior to extension secreted significantly more IL-6 than persistent FLS (1.6-fold increase, p = 0.0239). Conditioned media from ETB FLS induced IL-6 production in persistent FLS to levels comparable to ETB FLS, demonstrating that soluble factors secreted early by ETB FLS can reprogram persistent FLS toward an inflammatory phenotype, even though these persistent FLS came from patients who remained clinically persistent throughout their disease course. CONCLUSIONS: Our findings suggest factors secreted by ETB FLS including IL-6 protein may contribute to disease extension. These data highlight the potential role of early synovial signaling in shaping disease trajectory and support further investigation into IL-6 and FLS as possible therapeutic targets to prevent progression.
2026-01-28 | Open-Label Phase II Study of Olokizumab in Adolescent Patients with Polyarticular Juvenile Idiopathic Arthritis: Results of the 24-Week Treatment Period.
Background/Objectives: This study aimed to evaluate the pharmacokinetics (PK), effectiveness, and safety of the direct interleukin-6 (IL-6) inhibitor olokizumab (OKZ) in adolescent patients with active polyarticular juvenile idiopathic arthritis (pJIA) who had an inadequate response or intolerance to methotrexate (MTX). Methods: We analyzed results from an open-label, single-arm trial of OKZ therapy at a dose of 64 mg every 4 weeks for 24 weeks. We evaluated pharmacokinetic (PK) parameters, clinical effectiveness, serum C-reactive protein (CRP) dynamics, and adverse events (AEs). Results: Sixteen patients were included in the study, of whom 13 (81.2%) received OKZ through Week 24. The PK profile was consistent with observations in adults with rheumatoid arthritis (RA). By Week 16, 12 (80%) patients achieved an ACRpedi30 response, 11 (73.3%) achieved an ACRpedi50 response, and 2 (13.3%) reached inactive disease status. This response was sustained through Week 24, and no disease flares were observed. A trend toward a better response was noted among patients with baseline CRP > 10 mg/L, higher baseline IL-6, and those naïve to biologic DMARDs. Twelve patients (75.0%) experienced twenty-three mild or moderate AEs. Infections were the most frequent AEs (in 6 patients, 37.5%). No serious AEs or deaths occurred. Conclusions: OKZ treatment reduced pJIA disease activity and was well tolerated. The safety profile was consistent with that of other IL-6 inhibitors, and the PK profile matched that seen in adult RA patients.
2026-01-14 | Use of biologic drugs in juvenile idiopathic arthritis patients followed in an adult rheumatology clinic: real-life data from the HUR-BIO biologic registry.
This study aimed to determine whether there are differences in biologic treatment and complications according to subgroups of juvenile idiopathic arthritis (JIA) patients in adulthood. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) has been a single-center biologic disease-modifying anti-rheumatic drug registry since 2005. Patients were selected from HUR-BIO who met the International League of Associations for Rheumatology classification criteria for juvenile idiopathic arthritis. Enthesitis-related arthritis (82, 49.1%), rheumatoid factor (-) polyarthritis (39, 23.4%), and rheumatoid factor ( +) polyarthritis (26, 15.6%) were the most prevalent subgroups in 167 JIA patients. Etanercept (105, 62.9%), adalimumab (28, 16.8%), and infliximab (21, 12.6%) were the most prescribed first-line biologic drugs. Secondary failure was the most common reason for the treatment changes among 42 (43.3%) patients, followed by non-life-threatening side effects in 12 (12.4%) and primary failure in 11 (11.3%). Polyarticular JIA showed higher HAQ (p = 0.020) and DAS28-ESR (p < 0.001) before biologics and had a longer disease duration to initiation of biologic treatment than enthesitis-related arthritis (p < 0.001). Only one patient (1.2%) in the enthesitis-related arthritis group needed the hip prosthesis, while 12 patients (18.5%) in the polyarticular JIA group required the same procedure (p < 0.001). In adult rheumatology departments, the most common JIAs present with ongoing disease are enthesitis-related arthritis and polyarthritis. Secondary failure was the main reason nearly half of the patients needed biologic changes during follow-up. The polyarticular group appears to have a higher disease severity and level of disability. Key Points • The most of juvenile idiopathic arthritis patients in adult rheumatology clinics require biologics are enthesitis-related arthritis and polyarticular arthritis. • Approximately half of the patients require biologic changes during follow-up, most of these due to secondary failure. • Disease severity and disability appear to be higher in the polyarticular group, therefore treatment intensification may be considered.
oligonucleotides
2023-06-05 | MicroRNA-27a-3p enhances the inflammatory phenotype of Juvenile Idiopathic Arthritis fibroblast-like synoviocytes
Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic pediatric rheumatic disorder. In joints of JIA patients, aggressive phenotypic changes in fibroblast-like synoviocytes (FLS) of the synovial lining play a key role in inflammation. MicroRNAs are dysregulated in rheumatoid arthritis and JIA, including miR-27a-3p. However, it is not understood if miR-27a-3p, enriched in JIA synovial fluid (SF) and leukocytes, alters FLS function.Primary JIA FLS cells were transfected with a miR-27a-3p mimic or a negative control microRNA (miR-NC) and stimulated with pooled JIA SF or inflammatory cytokines. Viability and apoptosis were analyzed by flow cytometry. Proliferation was evaluated using a 3H-thymidine incorporation assay. Cytokine production was assessed by qPCR and ELISA. Expression of TGF-β pathway genes was determined using a qPCR array.MiR-27a-3p was constitutively expressed in FLS. Overexpression of miR-27a-3p caused increased interleukin-8 secretion in resting FLS, and interleukin-6 was elevated in SF-activated FLS compared to miR-NC. Furthermore, stimulation with pro-inflammatory cytokines augmented FLS proliferation in miR-27a-3p-transfected FLS relative to miR-NC. Expression of multiple TGF-β pathway genes was modulated by overexpression of miR-27a-3p.MiR-27a-3p significantly contributes to FLS proliferation and cytokine production, making it a potential candidate for epigenetic therapy that targets FLS in arthritis.
2019-10-22 | Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis
Abstract Background Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA). The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA. Methods Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients. The relative expressions of miR-21, STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay. Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21. The expression of STAT3/p-STAT3 was measured by western blot, and the levels of interleukin (IL)-17A, p65, matrix metalloproteinases (MMP)-3, MMP-4 and receptor activator of nuclear factor-κB after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay. Finally, the miR-21 targeted STAT3 gene was detected by the dual-luciferase reported assay. Results The expression of miR-21 was significantly lower in JIA patients than in healthy control ( P < 0.05). The level of STAT3 was increased in PBMCs of JIA group compared with control group ( P < 0.05). Furthermore, the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 ( r = − 0.5854/ r = − 0.6134, P < 0.05). The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21. The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 ( P < 0.05). RASFs were induced into osteoclasts using M-CSF. The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group ( P < 0.05). Conclusions We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control. MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3. MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.
2019-02-27 | Micro-RNAs in inflammatory arthritis: From physiopathology to diagnosis, prognosis and therapeutic opportunities
Micro-RNAs are an area of research exponentially expanding over the past years. These small sequences of 20-22 nucleotides have a strong role as post-transcriptional regulators of gene expression. Inflammatory arthritis pathophysiology involves various key players from innate to adaptive immunity, as well as various signalling pathways of inflammation. In this review, we discuss how micro-RNAs are involved in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile inflammatory arthritis, from pre-clinical phases to established diseases. We describe mi-RNAs key roles in fibroblast like synoviocytes migration, proliferation, apoptosis and cytokine production, in macrophages polarization, as well as in B cells and T cell proliferation and differentiation, with a special emphasis on Treg/Th17 imbalance. We finally discuss the application of these findings in pre-clinical models and highlight opportunities and limits of a therapeutic approach using mi-RNAs agonists or antagonists.
2016-08-15 | Using the attract method to identify core pathways in juvenile idiopathic arthritis
The aim of this study was to identify core pathways associated with juvenile idiopathic arthritis (JIA) using the attract method. Kyoto Encyclopedia of Genes and Genomes pathways were determined using the GSEA-ANOVA method, based on the gene expression data of JIA. Syn-expression groups within core attractor pathways were identified by hierarchical clustering. Correlated sets of genes exhibiting highly similar profiles to the syn-expression groups were identified and each correlated set was subjected to a gene ontology functional enrichment analysis to discover potentially shared biological themes. Based on a false-discovery rate < 0.05, we identified 11 significant pathways were identified as potential attractors. Flag genes or uninformative genes were removed and 5 discriminative pathways: the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were identified. A final set of syn-expression groups with a consistent trend of relative expression of pathway-related genes was obtained; that is, the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were composed of 2, 2, 1, 2, and 3 clusters, respectively. Genes in each correlated set shared common roles, and changes at the pathway level were more likely to be real. In light of these, the attract method was able to on expand important context to find distinguishing expression patterns within pathways. This paper predicted that the functional themes involved in protein synthesis (such as proteasome, ribosome, spliceosome) were closely related to the progression of JIA, which might contribute to the detection of therapy target for JIA.
other
2024-08-26 | Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study
Abstract Background Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition. Methods We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm. Results Case–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1 . HLA-DRB1* 08:01, HLA-DQA1* 04:01, and HLA-DQB1* 04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1* 08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1* 11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1* 11, and HLA-DPB1* 02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity. Conclusions This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.
small molecules
2026-07-31 | Comprehensive Rehabilitation in Polyarticular Juvenile Idiopathic Arthritis: Functional Recovery in an Adolescent: A Case Report
Background: During a crucial stage of development, juvenile idiopathic arthritis (JIA) can result in chronic pain, stiffness, decreased mobility, and participation restrictions. When pharmaceutical treatment is not enough to restore function, rehabilitation is required. Case Presentation: A 15-year-old kid with rheumatoid factor-positive polyarticular JIA complained of pain and restricted movement in his right ankle, left knee, and both hands. The patient had stopped going to school, needed help with several everyday tasks, and had trouble walking. VAS discomfort of 6/10, CHAQ of 2/3, Barthel Index of 80/100, PedsQL problem score of 59/100, and a 6-minute walk test distance of 228 m were among the initial findings. Rehabilitation Intervention: The four-month multidisciplinary program consists of low-impact endurance exercises, range-of-motion exercises within pain limits, progressive strengthening, occupational therapy for hand function and self-care, paraffin baths, low-level laser therapy, joint protection education, and a home exercise regimen overseen by a carer. Outcome: VAS decreased from 6 to 0–2, CHAQ decreased from 2 to 0.125, and the 6-minute walk test distance increased from 228 to 448 meters at serial evaluations conducted at weeks 4, 9, 14, and 18. The BMI rose from 17.1 to 19.7 kg/m². The patient was able to walk, take care of themselves, and participate in school activities on their own once more. There were no negative effects linked to the treatment. Conclusion: Adolescents with polyarticular JIA who get individual rehabilitation in addition to continued medical therapy report significant clinical improvements in pain, disability, endurance, and participation.
2026-07-10 | Therapeutic efficacy of upadacitinib in refractory juvenile idiopathic arthritis: a case report
Background Juvenile idiopathic arthritis (JIA) remains a clinical challenge when conventional and biological therapies fail. Case presentation This report describes a case of highly refractory JIA and evaluates the efficacy of the Janus kinase (JAK) inhibitor upadacitinib, providing a potential therapeutic reference for difficult-to-treat pediatric autoimmune diseases. A 16-year-old female presented with a 3-year history of polyarticular swelling and pain that worsened over 1 month. Physical examination revealed extensive tenderness in the small joints of the hands, feet, and knees. Functional impairment was noted in the shoulder joints (restricted abduction and lifting) and wrist joints (limited flexion and extension). Laboratory results showed an erythrocyte sedimentation rate of 26 mm/h and a C-reactive protein level of 18.39 mg/L. Musculoskeletal ultrasound indicated grade 1 synovitis with effusion in the bilateral metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, as well as both wrist joints. Effusion was also observed in the suprapatellar bursae of both knees. The patient's condition was classified as refractory, with prior failure of multiple lines of therapy, including conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), various biologic DMARDs (bDMARDs) (such as TNF, IL-6, and IL-1 inhibitors), and targeted synthetic DMARDs, such as tofacitinib. Following initiation of upadacitinib, the patient achieved marked clinical remission and improved joint mobility. Conclusions Upadacitinib demonstrated potent efficacy in a pediatric patient with JIA who was nonresponsive to multiple bDMARDs and tofacitinib. These findings suggest that upadacitinib may be a viable salvage therapy for refractory JIA.
2026-04-01 | Management of Polyarticular Course Juvenile Idiopathic Arthritis and Temporomandibular Joint Arthritis: A Systematic Literature Review and Meta‐Analysis Informing the APLAR Consensus Recommendations
INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases and requires coordinated and targeted treatment strategies to avoid long-term disability. Existing guidelines from Western countries may not address region-specific factors, including genetic heterogeneity, limited treatment availability, and limitations in healthcare infrastructure, in the Asia Pacific region. The aim of this systematic literature review (SLR) and meta-analysis was to provide up-to-date evidence for the Asia Pacific League of Associations for Rheumatology (APLAR) recommendations for managing polyarticular course JIA (pcJIA) and temporomandibular joint (TMJ) arthritis. METHODS: This systematic review followed PRISMA guidelines, with searches conducted on MEDLINE, Embase, Web of Science, Scopus, and CENTRAL through January 2025. Included studies addressed pharmacologic or non-pharmacologic treatments for pcJIA and TMJ involvement. Studies were limited to publications not already covered in existing guidelines. The Cochrane Rob2 tool and GRADE approach were used to assess quality and evidence certainty. Meta-analyses were performed where applicable. RESULTS: Of the initial 9424 records, 86 studies were included in the qualitative analysis. Methotrexate remains the csDMARD of choice, and subcutaneous administration may be more advantageous. Biological DMARDs, particularly abatacept and tocilizumab, have evidence for good efficacy and acceptable safety profiles. Emerging evidence supports the use of JAK inhibitors. Biosimilars were reported to have efficacy and safety comparable to those of originator biologics in observational studies. Limited evidence suggests that gradual medication tapering after achieving inactive disease status reduces the risk of flares. Evidence for physiotherapy, occupational therapy, and complementary medicine was of very low certainty due to methodological heterogeneity. CONCLUSION: This SLR offers new evidence to support region-specific clinical practice in JIA. While many findings support global recommendations, important evidence gaps remain, particularly in tapering, biosimilar use, TMJ management, and non-pharmacological therapies. These insights will directly inform APLAR's upcoming clinical practice guideline for pcJIA and TMJ arthritis.
2026-03-26 | A Case of Refractory Polyarticular Juvenile Idiopathic Arthritis Post-hematopoietic Stem Cell Transplantation Successfully Treated With Ruxolitinib.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may trigger secondary autoimmune diseases, with autoimmune arthritis representing a rare yet challenging complication. Here, we report a six-year-old male who developed polyarticular juvenile idiopathic arthritis (JIA) three years after allo-HSCT for lymphoma. Despite resistance to multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs), including adalimumab and tocilizumab, treatment with the Janus kinase 1/2 inhibitor ruxolitinib achieved clinical remission sustained for over two years without significant adverse events or lymphoma relapse. Ruxolitinib may represent a viable therapeutic option for refractory secondary JIA post-allo-HSCT, particularly when conventional bDMARDs fail.
2026-03-01 | Juvenile Idiopathic Arthritis: A Deep Dive into Pediatric Autoimmune Arthritis
Arthritis is an autoimmune disease that causes inflammation of the joints, with seven major types identified.One of these is Juvenile Idiopathic Arthritis (JIA), which begins before the age of 16 years.JIA is further classified into six subtypes based on clinical and laboratory findings: systemic, oligoarticular, polyarticular with or without rheumatoid factor, enthesitis-related arthritis (ERA), psoriatic arthritis, and undifferentiated arthritis.Among these, polyarticular JIA is the most common type seen in children.Although the exact cause of JIA remains unknown, it cannot be completely prevented; however, adopting a healthy lifestyle, preventing infections, early diagnosis, and proper management can help reduce its severity and complications.Diagnosis varies depending on the subtype, for example, anti-CCP antibodies are used for polyarticular JIA, while HLA-B27 testing and MRI of joints aid in diagnosing ERA.Management strategies have evolved significantly: initially, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids were the primary treatments, but the introduction of biologic medications has greatly improved outcomes.Agents such as abatacept and tocilizumab have shown particular benefit in polyarticular JIA, while methotrexate, TNF inhibitors, and abatacept are effective in treating JIA-related uveitis.Looking ahead, the future of JIA treatment is moving towards more targeted, personalized, and less toxic therapies, including JAK inhibitors, IL-17/23 blockers, stem cell therapy, microbiome-based interventions, and nanomedicine.Early diagnosis and comprehensive management are crucial for preventing joint damage and improving long-term outcomes and adopting a healthy lifestyle, preventing infections, early diagnosis, and proper management can help reduce its severity and complications.Continued research on immunogenetics and novel biologics holds promise for personalized and more effective therapies in the future.
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2025-06-04 | Inflammation-induced leg length discrepancy in children: from molecular mechanisms to clinical implications.
Leg length discrepancy (LLD) refers to a condition where the lower limbs are of unequal length, which can result from various underlying causes. Inflammatory conditions in children, such as monoarticular, pauciarticular or polyarticular juvenile idiopathic arthritis (JIA), can lead to the development of LLD when predominantly affecting one leg. To date, no review has addressed inflammation-induced LLD. Depending on the localization of the inflammation and age of onset, bone growth can be either locally retarded or accelerated in the affected leg. The resulting LLD can range from mild forms, where treatment is not necessary, to severe forms, leading to premature growth plate fusion and/or an LLD of 5 cm or more. The overall aim of this review is to provide an overview of inflammation-induced LLD and to discuss the possible underlying mechanisms at the growth plate level. In addition, this review offers guidance regarding the natural course of the disease and explores potential new treatment strategies for patients with inflammation-induced LLD.
2025-05-20 | Table 1_Inflammation-induced leg length discrepancy in children: from molecular mechanisms to clinical implications.docx
Leg length discrepancy (LLD) refers to a condition where the lower limbs are of unequal length, which can result from various underlying causes. Inflammatory conditions in children, such as monoarticular, pauciarticular or polyarticular juvenile idiopathic arthritis (JIA), can lead to the development of LLD when predominantly affecting one leg. To date, no review has addressed inflammation-induced LLD. Depending on the localization of the inflammation and age of onset, bone growth can be either locally retarded or accelerated in the affected leg. The resulting LLD can range from mild forms, where treatment is not necessary, to severe forms, leading to premature growth plate fusion and/or an LLD of 5 cm or more. The overall aim of this review is to provide an overview of inflammation-induced LLD and to discuss the possible underlying mechanisms at the growth plate level. In addition, this review offers guidance regarding the natural course of the disease and explores potential new treatment strategies for patients with inflammation-induced LLD.
2024-06-26 | S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25-5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48-9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03-8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02-5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57-5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23-5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46-9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76-7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07-3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10-4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15-8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.
2023-12-01 | GH therapy in children with juvenile idiopathic arthritis: a four-decade review
Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.
2021-03-12 | Growth and puberty in children with juvenile idiopathic arthritis
Abstract Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2–20 cases per 100,000 and a prevalence of 16–150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function . Although new therapeutic options are available to control inflammation, there are still 10–20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient’s bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients . Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
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2026-08-12 | Case Report: Telitacicept in the treatment of refractory juvenile idiopathic arthritis: clinical experience from three cases.
Refractory juvenile idiopathic arthritis (JIA) remains difficult to manage, particularly in patients with persistent disease activity despite multiple conventional synthetic disease-modifying antirheumatic drugs and biologic agents. Telitacicept is a dual inhibitor of B-cell activating factor and a proliferation-inducing ligand, but its use in JIA has not been well described. We report three pediatric patients with refractory JIA treated with telitacicept. Case 1 was a 6-year-old girl with extended oligoarticular JIA who presented with recurrent swelling, pain, and limited motion of multiple joints, and elevated inflammatory markers after previous treatment with methotrexate, leflunomide, adalimumab, and intra-articular glucocorticoids. After switching to telitacicept combined with tofacitinib and methotrexate, joint symptoms and inflammatory markers improved, and an ACR70 response was achieved; clinical improvement was maintained during 12 months of follow-up. Case 2 was a 17-year-old boy with RF-positive polyarticular JIA and long-standing active disease involving the wrists and small joints of the hands. After telitacicept was added to background therapy, joint swelling resolved, inflammatory markers normalized, and ACR90 response was achieved during 9 months of follow-up. Case 3 was an 11-year-old boy with systemic JIA whose systemic manifestations had been controlled but who continued to have predominant polyarticular involvement. After telitacicept initiation, wrist swelling and inflammatory markers improved during the first 2 months, and an early ACR90 response was observed; however, relapse occurred at month 3 with recurrence of systemic symptoms, leading to discontinuation of telitacicept. No serious adverse events were observed. One patient developed a mild upper respiratory tract infection that resolved with symptomatic treatment. These cases provide preliminary clinical observations on telitacicept use in refractory JIA. BAFF/APRIL inhibition may warrant further investigation in selected patients with refractory JIA, particularly those with persistent articular involvement; however, prospective controlled studies are needed to evaluate efficacy and safety.
2026-04-14 | [Clinical characteristics and outcomes of children with rheu-matoid factor-positive polyarticular juvenile idiopathic arthritis].
To compare the clinical characteristics and outcomes between patients with rheumatoid factor (RF)-positive and RF-negative polyarticular juvenile idiopathic arthritis (pJIA). A retrospective analysis was conducted on clinical data of 131 children diagnosed with pJIA at the Children's Hospital, Zhejiang University School of Medicine from January 2019 to January 2025. Patients were divided into an RF-positive group (n=59) and an RF-negative group (n=72) based on serum RF status. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27). All patients were followed for at least 6 months, with a maximum follow-up duration of 6 years. Clinical features, laboratory findings, and outcomes were compared between the two groups. Among the 131 pJIA patients, 122 (93.1%) had high disease activity at baseline. Compared with the RF-negative group, the RF-positive group had a higher proportion of females (58.3% vs. 84.7%, P<0.01), an older age at onset (7.14±3.98 years vs. 8.86±4.02 years, P<0.05), and a higher prevalence of interstitial lung disease (4.2% vs. 23.7%, P<0.01). The most frequently affected joints were the wrist in the RF-positive group, and the knee joints in the RF-negative group. At baseline, serum levels of IL-2, IL-6, IL-10, and tumor necrosis factor-α were significantly higher in the RF-positive group than those in the RF-negative group (all P<0.05). A total of 101 patients (77.1%) received biologic-targeted therapies, 46 (78.0%) in RF-positive group, and 55 (76.4%) in RF-negative group. Among them, 23 RF-positive patients (50.0%) and 12 RF-negative patients (21.8%) required two or more biologic-targeted drugs. RF positivity was identified as an independent risk factor for the use of two or more biologic-targeted drugs (OR=3.232, 95%CI: 1.109-9.421, P<0.05). Both groups showed significant reductions in JADAS-27 scores at 3, 6, 12, 24, 36, 48, 60, 72 months after treatment initiation compared with baseline (all P<0.01), with no significant differences in JADAS-27 scores or remission rates between the two groups at any follow-up time point (all P>0.05). The median time to achieve first clinical remission after treatment was 24 months in both groups (P>0.05). No significant differences were observed in remission rates or the proportion of patients requiring two or more biologic-targeted drugs among different types of biologic-targeted drugs (all P>0.05). Children with RF-positive pJIA showed higher baseline inflammatory status and a higher incidence of pulmonary involvement, yet they achieved comparable remission rates to those with RF-negative pJIA. Biologic-targeted therapies may contribute to improved remission rates and outcomes, but RF-positive patients may require switching or combination therapy with different targets to achieve clinical remission.
2026-03-07 | Soluble factors released from fibroblast-like synoviocytes of JIA patients with future extended course can condition persistent JIA synovial fibroblasts for increased IL-6 production
BACKGROUND: Juvenile Idiopathic Arthritis (JIA) includes a subset of oligoarticular patients who later extend to a polyarticular course (extended-to-be, ETB), resulting in worse outcomes. Predictors of extension remain poorly defined. We investigated whether interleukin-6 (IL-6) and fibroblast-like synoviocytes (FLS) contribute to this progression. METHODS: Synovial fluid samples from persistent oligoarticular patients who remained persistent (≤ 4 joints involved) throughout their disease course and ETB patients were analyzed using protein antibody arrays and ELISA. Importantly, ETB samples were collected prior to clinical extension, and persistent samples were from patients who never extended during the course of their disease. FLS were isolated from synovial fluid and cultured to assess IL-6 secretion. Conditioned media experiments were performed to evaluate whether factors secreted by ETB FLS could influence IL-6 expression in persistent FLS. RESULTS: MANOVA revealed that (Wilks’ λ = 0.5446, F(9, 31) = 2.88, p = 0.0136) IL-6 and multiple IL-6–related cytokines were significantly elevated in synovial fluid from ETB patients compared to persistent patients. Quantitative ELISA confirmed higher IL-6 concentrations in ETB samples (1.46-fold increase, p = 0.047). FLS isolated from ETB patients prior to extension secreted significantly more IL-6 than persistent FLS (1.6-fold increase, p = 0.0239). Conditioned media from ETB FLS induced IL-6 production in persistent FLS to levels comparable to ETB FLS, demonstrating that soluble factors secreted early by ETB FLS can reprogram persistent FLS toward an inflammatory phenotype, even though these persistent FLS came from patients who remained clinically persistent throughout their disease course. CONCLUSIONS: Our findings suggest factors secreted by ETB FLS including IL-6 protein may contribute to disease extension. These data highlight the potential role of early synovial signaling in shaping disease trajectory and support further investigation into IL-6 and FLS as possible therapeutic targets to prevent progression.
2026-01-28 | Open-Label Phase II Study of Olokizumab in Adolescent Patients with Polyarticular Juvenile Idiopathic Arthritis: Results of the 24-Week Treatment Period.
Background/Objectives: This study aimed to evaluate the pharmacokinetics (PK), effectiveness, and safety of the direct interleukin-6 (IL-6) inhibitor olokizumab (OKZ) in adolescent patients with active polyarticular juvenile idiopathic arthritis (pJIA) who had an inadequate response or intolerance to methotrexate (MTX). Methods: We analyzed results from an open-label, single-arm trial of OKZ therapy at a dose of 64 mg every 4 weeks for 24 weeks. We evaluated pharmacokinetic (PK) parameters, clinical effectiveness, serum C-reactive protein (CRP) dynamics, and adverse events (AEs). Results: Sixteen patients were included in the study, of whom 13 (81.2%) received OKZ through Week 24. The PK profile was consistent with observations in adults with rheumatoid arthritis (RA). By Week 16, 12 (80%) patients achieved an ACRpedi30 response, 11 (73.3%) achieved an ACRpedi50 response, and 2 (13.3%) reached inactive disease status. This response was sustained through Week 24, and no disease flares were observed. A trend toward a better response was noted among patients with baseline CRP > 10 mg/L, higher baseline IL-6, and those naïve to biologic DMARDs. Twelve patients (75.0%) experienced twenty-three mild or moderate AEs. Infections were the most frequent AEs (in 6 patients, 37.5%). No serious AEs or deaths occurred. Conclusions: OKZ treatment reduced pJIA disease activity and was well tolerated. The safety profile was consistent with that of other IL-6 inhibitors, and the PK profile matched that seen in adult RA patients.
2026-01-14 | Use of biologic drugs in juvenile idiopathic arthritis patients followed in an adult rheumatology clinic: real-life data from the HUR-BIO biologic registry.
This study aimed to determine whether there are differences in biologic treatment and complications according to subgroups of juvenile idiopathic arthritis (JIA) patients in adulthood. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) has been a single-center biologic disease-modifying anti-rheumatic drug registry since 2005. Patients were selected from HUR-BIO who met the International League of Associations for Rheumatology classification criteria for juvenile idiopathic arthritis. Enthesitis-related arthritis (82, 49.1%), rheumatoid factor (-) polyarthritis (39, 23.4%), and rheumatoid factor ( +) polyarthritis (26, 15.6%) were the most prevalent subgroups in 167 JIA patients. Etanercept (105, 62.9%), adalimumab (28, 16.8%), and infliximab (21, 12.6%) were the most prescribed first-line biologic drugs. Secondary failure was the most common reason for the treatment changes among 42 (43.3%) patients, followed by non-life-threatening side effects in 12 (12.4%) and primary failure in 11 (11.3%). Polyarticular JIA showed higher HAQ (p = 0.020) and DAS28-ESR (p < 0.001) before biologics and had a longer disease duration to initiation of biologic treatment than enthesitis-related arthritis (p < 0.001). Only one patient (1.2%) in the enthesitis-related arthritis group needed the hip prosthesis, while 12 patients (18.5%) in the polyarticular JIA group required the same procedure (p < 0.001). In adult rheumatology departments, the most common JIAs present with ongoing disease are enthesitis-related arthritis and polyarthritis. Secondary failure was the main reason nearly half of the patients needed biologic changes during follow-up. The polyarticular group appears to have a higher disease severity and level of disability. Key Points • The most of juvenile idiopathic arthritis patients in adult rheumatology clinics require biologics are enthesitis-related arthritis and polyarticular arthritis. • Approximately half of the patients require biologic changes during follow-up, most of these due to secondary failure. • Disease severity and disability appear to be higher in the polyarticular group, therefore treatment intensification may be considered.
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2023-06-05 | MicroRNA-27a-3p enhances the inflammatory phenotype of Juvenile Idiopathic Arthritis fibroblast-like synoviocytes
Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic pediatric rheumatic disorder. In joints of JIA patients, aggressive phenotypic changes in fibroblast-like synoviocytes (FLS) of the synovial lining play a key role in inflammation. MicroRNAs are dysregulated in rheumatoid arthritis and JIA, including miR-27a-3p. However, it is not understood if miR-27a-3p, enriched in JIA synovial fluid (SF) and leukocytes, alters FLS function.Primary JIA FLS cells were transfected with a miR-27a-3p mimic or a negative control microRNA (miR-NC) and stimulated with pooled JIA SF or inflammatory cytokines. Viability and apoptosis were analyzed by flow cytometry. Proliferation was evaluated using a 3H-thymidine incorporation assay. Cytokine production was assessed by qPCR and ELISA. Expression of TGF-β pathway genes was determined using a qPCR array.MiR-27a-3p was constitutively expressed in FLS. Overexpression of miR-27a-3p caused increased interleukin-8 secretion in resting FLS, and interleukin-6 was elevated in SF-activated FLS compared to miR-NC. Furthermore, stimulation with pro-inflammatory cytokines augmented FLS proliferation in miR-27a-3p-transfected FLS relative to miR-NC. Expression of multiple TGF-β pathway genes was modulated by overexpression of miR-27a-3p.MiR-27a-3p significantly contributes to FLS proliferation and cytokine production, making it a potential candidate for epigenetic therapy that targets FLS in arthritis.
2019-10-22 | Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis
Abstract Background Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA). The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA. Methods Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients. The relative expressions of miR-21, STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay. Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21. The expression of STAT3/p-STAT3 was measured by western blot, and the levels of interleukin (IL)-17A, p65, matrix metalloproteinases (MMP)-3, MMP-4 and receptor activator of nuclear factor-κB after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay. Finally, the miR-21 targeted STAT3 gene was detected by the dual-luciferase reported assay. Results The expression of miR-21 was significantly lower in JIA patients than in healthy control ( P < 0.05). The level of STAT3 was increased in PBMCs of JIA group compared with control group ( P < 0.05). Furthermore, the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 ( r = − 0.5854/ r = − 0.6134, P < 0.05). The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21. The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 ( P < 0.05). RASFs were induced into osteoclasts using M-CSF. The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group ( P < 0.05). Conclusions We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control. MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3. MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.
2019-02-27 | Micro-RNAs in inflammatory arthritis: From physiopathology to diagnosis, prognosis and therapeutic opportunities
Micro-RNAs are an area of research exponentially expanding over the past years. These small sequences of 20-22 nucleotides have a strong role as post-transcriptional regulators of gene expression. Inflammatory arthritis pathophysiology involves various key players from innate to adaptive immunity, as well as various signalling pathways of inflammation. In this review, we discuss how micro-RNAs are involved in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile inflammatory arthritis, from pre-clinical phases to established diseases. We describe mi-RNAs key roles in fibroblast like synoviocytes migration, proliferation, apoptosis and cytokine production, in macrophages polarization, as well as in B cells and T cell proliferation and differentiation, with a special emphasis on Treg/Th17 imbalance. We finally discuss the application of these findings in pre-clinical models and highlight opportunities and limits of a therapeutic approach using mi-RNAs agonists or antagonists.
2016-08-15 | Using the attract method to identify core pathways in juvenile idiopathic arthritis
The aim of this study was to identify core pathways associated with juvenile idiopathic arthritis (JIA) using the attract method. Kyoto Encyclopedia of Genes and Genomes pathways were determined using the GSEA-ANOVA method, based on the gene expression data of JIA. Syn-expression groups within core attractor pathways were identified by hierarchical clustering. Correlated sets of genes exhibiting highly similar profiles to the syn-expression groups were identified and each correlated set was subjected to a gene ontology functional enrichment analysis to discover potentially shared biological themes. Based on a false-discovery rate < 0.05, we identified 11 significant pathways were identified as potential attractors. Flag genes or uninformative genes were removed and 5 discriminative pathways: the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were identified. A final set of syn-expression groups with a consistent trend of relative expression of pathway-related genes was obtained; that is, the proteasome, ribosome, protein export, spliceosome, and Parkinson's disease pathways were composed of 2, 2, 1, 2, and 3 clusters, respectively. Genes in each correlated set shared common roles, and changes at the pathway level were more likely to be real. In light of these, the attract method was able to on expand important context to find distinguishing expression patterns within pathways. This paper predicted that the functional themes involved in protein synthesis (such as proteasome, ribosome, spliceosome) were closely related to the progression of JIA, which might contribute to the detection of therapy target for JIA.
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2024-08-26 | Genetic association of antinuclear antibodies with HLA in JIA patients: a Swedish cohort study
Abstract Background Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition. Methods We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm. Results Case–control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1 . HLA-DRB1* 08:01, HLA-DQA1* 04:01, and HLA-DQB1* 04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1* 08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1* 11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1* 11, and HLA-DPB1* 02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity. Conclusions This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.
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Drug Discovery Landscape
3 orphan drug designations for Polyarticular juvenile idiopathic arthritis, including 3 approved therapies.
3 orphan drug designations for Polyarticular juvenile idiopathic arthritis, including 3 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
methotrexate oral solution [Xatmep] | small molecules | FDA | 2015-08-27 | 2017-04-25 | Silvergate Pharmaeuticals, Inc. |
golimumab [SIMPONI ARIA®] | antibodies | FDA | 2015-04-02 | 2020-09-29 | Janssen Research & Development, LLC |
tocilizumab [Actemra] | antibodies | FDA | 2012-07-31 | 2013-04-29 | Genentech, Inc. |
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