Juvenile psoriatic arthritis and enthesitis-related arthritis are two categories of juvenile idiopathic arthritis (JIA). Despite available treatments including non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs, a substantial proportion of people do not adequately respond to treatment or do not have long-lasting clinical remission. The aim of this trial was to show the efficacy and safety of ixekizumab in children with active enthesitis-related arthritis and juvenile psoriatic arthritis. COSPIRIT-JIA is an ongoing multicentre, open-label, phase 3 study of ixekizumab, with a randomised adalimumab reference group, in children with a diagnosis of enthesitis-related arthritis (aged 6 to <18 years) and juvenile psoriatic arthritis (aged 2 to <18 years). Eligible participants had three or more active peripheral joints (presence of swelling or limited motion with pain or tenderness) and a bodyweight of at least 10 kg. Participants received subcutaneous administration of either ixekizumab or adalimumab using a weight-based dosing regimen (ixekizumab 40-160 mg starting dose then 20-80 mg once every 4 weeks; and adalimumab 20-40 mg once every 2 weeks). The primary endpoint was the percentage of ixekizumab-treated participants meeting the JIA-American College of Rheumatology (ACR) 30 (defined as at least 30% improvement from baseline in three of any six core outcome variables, with no more than one of the other variables worsening by more than 30%) response criteria at week 16. A Bayesian analysis was used to assess JIA-ACR30 response rate at week 16. Safety data were summarised using descriptive statistics for all participants who received at least one dose of either treatment. People with lived experience of JIA were not involved in the design or conduct of this study. The trial was registered with ClinicalTrials.gov, NCT04527380. The study enrolled 101 patients (ixekizumab n=81, adalimumab n=20) between April 13, 2021, and April 2, 2024, of whom the initial 40 participants naive to biological DMARD treatment were randomly assigned 1:1 to ixekizumab or adalimumab and the additional 61 participants were assigned to ixekizumab. Of the 81 participants who received ixekizumab, 60 were biological DMARD naive (40 with enthesitis-related arthritis and 20 with juvenile psoriatic arthritis) and 21 were biological DMARD experienced (14 with enthesitis-related arthritis and seven with juvenile psoriatic arthritis). The median age of the participants in the ixekizumab group was 14 years (12·0-15·0), of whom 36 (44%) of 81 were female, and 69 (85%) of 81 were White. At week 16, 90% (54 of 60; 95% CI 82·4-97·6) of biological DMARD-naive participants and 86% (18 of 21; 70·7-100·0) of biological DMARD-experienced participants receiving ixekizumab had a JIA-ACR30 response. Treatment-emergent adverse events were mostly mild (46%) or moderate (36%) for the ixekizumab group, with no severe treatment-emergent adverse events reported. The safety profile was consistent with adult psoriatic arthritis or spondyloarthritis and paediatric psoriasis indications. Ixekizumab was well tolerated and effective for the treatment of children with enthesitis-related arthritis and juvenile psoriatic arthritis who are candidates for biological DMARD therapy. Eli Lilly and Company.

Coxitis with rapid hip chondrolysis in juvenile patients requires careful diagnosis and treatment. This report describes a case that was initially diagnosed as idiopathic hip chondrolysis but finally diagnosed as enthesis-related juvenile idiopathic arthritis (JIA). Case: A 15-year-old boy complained of bilateral hip pain and difficulty in walking. Initially, a diagnosis of idiopathic hip chondrolysis was made based on the imaging findings of centralised joint space narrowing on plain radiography and high-signal areas in the femoral head and acetabulum on T2-weighted fat-suppressed magnetic resonance imaging (MRI) without joint effusion. After the patient was admitted to our hospital, a diagnosis of enthesis-related JIA was made. Enthesis-related JIA was suspected based on arthritic changes in the sacroiliac joints that were detected incidentally during computed tomography and MRI. After initiating adalimumab administration, MRI revealed the disappearance of abnormalities in the acetabulum and femoral head. Moreover, the hip pain and contracture gradually improved, and the patient could return to daily activities without pain. Our report highlights the importance of awareness regarding the possibility of enthesis-related JIA in juvenile patients presenting with coxitis and rapid chondrolysis of the hip joint without joint effusion.

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatological disease, yet cervical spine involvement remains an underrecognized but potentially devastating manifestation. Atlantoaxial subluxation (AAS) arises from inflammatory changes causing ligamentous laxity and instability. A 13-year-old female presented with progressive neck pain. Imaging revealed a 10-mm atlantodental interval on CT, along with hyperintensity and stretching of the transverse atlantal ligament on MRI. She underwent a posterior C1-2 open reduction and fusion. Subsequent rheumatological workup confirmed enthesitis-related JIA, based on polyarticular arthritis, HLA-B27 positivity, and elevated inflammatory markers. To contextualize this case, the authors performed a systematic review and meta-analysis of JIA-related AAS across 21 studies. The pooled incidence of AAS was 14%, with a mean age at JIA onset of 8.47 years and a female predominance of 62%. Enthesitis-related arthritis emerged as the most frequently reported subtype, and 94.4% of patients with AAS improved posttreatment. This case and supporting literature underscore the importance of early detection and multidisciplinary management of AAS in pediatric patients with JIA. Timely neurosurgical stabilization, combined with optimized immunosuppressive therapy, can prevent neurological compromise. Future research should focus on standardized diagnostic thresholds and outcome measures to guide best practices. https://thejns.org/doi/10.3171/CASE25121.

To measure fatigue in axial spondyloarthropathy patients and find its correlation with the disease activity measures. Cross-sectional, descriptive study. Place and Duration of the Study: Rheumatology Unit, Federal Government Polyclinic Hospital, from November 2021 to May 2022. This study included 45 patients fulfilling the ASAS criteria for spondyloarthropathy. Bathankylosing spondylitis disease activity (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and functional assessment of chronic illness therapy- fatigue (FACIT-F) scores were measured for each patient. In this study, there were 9 (20%) female patients and 36 (80%) male patients. There were 39 (86.7%) patients who had ankylosing spondylitis, 4 (8.9%) had axial spondyloarthropathy with peripheral arthritis and 2 (4.4%) had enthesitis-related juvenile idiopathic arthritis. The mean duration of the disease was 5.45 ± 4.19 years. Active disease with a BASDAI score of ≥4 was found in 16 (35.6%) patients while 29 (64.4%) had a BASDAI score <4. Severe fatigue with a FACIT-F score of <30 was found in 31 (68.9%) of the patients while less fatigue with FACIT-F score >30 was found in 14 (31.1%). The mean BASFI score of the cohort was 3.23 ± 2.01. Spearman's rho correlation analysis showed a significant strong correlation between the FACIT-F score, BASDAI and BASFI scores (p<0.001). Patients with active disease and higher BASFI scores had a lower FACIT-F score suggesting more fatigue, thus correlating with the disease activity. Bath ankylosing spondylitis disease activity (BASDAI), Functional assessment of chronic illness therapy-fatigue (FACIT-F), Ankylosing spondylitis (AS), Bath ankylosing spondylitis functional index (BASFI), Assessment in ankylosing spondylitis (ASAS).

IL-36 has been implicated in the pathogenesis of spondyloarthropathies (SpA) like psoriasis and inflammatory bowel disease. Enthesitis-related arthritis (ERA) category of juvenile idiopathic arthritis is a form of juvenile SpA, however, no data is available on the role of IL-36 in this disease. IL-36α, β, γ and IL-36R mRNA expression in blood and synovial fluid mononuclear cells and IL-36α, γ, IL-36Ra, IL-6, and IL-17 levels were measured in serum and synovial fluid (SF). IL-36γ production by fibroblast-like synoviocytes (FLS) upon stimulation with pro-inflammatory cytokines and its effect on FLS were also studied. mRNA levels of IL-36α, IL-36γ, and IL-36R were increased in PBMCs of ERA patients as compared to healthy controls however only IL-36γ was measurable in the serum of one-third of patients. In SFMCs, all four mRNA were detectable but were lower than RA patients. SF IL-36γ levels correlated with disease activity score (r = 0.51, P < 0.0001), SF IL-6 (r = 0.4, P = 0.0063) and IL-17 levels (r = 0.57, P = 0.0018). Pro-inflammatory cytokines increased the expression of IL-36γ and IL-6 in FLS cultures. SFs from five ERA patients also increased expressions of IL-36γ and IL-6 in FLS which could be blocked by using IL-36Ra. This suggests that pro-inflammatory cytokines aid in the upregulation of IL-36γ which in turn may upregulate the expression of IL-6. This might lead to a positive feedback loop of inflammation in ERA. Association of SF levels of IL-36γ with disease activity further supports this possibility. IL-36Ra based therapy may have a role in ERA.