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Objective: The objective of this study was to investigate occupational and hobby exposures to silica, solvents, and heavy metals and the odds of having the idiopathic inflammatory myopathy (IIM) phenotypes dermatomyositis (DM) and polymyositis (PM) versus inclusion body myositis (IBM), lung disease plus fever or arthritis (LD+), and systemic autoimmune rheumatic disease–associated overlap myositis (OM). Methods: The sample included 1,390 patients (598 with DM, 409 with PM, and 383 with IBM) aged ≥18 years from a national registry. Of these, 218 (16%) were identified with LD+, and 166 (12%) with OM. Of these, 218 (16%) were identified with LD+, and 166 (12%) with OM. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and explored joint effects with smoking. Results: High silica exposure was associated with increased odds of having DM (OR 2.02, 95% CI 1.18–3.46, compared to no exposure; P trend = 0.004), LD+ (OR 1.75, 95% CI 1.10–2.78, vs no LD; P trend = 0.005), and OM (OR 2.07, 95% CI 1.19–3.61, P trend = 0.020). Moderate to high heavy metals exposure was associated with greater odds of having LD+ (OR 1.49, 95% CI 1.00–2.14, P trend = 0.026) and OM (OR 1.59, 95% CI 0.99–2.55, P trend = 0.051). Greater odds of having LD+ were seen among smokers with moderate to high silica exposure versus nonsmokers with low or no exposure (high‐certainty assessment OR 2.53, 95% CI 1.31–4.90, P interaction = 0.061). Conclusion: These findings, based on a systematic exposure assessment, suggest that occupational and hobby exposures to silica and heavy metals contribute to adult IIM phenotypes, including DM, OM, and LD+, a possible marker for antisynthetase syndrome or other autoantibody‐associated lung diseases. [ABSTRACT FROM AUTHOR]

Objective: We examine levels of candidate blood‐based biomarkers (CBBs) in patients with juvenile idiopathic arthritis (JIA) treated with tofacitinib. Methods: Patients with JIA who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBBs (S100A8/9, S100A12, interleukin‐18 [IL‐18], serum amyloid A, resistin, vascular endothelial growth factor, angiopoietin‐1, angiopoietin‐2, matrix metalloproteinase 8 [MMP8], MMP2, tissue inhibitor of metalloproteinases 1, leptin, chemokine [C‐X‐C motif] ligand 9, soluble IL‐2 receptor, intercellular adhesion molecule 1, soluble tumor necrosis factor receptor, IL‐6, IL‐23, monocyte chemotactic protein 1, chemokine [C‐C motif] ligand 18 [CCL18], and CCL20). Association of CBBs with JIA response to treatment from baseline to week 18 were assessed. Results: This study included 166 patients with polyarticular‐course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. Thirty‐five percent (50 of 143) of patients had a JIA‐American College of Rheumatology 90 (JIA‐ACR90) level improvement, whereas 90, 121, and 137 (63%, 85%, and 96%) achieved JIA‐ACR70, 50, and 30 improvement at week 18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in Juvenile Arthritis Disease Activity Score (JADAS‐27) or JIA‐ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with week 18 improvement in JADAS‐27 and JIA‐ACR90 response after adjusting for age, sex, JIA disease duration, and baseline resistin (r2 0.79, SE 0.070, P < 0.01, and odds ratio [95% confidence interval] 1.134 [1.018–1.264]). HLA‐B27 positivity was significantly associated with not achieving a JIA‐ACR90 response at week 18 (P = 0.0097). Conclusion: Among the CBBs included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA‐B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study. [ABSTRACT FROM AUTHOR]

BackgroundTo reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in the US. Further, we aimed to explore the safety and effectiveness of the treatments for induction therapy.MethodsForty-one patients were enrolled from 10 CARRA sites. Patients had new-onset biopsy proven ISN/RPS class III or IV proliferative LN, were starting induction therapy with MMF or IV CYC and high-dose steroids and were followed for up to 24 months. Routine clinical data were collected at each visit. Provider reasons for CTP selection were assessed at baseline. Adherence to the CTPs was evaluated by provider survey and medication logs. Complete and partial renal responses were reported at 6 months.ResultsThe majority of patients were female (83%) with a mean age of 14.7 years, SD 2.8. CYC was used more commonly than MMF for patients with ISN/RPS class IV LN (vs. class III), those who had hematuria, and those with adherence concerns. Overall adherence to the immunosuppression induction CTPs was acceptable with a majority of patients receiving the target MMF (86%) or CYC (63%) dose. However, adherence to the steroid CTPs was poor (37%) with large variability in dosing. Renal response endpoints were exploratory and did not show a significant difference between CYC and MMF.ConclusionsOverall, the immunosuppression CTPs were followed as intended in the majority of patients however, adherence to the steroid CTPs was poor indicating revision is necessary. In addition, our pilot study revealed several sources of treatment selection bias that will need to be addressed in for future comparative effectiveness research.

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P

ObjectiveParticipants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy.MethodsSubgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score≥4 as post-pubertal or

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease with a multisystemic involvement diagnosed during childhood. The disease is marked by the production of autoantibodies targeting self-antigens, often before symptoms emerge. The presentation, clinical course, and outcome vary significantly among patients with cSLE. The onset of cSLE can be at any age during childhood while a diagnosis of cSLE before the age of 5 years is rare and raises a suspicion of monogenic lupus. Childhood-onset systemic lupus erythematosus affects various organs and systems, most frequently presenting with mucocutaneous, musculoskeletal, renal, and neuropsychiatric manifestations. Multiple disease flares can be seen during the disease course. Childhood-onset systemic lupus erythematosus causes significant morbidity and mortality. Children and adolescents with cSLE show higher disease activity and damage, and more aggressive immunosuppressive treatments are needed compared to adultonset SLE. Early diagnosis can be difficult due to the insidious onset with nonspecific symptoms. Disease activity and damage measures aim to ensure an accurate evaluation of disease status. A multidisciplinary approach and individualized disease management are important. Disease management is complex including the control of disease activity, the reduction of flares and damage, and a limitation of drug toxicity while improving the health-related quality of life in patients with cSLE. [ABSTRACT FROM AUTHOR]

Abstract Introduction The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). Methods We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. Results There were 1020 patients aged

INTRODUCTION: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). METHODS: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. RESULTS: There were 1020 patients aged

The substantial morbidity and mortality associated with refractory systemic JIA underlies the need for new treatment approaches. However, progress in this area has been limited by the difficulty of enrolling these patients in clinical trials with traditional designs, particularly in patients presenting with the life-threatening macrophage activation syndrome. At the NextGen 2022 conference, there was group consensus that using historical cohorts as a control group to avoid the need for a placebo-arm or drug withdrawal was highly desirable and might be acceptable for clinical trials in MAS to support medication efficacy and safety. However, if historic controls were used in a trial, it would be important to ensure that the historic cohort matches the study group in terms of clinical characteristics (such as disease severity and exposure to other medications), and that disease outcome in both groups is assessed using the same outcome measures. The discussions at the NextGen 2022 conference focused on the potential strategies to achieve these goals. [ABSTRACT FROM AUTHOR]

Objective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders. Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA. Regulatory, academic, and industry stakeholders, as well as patient representatives, participated in the workshop, which consisted of 4 sessions, including panel discussions. Results: The workshop facilitated broad public discussion of challenges facing the development of pJIA therapeutics, highlighting areas of need and outlining opportunities to expedite development, while underscoring the necessity of close collaboration between all stakeholders, including patients and families. Conclusion: This report summarizes key aspects of the workshop, including the appropriate application of innovative approaches to the development of pJIA therapeutics, including extrapolation, to address current challenges and provide timely access to newer safe and effective treatments. Long‐term safety assessment is of pressing concern to stakeholders and cannot be fully extrapolated from adult studies but requires consistent postmarketing long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Objective: To describe longitudinal changes in patient‐reported outcomes (PROs) in children with polyarticular‐course juvenile idiopathic arthritis (pJIA) treated with subcutaneous abatacept. Methods: Secondary analysis of a single‐arm, open‐label 24‐month study of patients ages 6–17 years and 2–5 years. PROs included Childhood Health Assessment Questionnaire‐Disability Index (CHAQ‐DI), parent global assessment of child well‐being (PaGA), pain assessment, and Activity Limitation Questionnaire (ALQ). Clinical outcomes included 50% or greater improvement in JIA American College of Rheumatology (ACR) criteria, clinically inactive disease, and Juvenile Arthritis Disease Activity Score. Results: For the 6‐ to 17‐year‐old (n = 173) and 2‐ to 5‐year‐old (n = 46) cohorts, respectively, median (Q1, Q3) changes from baseline in CHAQ‐DI at months 4 and 24 were −0.3 (−0.8, 0.0) and −0.5 (−1.0, −0.1), and −0.4 (−0.8, 0.0) and −0.5 (−1.0–−0.1). Median pain scores were below cutoff threshold for clinically relevant pain (<35 mm) by month 1 (6 to 17 years, 32.3 mm; 2 to 5 years, 25.7 mm), reaching a nadir at month 24 (6 to 17 years, 6.0 mm; 2 to 5 years, 2.0 mm). For the 6‐ to 17‐year‐old and 2‐ to 5‐year‐old cohorts, respectively, median PaGA scores were 47.8 (n = 172) and 42.1 (n = 46) at baseline and 6.3 (n = 107) and 2.0 (n = 37) at month 24. In both cohorts, ALQ components improved from baseline to month 4 and were largely maintained to month 24. Clinical outcomes improved through to month 24. Conclusion: Early and sustained PRO improvements were reported in this phase III, open‐label trial of subcutaneous abatacept in patients with pJIA. [ABSTRACT FROM AUTHOR]