Juvenile Idiopathic Arthritis (JIA) Associated Uveitis (JIA-U) remains one of the most serious complications of JIA in children. Historically, pediatric JIA is diagnosed by an Optometrist or ...Ophthalmologist; however, barriers to scheduling increase wait times that may delay diagnosis and treatment. The purpose of this study was to evaluate laser flare photometry (LFP) use to diagnose JIA-U in the Pediatric Rheumatology clinic for patients with JIA.
This prospective, observational study assessed pediatric patients diagnosed with JIA without a previous history of uveitis between January 2020 and September 2022. All patients underwent at least one evaluation of both eyes using a Kowa FM-600 laser flare photometer during a routine Rheumatology appointment, as well as a standard slit lamp examination (SLE) by optometry or ophthalmology during routine clinical care. Data collected at patient visits included demographics, JIA characteristics, treatment, LFP readings, and anterior chamber (AC) cell grade score utilizing the SUN grading system. Data were summarized using descriptive analyses and the uveitis false positive rate was calculated.
The study cohort included 58 pediatric patients diagnosed with JIA. The mean age was 8.4 years (1.2-16.3 years) at diagnosis and 11.9 (4.8-16.5 years) at enrollment. The mean duration of disease at time of enrollment was 42 months (range; 0-157 months). Participants were predominantly female (n = 43, 74.1%) and white/Caucasian race (n = 37, 63.8%). The most common JIA subtypes included persistent oligoarticular JIA (n = 19, 32.8%), and RF negative polyarticular JIA (n = 12, 20.7%). There were 12 ANA positive patients (20.7%). At enrollment, 16 patients (27.6%) were not on medications, with 20 (34.5%) on methotrexate, 20 (34.5%) on adalimumab, 6 (10.3%) on tocilizumab, and 5 (8.6%) on etanercept. During the study period, no eye exams detected active uveitis based on SLE with a SUN grade over 0. However, of the 135 LFP readings, 131 (97.0%) were normal, yielding a false positive rate of 3% (95% CI: 0.8%, 7.4%).
LFP is a non-invasive tool that can be utilized in the pediatric rheumatology clinic to evaluate for JIA-U. There is a low false positive rate of LFP when compared with standard slit lamp exam.
Objective
To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed ...treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment.
Methods
A consensus meeting was held in Chicago on April 23–24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion.
Results
Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed.
Conclusion
We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence‐based treatment recommendations for moderate juvenile DM.
Objective
To describe the selection, development, and implementation of quality measures (QMs) for juvenile idiopathic arthritis (JIA) by the Pediatric Rheumatology Care and Outcomes Improvement ...Network (PR‐COIN), a multihospital learning health network using quality improvement methods and leveraging QMs to drive improved outcomes across a JIA population since 2011.
Methods
An American College of Rheumatology–endorsed multistakeholder process previously selected initial process QMs. Clinicians in PR‐COIN and parents of children with JIA collaboratively selected outcome QMs. A committee of rheumatologists and data analysts developed operational definitions. QMs were programmed and validated using patient data. Measures are populated by registry data, and performance is displayed on automated statistical process control charts. PR‐COIN centers use rapid‐cycle quality improvement approaches to improve performance metrics. The QMs are revised for usefulness, to reflect best practices, and to support network initiatives.
Results
The initial QM set included 13 process measures concerning standardized measurement of disease activity, collection of patient‐reported outcome assessments, and clinical performance measures. Initial outcome measures were clinical inactive disease, low pain score, and optimal physical functioning. The revised QM set has 20 measures and includes additional measures of disease activity, data quality, and a balancing measure.
Conclusion
PR‐COIN has developed and tested JIA QMs to assess clinical performance and patient outcomes. The implementation of robust QMs is important to improve quality of care. PR‐COIN's set of JIA QMs is the first comprehensive set of QMs used at the point‐of‐care for a large cohort of JIA patients in a variety of pediatric rheumatology practice settings.
Biologics treatment with antitumour necrosis factor alpha (TNFα) is efficacious in patients with juvenile idiopathic arthritis (JIA). Despite displaying clinical inactivity during treatment, many ...patients will flare on cessation of therapy. The inability to definitively discriminate patients who will relapse or continue to remain in remission after therapy withdrawal is currently a major unmet medical need. CD4 T cells have been implicated in active disease, yet how they contribute to disease persistence despite treatment is unknown.
We interrogated the circulatory reservoir of CD4
immune subsets at the single-cell resolution with mass cytometry (cytometry by time of flight) of patients with JIA (n=20) who displayed continuous clinical inactivity for at least 6 months with anti-TNFα and were subsequently withdrawn from therapy for 8 months, and scored as relapse or remission. These patients were examined prior to therapy withdrawal for putative subsets that could discriminate relapse from remission. We verified on a separate JIA cohort (n=16) the dysregulation of these circulatory subsets 8 months into therapy withdrawal. The immunological transcriptomic signature of CD4 memory in relapse/remission patients was examined with NanoString.
An inflammatory memory subset of CD3
CD4
CD45RA
TNFα
T cells deficient in immune checkpoints (PD1
CD152
) was present in relapse patients prior to therapy withdrawal. Transcriptomic profiling reveals divergence between relapse and remission patients in disease-centric pathways involving (1) T-cell receptor activation, (2) apoptosis, (3) TNFα, (4) nuclear factor-kappa B and (5) mitogen-activated protein kinase signalling.
A unique discriminatory immunomic and transcriptomic signature is associated with relapse patients and may explain how relapse occurs.
Objective
The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant ...levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA.
Methods
DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti–tumor necrosis factor (anti‐TNF) therapy. Recombinant His‐tagged full‐length DEK protein (1–375 amino acids aa) and the 187–375‐aa and 1–350‐aa His‐tagged DEK fragments made in a baculovirus system were used for enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. The C‐terminal 25‐aa fragment of DEK was expressed in a glutathione S‐transferase–tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule.
Results
DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti‐TNF therapy. Immunoblotting against the C‐terminal 25‐aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain.
Conclusion
DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti‐TNF therapy. The C‐terminal 25‐aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management.
Objective
Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile ...idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.
Methods
Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6‐month period. Reporting rates were calculated per 100 person‐years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution.
Results
Thirty‐seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person‐years (95% CI 0.95–1.19). The rates for SAEs and IMEs were 0.54 per 100 person‐years (95% CI 0.45–0.63) and 0.53 per 100 person‐years (95% CI 0.49–0.62), respectively.
Conclusion
The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product‐based registry.
Background/Purpose:
Treatment with anti‐TNF therapies (anti‐TNF) for polyarticular forms (extended oligo, Poly RF +/−) of JIA (PF‐JIA) results in >50% demonstrating clinically inactive disease (CID). ...The aims of this study were to determine the frequency, timing and predictors of flare upon withdrawal of anti‐TNF in PF‐JIA in CID.
Methods:
In 16 centers 137 children with PF‐JIA in CID on anti‐TNF were enrolled and followed for ≥14 mos. If CID was maintained for the first 6 study mos, then anti‐TNF was stopped. The primary outcome variable was a validated definition of disease flare within 8 months after stopping anti‐TNF. Background meds were stable. Blood for S100, DEK, DNA and RNA was drawn for current and future biomarker and genetic studies.
Results:
The study population included 18 (13%) extended oligarticular, 17 (12%) RF+ Poly and 102 (74%) RF‐ Poly JIA patients. At enrollment, age (mean/median/range) was 11.3/11.6/3.4–20.1 yrs; disease duration was 5.0/4.1/0.6–18.6 years; 103 (75%) were females and 64 (47%) were ANA+. Duration of CID at baseline was 1.2/0.5/1 day–12.1 yrs. Anti‐TNF was etanercept in 106 (77%), 25 (18%) adalimumab and 6 (5%) infliximab. 40% were on MTX at baseline (mean/median dose 0.4/0.4 mg/kg/week). Other meds: 1 leflunomide, 2 hydroxychloroquine, and 1 prednisolone.
31 (23%) subjects were discontinued from the study in the first 6 mos: 23 (17%) due to loss of CID, 5 (4%) med noncompliance, 2 (1%) moved/LTF, 1 (1%) ILAR subtype changed (oligo to psoriatic). For the extended oligo, Poly RF− and Poly RF+ categories 94%, 82% and 60%, respectively, maintained CID for the first 6 months (c2 6.7, p 0.03). ANA status, MTX use, and type of anti‐TNF were not associated with the ability to maintain CID (c2 p values 0.48, 0.14, and 0.75, respectively).
106 (77%) subjects maintained CID for the first 6 months and stopped anti‐TNF as per protocol. 67/106 (63%) maintained CID for ≥8 mos off anti‐TNF while 39 (37%) flared. Time without flaring after stopping anti‐TNF therapy was duration from the month 6 visit to the last study visit (mean/median/range for duration of followup was 249/250/126–322 days). The mean/median/range for time to flare was 108/105/7–271 days. Time to flare (days) for etanercept was 105/105/7–271, adalimumab 119/120/28–238 and infliximab 28/28/28. Flare was seen in 47% (8/17) extended oligo, 37% (30/80) poly RF– and 11% (1/9) poly RF+ ((c2 p‐value 0.19). In those on background MTX, 33% (13/40) flared at a mean of 90 days, while those not on background MTX, 39% (26/66) flared at a mean of 113 days ((c2 p‐value 0.48). Using univariate analysis of variance, only weak correlations of MTX dose, disease duration, and CID duration with flare/no flare were seen (Spearman correlations −0.03, −0.17, −0.19, respectively).
Conclusion:
In this prospective multicenter study, 77% of the PF‐JIA patients were able to maintain CID for the first 6 months on anti‐TNF. Discontinuation of anti‐TNF in PR‐JIA (who have demonstrated on average 1.8 years of CID) resulted in a flare rate of 37% within 8 mos. Clinical parameters had only minimal predictive ability. Ongoing work includes biomarker identification and continued follow‐up of the cohort.
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