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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 (r 2 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., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis., (© 2024. Springer Nature Limited.)

Objective: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity., Methods: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement., Results: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity., Conclusion: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erin Balay-Dustrude reports travel was provided by Omeract - Outcome Measures in Rheumatology. Ben Horgan reports travel was provided by Omeract - Outcome Measures in Rheumatology. Grayson Shultz reports travel was provided by Omeract - Outcome Measures in Rheumatology. Alessandro Consolaro reports a relationship with Pfizer that includes: funding grants and speaking and lecture fees. Joost F. Swart reports a relationship with Amgen Inc that includes: consulting or advisory. Esi M Morgan reports a relationship with Pfizer that includes: funding grants. Esi M Morgan reports a relationship with Agency for Healthcare Research and Quality that includes: funding grants. Esi M Morgan reports a relationship with American College of Rheumatology that includes: speaking and lecture fees and travel reimbursement. Esi M Morgan reports a relationship with Pediatric Rheumatology Care and Outcomes Improvement Network that includes: board membership., (Copyright © 2023. Published by Elsevier Inc.)

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., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios., Methods: An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation., Results: The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72)., Conclusions: In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Prompt escalation to tumor necrosis factor inhibitors (TNFis) is recommended for children with juvenile idiopathic arthritis (JIA) and ongoing disease activity despite treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). It is unknown whether these recommendations are equitably followed for children with different insurance types. We assessed the association of insurance coverage on the odds and timing of TNFi use., Methods: We conducted a retrospective study of children with newly diagnosed JIA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We compared the odds of starting a TNFi in the first year and time from cDMARD to TNFi initiation between those with public and private insurance., Results: We identified 1086 children with new JIA diagnoses. Publicly insured children had significantly higher active joint counts and parent/patient global assessment scores at the enrollment visit. They were also more likely to have polyarticular arthritis compared to those with private insurance. Odds of any TNFi use in the first year did not differ between publicly and privately insured children. Publicly insured children were escalated from cDMARD to TNFi more quickly than privately insured children., Conclusion: Children who were publicly insured had more severe disease and polyarticular involvement at registry enrollment compared to those who were privately insured. Whereas overall TNFi use did not differ between children with different insurance types, publicly insured children were escalated more quickly, consistent with their increased disease severity. Further research is needed to determine why insurance coverage type is associated with disease severity, including how other socioeconomic factors affect presentation to care., (Copyright © 2023 by the Journal of Rheumatology.)

Background: Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic condition and is associated with symptoms such as joint pain that can negatively impact health-related quality of life. To effectively manage pain in JIA, young people, their families, and health care providers (HCPs) should be supported to discuss pain management options and make a shared decision. However, pain is often under-recognized, and pain management discussions are not optimal. No studies have explored decision-making needs for pain management in JIA using a shared decision making (SDM) model. We sought to explore families' decision-making needs with respect to pain management among young people with JIA, parents/caregivers, and HCPs., Methods: We conducted semi-structured virtual or face-to-face individual interviews with young people with JIA 8-18 years of age, parents/caregivers and HCPs using a qualitative descriptive study design. We recruited participants online across Canada and the United States, from a hospital and from a quality improvement network. We used interview guides based on the Ottawa Decision Support Framework to assess decision-making needs. We audiotaped, transcribed verbatim and analyzed interviews using thematic analysis., Results: A total of 12 young people (n = 6 children and n = 6 adolescents), 13 parents/caregivers and 11 HCPs participated in interviews. Pediatric HCPs were comprised of rheumatologists (n = 4), physical therapists (n = 3), rheumatology nurses (n = 2) and occupational therapists (n = 2). The following themes were identified: (1) need to assess pain in an accurate manner; (2) need to address pain in pediatric rheumatology consultations; (3) need for information on pain management options, especially nonpharmacological approaches; (4) importance of effectiveness, safety and ease of use of treatments; (5) need to discuss young people/families' values and preferences for pain management options; and the (6) need for decision support. Themes were similar for young people, parents/caregivers and HCPs, although their respective importance varied., Conclusions: Findings suggest a need for evidence-based information and communication about pain management options, which would be addressed by decision support interventions and HCP training in pain and SDM. Work is underway to develop such interventions and implement them into practice to improve pain management in JIA and in turn lead to better health outcomes., (© 2023. The Author(s).)

Objectives: Most juvenile idiopathic arthritis (JIA) biologic disease-modifying antirheumatic drugs (bDMARDs) trials used an open-label run-in period followed by randomized medication withdrawal. We used data from the run-in period of 4 bDMARD trials to 1) delineate early response trajectory to bDMARDs and 2) identify predictors of early response., Methods: Data from the first 16 weeks of 4 bDMARD trials were used. The primary outcome was the American College of Rheumatology (ACR) Pediatric 50 (Pedi 50) response criteria: clinically significant response defined as ACR Pedi 50 or greater. The secondary outcome was the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) minimal disease activity state. Response transition rates and predictors were modeled using an inhomogeneous Markov multistate model., Results: Five hundred thirty-two participants (70% receiving methotrexate, 41% prednisone) were included. By month 4, the probability of attaining ACR Pedi 50 or greater was 0.698. If ACR Pedi 50 or more was not achieved by month 1, the probability of achieving it by month 4 was 0.60. If ACR Pedi 50 or more was not achieved by month 3, the probability of achieving this by month 4 was 0.31. Age at diagnosis, disease duration, baseline rheumatoid factor, and active joint counts predicted ACR and cJADAS state transitions, adjusted for concomitant treatment., Conclusions: No response ACR Pedi 50 or more by month 1 after treatment was associated with a 0.60 probability of responding by month 4, but not responding by month 3 was associated with a 0.31 probability of response by month 4. Baseline disease duration, rheumatoid factor, and active joint counts predicted early treatment response (ACR and cJADAS10 states)., (© 2022 American College of Rheumatology.)

Objective: Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare., Methods: Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare., Results: A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P = 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22-18.78] and OR 2.74 [95% CI 1.62-4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72-0.95])., Conclusion: Approximately half of JIA flares post-discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision-making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed., (© 2022 American College of Rheumatology.)

Objective: Musculoskeletal ultrasound (MSUS) is increasingly being used in the evaluation of pediatric musculoskeletal diseases. In order to provide objective assessments of arthritis, reliable MSUS scoring systems are needed. Recently, joint-specific scoring systems for arthritis of the pediatric elbow, wrist, and finger joints were proposed by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) MSUS workgroup. This study aimed to assess the reliability of these scoring systems when used by sonographers with different levels of expertise., Methods: Members of the CARRA MSUS workgroup attended training sessions for scoring the elbow, wrist, and finger. Subsequently, scoring exercises of B mode and power Doppler (PD) mode still images for each joint were performed. Interreader reliability was determined using 2-way single-score intraclass correlation coefficients (ICCs) for synovitis and Cohen [Formula: see text] for tenosynovitis., Results: Seventeen pediatric rheumatologists with different levels of MSUS expertise (1-15 yrs) completed a 2-hour training session and calibration exercise for each joint. Excellent reliability (ICC > 0.75) was found after the first scoring exercise for all the finger and elbow views evaluated on B mode and PD mode, and for all of the wrist views on B mode. After a second training session and a scoring exercise, the wrist PD mode views reached excellent reliability as well., Conclusion: The preliminary CARRA MSUS scoring systems for assessing arthritis of the pediatric elbow, wrist, and finger joints demonstrate excellent reliability among pediatric MSUS sonographers with different levels of expertise. With further validation, this reliable joint-specific scoring system could serve as a clinical tool and scientific outcome measure., (Copyright © 2023 by the Journal of Rheumatology.)

Objectives: Evaluate construct validity of Patient-Reported Outcomes Measurement Information System (PROMIS) Paediatric measures of symptoms and functioning against measures of disease activity among youth with juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE)., Design: Cross-sectional associations among PROMIS measures and clinical metrics of disease activity were estimated., Setting: Seven clinical sites of the Childhood Arthritis and Rheumatology Alliance (CARRA) in the USA., Participants: Youth aged 8-17 years enrolled in the CARRA Registry., Intervention: PROMIS measures were collected and associations with clinical measures of disease activity estimated, by condition, in bivariate and multivariable analyses with adjustment for sociodemographics, insurance status, medications and disease duration., Main Outcome Measures: PROMIS Paediatric measures of mobility, physical activity, fatigue, pain interference, family relationships, peer relationships, depressive symptoms, psychological stress, anxiety, and meaning and purpose, and clinical metrics of disease., Results: Among 451 youth (average age 13.8 years, 71% female), most (n=393, 87%) had a JIA diagnosis and the remainder (n=58, 13%) had SLE. Among participants with JIA, those with moderate/high compared with low/inactive disease had, on average, worse mobility (multivariable regression coefficient and 95% CIs) (-7.40; -9.30 to -5.50), fatigue (3.22; 1.02 to 5.42), pain interference (4.76; 3.04 to 6.48), peer relationships (-2.58; -4.52 to -1.64), depressive symptoms (3.00; 0.96 to 5.04), anxiety (2.48; 0.40 to 4.56) and psychological stress (2.52; 0.68 to 4.36). For SLE, youth with active versus inactive disease had on average worse mobility (-5.07; -10.15 to 0.01) but PROMIS Paediatric measures did not discriminate participants with active and inactive disease in adjusted analyses., Conclusions: Seven PROMIS Paediatric measures discriminated between active and inactive disease in youth with JIA. Results advance the usefulness of PROMIS for understanding well-being and improving interventions for youth with JIA, but larger studies are needed to determine utility in SLE cohorts., Trial Registration Number: National Institute of Arthritis and Musculoskeletal and Skin Diseases (U19AR069522)., Competing Interests: Competing interests: Two authors have conflicts of interest: SR has salary support from CARRA and is co-PI of a PCORI-funded study that is receiving a study drug (abatacept) from Bristol Myers Squibb. Both SR and FD receive royalties from UpToDate, a Wolters Kluwer evidence-based clinical decision support resource., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking., Methods: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher's exact test was used to compare the distribution of responses to each survey question., Results: One hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1-2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience., Conclusion: Most respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Systemic juvenile idiopathic arthritis (SJIA) is a rare disease with distinct features not seen in other categories of juvenile idiopathic arthritis. In recent years, advances in the understanding of disease immunopathogenesis have led to improved targeted therapies with significant improvement in patient outcomes. Despite these advances, there remain subsets of SJIA with refractory disease and severe disease-associated complications. This review highlights existing options for treatment of refractory SJIA and explores potential future therapeutics for refractory disease.Key Points:Despite targeted Interleukin IL-1 and IL-6 inhibitors a subset of SJIA remains refractory to therapy. About 1 in 7 SJIA patients will be refractory to targeted IL-1 or IL-6 therapy.There is no current agreed upon definition for refractory SJIA and we propose in this review that refractory SJIA is presence of active systemic or arthritic features despite treatment with anti-IL-1 or anti-IL-6 therapy or disease requiring glucocorticoids for control beyond 6 months.SJIA disease associated complications include presence of associated macrophage activation syndrome (MAS), interstitial lung disease (ILD) or amyloidosis and management of each differs.Refractory SJIA treatment options currently include additional conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), biologic (bDMARDS), combination biologic therapy, targeted synthetic (tsDMARDS) or other immunomodulatory therapies.

Aims: 1) To delineate latent classes of treatment response to biologics in juvenile idiopathic arthritis (JIA) patients in the first 16 weeks after initiation. 2) To identify predictors of early disease response., Methods: The study population was drawn from four biologics trials in polyarticular course JIA: Etanercept 2000, Abatacept 2008, TRial of Early Aggressive Therapy (TREAT) 2012 and Tocilizumab 2014. The outcome was active joint counts (AJC). Semiparametric latent class trajectory analysis was applied to identify latent classes of response to treatment; AJC was transformed for this modelling. We tested baseline disease and treatment characteristics for their abilities to predict class membership of response., Results: There were 480 participants, 74% females. At baseline, 26% were rheumatoid factor positive. 67% were on methotrexate at enrollment. Three latent class solution provided the best fit. Baseline AJC was the sole best predictor of class membership. Participants classified by their highest membership probabilities into high baseline AJC (> 30) and slow response (26.5%), low baseline AJC (< 10), early and sustained response (29.7%), and moderate baseline AJC progressive response (43.8%). Participants were classified into the latent classes with a mean class membership posterior probability of 0.97. Those on methotrexate at baseline were less likely to belong to high baseline AJC class., Conclusions: Three latent classes of responses were detectable in the first 16 weeks of biologics therapy. Those with the highest baseline AJC demonstrated very slow response in this window and were less likely to be on concomitant methotrexate., Trials Registration: TREAT 2012 (NCT NCT00443430 ) (Wallace et. al, Arthritis Rheum 64:2012-21, 2012), tocilizumab trial 2014 ( NCT00988221 ), abatacept trial 2008 ( NCT00095173 ). Etanercept 2000 from Amgen does not have a trial registration number., (© 2022. The Author(s).)

Objective: Maternal infection has been posited as a risk factor for childhood autoimmune disease such as type I diabetes. Given that similar studies in JIA are scant, our objective was to evaluate the association between Juvenile Idiopathic Arthritis (JIA) and maternal infection., Methods: This case-control study used an existing database that included 1290 JIA cases and 6072 controls matched on birth year. Maternal infection information was obtained from Washington State birth records. JIA diagnosis and categories were confirmed through chart review. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs)., Results: JIA was not associated with maternal infection (OR = 1.02, 95%CI: 0.8-1.3). There was no association between JIA and maternal infection for persistent oligoarticular, RF negative polyarticular, or enthesitis-related JIA. There was suggestive evidence of an increased association of maternal infection with JIA in females in sex-stratified analysis., Conclusions: We did not observe an increased risk of JIA in children exposed to maternal infection. Suggestive evidence of differential sex-specific results warrants further study., (© 2022. The Author(s).)

Objective: Treat to target (T2T) is a strategy of adjusting treatment until a target is reached. An international task force recommended T2T for juvenile idiopathic arthritis (JIA) treatment. Implementing T2T in a standard and reliable way in clinical practice requires agreement on critical elements of (1) target setting, (2) T2T strategy, (3) identifying barriers to implementation, and (4) patient eligibility. A consensus conference was held among Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) stakeholders to inform a statement of understanding regarding the PR-COIN approach to T2T., Methods: PR-COIN stakeholders including 16 healthcare providers and 4 parents were invited to form a voting panel. Using the nominal group technique, 2 rounds of voting were held to address the above 4 areas to select the top 10 responses by rank order., Results: Incorporation of patient goals ranked most important when setting a treatment target. Shared decision making (SDM), tracking measurable outcomes, and adjusting treatment to achieve goals were voted as the top elements of a T2T strategy. Workflow considerations, and provider buy-in were identified as key barriers to T2T implementation. Patients with JIA who had poor prognostic factors and were at risk for high disease burden were leading candidates for a T2T approach., Conclusion: This consensus conference identified the importance of incorporating patient goals as part of target setting and of the influence of patient stakeholder involvement in drafting treatment recommendations. The network approach to T2T will be modified to address the above findings, including solicitation of patient goals, optimizing SDM, and better workflow integration., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided., Methods: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional., Conclusion: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver., (© 2022 American College of Rheumatology.)

Objective: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype., Methods: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional., Conclusion: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver., (© 2022 American College of Rheumatology.)

Background: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of 7 chronic arthritides categories that affects children younger than 16 years. This case series elucidates the characteristics of patients from a single center diagnosed with JIA at younger than 12 months., Methods: We included patients who presented to the rheumatology clinic for JIA with symptom onset at younger than 1 year. Chart review was conducted to complete case report forms that included demographics, historical features, examination features, laboratory results, imaging results, and treatment courses., Results: We identified 12 patients who met our inclusion criteria. Eight of our patients were diagnosed with oligoarticular JIA, 3 had polyarticular JIA, and 1 was diagnosed with systemic JIA. Overall, 58% (7/12) of patients had joint contractures at their initial visit. Of the patients with oligoarticular JIA, 50% (4/8) required a disease-modifying antirheumatic drug to achieve disease remission; 12.5% (1/8) required biologic therapy. All of the polyarticular JIA patients had highly positive antinuclear antibodies, as well as elevated inflammatory markers., Conclusions: Children with infantile JIA are overall similar to the larger population of patients with JIA. Disease severity may not be different compared with that of older children with JIA; however, there is likely a larger delay in diagnosis and the presence of contractures, which occurred in more than half of our patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To standardize and improve the accuracy of detection of arthritis by thermal imaging., Methods: Children with clinically active arthritis in the knee or ankle, as well as healthy controls, were enrolled to the development cohort; another group of children with knee symptoms was enrolled to the validation cohort. Ultrasound was performed in the arthritis subgroup for the development cohort. Joint exam by certified rheumatologists was used as a reference for the validation cohort. Infrared thermal data were analyzed using custom software. Temperature after within-limb calibration (TAWiC) was defined as the temperature differences between joint and ipsilateral mid-tibia. TAWiC of knees and ankles was evaluated using ANOVA across subgroups. Optimal thresholds were determined by receiver-operating characteristic analysis using Youden index., Results: There were significant differences in mean and 95th TAWiC of knee in anterior, medial, lateral views, and of ankles in anterior view, between inflamed and uninflamed counterparts ( P < 0.05). The area under the curve was higher by 30% when using TAWiC knee than that when using absolute temperature. Within the validation cohort, the sensitivity of accurate detection of arthritis in the knees using both mean and 95th TAWiC from individual views or all 3 views combined ranged from 0.60 to 0.70, and the specificity was > 0.90 in all views., Conclusion: Children with active arthritis or tenosynovitis in knees or ankles exhibited higher TAWiC than healthy joints. Our validation cohort study showed promise for the clinical utility of infrared thermal imaging for arthritis detection., (© 2022 The Journal of Rheumatology.)

Background: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA)., Methods: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434., Findings: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study., Interpretation: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections., Funding: Pfizer., Competing Interests: Declaration of interests NR has received honoraria for consultancy fees or speaker bureaus from Ablynx, AstraZeneca/MedImmune, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, EMD Serono, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, R-Pharm, Sanofi, Servier, Sinergie, and Sobi. The IRCCS Istituto Giannina Gaslini, where NR works as a full-time public employee, has received contributions from the following pharmaceutical companies in the past 3 years: Bristol-Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, and Sobi; this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any involvement of third parties. HIB has received research grants from Bristol-Myers Squibb, MedImmune, Novartis, and Pfizer; is an employee of Cincinnati Children's Hospital Medical Center; has received consulting fees or other remuneration from AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Janssen, Lilly, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and R-Pharm; and is a member of speaker bureaus for GlaxoSmithKline, Novartis, and Roche. OS is a member of a speaker bureau for Sanofi. AS is a member of a speaker bureau for Eli Lilly. KM has received research grants from Novartis and Pfizer. SP has received consulting fees or other remuneration from Novartis. EZ is a member of speaker bureaus for AbbVie, Novartis, Pfizer, and Roche. ML has received research grants from Amgen. KN has received research grants from Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Patient-Centered Outcomes Research Institute, and Roche. HS has received research grants from Bristol-Myers Squibb, Janssen, Pfizer, Roche, Sanofi, and USB Bioscience. YU is a member of a speaker bureau for Pfizer. DOV has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and Pfizer; and is a member of speaker bureaus for AbbVie and Bristol-Myers Squibb. HBP, KSK, AW, CC, RZ, M-AH, and RMS are employees and stockholders of Pfizer. IL is an employee of IQVIA, who were paid contractors to Pfizer in the development of this manuscript and in providing statistical support. AM has received consulting fees or other remuneration from Aurinia, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Janssen, and Pfizer. DJL's institution, the Cincinnati Children's Hospital Medical Center, has received research grants from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, and UCB; and has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Roche, Takeda, and UCB for the work of DJL. DJL is a Data Safety and Monitoring Board chairperson for Forest Research and the National Institutes of Health. All otjer authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist., Methods: The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability., Results: The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years., Conclusion: The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Juvenile idiopathic arthritis is a group of heterogeneous chronic inflammatory arthropathies occurring in childhood without a known cause. This article discusses the key clinical features of juvenile idiopathic arthritis and treatment updates for oligoarthritis, polyarthritis, enthesitis-related arthritis, psoriatic arthritis, and systemic arthritis. Paradigm changes in management include the earlier use of biologic agents and the introduction of biosimilars and targeted synthetic disease modifying agents like tofacitinib. This review summarizes recent developments while considering potential areas for improvement and study., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA)., Methods: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA., Results: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ., Conclusion: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use., Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate the effects of early introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the disease course in untreated polyarticular juvenile idiopathic arthritis (JIA)., Methods: We analyzed data on patients with polyarticular JIA participating in the Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) study (n = 400) and a comparator cohort (n = 248) from the Childhood Arthritis and Rheumatology Research Alliance Registry. Latent class trajectory modeling (LCTM) was applied to identify subgroups of patients with distinct disease courses based on disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints) over 12 months from baseline., Results: In the STOP-JIA study, 198 subjects (49.5%) received bDMARDs within 3 months of baseline assessment. LCTM analyses generated 3 latent classes representing 3 distinct disease trajectories, characterized by slow, moderate, or rapid disease activity improvement over time. Subjects in the rapid improvement trajectory attained inactive disease within 6 months from baseline. Odds of being in the rapid improvement trajectory versus the slow improvement trajectory were 3.6 times as high (95% confidence interval 1.32-10.0; P = 0.013) for those treated with bDMARDs ≤3 months from baseline compared with subjects who started bDMARDs >3 months after baseline, after adjusting for demographic characteristics, clinical attributes, and baseline disease activity. Shorter disease duration at first rheumatology visit approached statistical significance as a predictor of favorable trajectory without bDMARD treatment., Conclusion: Starting bDMARDs within 3 months of baseline assessment is associated with more rapid achievement of inactive disease in subjects with untreated polyarticular JIA. These results demonstrate the utility of trajectory analysis of disease course as a method for determining treatment efficacy., (© 2021, American College of Rheumatology.)

Objective: The optimal time to start biologics in polyarticular juvenile idiopathic arthritis (JIA) remains uncertain. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed 3 consensus treatment plans (CTPs) for untreated polyarticular JIA to compare strategies for starting biologics., Methods: Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) was a prospective, observational, CARRA Registry study comparing the effectiveness of 3 CTPs: 1) the step-up plan (initial nonbiologic disease-modifying antirheumatic drug [DMARD] monotherapy, adding a biologic if needed, 2) the early combination plan (DMARD and biologic started together), and 3) the biologic first plan (biologic monotherapy). The primary outcome measure was clinically inactive disease according to the provisional American College of Rheumatology (ACR) criteria, without glucocorticoids, at 12 months. Secondary outcome measures included Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and mobility scores, inactive disease as defined by the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS-10), and the ACR Pediatric 70 criteria (Pedi 70)., Results: Of 400 patients enrolled, 257 (64%) began the step-up plan, 100 (25%) the early combination plan, and 43 (11%) the biologic first plan. After propensity score weighting and multiple imputation, clinically inactive disease according to the ACR criteria was achieved in 37% of those on the early combination plan, 32% on the step-up plan, and 24% on the biologic first plan (P = 0.17). Inactive disease according to the clinical JADAS-10 (score ≤2.5) was also achieved in more patients on the early combination plan than the step-up plan (59% versus 43%; P = 0.03), as was ACR Pedi 70 (81% versus 62%; P = 0.008), but generalizability was limited by missing data. PROMIS measures improved in all groups, but without significant differences. Twenty serious adverse events were reported (mostly infections)., Conclusion: Achievement of clinically inactive disease without glucocorticoids did not significantly differ between groups at 12 months. While there was a significantly higher likelihood of early combination therapy achieving inactive disease according to the clinical JADAS-10 and ACR Pedi 70, these results require further exploration., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Biologic medications have significantly improved disease control and outcomes of patients with juvenile idiopathic arthritis (JIA). Current treatment recommendations suggest escalating therapy, including changing biologics if needed, when inactive or low disease activity is not attained. The patterns and reasons for switching biologics in clinical practice in North America are not well described., Methods: We used the Childhood Arthritis and Rheumatology Research Alliance Registry and included individuals with JIA if they newly started a biologic after January 1, 2008, and had at least 12 months of subsequent observable time. Subjects with systemic JIA were excluded. We compared characteristics of switchers and nonswitchers using chi-square for categorical variables and Wilcoxon rank-sum test for continuous variables, and used linear regression for time analysis., Results: Of the eligible children, 1361 with JIA in the registry started a biologic (94% tumor necrosis factor inhibitors [TNFi]). Median followup time was 30 months and 349 (26%) switched biologics. Among biologic switchers, ineffectiveness/disease flare was the most common reason for switch (202, 58%). The most common documented switch was from etanercept to another TNFi (221, 63%). The median time to switch to a second biologic decreased substantially from 55.2 months in 2008 to 7.2 months in 2016., Conclusion: In a multicenter cohort of patients with JIA starting a biologic, one-quarter switched to a second biologic, and the time to switching decreased in recent years. Additional studies should evaluate the outcomes and optimal timing of switching and preferred sequence of biologic use., (© 2021 The Journal of Rheumatology.)

Objective: To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA)., Study Design: International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS., Results: Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab., Conclusions: The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: With the advent of innovative therapies including biologics and Janus kinase inhibitors, children with rheumatic diseases are more likely to have improved outcomes. Despite these advances, some children do not respond, or they, or their parents fear adverse events and seek other alternatives. Increasingly, private companies are offering mesenchymal stem cells (MSC) as an alternative, which are described as natural therapies for rheumatic diseases, often insinuating them as a cure. MSC have immunomodulatory properties, and transplantation of these stem cells have been used to successfully treat immunologic conditions like graft-versus-host disease. Lately, MSC research in adult lupus has been encouraging, but the clinical trials are still underway and in most, MSC therapy is not a standalone treatment. This retrospective case series will highlight three cases of pediatric refractory autoimmune disease whose parents sought out and received MSC therapy as a self-decision without first seeking medical advice from our specialty. The three families felt that their children were improved and in two believed that their child was cured. MSC have the potential of beneficial immunomodulation and may be a powerful tool in the therapy of rheumatic disease, but well controlled clinical trials are necessary and should be designed and monitored by experts in childhood rheumatic disease., Case Presentation: Three children with three different rheumatic diseases; systemic lupus erythematosus, mixed connective tissue disease and juvenile idiopathic arthritis were under the care of pediatric rheumatology at a large, tertiary-care, teaching institution. Multiple non-biologic and biologic disease-modifying anti-rheumatic drugs failed to significantly decrease disease activity, and as a result, the families chose to undergo MSC therapy. After transplantation, all children improved per patient and parent report and tapered off conventional immunosuppressive drugs. No serious adverse events occurred in these three patients., Conclusion: The three cases presented in this report reflect comparable beneficial outcomes and minimal risks published in adult studies. These were not controlled studies, however, and benefit was reported rather than documented. These cases suggest that MSC transplantation may prove a promising adjunctive treatment option; however, further research, development of standardized infusion therapy protocols, and well-designed monitored clinical trials are essential.

Objective: Improved treatments for juvenile idiopathic arthritis (JIA) have increased remission rates. We conducted this study to investigate how patients and caregivers make decisions about stopping medications when JIA is inactive., Methods: We performed a mixed-methods study of caregivers and patients affected by JIA, recruited through social media and flyers, and selected by purposive sampling. Participants discussed their experiences with JIA, medications, and decision-making through recorded telephone interviews. Of 44 interviewees, 20 were patients (50% ages <18 years), and 24 were caregivers (50% caring for children ages ≤10 years). We evaluated characteristics associated with high levels of reported concerns about JIA or medicines using Fisher's exact testing., Results: Decisions about stopping medicines were informed by competing risks between disease activity and treatment. Participants who expressed more concerns about JIA were more likely to report disease-related complications (P = 0.002) and more motivated to continue treatment. However, participants expressing more concern about medicines were more likely to report treatment-related complications (P = 0.04) and felt more compelled to stop treatment. Additionally, participants considered how JIA or treatments facilitated or interfered with their sense of normalcy and safety, expressed feelings of guilt and regret about previous or potential adverse events, and reflected on uncertainty and unpredictability of future harms. Decision-making was also informed by trust in rheumatologists and other information sources (e.g., family and online support groups)., Conclusion: When deciding whether to stop medicines whenever JIA is inactive, patients and caregivers weigh competing risks between disease activity and treatment. Based on our results, we suggest specific approaches for clinicians to perform shared decision-making regarding stopping medicines for JIA., (© 2019, American College of Rheumatology.)

Objectives: To determine the feasibility of comparing the Childhood Arthritis and Rheumatology ResearchAlliance (CARRA) consensus treatment plans (CTP) in treating moderate new-onset juvenile dermatomyositis (JDM) using the CARRA registry, and to establish appropriate analytic methods to control for confounding by indication and missing data., Methods: A pilot cohort of 39 patients with JDM from the CARRA registry was studied. Patients were assigned by the treating physician, considering patient/family preferences, to 1 of 3 CTP: methotrexate (MTX) and prednisone (MP); intravenous (IV) methylprednisolone, MTX, and prednisone (MMP); or IV methylprednisolone, MTX, prednisone, and IV immunoglobulin (MMPI). The primary outcome was the proportion of patients achieving moderate improvement at 6 months under each CTP. Statistical methods including multiple imputation and inverse probability of treatment weighting were used to handle missing data and confounding by indication., Results: Patients received MP (n = 13), MMP (n = 18) and MMPI (n = 8). Patients in all CTP had significant improvement in disease activity. Of the 36 patients who remained in our pilot study at 6 months, 16 (44%) of them successfully achieved moderate improvement at 6 months (6/13, 46% for MP; 7/15, 47% for MMP; 3/8, 38% for MMPI). After correcting for confounding, there were no statistically significant pairwise differences between the CTP ( P = 0.328-0.88)., Conclusion: We gained valuable experience and insight from our pilot study that can be used to guide the design and analysis of comparative effectiveness studies using the CARRA registry CTP approach. Our analytical methods can be adopted for future comparative effectiveness studies and applied to other rare disease observational studies.

Objective: To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry., Methods: STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA ± MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA ± MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27 CRP )., Results: At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA ± MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA ± MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA ± MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA ± MTX arm showed a trend toward lower mean JADAS-27 CRP compared with new users in the MTX arm in the first year of STRIVE., Conclusion: The STRIVE registry 7-year interim results support the idea that ADA ± MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date., (© 2019 AbbVie Inc. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Purpose: A key limitation to widespread adoption of patient-reported outcome (PRO) measures is the lack of interpretability of scores. We aim to identify clinical severity thresholds to distinguish categories of no problems, mild, moderate, and severe along the PROMIS® Pediatric T-score metric for measures of anxiety, mobility, fatigue, and depressive symptoms for use in populations with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE)., Methods: We used a modified standard setting methodology from educational testing to identify clinical severity thresholds (clinical cut scores). Using item response theory-based parameters from PROMIS item banks, we developed a series of clinical vignettes that represented different severity or ability levels along the PROMIS Pediatric T-score metric. In stakeholder workshops, participants worked individually and together to reach consensus on clinical cut scores. Median cut-score placements were taken when consensus was not reached. Focus groups were recorded and qualitative analysis was conducted to identify decision-making processes., Results: Nine adolescents (age 13-17 years) with JIA (33% female) and their caregivers, five adolescents (age 14-16 years) with cSLE (100% female) and their caregivers, and 12 pediatric rheumatologists (75% female) participated in bookmarking workshops. Placement of thresholds for bookmarks was highly similar across stakeholder groups (differences from 0 to 5 points on the PROMIS t-score metric) for all but one bookmark placement., Conclusion: This study resulted in clinical thresholds for severity categories for PROMIS Pediatric measures of anxiety, mobility, fatigue, and depressive symptoms, providing greater interpretability of scores in JIA and cSLE populations.

Ten patients with scurvy were evaluated by rheumatology; we review their clinical, laboratory, and dietary presentations. Eight patients had developmental delay or autism. All had elevated inflammatory markers. These clinical and laboratory features with imaging findings can mimic rheumatic conditions such as arthritis, vasculitis, and chronic nonbacterial osteomyelitis (CNO)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA)., Methods: A cross-sectional exploratory study of subjects aged 10-18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing., Results: The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented., Conclusion: Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.

Objective: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA)., Methods: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data., Results: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features., Conclusions: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed., Competing Interests: Competing interests: VES reports personal fees from Novartis. GD reports personal fees from Novartis. SC reports personal fees from Novartis and grants from AB2 Bio. GS reports personal fees from Novartis. KB reports personal fees from Novartis. RQC is co-PI of an investigator-initiated clinical trial funded by SOBI. RD reports personal fees from Boehringer Ingelheim, other from NowVitals, personal fees and other from Triple Endoscopy, other from Earables, and NowVitals with patents and lung-related device development. AAG reports grants and personal fees from Novartis and grants from NovImmune. SL reports personal fees from Novartis. RS reports personal fees from Novartis, NovImmune and SOBI. SS reports personal fees from Novartis. MLS reports personal fees from Novartis. LRY reports other from Up-To-Date and other from Boehringer Ingelheim, outside the submitted work. EDM reports grants from Novartis., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A meeting was organized to bring together multiple stakeholders involved in the testing and authorization of new medications for juvenile idiopathic arthritis (JIA) to discuss current issues surrounding clinical trials and access to new medications for children and adolescents with JIA. The Childhood Arthritis and Rheumatology Research Alliance invited representatives of regulatory agencies (Food and Drug Administration and European Medicines Agency), and major pharmaceutical companies with JIA-approved products or products in development, patient and parent representatives, representatives of an advocacy organization (Arthritis Foundation), and pediatric rheumatology clinicians/investigators to a 1-day meeting in April 2018. The participants engaged in discussion regarding issues in clinical trials. As the pharmacologic options to treat inflammatory arthritis rapidly expand, registration trial designs to test medications in JIA patients must adapt. Many methodologies successfully used in the recent past are no longer feasible. The pool of patients meeting entry criteria who are willing to participate is shrinking while the number of medications to be tested is growing. Suggested solutions included proposing innovative clinical trial methods to regulatory agencies, as well as open discussions among stakeholders. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critical. Approaches should include open dialog between regulatory agencies, pharmaceutical companies, and other stakeholders to develop and implement novel study designs, including patient and clinician perspectives to define meaningful trial outcomes, and changing existing study plans., (© 2019, American College of Rheumatology.)

Background: Early diagnosis and treatment of juvenile idiopathic arthritis (JIA) with conventional and biologic disease-modifying anti-rheumatic drugs have vastly improved outcomes for children with these diseases. Currently, a large proportion of children with JIA are able to achieve clinical inactive disease and remission. With this success, important questions have arisen about when medications can be stopped and how to balance the risks and benefits of continuing medications versus the potential for flare after stopping., Aim: The aim was to conduct a systematic review of the available literature to summarize current evidence about medication withdrawal for JIA in remission., Methods: We conducted a systematic literature search in PubMed and Embase from 1990 to 2019. References were first screened by title and then independently screened by title and abstract by two authors. A total of 77 original papers were selected for full-text review. Data were extracted from 30 papers on JIA and JIA-associated uveitis, and the quality of the evidence was evaluated using National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) tools. Studies on biochemical and radiologic biomarkers were also reviewed and summarized., Results: Most studies investigating treatment withdrawal in JIA have been observational and of poor or fair quality; interpretations of these studies have been limited by differences in study populations, disease and remission durations, the medications withdrawn, approaches to withdrawal, and definitions of disease outcomes. Overall the data suggest that flares are common after stopping JIA medications, particularly biologic medications. Clinical characteristics associated with increased risks of flare have not been consistently identified. Biochemical biomarkers and ultrasound findings have been shown to predict outcomes after stopping medications, but to date, no such predictor has been consistently validated across JIA populations. Studies have also not identified optimal strategies for withdrawing medication for well-controlled JIA. Promising withdrawal strategies include discontinuing methotrexate before biologic medications in children receiving combination therapy, dose reduction for children on biologics, and treat-to-target approaches to withdrawal. These and other strategies require further investigation in larger, high-quality studies., Conclusions: The published literature on treatment withdrawal in JIA has varied in design and quality, yielding little conclusive evidence thus far on the management of JIA in remission. Given the importance of this question, international collaborative efforts are underway to study clinical and biologic predictors of successful medication withdrawal in JIA. These efforts may ultimately support the development of personalized approaches to withdrawing medication in children with JIA in remission.

Objective: The current Juvenile Idiopathic Arthritis (JIA) Core Set used in randomized controlled trials (RCT) and longitudinal observational studies (LOS) was developed without the input of patients/parents. At the Outcome Measures in Rheumatology (OMERACT) 2016, a special interest group voted to reconsider the core set, incorporating broader input. We describe subsequent work culminating in an OMERACT 2018 plenary and consensus voting., Methods: Candidate domains were identified through literature review, qualitative surveys, and online discussion boards (ODB) held with patients with JIA and parents in Australia, Italy, and the United States. A Delphi process with parents, patients, healthcare providers, researchers, and regulators served to edit the domain list and prioritize candidate domains. After the presentation of results, OMERACT workshop participants voted, with consensus set at > 70%., Results: Participants in ODB were 53 patients with JIA (ages 15-24 yrs) and 55 parents. Three rounds of Delphi considering 27 domains were completed by 190 (response rate 85%), 201 (84%), and 182 (77%) people, respectively, from 50 countries. There was discordance noted between domains prioritized by patients/parents compared to others. OMERACT conference voting approved domains for JIA RCT and LOS with 83% endorsement. Mandatory domains are pain, joint inflammatory signs, activity limitation/physical function, patient's perception of disease activity (overall well-being), and adverse events. Mandatory in specific circumstances: inflammation/other features relevant to specific JIA categories., Conclusion: Following the OMERACT methodology, we developed an updated JIA Core Domain Set. Next steps are to identify and systematically evaluate best outcome measures for these domains.

Background: We describe a Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey of North American pediatric rheumatologists that assesses physician attitudes on withdrawal of medications in systemic juvenile idiopathic arthritis (SJIA)., Methods: A REDCap anonymous electronic survey was distributed to 100 random CARRA JIA workgroup physician-voting members. The survey had three broad sections including: A) demographic information; B) physicians' opinions on clinical inactive disease (CID) in SJIA and C) existing practices for withdrawing medications in SJIA., Results: The survey had an 86% response rate. 88 and 93% of participants agreed with the current criteria for CID and clinical remission on medications (CRM) respectively. 78% thought it necessary to meet CRM before tapering medications except steroids. 76% use CARRA SJIA consensus treatment plans always or the majority of the time. All participants weaned steroids first in SJIA patients on combination therapy, 47% waited > 6 months before tapering additional medications. 35% each tapered methotrexate over > 6 months and 2-6 months; however, 39% preferred tapering anakinra, canakinumab and tocilizumab more quickly over 2-6 months and favored spacing the dosing interval for canakinumab and tocilizumab. When patients are on combination therapy with methotrexate and biologics, 58% preferred tapering methotrexate first while others considered patient/family preference and adverse effects to guide their choice., Conclusion: Most CARRA members surveyed use published consensus treatment plans for SJIA and agree with validated definitions of CID and CRM. There was agreement with tapering steroids first in SJIA. There was considerable variability with tapering decisions of all other medications.

Objective: The use of musculoskeletal ultrasound is increasing among pediatric rheumatologists. Reliable scoring systems are needed for the objective assessment of synovitis. The aims of this study were to create a standardized and reproducible image acquisition protocol for B-mode and Doppler ultrasound of the pediatric knee, and to develop a standardized scoring system and determine its reliability for pediatric knee synovitis., Methods: Six pediatric rheumatologists developed a set of standard views for knee assessment in children with juvenile arthritis. Subsequently, a comprehensive literature review, practical exercises, and a consensus process were performed. A scoring system for both B-mode and Doppler was then developed and assessed for reliability. Interreader reliability or agreement among a total of 16 raters was determined using 2-way single-score intraclass correlation coefficient (ICC) analysis., Results: Twenty-one views to assess knee arthritis were initially identified. Following completion of practical exercises and subsequent consensus processes, 3 views in both B-mode and Doppler were selected: suprapatellar longitudinal and medial/lateral parapatellar transverse views. Several rounds of scoring and modifications resulted in a final ICC of suprapatellar view B-mode 0.89 (95% confidence interval [95% CI] 0.86-0.92) and Doppler 0.55 (95% CI 0.41-0.69), medial parapatellar view B-mode 0.76 (95% CI 0.68-0.83) and Doppler 0.75 (95% CI 0.66-0.83), and lateral parapatellar view B-mode 0.82 (95% CI 0.75-0.88) and Doppler 0.76 (95% CI 0.66-0.84)., Conclusion: A novel B-mode and Doppler image acquisition and scoring system for assessing synovitis in the pediatric knee was successfully developed through practical exercises and a consensus process. Study results demonstrate overall good-to-excellent reliability., (© 2018, American College of Rheumatology.)

Objective: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis., Methods: The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions., Results: Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies., Conclusion: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies., (© 2019, American College of Rheumatology.)

Objective: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA)., Methods: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong., Results: Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss., Conclusion: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values., (© 2019, American College of Rheumatology.)

Objectives: To evaluate the prevalence of special diet adoption in juvenile idiopathic arthritis (JIA) and parental perceptions of efficacy. Design: An online survey was distributed over a year to nearly 20,000 individuals. Results: Responses from 261 parents of patients with JIA were received. One of three ( n  = 79) had tried special diets, including gluten-free (66%), anti-inflammatory (41%), and lactose-free (25%). Overall, >50% of 79 parents reported that patients had improved pain or joint swelling. Conclusions: Special diets have been trialed by a third of the patients, with over half reporting symptom improvement. A prospective, controlled trial is warranted to test the efficacy of a dietary approach to JIA.

Objective: To propose multidisciplinary, consensus-based, standardization of operational terminology and method of assessment for temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA)., Methods: Using a sequential expert group-defined terminology and methods-of-assessment approach by (1) establishment of task force, (2) item generation, (3) working group consensus, (4) external expert content validity testing, and (5) multidisciplinary group of experts final Delphi survey consensus., Results: Seven standardized operational terms were defined: TMJ arthritis, TMJ involvement, TMJ arthritis management, dentofacial deformity, TMJ deformity, TMJ symptoms, and TMJ dysfunction. CONCLUSION: Definition of 7 operational standardized terms provides an optimal platform for communication across healthcare providers involved in JIA-TMJ arthritis management.

Objective: To determine the efficacy in improving pain and health-related quality of life (HRQOL) of an online self-management program for adolescents with juvenile idiopathic arthritis (JIA)., Methods: Youth ages 12-18 years with JIA were recruited from 10 rheumatology clinics across the United States and randomized to complete an online self-management program (n = 144) or an online disease education program (n = 145). Participants in the self-management group worked through multimedia-based modules comprising psychoeducation, training in cognitive-behavioral coping skills and stress management, and other self-management topics over a 12-week period. Participants in the control group viewed a series of preselected quality educational websites about JIA over the same interval. Online content for both groups was made available in English and Spanish to facilitate inclusion of Hispanic participants. Blinded assessment of main outcomes (pain intensity, pain interference, and HRQOL) and process outcomes (disease knowledge, self-efficacy, pain coping, and emotional adjustment) occurred at baseline, posttreatment, and at 6- and 12-month postrandomization follow-up visits., Results: Participants on average demonstrated significant improvements over the study period in the main outcomes, with no significant group differences in the degree of improvement. Effect sizes for these improvements were small. The amount of improvement in self-efficacy, emotional avoidance coping, disease knowledge, and emotional functioning in part predicted improvement in pain and HRQOL outcomes., Conclusions: Primarily self-directed online self-management training and online disease education comparably and modestly improve pain and HRQOL in youth with JIA., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases., Methods: The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria., Results: In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities., Conclusion: An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term JIA . These preliminary criteria will be formally validated with a dedicated project.