Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening.

BACKGROUND: Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results. METHODS: Initiated as part of the COACH multicenter observational study, outpatients aged 12 to 21 years participating in the National Pediatric Rheumatological Database (NPRD) were prospectively screened for mental health using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder Scale-7 (GAD-7). RESULTS: Data from 1,150 adolescents with JIA (mean age 15.6 ± 2.2 years; mean disease duration 7.2 ± 4.9 years, 69% female, 43% oligoarthritis, 26% polyarthritis) were analysed. Overall, 32.7% (n = 316) of AYA showed conspicuous screening results, of whom 30.4% reported clinically relevant suicidal or self-harm thoughts. About 19% of screened patients showed moderate to severe depressive or anxious symptoms. AYA with conspicuous screening results were older (15.8 vs. 15.2 years; p < 0.0001), more often female (81% vs. 64%; p < 0.0001) and more often overweight (25% vs. 17%; p = 0.006). They had higher disease activity (physician global assessment on NRS 0-10; 1.7 vs. 1.2; p < 0.0001), more functional limitations (CHAQ; 0.44 vs. 0.14; <0.0001) and rated their health status worse (NRS 0-10; 3.5 vs. 1.8; p < 0.0001) than AYA with inconspicuous screening results. Females (OR 2.33 [CI 1.53-3.56]; p < 0.0001), older age (OR 1.09 [CI 1.01-1.18]; p = 0.026), patients with more functional limitations (OR 3.36 [CI 1.98-5.72]; p < 0.0001), and patients with worse subjective health status (OR 1.17 [CI 1.07-1.27]; p < 0.0001) were more likely to have a conspicuous screening result. Regular sports participation was associated with a lower likelihood of conspicuous screening result (OR 0.69 [CI 0.49-0.98]; p = 0.039). CONCLUSIONS: A large-scale outpatient screening of AYA with JIA in Germany shows a high prevalence of anxiety and depression symptoms. The need for routine screening for early detection of mental health problems became apparent.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxoedema and scleroedema.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke).

Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry.

OBJECTIVE: Interim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS). METHODS: From September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit. RESULTS: At the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0-79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician's global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout. CONCLUSION: Data from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.

Safety and effectiveness of abatacept in juvenile idiopathic arthritis: results from the PRINTO/PRCSG registry.

OBJECTIVE: To report the interim 5-year safety and effectiveness of abatacept in patients with juvenile idiopathic arthritis (JIA) in the PRINTO/PRCSG registry. METHODS: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% confidence interval [CI]: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections (IR 1.48 [95% CI: 0.88, 2.34]). As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improved over 5 years across JIA categories. CONCLUSION: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01357668.

How should we approach management of childhood onset chronic anterior uveitis refractory to adalimumab?

INTRODUCTION: The management of refractory juvenile idiopathic associated uveitis (JIAU) or childhood-onset chronic anterior uveitis (CAU) is a challenge. There is no clear consensus or evidence base for to suggest the most appropriate therapy after primary or secondary failure of biweekly adalimumab. In this scenario, most clinicians advocate switching to another anti-tumor necrosis factor alpha inhibitor; however, there are a variety of other disease modifying agents to choose from albeit with a differing levels of evidence. AREAS COVERED: We discuss how to define nonresponse and potential treatment options for patients with JIAU and CAU refractory to biweekly adalimumab. EXPERT OPINION: Uncontrolled CAU and JIAU remain one of the most challenging diseases to manage and can lead to irreversible loss of vision in a third of those affected. Amongst the possible choices, weekly adalimumab, infliximab, tocilizumab and abatacept have more evidence to support their use. JAK inhibitors seem to be a promising option. Golimumab and Rituximab has also been thought to be partially effective in some refractory cases, whereas IL-17, IL-23, and IL-12 inhibition along with apremilast seem not to be a therapeutic option currently. The route of administration should also be considered as there can be significant pros and cons for different children.

Ten-year safety and clinical benefit from open-label etanercept treatment in children and young adults with juvenile idiopathic arthritis.

OBJECTIVES: CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. METHODS: Participants with eoJIA (2-17 years old), ERA or PsA (each 12-17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. RESULTS: Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months' follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin's disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. CONCLUSIONS: Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit-risk assessment of etanercept in these JIA categories remains favourable. TRIAL REGISTRATION: ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069).

Best clinical practice in the treatment of juvenile systemic sclerosis: expert panel guidance - the result of the International Hamburg Consensus Meeting December 2022.

INTRODUCTION: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed. AREAS COVERED: Treatment options were reviewed, and opinions were provided for most facets of jSSc including general management, some of which differs from adult systemic sclerosis, such as the use of corticosteroids, and specific organ involvement, such as skin, musculoskeletal, pulmonary, and gastroenterology. EXPERT OPINION: We are suggesting the treat to target strategy to treat early to prevent cumulative disease damage in jSSc. Conclusions are derived from both expert opinion and available literature, which is mostly based on adult systemic sclerosis (aSSc), given shared pathophysiology, extrapolation of results from aSSc studies was judged reasonable.

Application and performance of disease activity indices proposed for patients with systemic sclerosis in an international cohort of patients with juvenile systemic sclerosis.

Objectives: Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. Methods: The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians' and the patients' global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Results: Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Conclusion: Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.

Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial.

BACKGROUND: Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. METHODS: This phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial was conducted in 75 centres in 20 countries. We enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or juvenile psoriatic arthritis, and an inadequate response (after ≥12 weeks of treatment) or intolerance to one or more conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period (10 weeks for the safety and pharmacokinetic subcohort), and an up to 32-week placebo-controlled double-blind withdrawal period. After age-based dosing was established in the safety and pharmacokinetic period, patients received a once-daily 4 mg adult-equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib, and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Patients and any personnel interacting directly with patients or sites were masked to group assignment. The primary endpoint was time to disease flare during the double-blind withdrawal period and was assessed in the intention-to-treat population of all randomly assigned patients. Safety was assessed in all patients who received at least one dose of baricitinib throughout the three trial periods. For adverse events in the double-blind withdrawal period, exposure-adjusted incidence rates were calculated. The trial was registered on ClinicalTrials.gov, NCT03773978, and is completed. FINDINGS: Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled and received at least one dose of baricitinib (152 [69%] girls and 68 [31%] boys; median age 14·0 years [IQR 12·0-16·0]). 219 patients received baricitinib in the open-label lead-in period, of whom 163 (74%) had at least a JIA-ACR30 response at week 12 and were randomly assigned to placebo (n=81) or baricitinib (n=82) in the double-blind withdrawal period. Time to disease flare was significantly shorter with placebo versus baricitinib (hazard ratio 0·241 [95% CI 0·128-0·453], p<0·0001). Median time to flare was 27·14 weeks (95% CI 15·29-not estimable) in the placebo group, and not evaluable for patients in the baricitinib group (<50% had a flare event). Six (3%) of 220 patients had serious adverse events during the safety and pharmacokinetic period or open-label lead-in period. In the double-blind withdrawal period, serious adverse events were reported in four (5%) of 82 patients (incidence rate [IR] 9·7 [95% CI 2·7-24·9] per 100 patient-years at risk) in the baricitinib group and three (4%) of 81 (IR 10·2 [2·1-29·7]) in the placebo group. Treatment-emergent infections were reported during the safety and pharmacokinetic or open-label lead-in period in 55 (25%) of 220 patients, and during the double-blind withdrawal period in 31 (38%) of 82 (IR 102·1 [95% CI 69·3-144·9]) in the baricitinib group and 15 (19%) of 81 (IR 59·0 [33·0-97·3]) in the placebo group. Pulmonary embolism was reported as a serious adverse event in one patient (1%; IR 2·4 [95% CI 0·1-13·3]) in the baricitinib group in the double-blind withdrawal period, which was judged to be related to study treatment. INTERPRETATION: Baricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy. FUNDING: Eli Lilly and Company under licence from Incyte.

Systemic therapy in juvenile localized scleroderma.

INTRODUCTION: Juvenile localized scleroderma (JLS) is a rare sclerosing disorder of childhood which can result in permanent morbidity and functional disability, if not effectively treated. Treatment should be started in the inflammatory phase before the development of any complication and/or damage. AREAS COVERED: In this review, we will discuss how to assess disease activity and damage in JLS, and propose an escalation plan for systemic treatment, according to a treat-to-target concept. We will discuss the definition of inactive disease and how and when to discontinue medications. EXPERT OPINION: Before starting treatment, it is extremely important to assess baseline disease activity for treatment response to be adequately checked. Moreover, the activity of the extra cutaneous involvement is an important part of the assessment. Patients should be treated in the 'therapeutic window,' before significant fibrosis results. Most patients should receive systemic treatments; in these patients, Methotrexate should be used as the first-line disease-modifying anti-rheumatic drug (DMARD). However, methotrexate intolerance or non-response is an issue, and these patients should be proposed a treatment escalation according to results of latest studies. Future research can develop better prognostic markers to help to guide our decision.

Gender differences in juvenile systemic sclerosis patients: Results from the international juvenile scleroderma inception cohort.

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

Proposed Response Parameters for Twelve-Month Drug Trial in Juvenile Systemic Sclerosis: Results of the Hamburg International Consensus Meetings.

OBJECTIVE: Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. METHODS: This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. RESULTS: After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. CONCLUSION: We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development.

Long-Term Maintenance of Clinical Responses by Individual Patients With Polyarticular-Course Juvenile Idiopathic Arthritis Treated With Abatacept.

OBJECTIVE: To investigate the frequency and trajectories of individual patients with polyarticular-course juvenile idiopathic arthritis (JIA) achieving novel composite end points on abatacept. METHODS: Data from a clinical trial of subcutaneous abatacept (NCT01844518) and a post hoc analysis of intravenous abatacept (NCT00095173) in patients with polyarticular-course JIA were included. Three end points were defined and evaluated: combined occurrence of low disease activity (LDA) measured by the Juvenile Arthritis Disease Activity Score; 50% improvement in American College of Rheumatology criteria for JIA (ACR50); and patient-reported outcomes. Patient-reported outcomes included visual analog scale score of minimal pain (pain-min) and Childhood Health Assessment Questionnaire disability index score of 0 (C-HAQ DI0). In this post hoc analysis, maintenance of month 13 and 21 end points (LDA+pain-min, LDA+C-HAQ DI0, and ACR50+pain-min) in those who achieved them at month 4 was determined. RESULTS: Composite end points (LDA+pain-min, LDA+C-HAQ DI0, and ACR50+pain-min) were achieved at month 4 (44.7%, 19.6%, and 58.9% of the 219 patients treated with subcutaneous abatacept, respectively). Of those who achieved LDA+pain-min at month 4, 84.7% (83 of 98) and 65.3% (64 of 98) maintained LDA+pain-min at months 13 and 21, respectively. The proportions of patients meeting LDA+pain-min outcomes increased from 44.7% (98 of 219) at month 4 to 54.8% (120 of 219) at month 21. The frequency of patients who met an LDA+C-HAQ DI score of 0 increased from 19.6% (43 of 219) at month 4 to 28.8% (63 of 219) at month 21. CONCLUSION: Among individual patients with polyarticular-course JIA treated with abatacept who achieved 1 of the combined clinical and patient-reported outcomes composite end points, many maintained them over 21 months of abatacept treatment.

Approach to Systemic Sclerosis Patient Assessment: How Does Patient Subsetting Help?

Systemic sclerosis (SSc) is a heterogeneous disease comprising of a wide spectrum of ages of onset, sex-based differences, ethnic variations, disease manifestations, differential serologic profiles, and variable response to therapy resulting in reduced health-related quality of life, disability, and survival. The ability to subset groups of patients with SSc can assist with refining the diagnosis, guide appropriate monitoring, inform aggressiveness of immunosuppression, and predict prognosis. The ability to subset patients with SSc has several important practical implications for patient care.

Adherence, helpfulness and barriers to treatment in juvenile idiopathic arthritis - data from a German Inception cohort.

OBJECTIVES: To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in patients with juvenile idiopathic arthritis (JIA). METHODS: The PARQ and CARQ were translated into German, cross-culturally adapted and administered to patients (age ≥ 8 years) and their parents enrolled in the Inception Cohort Study of newly diagnosed JIA patients (ICON). The psychometric issues were explored by analyzing their test-retest reliability and construct validity. RESULTS: Four hundred eighty-one parents and their children with JIA (n = 465) completed the PARQ and CARQ at the 4-year follow-up. Mean age and disease duration of patients were 10.1 ± 3.7 and 4.7 ± 0.8 years, respectively. The rate of missing values for PARQ/CARQ was generally satisfactory, test-retesting showed sufficient reliability. PARQ/CARQ mean child ability total scores (0-100, 100 = best) for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. Construct validity was supported by PARQ and CARQ scores for medications, exercise and splints showing a fair to good correlation with the Global Adherence Assessment (GAA) and selected PedsQL scales. Adolescents showed poorer adherence than children. About one third of the parents and children reported medication errors. Perceived helpfulness was highest for medication, and adverse effects were reported the greatest barrier to treatment adherence. CONCLUSIONS: The German versions of the PARQ and CARQ appear to have a good reliability and sufficient construct validity. These questionnaires are valuable tools for measuring treatment adherence, identifying potential barriers and evaluating helpfulness of treatments in patients with JIA.

Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics.

OBJECTIVE: The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development. METHODS: Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively. RESULTS: In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher. CONCLUSIONS: In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.