current clinical practice and available resources

Objective To assess European pediatric rheumatology providers’ current clinical practices and resources used in the transition from child-centered to adult-oriented care. Methods European pediatric rheumatologists were invited to complete a 17-item anonymized e-survey assessing current transition practices, transition policy awareness, and needs in advance of the publication of EULAR/PReS recommendations on transition. Results The response rate was 121/276 (44%), including responses from 115 centers in 22 European Union countries. Although 32/121 (26%) responded that their centers did not offer transition services, the majority (99%) agreed that a formalized process in transitioning patients to adult care is necessary. A minority (<30%) of respondents stated that they have a written transition policy although 46% have an informal transition process. Designated staff to support transitional care were available in a minority of centers: nurse (35%), physiotherapist (15%), psychologist (15%), social worker (8%), and occupational therapist (2%). The existence of a designated team member to coordinate transition was acknowledged in many centers (64% of respondents) although just 36% use a checklist for young people as part of individualized transitional care. Conclusion This survey of European pediatric rheumatology providers regarding transitional care practices demonstrates agreement that transitional care is important, and wide variation in current provision of transition services exists

Juvenile arthritis caused by a novel FAMIN (LACC1) mutation in two children with systemic and extended oligoarticular course

Background The pathophysiological origin of juvenile idiopathic arthritis (JIA) is largely unknown. However, individuals with presumably pathogenic mutations in FAMIN have been reported, associating this gene with a rare subtype of this disorder. FAMIN, that is formerly also referred to as LACC1 or C13orf31, has recently been shown to play a crucial role in immune-metabolic functions and is involved in regulation of inflammasome activation and promotion of ROS production. Case presentation We describe two siblings with severe familial forms of juvenile arthritis in which whole-exome-sequencing revealed a novel homozygous frameshift mutation (NM_153218.2:c.827delC¸. p.(T276fs*2) in FAMIN. Conclusions The observation of a new deleterious mutation adds further evidence that pathogenic mutations in FAMIN are causal for a monogenic form of JIA. Furthermore the associated phenotype is not restricted to systemic JIA, but can also be found in other forms of familial juvenile arthritis

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

Background Treatment response, remission rates and compliance in patients with polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab, etanercept, or tocilizumab were analyzed in clinical practice. Methods Data collected in the German BIKER registry were analyzed in patients with polyJIA who started treatment with approved biologics, adalimumab, etanercept or tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment response, safety and drug survival were compared. Results Two hundred thirty- six patient started adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/−7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs etanercept, p = 0.01), and Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55, respectively (adalimumab vs etanercept, p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73; p < 0.001). Balanced patients’ samples were obtained by a generalized propensity score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab in 20.2%. There were no important differences in efficacy between first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab 1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not differ significantly in patients on biologic monotherapy compared with combination therapy with methotrexate. Over 4 years observation under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26 serious adverse events, respectively, were reported. Conclusions In clinical practice, etanercept is most frequently used as first-line biologic. Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA. Overall, tolerance was acceptable. Interestingly, compliance was highest with tocilizumab and lowest with adalimumab. This study provides the first indication for the comparison of different biologic agents in polyarticular JIA based on observational study data with all their weaknesses and demonstrates the need for well-controlled head-to-head studies for confirmation

a comparative study with ultrasonography

Background Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases. Methods FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0–3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1–P3) were analyzed with CE and GSUS/PDUS as reference. Results For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS. Conclusions Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology. Trial registration Deutsches Register Klinischer Studien DRKS00012572. Registered 31 July 2017

The German version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the German language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. The participating centres were asked to collect demographic and clinical data along the JAMAR questionnaire in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach\u2019s alpha, interscale correlations, test\u2013retest reliability, and construct validity (convergent and discriminant validity). A total of 319 JIA patients (2.8% systemic, 36.7% oligoarticular, 23.5% RF negative polyarthritis, and 37% other categories) and 100 healthy children were enrolled in eight centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the German version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research

Therapeutic approaches to pediatric COVID-19: an online survey of pediatric rheumatologists

Data on therapy of COVID-19 in immunocompetent and immunosuppressed children are scarce. We aimed to explore management strategies of pediatric rheumatologists. All subscribers to international Pediatric Rheumatology Bulletin Board were invited to take part in an online survey on therapeutic approaches to COVID-19 in healthy children and children with autoimmune/inflammatory diseases (AID). Off-label therapies would be considered by 90.3% of the 93 participating respondents. In stable patients with COVID-19 on oxygen supply (stage I), use of remdesivir (48.3%), azithromycin (26.6%), oral corticosteroids (25.4%) and/or hydroxychloroquine (21.9%) would be recommended. In case of early signs of 'cytokine storm' (stage II) or in critically ill patients (stage III) (a) anakinra (79.5% stage II; 83.6% stage III) or tocilizumab (58.0% and 87.0%, respectively); (b) corticosteroids (oral 67.2% stage II, intravenously 81.7% stage III); (c) intravenous immunoglobulins (both stages 56.5%); or (d) remdesivir (both stages 46.7%) were considered. In AID, &amp;gt; 94.2% of the respondents would not support a preventive adaptation of the immunomodulating therapy. In case of mild COVID-19, more than 50% of the respondents would continue pre-existing treatment with immunoglobulins (100%), hydroxychloroquine (94.2%), anakinra (79.2%) or canakinumab (72.5%), or tocilizumab (69.8%). Long-term corticosteroids would be reduced by 26.9% (&amp;lt; = 2 mg/kg/d) and 50.0% (&amp;gt; 2 mg/kg/day), respectively, with only 5.8% of respondents voting to discontinue the therapy. Conversely, more than 75% of respondents would refrain from administering cyclophosphamide and anti-CD20-antibodies. As evidence on management of pediatric COVID-19 is incomplete, continuous and critical expert opinion and knowledge exchange is helpful

Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC)

Correction: PEDIATRIC RHEUMATOLOGY Volume: 18 Issue: 1 Article Number: 14 DOI: 10.1186/s12969-019-0396-4Background JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. Methods The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365-72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. Results A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists' VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists' VAS and the joint score. Conclusions We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.Peer reviewe

Long‐term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years

ClinicalTrials.gov identifier: NCT00095173[Abstract] Objective. The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period, a 6‐month double‐blind withdrawal period, and a long‐term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient‐reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Methods. Patients enrolled in the phase III trial could enter the open‐label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double‐blind period. Results. One hundred fifty‐three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient‐years) of adverse events decreased during the LTE phase (433.61 events during the short‐term phase [combined lead‐in and double‐blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Conclusion. Long‐term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality‐of‐life benefits in patients with JIA

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

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: the inception cohort project is supported by an unrestricted grant from the Joachim Herz Stiftung, Hamburg, Germany. Publisher Copyright: © The Author(s) 2023.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.Peer reviewe