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

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity

Patients with juvenile idiopathic arthritis become adults: the role of transitional care

Most juvenile idiopathic arthritis (JIA) patients need to attend adult rheumatology centres to continue the clinical management of their disease and to receive adequate long-term treatment. Transition from the paediatric to the adult health care team is a critical moment in the clinical history of these patients, but unfortunately, about 50% of the transfer processes to adult rheumatology are not successful, putting these patients at high risk of unfavourable outcomes. There are several obstacles to the success of transitional care for JIA patients, such as the absence of specific criteria for the assessment of disease activity, the lack of specific treatment recommendations for JIA adult patients, the poor adolescent-specific training for adult rheumatologists, and the shortage of resources. The improvement in the transition process in medical care has become a priority in many health care systems, but not many studies evaluating transition models, and common methodologies for measuring transition outcomes are available. The aim of this review is to identify and describe the models of transitional care in JIA, providing insights and recommendations to develop effective transitional care models in this disease

Juvenile Idiopathic Arthritis, Uveitis and Multiple Sclerosis: Description of Two Patients and Literature Review

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, while multiple sclerosis (MS) is a demyelinating disease of the central nervous system, characterized by remission and exacerbation phases. An association between MS and rheumatologic diseases, in particular rheumatoid arthritis, has been described and numerous studies acknowledge anti-TNF-α drugs as MS triggers. Conversely, the association between MS and JIA has been reported merely in five cases in the literature. We describe two cases of adult patients with longstanding JIA and JIA-associated uveitis, who developed MS. The first patient was on methotrexate and adalimumab when she developed dizziness and nausea. Characteristic MRI lesions and oligoclonal bands in cerebrospinal fluid led to MS diagnosis. Adalimumab was discontinued, and she was treated with three pulses of intravenous methylprednisolone. After a few months, rituximab was started. The second patient had been treated with anti-TNF-α and then switched to abatacept. She complained of unilateral arm and facial paraesthesias; brain MRI showed characteristic lesions, and MS was diagnosed. Three pulses of intravenous methylprednisolone were administered; neurological disease remained stable, and abatacept was reintroduced. Further studies are warranted to define if there is an association between JIA and MS, if MS represents JIA comorbidity or if anti-TNF-α underpins MS development

IL1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with TNF inhibitors

Objective: To investigate the genetic contribution of cytokine gene polymorphisms (interleukin 1 (IL1) and tumour necrosis factor (TNF)) on disease phenotype and on response to TNF-blocking agents in a population of patients with juvenile idiopathic arthritis (JIA). Methods: A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents was enrolled in this study. Analysis of genetic polymorphisms for IL1B +3954, IL1RA +2018, TNF \u2013238 and TNF \u2013308 was performed by enzyme-linked oligo sorbent assay, and compared with those obtained from 630 healthy Caucasians and 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical and laboratory data were collected from clinical charts and entered into a customised database, and 2 analysis was performed to compare cytokine polymorphisms with disease type according to the International League of Associations for Rheumatology criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti-TNF and clinical response after 3 months. Results: The T/T genotype of the IL1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered. Conclusion: In our cohort, the absence of the rare IL1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL1 gene polymorphism studied did not seem to be associated with response to anti-TNF treatment

Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA)

To define the correlation between joint ultrasonography and clinical examination in patients with juvenile idiopathic arthritis (JIA) and to assess whether synovitis detected by ultrasonography in clinically inactive patients predicts arthritis flares

Development of Inflammatory Bowel Disease in Patients with Juvenile Idiopathic Arthritis Treated with Etanercept

OBJECTIVE: With the increasing use of etanercept for juvenile idiopathic arthritis (JIA) new possible adverse events are reported including new autoimmune diseases. Our purpose was to examine if the incidence of inflammatory bowel disease (IBD) in patients with JIA using etanercept is higher than in the healthy age-matched population. We give the clinical characteristics of the IBD in patients with JIA using etanercept. METHODS: The national JIA registries for etanercept of The Netherlands, Germany, Finland, Denmark, and Italy were searched for patients with JIA and IBD. The total number of patient-years was used to calculate incidence. The physicians of the identified patients were asked to give clinical details. RESULTS: Thirteen cases of IBD in JIA patients were identified in the registries between 1999 and 2008. The IBD incidence in JIA patients while using etanercept was 362 per 100,000 patient-years under etanercept, about 43 times higher than in the general pediatric population. Clinical presentation of IBD in JIA patients using etanercept was similar to that in non-JIA patients. The median time between onset of JIA and onset of IBD was 6 years and 10 months. The time between the start of etanercept and the first appearance of IBD symptoms was between 9 days and 4.5 years. CONCLUSION: The incidence of IBD in JIA patients using etanercept seems to be markedly increased, analyzing data from European registries. This incidence of IBD in the etanercept registries cannot be compared to the incidence of IBD in JIA patients using other treatment without etanercept, because such registries do not exist yet in all European countries. These findings are in keeping with a report of 8 new IBD cases occurring in French children with JIA using etanercept. These findings illustrate the need for large international disease-specific registries focused on outcome and pharmacovigilance

Safety and Efficacy of Infliximab and Adalimumab for Refractory Uveitis in Juvenile Idiopathic Arthritis: 1-year Followup Data from the Italian Registry

Objective. To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU). Methods. Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were cortico - steroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications. Results. Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-agents were recorded in the NIR and data from 91, with at least 12 months’ followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3%) achieved remission of AU, 28 (32.9%) had recurrent AU, and 10 (11.8%) maintained a chronic course. A higher remission rate was observed with ADA (67.4% vs 42.8% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8%) experienced 11 minor AE (9 with IFX, 2 with ADA). Conclusion. IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period