Lianne Kearsley-Fleet

Medically Significant Infections Are Increased in Patients With Juvenile Idiopathic Arthritis Treated With Etanercept: Results From the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study.

The association between anti–tumor necrosis factor therapy and increased rates of infection is widely documented in adults with rheumatoid arthritis. Findings in children with juvenile idiopathic arthritis (JIA) have been less well documented. The aims of this analysis were to compare the rates of medically significant infections (MSIs) in children with JIA treated with etanercept (ETN) versus methotrexate (MTX) and to compare the rates between combination therapy with ETN plus MTX and monotherapy with ETN.

The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis

Objective. To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy. Methods. The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort. Results. We identified 425 patients with a prior malignancy from 18 000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1000 person-years (py) in the TNFi cohort, 24.7 events/1000 py in the RTX cohort and 53.8 events/1000 py in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% CI: 0.35, 0.86) for the TNFi cohort and 0.43 (95% CI: 0.10, 1.80) for the RTX cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and RTX cohorts, respectively. Conclusions. Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or RTX in the UK do not have an increased risk of future incident malignancy.

Factors associated with choice of biologic among children with Juvenile Idiopathic Arthritis: results from two UK paediatric biologic registers

Objective. The objectives of this study were to describe patients starting first-line biologics for JIA, to describe characteristics over time among patients starting etanercept, and to describe patterns of second biologic prescribing. Methods. The British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study, and the Biologics for Children with Rheumatic Diseases study are ongoing prospective observational cohorts, collecting data on patients starting biologic therapy for JIA. Patients registered from 1 January 2010 starting their first biologic were compared between therapies. Patients starting etanercept before 2010 were included to analyse changes in etanercept prescribing. The pathway of patients starting a second biologic was recorded in all patients. Results. To 26 August 2014, 931 patients were recruited starting a first-line biologic (142 Biologics for Children with Rheumatic Diseases; 789 British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study). From 2010, patients with systemic JIA (sJIA) were almost exclusively prescribed anakinra or tocilizumab. Choice between anti-TNF therapies was largely driven by history of chronic anterior uveitis (CAU). When investigating trends in patients starting etanercept over time, disease duration at etanercept start, patients with sJIA, a history of CAU, and those who received concomitant oral corticosteroids decreased over time. Patients who started a second biologic from 1 January 2010 showed a similar stratification. Conclusion. Although etanercept remains the most common biologic prescribed for JIA, there has been a clear shift towards the use of alternative biologics, largely driven by disease subtype and history of CAU. This channelling of children towards specific therapies should be considered carefully in future studies and in clinical guidelines and ongoing research.

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers

OBJECTIVE Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers.

Factors associated with improvement in disease activity following initiation of etanercept in children and young people with Juvenile Idiopathic Arthritis: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

Objectives. The objectives of this study were to investigate change in disease activity, and explore factors associated with response, in children with JIA over the initial year of etanercept treatment. Methods. This analysis included children with JIA starting etanercept in the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study. Response was assessed using change in juvenile arthritis disease activity score-71 (JADAS-71), an excellent response (ACR Pedi 90), and achieving minimal disease activity (MDA) at 1 year. Change in JADAS-71 was evaluated over time. Multivariable backward stepwise logistic regression was performed to identify factors associated with ACR Pedi 90 and MDA. Results. A total of 496 children were included. Over the first year, 17 stopped due to inefficacy, 9 due to adverse events and 7 for other reasons. One child stopped for remission. At 1 year, 74, 69 and 38% reached ACR Pedi 30, 50 and 90, respectively, and 48% had achieved MDA. Independent predictors of achieving ACR Pedi 90 at 1 year included shorter disease duration [odds ratio (OR) 0.91; 95% CI: 0.85, 0.97)], no concurrent oral corticosteroid use (OR 0.48; 95% CI: 0.29, 0.80) and history of uveitis (OR 2.26; 95% CI: 1.08, 4.71). Independent predictors of achieving MDA at 1 year included younger patients (OR 0.60; 95% CI: 0.38, 0.95), and disease not treated with concurrent oral corticosteroids (OR 0.57; 95% CI: 0.35, 0.93). Conclusion. Among this real-world cohort of children with severe JIA, a significant proportion of children achieved an excellent ACR Pedi response and MDA within 1 year of starting etanercept, although few clinical factors could predict this outcome.

Growth in children and adolescents with juvenile idiopathic arthritis over 2 years of treatment with etanercept: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

OBJECTIVES Children with JIA can experience delayed and restricted growth. The objectives of this study were to investigate the influence of etanercept (ETN) on vertical growth and factors associated with improved growth in patients with JIA over the initial 2 years of treatment. METHODS This analysis was restricted to ETN-treated patients in the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study with complete height data recorded at baseline, 1 and 2 years. Height z-scores were calculated using the World Health Organization growth standards for age and gender. Change in height z-score was evaluated over time. Multivariable linear regression was used to identify factors associated with change in height z-score from baseline. RESULTS A total of 191 ETN-treated patients were included: 65% female, median baseline age 11.0 years [interquartile range (IQR) 7.3-12.9], median disease duration 3.5 years (IQR 1.7-7.1). At baseline mean height z-score was -0.74 (s.d. 1.4). After 2 years mean height z-score increased to -0.45 (1.4) (change +0.29; P < 0.001). In multivariable analysis, factors associated with an improvement in height z-score included lower baseline height z-score [-0.110 per unit (95% CI -0.161, -0.059), P < 0.001] and no oral corticosteroid use at baseline [-0.192 (95% CI -0.343, -0.040), P = 0.013]. CONCLUSION ETN therapy was associated with an improvement in height z-score over the first 2 years of therapy in this real-world cohort of children with severe JIA. The lack of a strong association of improvements in height with improvements in disease activity warrants further exploration.

Pregnancy outcomes in women with rheumatoid arthritis ever treated with rituximab

Hedva Chiu, Samantha Hollingworth, Mieke Van Driel, Parker Magin and Helen Benham School of Medicine, University of Queensland, Herston, School of Pharmacy, University of Queensland, Brisbane, QLD and Discipline of General Practice, University of Newcastle, Callaghan, NSW, Australia Revised version accepted 16 November 2016 Correspondence to: Helen Benham, School of Medicine, University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4012, Australia. E-mail: h.benham@uq.edu.au

How Common is Remission in Juvenile Idiopathic Arthritis: A Systematic Review

Objectives The ideal goal of treatment for juvenile idiopathic arthritis (JIA) is disease remission. However, many sets of remission criteria have been developed and no systematic review of remission in JIA exists. The current systematic review investigated (1) how remission has been defined across JIA clinical cohorts and (2) the frequency of remission overall and within disease categories. Methods Studies using prospective inception cohorts published after 1972 were selected if they estimated remission in cohorts of ≥50 patients. Articles focusing on specific medical interventions, not defining remission clearly or not reporting disease duration at remission assessment were excluded. Studies were selected from Medline, Embase, PubMed and bibliographies of selected articles. Risks of selection, missing outcome data and outcome reporting biases were assessed. Results Within 17 studies reviewed, 88% had majority female participants and patient disease duration ranged from 0.5 to 17 years. Thirteen sets of criteria for clinically inactive disease and remission were identified. Uptake of Wallace’s preliminary criteria was good in studies recruiting or following patients after their publication (78%). Remission frequencies increased with longer disease duration from 7% within 1.5 years to 47% by 10 years following diagnosis. Patients with persistent oligoarticular and rheumatoid-factor positive polyarticular JIA were most and least likely to achieve remission, respectively. Conclusions Achievement of remission increased with longer disease duration, but many patients remain in active disease, even in contemporary cohorts. Multiple sets of outcome criteria limited comparability between studies.

The influence of TNF inhibitors on dementia incidence in patients with rheumatoid arthritis

dyscontrol, and tendencies to be avoidant and stubborn. Based on clinical observations, neuropsychological assessments, social cognition impairment, and personal history of inappropriate behaviour, we hypothesised that this patient’s Diogenes syndrome could be a clinical manifestation of undiagnosed Asperger’s syndrome. We think more broadly that independently of the age factor, some Diogenes behaviours could be atypical presentations of Asperger’s syndrome.

Biologic refractory disease in rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Objectives Biologic disease-modifying antirheumatic drugs (bDMARDs) have revolutionised treatment and outcomes for rheumatoid arthritis (RA). The expanding repertoire allows the option of switching bDMARD if current treatment is not effective. For some patients, even after switching, disease control remains elusive. This analysis aims to quantify the frequency of, and identify factors associated with, bDMARD refractory disease. Methods Patients with RA starting first-line tumour necrosis factor inhibitor in the British Society for Rheumatology Biologics Register for RA from 2001 to 2014 were included. We defined patients as bDMARD refractory on the date they started their third class of bDMARD. Follow-up was censored at last follow-up date, 30 November 2016, or death, whichever came first. Switching patterns and stop reasons of bDMARDs were investigated. Cox regression identified baseline clinical factors associated with refractory disease. Multiple imputation of missing baseline data was used. Results 867 of 13 502 (6%) patients were bDMARD refractory; median time to third bDMARD class of 8 years. In the multivariable analysis, baseline factors associated with bDMARD refractory disease included patients registered more recently, women, younger age, shorter disease duration, higher patient global assessment, higher Health Assessment Questionnaire score, current smokers, obesity and greater social deprivation. Conclusions This first national study has identified the frequency of bDMARD refractory disease to be at least 6% of patients who have ever received bDMARDs. As the choice of bDMARDs increases, patients are cycling through bDMARDs quicker. The aetiopathogenesis of bDMARD refractory disease requires further investigation. Focusing resources, such as nursing support, on these patients may help them achieve more stable, controlled disease.