Adolescent Rheumatology Etanercept Cohort Study Research Articles

Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study.

SummaryBackgroundInformation is scarce about biological disease-modifying antirheumatic drug (DMARD) switching patterns in children and young people (aged ≤16 years) with juvenile idiopathic arthritis in an era of many biologic therapies. The best choice of biologic to use if the first biological DMARD is not beneficial also remains unclear. We aimed to quantify and characterise biologic switching patterns in children and young people with juvenile idiopathic arthritis, and to compare the effectiveness of using a second tumour necrosis factor inhibitor (TNFi) versus non-TNF is following failure of a first TNFi biologic in routine clinical practice.MethodsOur study population comprised patients with juvenile idiopathic arthritis who were enrolled in two parallel UK cohort studies (the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study [BSPAR-ETN] and the Biologics for Children with Rheumatic Diseases [BCRD] study) between Jan 1, 2004, and April 11, 2019. Data on disease characteristics and DMARD therapy were collected at the time of initiation of a first biologic, at 6 months, at 1 year, and annually thereafter. Biologic switching patterns were described in all patients who started their first biologic from Jan 1, 2010, onwards. Among patients who started treatment with their first biologic from Jan 1, 2004, onwards, had polyarticular course juvenile idiopathic arthritis (extended oligoarthritis or polyarthritis [positive or negative for rheumatoid factor]), and who had started a second biologic, we assessed changes in outcome variables at 6 months compared with baseline and compared the proportion of patients who achieved an American College of Rheumatology Pediatric (ACR Pedi) 90 response and minimal disease activity at 6 months on the basis of the class of the second biologic (a second TNFi vs non-TNFi biologic). Changes in outcome variables at 6 months were compared using linear regression or logistic regression, adjusted for propensity quintiles to account for confounding by indication. We used multiple imputation to account for missing data.FindingsBetween Jan 1, 2004, and April 11, 2019, 2361 patients were enrolled on initiation of biologic therapy. From Jan 1, 2010, onwards, 1152 patients started their first biologic, most of whom started treatment with TNFis (1050 [91%]). The median follow-up was 2·2 years (IQR 1·1–3·8). During this time, 270 (23%) of 1152 patients started a second biologic, 61 (5%) started a third biologic, and 11 (1%) started a fourth biologic. Among 240 patients with polyarticular-course juvenile idiopathic arthritis, 194 (81%) started a second TNFi and 46 (19%) started a non-TNFi after an initial TNFi had failed. Choice of second treatment (second TNFi vs non-TNFi biologic) did not affect the proportion of patients who achieved an ACR Pedi 90 response (adjusted odds ratio [OR] 2·5, 95% CI 0·8–7·9; p=0·11) or minimal disease activity (adjusted OR 1·6, 95% CI 0·6–3·8; p=0·33).InterpretationFor many children and young people with juvenile idiopathic arthritis, treatment with a first or second biologic is not beneficial. We found no evidence that switching to a second non-TNFi biologic was more beneficial than a second TNFi.FundingVersus Arthritis and The British Society for Rheumatology.

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.

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.

ObjectiveThe 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.MethodsA total of 852 ETN‐treated children and 260 MTX‐treated children had been recruited to the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR‐ETN). MSIs included infections that resulted in death or hospitalization or were deemed medically significant by the clinician. This on‐drug analysis followed the patients until the first MSI, treatment discontinuation, the last followup, or death. Cox proportional hazards models, which were adjusted using propensity deciles, were used to compare rates of MSI between cohorts. Sensitivity analyses were conducted specifically with regard to serious infections (SIs), which were defined as those requiring hospitalization or treatment with intravenous antibiotics/antivirals.ResultsThe ETN‐treated cohort was older and had a longer disease duration, but the disease activity was similar between the cohorts. A total of 133 first MSIs were reported (109 with ETN and 24 with MTX). Patients receiving ETN had higher rates of MSI than did the controls (propensity decile adjusted hazard ratio 2.13 [95% confidence interval 1.22–3.74]). The risk of MSI was higher whether patients were receiving combination or monotherapy. Sensitivity analysis showed no between‐group difference in the rate of SIs, which were much less common.ConclusionETN therapy is associated with an increased risk of MSI; however, this increased risk disappears when considering only SIs, which suggests that either there were differences in the severity of infections and/or there was a possible reporting bias.

PP2. Predicting treatment response to etanercept in JIA: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

PP2. Predicting treatment response to etanercept in JIA: results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

275. Predicting Treatment Response to Etanercept in Juvenile Idiopathic Arthritis: Results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

275. Predicting Treatment Response to Etanercept in Juvenile Idiopathic Arthritis: Results from the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study

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.

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. 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. 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]. 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.

287. 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

287. 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