Background/Purpose: Etanercept (ETN) is licensed in Europe for use in children with Juvenile Idiopathic Arthritis (JIA) and is routinely prescribed after failure of other DMARDs. Previous findings regarding response to treatment for JIA suggest that patients with less severe disease at start of treatment are those patients who are more likely to respond to treatment. The objectives of this study were to (1) investigate the influence of ETN on disease activity in patients with severe JIA over the initial first year of treatment and (2) explore factors associated with treatment response over this same period.

Methods: This analysis used patients in the British Society for Paediatric and Adolescent Rheumatology ETN Cohort study (BSPAR-ETN) with JIA starting ETN therapy who had follow up records at baseline and 1 year. Only patients with ILAR criteria of systemic arthritis, oligoarticular arthritis, polyarticular arthritis, and psoriatic arthritis were included. Univariable and multivariable backward stepwise logistic regression was performed to identify factors associated with (1) a good treatment response (ACR Pedi 50) and (2) achieving minimal disease activity (MDA) at 1 year. Patients who stopped ETN therapy within the 1^st year for an adverse event or unknown reason were excluded from the model as initial treatment response on therapy was not captured. Patients who stopped for inefficacy were classified as non-responders.  Imputation was used to account for missing baseline and 1 year disease activity measures.

Results: A total of 422 patients were included in this analysis; 73% female, median age at start of ETN therapy 11.0 years (interquartile range (IQR) 7.3, 13.3), disease duration at start of ETN 4 years (IQR 2, 7); 14 stopped ETN due to inefficacy, 8 due to adverse events and 7 for other reasons. No child stopped for remission within the 1^st year. Median baseline JADAS-71 was 17 (IQR 12, 26). At 1 year this decreased to 3 (IQR 1, 10; p<0.001). Of the 407 patients included in the model, at 1 year, 75%, 70%, 59%, and 41% had reached ACR Pedi 30, 50, 70 and 90 respectively, and 49% had achieved MDA. Independent predictors of achieving MDA at 1 year included a history of uveitis (Odds Ratio (OR) 2.60 [95% CI 1.06, 6.37]), younger age (OR age ≥ 9 years old compared to <9 years 0.57 [95% CI 0.35, 0.92]) and lower disability (OR 0.59 per unit CHAQ increase [95% CI 0.40, 0.87]). In addition, as age increased, patients had reduced odds of achieving ACR Pedi 50 at 1 year (OR 0.93 per unit increase [95% CI 0.88, 0.99]).

Conclusion: Among this “real-world” cohort of children with severe JIA, a significant proportion of children achieve MDA and good ACR Pedi response scores within 1 year of starting ETN although few clinical factors could predict this outcome. The finding of a lesser response in older children warrants further investigation and may relate to differences in disease phenotype, drug pharmacokinetics or adherence.