O29 Methotrexate response clusters in JIA

Abstract

Abstract Background Treatment response in juvenile idiopathic arthritis (JIA) is currently viewed as a binary outcome of response versus non-response. In a heterogenous disease such as JIA, it is likely that different, identifiable clusters of children and young people (CYP) may display varying patterns of the different features of the disease. Identifying these response clusters is an important step toward stratified medicine in JIA. The aim of the study was to explore trajectories of juvenile arthritis disease activity score (JADAS) components following methotrexate (MTX) initiation for JIA. Methods MTX-naïve CYP with JIA were selected if enrolled prior to January 2018 in either the UK BSPAR Etanercept Register or the Biologics for Children with Rheumatic Diseases Study at point of starting MTX. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were calculated based on data collected in the year following MTX initiation. Multivariate group-based trajectory models were used to explore MTX response clusters across the different JADAS components, using censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models. Optimal models were selected based on a combination of model fit (BIC), parsimony and clinical plausibility. Results Of 611 CYP selected, the majority were female (69%) and of white ethnicity (85%), with RF-negative JIA the most common disease category (33%). The optimal model identified multiple patterns of disease activity following initiation of MTX, which have greater complexity than simple ‘response’ versus ‘non-response’ clusters. Differences between clusters included initial intensity of disease features and speeds of improvement over time. In addition, the components of the JADAS did not always follow similar patterns over time, even within the same outcome cluster. Conclusion This study has identified that within CYP initiating MTX, different patterns of disease activity are apparent, suggesting that a simple responder/non-responder analysis at a set point may be inadequate. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA. Disclosures S.J.W. Shoop-Worrall None. K.L. Hyrich None. L.R. Wedderburn None. W. Thomson None. N. Geifman None.