OP0162 ETANERCEPT RESPONSE CLUSTERS IN JUVENILE IDIOPATHIC ARTHRITIS
Authors: S. Shoop-Worrall, K. Hyrich, L. Wedderburn, W. Thomson, N. Geifman
Journal: Annals of the Rheumatic Diseases (2021)

Background: In children and young people (CYP) with JIA, we have previously identified clusters with different patterns of disease impact following methotrexate (MTX) initiation. It is unclear whether clusters of treatment response following etanercept (ETN) therapy exist and whether, in a group of CYP who have responded inadequately to or had adverse events on methotrexate, similar treatment response patterns exist. Novel response patterns would aid stratified treatment approaches through better understanding and potential forecasting of more specific response patterns across multiple domains of disease. Objectives: To identify and characterise trajectories of juvenile arthritis disease activity score (JADAS) components following ETN initiation for JIA. Methods: ETN-naïve CYP with non-systemic JIA were selected if enrolled prior to January 2019 in at least one of four CLUSTER consortium studies: BSPAR-ETN, BCRD, CAPS and CHARMS, at point of starting ETN as their first biological therapy. JADAS components (active joint count, physician’s global assessment (0-10cm), parental global evaluation (0-10cm) and standardised ESR (0-10) were collected at ETN initiation and during the following year. Multivariate group-based trajectory models, that identify clusters of CYP with similar patterns of change over time, were used to explore ETN response clusters across the different JADAS components. Censored-normal (global scores, ESR) and zero-inflated Poisson (active joint count) models were used, adjusting for year of ETN initiation. Optimal models were selected based on a combination of model fit (BIC), parsimony, and clinical plausibility. Results: Of the 1003 CYP included, the majority were female (70%) and of white ethnicity (90%), with rheumatoid factor-negative JIA the most common disease category (39%). The optimal model identified five trajectory clusters of disease activity following initiation of ETN (Figure 1). Clusters following ETN were similar and covered similar proportions of CYP to those previously identified following MTX: Fast (Group 1: 13%) and Slow (Group 2: 10%) response, active joint count improves but either physician (Group 3: 6%) or parent global scores (Group 4: 34%) remain persistently raised and a group with persistent raised scores across all JADAS components (Group 5: 36%). Compared to the persistent disease cluster, those with greater improvement had lower age and higher functional ability at ETN initiation and those with persistent raised parent global scores had lower ESR levels and were less likely to be RF-positive at ETN initiation. Figure 1. Clusters identified following ETN initiation in children and young people recruited to the UK BSPAR-ETN, BCRD, CAPS and CHARMS studies. Conclusion: This study has identified that within CYP initiating ETN, similar response clusters are evident to those previously identified following MTX. This commonality suggests a new framework for understanding treatment response, beyond a simple responder/non-responder analysis at a set point, which applies across multiple drugs despite different mechanisms of action and previous unfavourable treatment outcomes. Understanding both clinical factors associated with, and biological mechanisms underpinning, these clusters would aid stratified medicine in JIA. Acknowledgements: We thank the children, young people and families involved in CLUSTER, as well as clinical staff, administrators and data management teams. Funding for CLUSTER has been provided by generous grants from the MRC, Versus Arthritis, GOSH children’s charity, Olivia’s vision and the NIHR Manchester and GOSH BRC schemes. Disclosure of Interests: Stephanie Shoop-Worrall: None declared, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: BMS, UCB, Pfizer, Lucy Wedderburn Speakers bureau: Pfizer, Grant/research support from: Abbvie, Sobi, Wendy Thomson Grant/research support from: Abbvie, Sobi, Nophar Geifman Grant/research support from: Abbvie, Sobi