Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

Tom, B. D.M., Symmons, D. and RA-MAP Consortium:, (2018) Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data. RMD Open, 4(2), e000721. (doi: 10.1136/rmdopen-2018-000721) (PMID:30487994) (PMCID:PMC6241979)

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Objectives: To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. Methods: Phase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time. Results: IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations. Conclusions: Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.

Item Type:Articles
Additional Information:This study was funded by the MRC/ABPI Inflammation and Immunology Initiative Grant (MRC reference numbers: G1001516 and G1001518). BDMT is supported by the UK Medical Research Council (Unit Programme numbers: MC_ UP_1302/3 and MC_UU_00002/2). DS was an NIHR Senior Investigator.
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Tulunay Virlan, Dr Aysin and Goodyear, Professor Carl and Porter, Dr Duncan and Gilmour, Miss Ashley and Donnelly, Mrs Iona
Authors: Tom, B. D.M., Symmons, D., and RA-MAP Consortium:,
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:RMD Open
Publisher:B M J Group
ISSN (Online):2056-5933
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in RMD Open 4(2):e000721
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
556111An Immunological Toolkit for Clinical Application - RA MAP consortiumIain McInnesMedical Research Council (MRC)G1001518/97748III -IMMUNOLOGY