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

Abstract

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.

Metadata

Item Type:	Article
Authors/Creators:	Tom, BDM Symmons, D Brockbank, S Carini, C Cope, AP Ehrenstein, MR Fisher, BA Goodyear, CS Gozzard, N Harris, R Hicks, K Hollis, S Hughes-Morley, A Isaacs, J Kola, B McInnes, IB Mela, CM Parker, G Pedersen, AW Ponchel, F https://orcid.org/0000-0002-3969-7701 Sabin, T Scott, DL Scott, IC Sleeman, MA Taylor, PC Tsuji, W Zhong, Y Hilkens, C Anderson, A Stocks, P Lendrem, D Tarn, J Smith, G Allen, B Casement, J Diboll, J Harry, R Simpson, G Toward, R Noble, H Parke, A Wu, W Clarke, F Galloway, J Lempp, H Ibrahim, F Schwank, S Molyneux, G Lazarov, T Geissmann, F Donnelly, I Gilmour, A Virlan, AT Porter, D Emery, P https://orcid.org/0000-0002-7429-8482 El-Jawhari, J Parmar, R McDermot, MF Buch, M https://orcid.org/0000-0002-8962-5642 Buckley, C Young, SP Jones, P Raza, K Filer, A Pitzalis, C Barnes, MR Watson, DS Tzanis, E Thorborn, G Fossati-Jimack, L Kelly, S Humby, F Bombardieri, M Rana, S Jia, Z Goldmann, K Lewis, M Altobelli, G John, C Martins, S Nguyen, D Ali, H Ciurtin, C Worthington, J Bruce, IN Sergeant, JC Verstappen, SMM Stirling, F Farewell, V Keidel, S Cuff, C Levesque, M Long, A Liu, Z Lipsky, S Harvey, B Macoritto, M Hong, F Kaymakcalan, S Ward, N Talbot, S Padhji, D Sleeman, M Finch, D Herath, A Lindholm, C Jenkins, M Ho, M Marshall, C Page, M Edwards, H Cuza, A Rowe, A Capdevila, FB Loza, M Curran, M Verbeeck, D Baker, D Vranic, I Mela, CT Wright, S Rowell, L Vernon, E Joseph, N Payne, N Rao, R Binks, M Belson, A Ludbrook, V Tipney, H Ellis, J Hasan, S Didierlaurent, A Burny, W Haynes, A Larminie, C Dastros-Pitel, D Jelinsky, S Hodge, M Maciejewski, M Ziemek, D Schulz-Knappe, P Zucht, H-D Budde, P Coles, MC Butler, JA Read, S Consortium, RA-MAP
Copyright, Publisher and Additional Information:	© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: http://creativecommons.org/licenses/by/4.0
Dates:	Accepted: 6 July 2018 Published (online): 25 October 2018 Published: 25 October 2018
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds)
Funding Information:	Funder Grant number MRC (Medical Research Council) G1001518
Depositing User:	Symplectic Publications
Date Deposited:	05 Mar 2019 13:19
Last Modified:	25 Jun 2023 21:44
Status:	Published
Identification Number:	10.1136/rmdopen-2018-000721
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:143215

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

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