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Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

Lookup NU author(s): Dr David Walker



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objectives: RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods: We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Results: Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Conclusion: Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. Trail registration: EudraCT,, 2010-020738-24; ISRCTN registry,, 28955701.

Publication metadata

Author(s): Ibrahim F, Lorente-Canovas B, Dore CJ, Bosworth A, Ma MH, Galloway JB, Cope AP, Pande I, Walker D, Scott DL

Publication type: Article

Publication status: Published

Journal: Rheumatology

Year: 2017

Volume: 56

Issue: 11

Pages: 2004-2014

Print publication date: 01/11/2017

Online publication date: 17/08/2017

Acceptance date: 02/04/2016

Date deposited: 21/11/2017

ISSN (print): 1462-0332

Publisher: Oxford University Press


DOI: 10.1093/rheumatology/kex315

PubMed id: 28968858


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Funder referenceFunder name
Arthritis Research UK