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Rheumatology (Oxford). 2017 Nov 1;56(11):2004-2014. doi: 10.1093/rheumatology/kex315.

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

Author information

Academic Department of Rheumatology, Division of Immunology, Infection and Inflammatory Disease, Faculty of Life Sciences and Medicine, King's College London.
Comprehensive Clinical Trials Unit, University College London, London.
National Rheumatoid Arthritis Society, Maidenhead.
Rheumatology Department, Nottingham University Hospitals NHS Trust, Nottingham.
Musculoskeletal Services, Freeman Hospital, Newcastle, UK.



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.


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.


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).


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.


RA; TNF; biologics; flare; interruption treatment; tapering

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