Dose REduction Strategy of Subcutaneous TNF Inhibitors in Rheumatoid Arthritis: Design of a Pragmatic Randomised Non Inferiority Trial, the DRESS Study

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2013 Oct 25

PMID 24152421

Citations 17

Authors

Alfons A den Broeder

Noortje van Herwaarden

Aatke van der Maas

Frank H J van den Hoogen

Johannes W Bijlsma

Ronald F van Vollenhoven

Bart J F van den Bemt

Affiliations

Soon will be listed here.

Abstract

Background: Preliminary, mostly uncontrolled studies suggest that dose reduction or discontinuation of tumour necrosis factor blockers can be achieved in a relevant proportion of patients with RA without loss of disease control. However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain.

Methods/design: This study is a 18-months pragmatic, non-inferiority, cost minimalisation, randomized controlled trial on dose reduction and discontinuation of the subcutaneous tumour necrosis factor (TNF) blockers adalimumab and etanercept in RA patients with low disease activity. 180 RA patients with low disease activity (DAS28 < 3.2 or clinical judgment of the rheumatologist) are randomized 2:1 to either increased spacing and eventually discontinuation after 6 months of the TNF blocker, and usual care. Implementation is done in routine daily care, using treat to target and feedback implementation in both treatment arms. The primary outcome is non-inferiority (NI margin 20%) in cumulative incidence of persistent (> 3 months) RA flare, according to a recently validated DAS28 based flare criterion (DAS28 change > 1.2, or DAS28 increase of 0.6 and current DAS28 ≥ 3.2). Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness. Cost per quality adjusted life year (QALY) differences between groups are expressed as a decremental cost effectiveness ratio (DCER), i.e. saved costs divided by (possible) loss in QALY.

Discussion: The design of this study targeted several clinical and methodological issues on TNF blocker dose de-escalation, including how to taper the TNF blockers, the satisfactory control condition, how to define flare, implementation in clinical practice, and the choice of the non-inferiority margin. Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance.

Trial Registration: Dutch Trial Register NTR3216, The study has received ethical review board approval (number NL37704.091.11).

Citing Articles

Disease activity-guided dose optimization including discontinuation of TNF inhibitors in rheumatoid arthritis is effective for up to 10 years: an observational follow-up of the DRESS study.

van der Togt C, den Broeder N, Boonstra M, van der Maas A, den Broeder A, van Herwaarden N Rheumatology (Oxford). 2024; 64(2):533-540.

PMID: 38346712 PMC: 11781578. DOI: 10.1093/rheumatology/keae103.

Discontinuation of biologic DMARDs in non-systemic JIA patients: a scoping review of relapse rates and associated factors.

Gieling J, van den Bemt B, Hoppenreijs E, Schatorje E Pediatr Rheumatol Online J. 2022; 20(1):109.

PMID: 36471348 PMC: 9721079. DOI: 10.1186/s12969-022-00769-5.

Extra-articular findings with FDG-PET/CT in rheumatoid arthritis patients: more harm than benefit.

Ulijn E, den Broeder A, Boers N, Gotthardt M, Bouman C, Landewe R Rheumatol Adv Pract. 2022; 6(1):rkac014.

PMID: 35311064 PMC: 8924972. DOI: 10.1093/rap/rkac014.

Dose reduction of the new generation biologics (IL-17 and IL-23 inhibitors) in psoriasis: study protocol for an international, pragmatic, multicenter, randomized, controlled, non-inferiority study-the BeNeBio study.

van der Schoot L, van den Reek J, Grine L, Schots L, Kievit W, Lambert J Trials. 2021; 22(1):707.

PMID: 34656148 PMC: 8520290. DOI: 10.1186/s13063-021-05681-z.

Rheumatoid Arthritis Relapse and Remission - Advancing Our Predictive Capability Using Modern Imaging.

Terslev L, Ostergaard M J Inflamm Res. 2021; 14:2547-2555.

PMID: 34163211 PMC: 8215903. DOI: 10.2147/JIR.S284405.

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