Dose REduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non inferiority trial, the DRESS study

BMC Musculoskeletal Disorders

Bart JF van den Bemt¹  Ronald F van Vollenhoven⁴  Johannes W Bijlsma³  Frank HJ van den Hoogen²  Aatke van der Maas²  Noortje van Herwaarden²  Alfons A den Broeder² 

[1] Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands;Department of Rheumatology, Sint Maartenskliniek, PO box 9011, Nijmegen 6500 GM, The Netherlands;University Medical Center Utrecht, Utrecht, the Netherlands;The Karolinska Institute, Stockholm, Sweden

关键词: Decremental cost effectiveness ratio (DCER);    Design;    Cost minimalisation;    Non-inferiority;    Randomised controlled trial;    Spacing;    Anti TNF;    Discontinuation;    Dose reduction;    Rheumatoid arthritis;   

Others  :  1129390
DOI  :  10.1186/1471-2474-14-299

 received in 2013-03-01, accepted in 2013-10-15,  发布年份 2013

【 摘 要 】

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)

【 授权许可】

   
2013 den Broeder et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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