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

den Broeder AA, van Herwaarden N, van der Maas A, van den Hoogen FH, Bijlsma JW, van Vollenhoven RF, van den Bemt BJ - BMC Musculoskelet Disord (2013)

Bottom Line: However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain.Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness.Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Sint Maartenskliniek, PO box 9011, Nijmegen 6500 GM, The Netherlands. a.denbroeder@maartenskliniek.nl.

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).

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Design of the induction and maintenance phase.
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Figure 1: Design of the induction and maintenance phase.

Mentions: We made a distinction in an induction phase (months 0-9 after the first dose reduction) and a maintenance phase (months 6-18), because the cost effectiveness is very different between these two time periods [14] (Figure 1). In the induction phase, medication costs are still high, patients are sometimes seen more often, and quality of life might be compromised by temporary flares. Therefore, the cost effectiveness ratio found in the stable maintenance phase can be better interpreted for subsequent years.


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

den Broeder AA, van Herwaarden N, van der Maas A, van den Hoogen FH, Bijlsma JW, van Vollenhoven RF, van den Bemt BJ - BMC Musculoskelet Disord (2013)

Design of the induction and maintenance phase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016115&req=5

Figure 1: Design of the induction and maintenance phase.
Mentions: We made a distinction in an induction phase (months 0-9 after the first dose reduction) and a maintenance phase (months 6-18), because the cost effectiveness is very different between these two time periods [14] (Figure 1). In the induction phase, medication costs are still high, patients are sometimes seen more often, and quality of life might be compromised by temporary flares. Therefore, the cost effectiveness ratio found in the stable maintenance phase can be better interpreted for subsequent years.

Bottom Line: However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain.Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness.Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Rheumatology, Sint Maartenskliniek, PO box 9011, Nijmegen 6500 GM, The Netherlands. a.denbroeder@maartenskliniek.nl.

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).

Show MeSH
Related in: MedlinePlus