Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial
Abstract Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden fo...
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doaj-57219f3f31494167bd5e7678b9c9b2fc2021-01-17T12:29:35ZengBMCTrials1745-62152020-01-0121111210.1186/s13063-019-4000-5Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trialCelia A. J. Michielsens0Nadine Boers1Nathan den Broeder2Mark H. Wenink3Aatke van der Maas4Elien A. M. Mahler5Michelle L. M. Mulder6Désirée van der Heijde7Frank H. J. van den Hoogen8Lise M. Verhoef9Alfons A. den Broeder10Department of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Leiden University Medical CentreDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekDepartment of Rheumatology, Sint MaartenskliniekAbstract Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Trial registration Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).https://doi.org/10.1186/s13063-019-4000-5SpondyloarthritisPsoriatic arthritisDose reductionTaperingRandomised controlled trialTNF inhibitors |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Celia A. J. Michielsens Nadine Boers Nathan den Broeder Mark H. Wenink Aatke van der Maas Elien A. M. Mahler Michelle L. M. Mulder Désirée van der Heijde Frank H. J. van den Hoogen Lise M. Verhoef Alfons A. den Broeder |
spellingShingle |
Celia A. J. Michielsens Nadine Boers Nathan den Broeder Mark H. Wenink Aatke van der Maas Elien A. M. Mahler Michelle L. M. Mulder Désirée van der Heijde Frank H. J. van den Hoogen Lise M. Verhoef Alfons A. den Broeder Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial Trials Spondyloarthritis Psoriatic arthritis Dose reduction Tapering Randomised controlled trial TNF inhibitors |
author_facet |
Celia A. J. Michielsens Nadine Boers Nathan den Broeder Mark H. Wenink Aatke van der Maas Elien A. M. Mahler Michelle L. M. Mulder Désirée van der Heijde Frank H. J. van den Hoogen Lise M. Verhoef Alfons A. den Broeder |
author_sort |
Celia A. J. Michielsens |
title |
Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
title_short |
Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
title_full |
Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
title_fullStr |
Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
title_full_unstemmed |
Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
title_sort |
dose reduction and withdrawal strategy for tnf-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial |
publisher |
BMC |
series |
Trials |
issn |
1745-6215 |
publishDate |
2020-01-01 |
description |
Abstract Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Trial registration Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018). |
topic |
Spondyloarthritis Psoriatic arthritis Dose reduction Tapering Randomised controlled trial TNF inhibitors |
url |
https://doi.org/10.1186/s13063-019-4000-5 |
work_keys_str_mv |
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