Prediction Aided Tapering In rheumatoid arthritis patients treated with biOlogicals (PATIO): protocol for a randomized controlled trial
Messelink, Marianne A.; van der Leeuw, Matthijs S.; den Broeder, Alfons A.; Tekstra, Janneke; van der Goes, Marlies C.; Heijstek, Marloes W.; Lafeber, Floris; Welsing, Paco M.J.
(2022) Trials, volume 23, issue 1
(Article)
Abstract
Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the treatment of rheumatoid arthritis (RA) but are expensive and increase the risk of infection. Therefore, in patients with a stable low level of disease activity or remission, tapering bDMARDs should be considered. Although tapering does not seem to affect long-term
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disease control, (short-lived) flares are frequent during the tapering process. We have previously developed and externally validated a dynamic flare prediction model for use as a decision aid during stepwise tapering of bDMARDs to reduce the risk of a flare during this process. Methods: In this investigator-initiated, multicenter, open-label, randomized (1:1) controlled trial, we will assess the effect of incorporating flare risk predictions into a bDMARD tapering strategy. One hundred sixty RA patients treated with a bDMARD with stable low disease activity will be recruited. In the control group, the bDMARD will be tapered according to “disease activity guided dose optimization” (DGDO). In the intervention group, the bDMARD will be tapered according to a strategy that combines DGDO with the dynamic flare prediction model, where the next bDMARD tapering step is not taken in case of a high risk of flare. Patients will be randomized 1:1 to the control or intervention group. The primary outcome is the number of flares per patient (DAS28-CRP increase > 1.2, or DAS28-CRP increase > 0.6 with a current DAS28-CRP ≥ 2.9) during the 18-month follow-up period. Secondary outcomes include the number of patients with a major flare (flare duration ≥ 12 weeks), bDMARD dose reduction, adverse events, disease activity (DAS28-CRP) and patient-reported outcomes such as quality of life and functional disability. Health Care Utilization and Work Productivity will also be assessed. Discussion: This will be the first clinical trial to evaluate the benefit of applying a dynamic flare prediction model as a decision aid during bDMARD tapering. Reducing the risk of flaring during tapering may enhance the safety and (cost)effectiveness of bDMARD treatment. Furthermore, this study pioneers the field of implementing predictive algorithms in clinical practice. Trial registration: Dutch Trial Register number NL9798, registered 18 October 2021, https://www.trialregister.nl/trial/9798. The study has received ethical review board approval (number NL74537.041.20).
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Keywords: bDMARD, Biological, Clinical decision aid, Dose reduction, Prediction model, Predictive algorithm, Randomized controlled trial, Rheumatoid arthritis, Study protocol, Tapering, Humans, Tumor Necrosis Factor-alpha, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Quality of Life, Antirheumatic Agents/adverse effects, Arthritis, Rheumatoid/diagnosis, Pharmacology (medical), Medicine (miscellaneous), Journal Article
ISSN: 1745-6215
Publisher: BioMed Central
Note: Funding Information: The University Medical Center Utrecht (UMCU) is the initiator and sponsor of this study, and the Department of Rheumatology & Clinical Immunology will be coordinating the study. The study is financed by a research grant from the Netherlands Organisation for Health Research and Development (ZonMW). Publisher Copyright: © 2022, The Author(s).
(Peer reviewed)