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  • Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set

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Rheumatoid arthritis
Exploring the effect on primary endpoints in trials testing targeted therapy interventions for rheumatoid arthritis: a meta-epidemiological study on the appropriate use of a core outcome set
  1. Philip Rask Lage-Hansen1,2,3,
  2. Nikoletta Svendsen1,
  3. Jamie Kirkham4,
  4. Sabrina Mai Nielsen3,
  5. Kirstine Amris3,
  6. Maarten de Wit5,
  7. Maarten Boers6,
  8. Torkell Ellingsen2,
  9. Robin Christensen2,3
  1. 1 Department of Rheumatology, Esbjerg and Grindsted Hospital, Esbjerg, Denmark
  2. 2 Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark
  3. 3 Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
  4. 4 Centre for Biostatistics, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  5. 5 OMERACT Patient Research Partner, Amsterdam, The Netherlands
  6. 6 Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Dr Philip Rask Lage-Hansen; philip.rask.lage-hansen3{at}rsyd.dk

Abstract

Objectives To explore which core domain is best associated with the American College of Rheumatology (ACR) 20% response in trials assessing the effect of targeted interventions in rheumatoid arthritis (RA).

Methods A meta-epidemiological study was performed on randomised trials investigating biologics and targeted agents compared with placebo or conventional disease-modifying antirheumatic drugs in patients with RA. The main outcome measures were ORs for the ACR 20% response and at least one of the eight core domains according to the existing RA core outcome set (COS) analysed based on standardised mean differences.

Results 115 trials involving 55 422 patients with RA were eligible. The OR for achieving ACR 20% response was 3.19 (95% CI 2.96 to 3.44) for the experimental interventions relative to the comparators. The median number of COS domains reported was 6; 18 trials reported only 1 domain, 17 all 8. Univariable meta-regression analyses indicated that each of the eight core domains was significantly associated with ACR 20% response, yet improvements in physical disability explain a successful ACR 20% response the most. Including only trials reporting on all eight core domains, univariable meta-regression analyses proved improvement in fatigue to explain a successful ACR 20% response the most.

Conclusions Within this dataset, it is evident that the conclusions concerning our primary objective were significantly influenced by both the amount and characteristics of missing data. Our data suggest that fatigue could be more important for the primary endpoint than previously assumed, but this is based on limited data.

  • Arthritis, Rheumatoid
  • Biological Therapy
  • Patient Reported Outcome Measures
  • Outcome Assessment, Health Care

Data availability statement

Data are available on reasonable request.

https://doi.org/10.1136/ard-2024-225523

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors PRL-H, JK, SMMN, KA, MB, MdW, TE and RC were responsible for editing and approval of the protocol before submission to PROSPERO. They all contributed to the methodological and statistical design of the study. PRL-H and NS performed the systematic literature search. In the cases of disagreements between the reviewers, a third reviewer (RC) was involved in discussion until consensus was achieved. PRL-H, SMMN and RC were all involved in the statistical analyses. All authors (PRL-H, NS, JK, SMMN, KA, MdW, MB, TE and RC) are responsible for editing and approval of the paper before submission. PRL-H and RC are the guarantors of this work.

    • Funding This work was supported by the clinical institute of Southern Danish University (SDU), Odense University hospital, Esbjerg Hospital and indirectly by unrestricted grants from the Oak Foundation (the Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL)).

    • Disclaimer The funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the manuscript, or in the decision to submit the results for publication. This study is independent of its funders/sponsors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.