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Design of a phase IV randomised, double-blind, placebo-controlled trial assessing the ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) patients (PREDICTRA)
  1. Paul Emery1,2,
  2. Gerd R Burmester3,
  3. Esperanza Naredo4,
  4. Yijie Zhou5,
  5. Maja Hojnik6,
  6. Philip G Conaghan1,2
  1. 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  2. 2 NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3 Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany
  4. 4 Department of Rheumatology, Joint and Bone Research Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
  5. 5 Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA
  6. 6 Global Medical Affairs Rheumatology, AbbVie, North Chicago, Illinois, USA
  1. Correspondence to Dr Paul Emery; p.emery{at}leeds.ac.uk

Abstract

Introduction The current American College of Rheumatology and European League Against Rheumatism treatment recommendations advise tapering biological disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) who achieve stable clinical remission while receiving bDMARDs. However, not all patients maintain remission or low disease activity after tapering or discontinuation of bDMARDs. The aim of the ImPact of Residual Inflammation Detected via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) study, or PREDICTRA, is to generate data on patient and disease characteristics that may predict the clinical course of a fixed dose-tapering regimen with the bDMARD adalimumab.

Methods and analysis PREDICTRA is an ongoing, multicentre, phase IV, randomised, double-blind, parallel-group study of adalimumab dose tapering controlled by withdrawal in participants with RA who achieved stable clinical remission while receiving adalimumab. The study includes a screening period, a 4-week lead-in period with open-label adalimumab 40 mg every other week and a subsequent 36-week double-blind period during which participants are randomised 5:1 to adalimumab 40 mg every 3 weeks (taper arm) or placebo (withdrawal arm). The primary explanatory efficacy variables are lead-in baseline hand and wrist MRI-detected synovitis and bone marrow oedema scores, as well as a composite of both scores; the dependent variable is the occurrence of flare up to week 40. Additional efficacy variables, safety, pharmacokinetics, biomarkers and immunogenicity will also be assessed, and an ultrasound substudy will be conducted.

Ethics and dissemination The study is conducted in accordance with the International Conference on Harmonisation guidelines, local laws and the ethical principles of the Declaration of Helsinki. All participants are required to sign a written informed consent statement before the start of any study procedures.

Trial registration number EudraCT 2014-001114-26 and NCT02198651; Pre-results.

  • rheumatology
  • rheumatoid arthritis
  • adalimumab
  • withdrawal
  • tapering
  • discontinuation

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Footnotes

  • Contributors Study concept and design: PE, GRB, EN, YZ, PGC. Protocol and statistical analysis plan development: PE, GRB, EN, YZ, MH, PGC. Drafting of the manuscript and critical revision of the manuscript for important intellectual content: All authors.

  • Funding AbbVie (North Chicago, Illinois, USA) funded this ongoing study (EudraCT 2014-001114-26 and NCT02198651), contributed to the design and was involved in the collection, analysis and interpretation of the data and in the writing, review and approval of this publication. PE and PGC are supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre.

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests PE has received research grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. GRB has received research grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz and UCB. EN has received speaker fees from AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen and Celgene GmbH and honoraria from AbbVie. YZ and MH are full-time employees of AbbVie and may hold AbbVie stock or stock options. PGC has received speakers’ bureau or consulting fees from AbbVie, Bristol- Myers Squibb, Lilly, Novartis, Pfizer and Roche.

  • Patient consent Not required.

  • Ethics approval The study protocol was approved by an independent ethics committee or institutional review board at each study site.

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

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