PMID- 29490959 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20190202 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 8 IP - 2 DP - 2018 Feb 28 TI - 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). PG - e019007 LID - 10.1136/bmjopen-2017-019007 [doi] LID - e019007 AB - 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. CI - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. FAU - Emery, Paul AU - Emery P AD - Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK. AD - NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. FAU - Burmester, Gerd R AU - Burmester GR AD - Department of Rheumatology and Clinical Immunology, Charite-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany. FAU - Naredo, Esperanza AU - Naredo E AD - Department of Rheumatology, Joint and Bone Research Unit, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Zhou, Yijie AU - Zhou Y AD - Data and Statistical Sciences, AbbVie, North Chicago, Illinois, USA. FAU - Hojnik, Maja AU - Hojnik M AD - Global Medical Affairs Rheumatology, AbbVie, North Chicago, Illinois, USA. FAU - Conaghan, Philip G AU - Conaghan PG AD - Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK. AD - NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK. LA - eng SI - ClinicalTrials.gov/NCT02198651 SI - EudraCT/2014-001114-26 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180228 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Antirheumatic Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - FYS6T7F842 (Adalimumab) SB - IM MH - Adalimumab/*administration & dosage/pharmacology MH - Antirheumatic Agents/*administration & dosage/pharmacology MH - Arthritis, Rheumatoid/*drug therapy MH - Double-Blind Method MH - Humans MH - Inflammation/drug therapy MH - Regression Analysis MH - Remission Induction MH - Research Design MH - Severity of Illness Index MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors MH - United Kingdom PMC - PMC5855387 OTO - NOTNLM OT - adalimumab OT - discontinuation OT - rheumatoid arthritis OT - rheumatology OT - tapering OT - withdrawal COIS- 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. EDAT- 2018/03/02 06:00 MHDA- 2018/09/11 06:00 PMCR- 2018/02/28 CRDT- 2018/03/02 06:00 PHST- 2018/03/02 06:00 [entrez] PHST- 2018/03/02 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2018/02/28 00:00 [pmc-release] AID - bmjopen-2017-019007 [pii] AID - 10.1136/bmjopen-2017-019007 [doi] PST - epublish SO - BMJ Open. 2018 Feb 28;8(2):e019007. doi: 10.1136/bmjopen-2017-019007.