Design of a phase IV randomised, double-blind, placebo-controlled trial assessing the Im P act of R esidual Inflammation Detected via Imaging T E chniques, D rug Levels and Patient Characteristics on the Outcome of Dose Taper I ng of Adalimumab in C linical Remission Rheumatoid Ar T hritis ( RA) patients (PREDICTRA)

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.

Keywords: adalimumab; discontinuation; rheumatoid arthritis; rheumatology; tapering; withdrawal.

Conflict of interest statement

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.

© 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.

Figures

Figure 1

Study design. *Flare at any time point; flare defined as either (1) DAS28(ESR) ≥2.6 with an increase in DAS28(ESR) by >0.6 or (2) an increase in DAS28(ESR) by ≥1.2 from dbBL irrespective of absolute DAS28(ESR) score. Participants who flare at any time during the randomised double-blind period will be switched to open-label ADA 40 mg eow and continue in the open-label rescue arm for 16 weeks up to a maximum study duration of 56 weeks. †If applicable. ADA, adalimumab; DAS28(CRP), Disease Activity Score based on 28 joints and C reactive protein; DAS28(ESR), Disease Activity Score based on 28 joints and erythrocyte sedimentation rate; dbBL, double-blind baseline; ew, every week; eow, every other week; e3w; every 3 weeks; F, flare; MTX, methotrexate; R, randomisation; RA, rheumatoid arthritis; sc, subcutaneously; US, ultrasound.