Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial

Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators re...

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Main Authors: Jon T. Giles, Pamela M. Rist, Katherine P. Liao, Ahmed Tawakol, Zahi A. Fayad, Venkatesh Mani, Nina P. Paynter, Paul M. Ridker, Robert J. Glynn, Fengxin Lu, Rachel Broderick, Meredith Murray, Kathleen M. M. Vanni, Daniel H. Solomon, Joan M. Bathon
Format: Article
Language:English
Published: Wiley 2021-06-01
Series:ACR Open Rheumatology
Online Access:https://doi.org/10.1002/acr2.11256
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spelling doaj-e842df4b45cc4bd49735e4e8887b967e2021-06-16T11:11:44ZengWileyACR Open Rheumatology2578-57452021-06-013637138010.1002/acr2.11256Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET TrialJon T. Giles0Pamela M. Rist1Katherine P. Liao2Ahmed Tawakol3Zahi A. Fayad4Venkatesh Mani5Nina P. Paynter6Paul M. Ridker7Robert J. Glynn8Fengxin Lu9Rachel Broderick10Meredith Murray11Kathleen M. M. Vanni12Daniel H. Solomon13Joan M. Bathon14Columbia UniversityVagelos College of Physicians & Surgeons New York New YorkBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsMassachusetts General Hospital and Harvard Medical School BostonTranslational and Molecular Imaging InstituteIcahn School of Medicine at Mount Sinai New YorkTranslational and Molecular Imaging InstituteIcahn School of Medicine at Mount Sinai New YorkBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsBrigham and Women's Hospital Boston MassachusettsColumbia UniversityVagelos College of Physicians & Surgeons New York New YorkBrigham and Women's Hospital Boston MassachusettsBrigham and Women's Hospital Boston MassachusettsBrigham and Women's Hospital and Harvard Medical School Boston MassachusettsColumbia UniversityVagelos College of Physicians & Surgeons New York New YorkIndividuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18‐Fluorodeoxyglucose [18F‐FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full‐body 18F‐FDG–labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat‐to‐target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target‐to‐background ratio of arterial 18F‐FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease‐modifying antirheumatic drugs.https://doi.org/10.1002/acr2.11256
collection DOAJ
language English
format Article
sources DOAJ
author Jon T. Giles
Pamela M. Rist
Katherine P. Liao
Ahmed Tawakol
Zahi A. Fayad
Venkatesh Mani
Nina P. Paynter
Paul M. Ridker
Robert J. Glynn
Fengxin Lu
Rachel Broderick
Meredith Murray
Kathleen M. M. Vanni
Daniel H. Solomon
Joan M. Bathon
spellingShingle Jon T. Giles
Pamela M. Rist
Katherine P. Liao
Ahmed Tawakol
Zahi A. Fayad
Venkatesh Mani
Nina P. Paynter
Paul M. Ridker
Robert J. Glynn
Fengxin Lu
Rachel Broderick
Meredith Murray
Kathleen M. M. Vanni
Daniel H. Solomon
Joan M. Bathon
Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
ACR Open Rheumatology
author_facet Jon T. Giles
Pamela M. Rist
Katherine P. Liao
Ahmed Tawakol
Zahi A. Fayad
Venkatesh Mani
Nina P. Paynter
Paul M. Ridker
Robert J. Glynn
Fengxin Lu
Rachel Broderick
Meredith Murray
Kathleen M. M. Vanni
Daniel H. Solomon
Joan M. Bathon
author_sort Jon T. Giles
title Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
title_short Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
title_full Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
title_fullStr Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
title_full_unstemmed Testing the Effects of Disease‐Modifying Antirheumatic Drugs on Vascular Inflammation in Rheumatoid Arthritis: Rationale and Design of the TARGET Trial
title_sort testing the effects of disease‐modifying antirheumatic drugs on vascular inflammation in rheumatoid arthritis: rationale and design of the target trial
publisher Wiley
series ACR Open Rheumatology
issn 2578-5745
publishDate 2021-06-01
description Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18‐Fluorodeoxyglucose [18F‐FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full‐body 18F‐FDG–labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat‐to‐target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target‐to‐background ratio of arterial 18F‐FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease‐modifying antirheumatic drugs.
url https://doi.org/10.1002/acr2.11256
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