Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Mar;82(3):324-330.
doi: 10.1136/ard-2022-223302. Epub 2022 Nov 30.

Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis

Daniel H Solomon  1 , Jon T Giles  2 , Katherine P Liao  3 , Paul M Ridker  3 , Pamela M Rist  3 , Robert J Glynn  3 , Rachel Broderick  2 , Fengxin Lu  3 , Meredith T Murray  3 , Kathleen Vanni  3 , Leah M Santacroce  3 , Shady Abohashem  4 , Philip M Robson  5 , Zahi Fayad  5 , Venkatesh Mani  5 , Ahmed Tawakol  4 , Joan Bathon  2 ; TARGET Trial Consortium
Collaborators, Affiliations
Randomized Controlled Trial

Reducing cardiovascular risk with immunomodulators: a randomised active comparator trial among patients with rheumatoid arthritis

Daniel H Solomon et al. Ann Rheum Dis. 2023 Mar.

Abstract

Objective: Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent.

Methods: Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up 18F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta.

Results: 115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (β=0.04, 95% CI -0.03 to 0.10).

Conclusion: We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy.

Trial registration number: NCT02374021.

Keywords: Arthritis, Rheumatoid; Cardiovascular Diseases; Tumor Necrosis Factor Inhibitors.

PubMed Disclaimer

Conflict of interest statement

Competing interests: DHS receives research support through his institution from Abbvie, Amgen, CorEvitas and Moderna. He receives royalties from UpToDate on unrelated chapters. JTG has been a consultant for AbbVie, Pfizer, Eli Lilly and Company, Bristol Meyers Squibb, Gilead, Novartis in the last 3 years and received an unrestricted grant from Pfizer. Over the past 36 months, PMR received investigator-initiated research grant support from Novartis, Kowa, Amarin, Pfizer, Esperion, NHLBI, NCI and Operation Warp Speed; served as a consultant to Corvidia, Novartis, Flame, Agepha, Alynlam, IQVIA, R-Pharma, Horizon Therapeutics, Inflazome, AstraZeneca, Jannsen, Civi Biopharm, SOCAR, Novo Nordisk, Health Outlook, Omeicos, the Baim Institute, Boehringer-Ingelheim, Montai Health, Cardiol Therapeutics, the Peter Munk Institute (University of Toronto); and the Foundation Leducq (Paris, FR); and received non-monetary research support from the Pfizer Bristol Myers Squibb Alliance and from Quidel, Inc to conduct federally funded COVID-19 research. PMRo is also listed as a co-inventor on patents held by his institution, the Brigham and Women’s Hospital. None of these conflicts relate to the current manuscript. JMB has nothing to declare.

Figures

Figure 1
Figure 1
This forest plot demonstrates subgroup results of the change in MDS TBR on the FDG-PET/CT scan. CV, cardiovascular; FDG-PET/CT, fluorodeoxyglucose positron emission tomography CT scan; MDS, most diseased segment; RA, rheumatoid arthritis; TBR, target to background ratio.
Figure 2
Figure 2
This figure demonstrates the correlation between change in rheumatoid arthritis disease activity (DAS28-CRP) and vascular inflammation (MDS TBR) (β=0.05, 95% CI −0.02 to 0.11). Additional adjustment for baseline TBR, randomised treatment assignment, age, gender, disease duration, smoking status, serologic status and body mass index did not change the results (β=0.04, 95% CI −0.03 to 0.10). CRP, C reactive protein; DAS28, disease activity in 28 joints; MDS, most diseased segment; TBR, target to background ratio.
See this image and copyright information in PMC

References

    1. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 2013;368:2004–13. 10.1056/NEJMra1216063 - DOI - PubMed
    1. Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012;11:633–52. 10.1038/nrd3800 - DOI - PMC - PubMed
    1. Libby P, Sukhova G, Lee RT, et al. . Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol 1995;25 Suppl 2:S9–12. 10.1097/00005344-199500252-00003 - DOI - PubMed
    1. Tyrrell DJ, Goldstein DR. Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6. Nat Rev Cardiol 2021;18:58–68. 10.1038/s41569-020-0431-7 - DOI - PMC - PubMed
    1. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. . C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010;375:132–40. 10.1016/S0140-6736(09)61717-7 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data