Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis is associated with an excess cardiovascular disease (CVD) burden. Fewer CVD events associated with specific DMARD therapies have been reported; however, causal effects on atherosclerosis have never been evaluated rigorously in a randomized trial. Radiolabeled fluorodeoxyglucose (FDG) is taken up by macrophages in atherosclerotic plaques, is detectable with positron emission tomography (PET), and is a surrogate for atherosclerosis. We designed a multi-center randomized controlled clinical trial to: 1) Compare the change (over 24 weeks) in FDG uptake in the aorta and carotid arteries among methotrexate (MTX) inadequate responders who will be randomized to adding either a TNF inhibitor (i.e. step-up MTX + TNFi) or sulfasalazine + hydroxychloroquine (i.e. step-up triple therapy), and 2) assess whether achieving low RA disease activity or remission (LDAR) is associated with a parallel reduction in arterial FDG uptake. Correlations of change in arterial FDG uptake with change in circulating biomarkers will also be performed.
Methods: The primary hypothesis of the
Results: From a published study of 17 RA patients, the mean ± SD baseline aortic MDSmax TBR was 2.51±0.33 units. In the same study, there was a 0.46 unit reduction in this measure after 8 weeks of TNFi. We calculated that the trial would require a pooled sample size of n=170 (n=85 per arm) to detect an absolute difference in the 6-month MDSmax TBR of 0.17 units between the treatment groups with 90% power should the highest projected crossover occur. This same sample size would also have 90% power to detect a 0.19 unit difference in MDSmax TBR between those achieving LDAR vs. moderate or high disease activity, using the same assumptions. The magnitude of these differences is consistent with studies comparing low vs. high dose statin use. Conservatively assuming a 15% drop-out, 100 patients per arm will be enrolled beginning in July 2016.
Conclusion: The TARGET trial, the first to explore the effect of immunomodulation on vascular inflammation in any rheumatic disease, is powered to detect meaningful differences in vascular inflammation between treatments. Further, the minimal detectable difference in arterial inflammation between those achieving LDAR compared with those not responding as may be small, yet clinically meaningful.
To cite this abstract in AMA style:Giles JT, Liao K, Paynter N, Wohlfahrt A, Zartoshti A, Broderick R, Solomon DH, Bathon J. Delineating the Effects of Rheumatoid Arthritis Pharmacotherapies on Vascular Inflammation: Rationale and Design of a Clinical Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/delineating-the-effects-of-rheumatoid-arthritis-pharmacotherapies-on-vascular-inflammation-rationale-and-design-of-a-clinical-trial/. Accessed August 4, 2021.
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