The TARGET trial
In a recent study of 17 patients with RA, Dr. Giles and his colleagues showed that TNF inhibitor therapy with either adalimumab (Humira) or etanercept significantly reduced aortic inflammation as measured by baseline and 8-week fluorodeoxyglucose (FDG) PET-CT.
“Is this proof that this helps? It’s not proof; there’s no control group, we don’t know that this is not the natural progression of vascular inflammation in these patients,” he said.
However, the findings were suggestive enough to prompt the launch of the TARGET trial, which is now enrolling patients at centers in the United States and Canada, Dr. Giles said.
The TARGET trial is a project involving his team at Columbia University along with researchers from Brigham and Women’s Hospital, Boston. They plan to enroll 200 RA patients without CVD who have an inadequate response to methotrexate. Participants will be randomized to receive an added TNF inhibitor or added triple therapy, and the primary outcome will be changes in inflammation in the aortic and carotid arteries on FDG PET-CT at 6 months versus baseline.
“So stay tuned and hopefully we’ll have some good information about the effect of two different types of treatments for rheumatoid arthritis on vascular inflammation,” Dr. Giles said.
A final question he addressed is whether the RA-CVD risk link is really a problem that has already been solved – one that “we’re just learning about after the fact.”
“The answer is partially yes and partially no,” he said.
The most up-to-date estimate of whether RA patients have a problem with CVD comes from a Swedish population-based study of more than 15,700 RA patients and nearly 70,900 comparators, which was published in 2018 and showed across-the-board declines in CVD rates over time.
RA and non-RA patients experienced an overall 40% reduction in acute coronary syndromes between 1997 and 2014, but the relative difference in event rates between the groups persisted (Ann Rheum Dis. 2017;76:1642-7).
“There is still a gap ... so we haven’t answered this question yet,” he said, adding that “the rates have been reduced, but we want those rates to be equal or maybe even less.
“Why can’t RA patients have less cardiovascular disease if we’re using drugs that are so effective for treating the inflammatory component of atherogenesis?” he asked.
The authors of the study noted that most RA patients in Sweden are in low disease activity by 3-6 months, so they were “a little confounded by why there is no equalization of these rates as of yet,” he said.
“I think we still have more to learn about this problem, and it is still a problem in our patients,” Dr. Giles said.
Dr. Giles is a consultant for Genentech, Lilly, Horizon, Bristol-Myers Squibb, and UCB, and he has received grant support from Pfizer.