Randomized Trial Finds DMARD Therapy for RA Has a Beneficial Effect on Vascular Inflammation, CV Risk

Richard Mark Kirkner

December 08, 2022

Use of a tumor necrosis factor inhibitor (TNFi) or triple therapy with conventional, synthetic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis have similar beneficial effects in reducing patients' vascular inflammation and cardiovascular risk, according to results from a randomized, active comparator trial.

Dr Daniel Solomon

"The good news is, providers can rest assured that aggressive treatment for RA does reduce vascular inflammation and therefore cardiovascular risk," lead author Daniel H. Solomon, MD, MPH, of Brigham and Women's Hospital in Boston, told Medscape Medical News. "Part of the reason that treating people with potent disease-modifying agents is important is not only because of reductions in pain and improvements in function on the level of arthritis, but also because of the vascular impact."

The small study, published November 30 in Annals of the Rheumatic Diseases, randomly assigned 115 patients with active RA despite methotrexate use to one of two treatment protocols for 24 weeks: addition of a TNFi or triple therapy with the addition of sulfasalazine and hydroxychloroquine. Participants had 18F-fluorodeoxyglucose (FDG)-PET/CT scans at baseline and 24 weeks to assess change in arterial inflammation, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta. The study achieved its outcomes despite a low 56.5% rate of adherence to 80% or more of randomized treatments.

Solomon said this is the first randomized trial comparing the effects of DMARDs on vascular inflammation in RA. The researchers hypothesized that TNFi would be superior to triple therapy for reducing vascular inflammation. "We found that they both reduced vascular inflammation on PET scanning to the same degree," Solomon said.

Study Results

In the TNFi group, the mean of the maximum of the TBR in the most diseased segment (MDS) of the index vessel declined from 2.72 to 2.47 for a delta of -0.24. In the triple therapy patients, MDS declined from 2.62 to 2.43 for a delta of -0.19 (difference in deltas -0.02 [95% CI, -0.19 to 0.15], P = .79).

Solomon explained the choice of FDG-PET/CT scanning to evaluate vascular inflammation in the study participants. "We know that FDG-PET/CT scanning correlates with CV risk, and we know that treatments like statins that impact CV risk reduce the inflammation as observed on FDG-PET/CT," he said.

Although the study found no difference between the TNFi and triple therapy in terms of vascular outcomes, the conclusion is "a bit more nuanced," Solomon said. "It tells us first that reducing inflammation with different strategies in rheumatoid arthritis can similarly impact vascular inflammation. That's great news. These are aggressive treatment strategies, so if you can reduce vascular inflammation in a significant manner, that should result in reduced cardiovascular risk over time." 

Although the choice of TNFi or triple therapy may not matter for reducing CV risk, Solomon said, "It matters that you choose something that's aggressive and that you use it in people who have active disease. That's another part of the story: People who have active disease have worse vascular inflammation, which translates into a reduction in cardiovascular risk — but it's not differentially reduced."

Underlying Mechanisms of CVD in RA

Dr Lihi Eder

Commenting on the research for Medscape Medical News, Lihi Eder, MD, PhD, co-director of the cardio-rheumatology program at Women's College Hospital in Toronto, Canada, said the study findings build on what's known about some of the underlying mechanisms of cardiovascular diseases in RA and how to optimize treatments to reduce the risk.

"Importantly," she said, "none of these treatment strategies was superior, suggesting that both treatment options are acceptable when considering cardiovascular risk reduction, in addition to controlling RA activity."

The strengths of the study are its randomized, controlled design "conducted by a strong team of investigators," and that it addressed questions relevant to routine practice, said Eder, who was not involved with the study.

The study's use of FDG-PET/CT as a surrogate outcome is a limitation, she noted. "Although it would have been very challenging to perform a similar study that will include clinical events as a study outcome." Another limitation, she said, was the low adherence rate to randomized treatments.

"Additional studies that will compare other modes of action (eg, interleukin-6 inhibitors, Janus kinase inhibitors, anti-CD20 monoclonal antibodies) could broaden our understanding regarding the inflammatory pathways driving CV risk in RA," Eder added.

The study received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. AbbVie and Amgen supplied drugs used in the study. Solomon disclosed receiving research support from AbbVie, Amgen, CorEvitas, and Moderna, and royalties from UpToDate. Eder reports no relevant financial relationships.

Ann Rheum Dis. Published online November 30, 2022. Full Text

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.

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