Adding TNF inhibitor, triple therapy to RA treatment improves vascular inflammation
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In patients with active rheumatoid arthritis despite methotrexate use, adding either a TNF inhibitor or triple therapy with sulfasalazine and hydroxychloroquine improves vascular inflammation, according to data.
“It has long been recognized that patients with RA suffer more frequent heart attacks and strokes,” Daniel Solomon, MD, MPH, of the division of rheumatology at Brigham and Women’s Hospital and Harvard Medical School, in Boston, told Healio. “However, it has been unclear whether certain disease-modifying antirheumatic drug (DMARD) strategies might be able to reduce cardiovascular risk. We studied two common DMARD strategies and assessed their impact on cardiovascular risk as measured by an FDG PET/CT scan.”
To investigate the impact of TNF inhibitors and triple therapy on cardiovascular risk in patients with RA, Solomon and colleagues conducted the Treatments Against RA and Effect on FDG-PET/CT trial. This randomized, multicenter, comparator-controlled study lasted 24 months and included patients with at least moderately active RA despite receiving 15 mg or more of methotrexate for at least 8 weeks before enrollment. The researchers also included patients who demonstrated an intolerance to higher levels of methotrexate and had been receiving a stable dose for at least 4 weeks.
Other enrollment criteria included being 50 years or older, for women, or 45 years or older for men. Patients receiving statins of higher than moderate intensity while receiving consistent dosages for 6 or more weeks, with no plans to change dosages for at least 6 months, were excluded.
Included patients remained on their baseline doses of methotrexate and were randomized to receive either a TNF inhibitor — adalimumab (Humira, AbbVie) 40 mg or etanercept (Enbrel, Amgen) 50 mg — or triple therapy with as sulfasalazine (Azulfidine, Watson Laboratories) 1g and hydroxychloroquine 200mg twice per day. Patients were able to switch medications if they did not reach low disease activity through 18 weeks. Patients underwent follow-up every 6 weeks for 24 weeks.
The primary outcome measure was change in the mean of the maximum target-to-background-ratio (TBR) in the most disease-impacted part of either the carotid artery or the aorta.
A total of 115 patients completed the study, with baseline TBR similar across both treatment groups. According to the researchers, there were significant TBR reductions in both groups, with a mean change of –0.24 (SD = 0.51) in the TNF inhibitor group vs. –0.19 (SD = 0.51) for triple therapy (difference = –0.02; 95%CI, –0.19 to 0.15). Although disease activity was significantly reduced across the two groups, there was no association with change in TBR ( = 0.04; 95%CI, –0.03 to 0.1), the researchers wrote in the Annals of the Rheumatic Diseases.
“Both strategies significantly reduced cardiovascular risk and to the same degree,” Solomon said. “This suggests that effective DMARD therapy in patients with RA reduces cardiovascular risk. The relationship between RA disease activity changes, and change in cardiovascular risk was not clear. We are currently studying biomarkers to assess whether they may clarify the relationship between different inflammatory pathways and cardiovascular risk.”
Perspective
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In this article, Solomon and colleagues examined rheumatoid arthritis and cardiovascular events, and whether our current therapies — TNF inhibitors, hydroxychloroquine, sulfasalazine and low-dose methotrexate — would mitigate that risk. We know that patients with RA have an increase in cardiovascular inflammation but, prior to this study, we were unclear whether our current treatments reduced the risk for cardiovascular events.
The good news is that strong evidence supports our current treatment strategies to significantly improve vascular inflammation for our rheumatoid patients, with or without the addition of a TNF inhibitor. Patient compliance for these medications is a priority and educating them on the significant benefits of maintaining control of their cardiovascular risk and keeping inflammation low is essential.
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