Conference Coverage

DMARDs improve vascular abnormalities in early RA



– Patients with newly diagnosed RA have subclinical abnormalities in vascular function that are favorably altered after they start to take disease-modifying anti-rheumatic drugs, Maya H. Buch, PhD, said at the annual meeting of the American College of Rheumatology.

Dr. Maya H. Buch Bruce Jancin/MDedge News

Dr. Maya H. Buch

She presented a study of 71 treatment-naive patients with recently diagnosed RA and no history of cardiovascular disease. Patients were randomized to either etanercept plus methotrexate or methotrexate with treat-to-target escalation to triple nonbiologic disease-modifying antirheumatic drug therapy by week 12. Patients in the latter group were switched to etanercept plus methotrexate at week 24 if at that point they had a Disease Activity Score 28 of 2.6 or more.

All participants underwent cardiovascular MRI at baseline and again after 1 and 2 years in order to measure change in aortic stiffness, the primary study endpoint chosen because it is clinically meaningful and can reliably and reproducibly be measured by MRI.

The study was designed to shed light on possible mechanisms for the epidemiologic observation that effective treatment with methotrexate and/or tumor necrosis factor (TNF) inhibitors curbs the excess risk of cardiovascular events that accompanies RA. The thinking is that abnormal aortic distensibility represents an early harbinger of the increased cardiovascular risk associated with this form of inflammatory arthritis, explained Dr. Buch, professor of rheumatology at the University of Leeds (England) and section head of clinical and translational rheumatology at the Leeds Institute of Rheumatic and Musculoskeletal Medicine.

The mean aortic distensibility at baseline, when the study population was treatment naive, was 2.99 x 10–3 mm Hg–1. This value is abnormally low when compared with values seen in healthy age- and sex-matched controls. After 1 year of treatment, however, mean aortic distensibility improved significantly to 3.59 x 10–3 mm Hg–1. This improvement was maintained at year 2, when the mean value was 3.55.

Interestingly, neither treatment response status or disease activity was associated with the improvement in aortic stiffness. However, in a prespecified exploratory comparison between the 20 responders to etanercept plus methotrexate and the 10 responders to first-line methotrexate who never received etanercept, the group on biologic therapy had a 16% greater improvement in aortic distensibility at 1 year.

“It’s not a statistically significant difference. The study wasn’t powered for that,” she said in an interview. “But these data suggest that an anti-TNF treatment strategy may confer additional benefit. Of course, that will need to be confirmed in a larger trial. And if it is confirmed, it would suggest a role for etanercept plus methotrexate in personalizing tailored therapy in early RA patients at particularly high cardiovascular risk.”

Dr. Buch reported receiving funding from Pfizer, Roche, UCB, AbbVie, Sanofi, Eli Lilly, and Sandoz, but reported having no financial conflicts of interest regarding this study, which was sponsored by the U.K. National Institute for Healthcare Research.

SOURCE: Buch MH et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L05.

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