Early RA Treatment Can Stave Off Heart Disease

Patients with early rheumatoid arthritis and no history of cardiovascular have signs of vascular stiffness which improve with DMARD treatment, and the effects seems to be independent of rheumatoid arthritis disease activity and treatment response, shows a study published in the Annals of the Rheumatic Diseases.

“Our research highlights the importance of commencing treatment of rheumatoid arthritis early in order to also lessen the risk of developing cardiovascular disease,” said lead researcher Maya Buch, professor of rheumatology and Director of Experimental Medicine at the Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health at the University of Manchester, UK.

Maya Buch

Patients with rheumatoid arthritis have a greater risk of premature cardiovascular disease (CVD), especially atherosclerosis and heart failure, and the magnitude of increased risk is similar to that associated with major CVD risk factors such as type 2 diabetes. It has been suspected that this heightened risk is mediated by inflammation, raising the possibility that rheumatoid arthritis immune-modulating therapies could influence CVD pathogenesis.

The researchers used cardiovascular magnetic resonance (CMR) - the most sensitive tool for the assessment of CVD – to determine whether 81 treatment naïve patients with early rheumatoid arthritis exhibited any myocardial or vascular changes compared with patients without rheumatoid arthritis. Thirty healthy volunteers, age and sex matched to the first thirty early rheumatoid arthritis patients and who had no history or risk factors for CVD, acted as controls.

The patients with rheumatoid arthritis were enrolled in a phase IV trial comparing first-line etanercept (ETN) plus methotrexate (MTX) with methotrexate alone in early rheumatoid arthritis. None had type 2 diabetes and all had no more than one traditional CVD risk factor.

The cardiovascular magnetic resonance assessments showed that both mean aortic distensibility (AD) and left ventricular (LV) mass were significantly lower in patients with early rheumatoid arthritis compared with controls, at 3.0×10−3 mm Hg−1 versus 4.4×10−3 mm Hg−1 and 78.2 g versus 92.9 g respectively, while extracellular volume (ECV) was increased at 27.1% compared with 24.9%.

The 81 patients with early rheumatoid arthritis enrolled in the phase IV trial were randomised to etanercept plus methotrexate (15 mg weekly, optimised to 25 mg weekly by week 8) or a methotrexate treat to target strategy (15 mg weekly increased to 25 mg weekly at 2 weeks with further escalation if indicated). Patients in the methotrexate treat to target arm were switched to etanercept plus methotrexate at week 24 if that had failed to go into remission (DAS28-ESR≥2.6).

After the trial had been running for one year, etanercept was stopped in all patients, and patients continued on standard of care for a further twelve months.

Patients were reassessed using cardiovascular magnetic resonance at the end of the first and second year to determine whether the myocardial and vascular changes detected at baseline had worsened, improved or stayed the same.

The results showed that average aortic distensibility had improved, increasing from 3.0×10−3 mm Hg−1 to 3.6×10–3 mm Hg−1 during the first year of rheumatoid arthritis treatment, and this improvement was maintained in the second year. There was no significant different in improvement between the two treatment arms and the size of improvement was also not influenced by the level of disease activity.

The fact that rheumatoid arthritis treatment improved vascular stiffness (an indicator of cardiovascular disease), regardless of how the patient responded to the rheumatoid arthritis medication, was “unexpected,” said Professor Buch. “It suggests that in addition to suppressing inflammation, rheumatoid arthritis treatments may influence CVD risk through other means. Maybe through changes to metabolic profile and/or a direct effect on the processes of heart and vascular disease.”

However, while vascular stiffness is an indicator of cardiovascular disease, it was too early to say whether the improvement shown in the study translated into a reduction in actual cardiovascular event so we should be cautious when tapering therapy, he added.

“Until further data are acquired, these data also suggest we should be cautious if considering a reduction in rheumatoid arthritis therapy (due to good joint control) for concern of risk of CVD progression. We should be cautious if tapering therapy – until we have specific studies that evaluate not only joint damage progression but also cardiovascular outcomes.”

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REFERENCE

Plein S, Erhayiem B, Fent G, Horton S, Dumitru RB, Andrews J, Greenwood JP, Emery P, Hensor EM, Baxter P, Pavitt S, Buch MH. Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis. Ann Rheum Dis. 2020 Nov;79(11):1414-1422. doi: 10.1136/annrheumdis-2020-217653. Epub 2020 Aug 28. PMID: 32859608; PMCID: PMC7569379.