Cardiovascular effects of biological versus conventional synthetic disease-modifying antirheumatic drug therapy in treatment-naïve, early rheumatoid arthritis

Author:

Plein Sven,Erhayiem Bara,Fent Graham,Horton Sarah,Dumitru Raluca BiancaORCID,Andrews Jacqueline,Greenwood John P,Emery PaulORCID,Hensor Elizabeth MA,Baxter Paul,Pavitt Sue,Buch Maya HORCID

Abstract

ObjectivesTo determine whether patients with early rheumatoid arthritis (ERA) have cardiovascular disease (CVD) that is modifiable with disease-modifying antirheumatic drug (DMARD) therapy, comparing first-line etanercept (ETN) + methotrexate (MTX) with MTX strategy.MethodsPatients from a phase IV ERA trial randomised to ETN+MTX or MTX strategy±month 6 escalation to ETN+MTX, and with no CVD and maximum one traditional risk factor underwent cardiovascular magnetic resonance (CMR) at baseline, years 1 and 2. Thirty matched controls underwent CMR. Primary outcome measure was aortic distensibility (AD) between controls and ERA, and baseline to year 1 AD change in ERA. Secondary analyses between and within ERA groups performed. Additional outcome measures included left ventricular (LV) mass and myocardial extracellular volume (ECV).ResultsEighty-one patients recruited. In ERA versus controls, respectively, baseline (geometric mean, 95% CI) AD was significantly lower (3.0×10−3 mm Hg−1 (2.7–3.3) vs 4.4×10−3 mm Hg−1 (3.7–5.2), p<0.001); LV mass significantly lower (78.2 g (74.0–82.7), n=81 vs 92.9 g (84.8–101.7), n=30, p<0.01); and ECV increased (27.1% (26.4–27.9), n=78 vs 24.9% (23.8–26.1), n=30, p<0.01). Across all patients, AD improved significantly from baseline to year 1 (3.0×10−3 mm Hg−1 (2.7–3.4) to 3.6×10–3 mm Hg−1 (3.1–4.1), respectively, p<0.01), maintained at year 2. The improvement in AD did not differ between the two treatment arms and disease activity state (Disease Activity Score with 28 joint count)-erythrocyte sedimentation rate-defined responders versus non-responders.ConclusionWe report the first evidence of vascular and myocardial abnormalities in an ERA randomised controlled trial cohort and show improvement with DMARD therapy. The type of DMARD (first-line tumour necrosis factor-inhibitors or MTX) and clinical response to therapy did not affect CVD markers.Trial registration numberISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.

Funder

Pfizer Ltd

National Institute for Health Research

Publisher

BMJ

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology

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