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

Abstract

Objectives: To 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.

Methods: Patients 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).

Results: Eighty-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.

Conclusion: We 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 number: ISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.

Keywords: arthritis; atherosclerosis; cardiovascular diseases; magnetic resonance imaging; rheumatoid; tumor necrosis factors.

Conflict of interest statement

Competing interests: PE has received consultant fees from AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Sandoz and UCB and received research grants paid to his employer from AbbVie, BMS, Pfizer, MSD and Roche. MHB has provided expert advice and received consultant fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Pfizer, Roche, Sandoz, Sanofi and UCB and has received research grants paid to her employer from Pfizer Bristol-Myers Squibb, Roche, UCB.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Cardiac MRI protocol. LGE, late gadolinium enhancement; LV, left ventricular; RV, right ventricular.

Figure 2

Consolidated Standards of Reporting Trials diagram. Etanercept-methotrexate (ETN-MTX) = treatment arm 1; MTX-treat to target (TT) = treatment arm 2. TA1 year 1: n=20 responders; n=17 non-responders; 3 unknown. TA2 year 1: n=15 responders; n=21 non-responders; 5 unknown. AE, adverse event; CADREA, Coronary Artery Disease in Early RA; CMR, cardiovascular magnetic resonance; SAE, serious adverse event.