Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors and/or the chronic systemic inflammation. We investigated the effect of a TNF antagonist (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients with active disease despite therapy with disease modifying antirheumatic drugs (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks. Disease activity markers as well as aortic stiffness indices (carotid-femoral pulse wave velocity-PWV, augmentation index-AIx), were measured at baseline and at the end of treatment. Eighteen RA patients treated with methotrexate (MTX) were included as controls. Patients were categorized as responders (decrease of Disease Activity Score-DAS28 > 1.2) or nonresponders. There was a statistically significant decrease in PWV (from 8.18 ± 2.03 to 7.01 ± 1.78 m/s, p = 0.00006) and DAS28 (from 6.65 ± 1.22 to 4.69 ± 1.46, p = 0.00007) in RA patients treated with ADA. The decrease in PWV was observed both in responders (n = 12) and nonresponders (n = 6). Multivariate analysis showed that the decrease of PWV was independent of changes in disease activity or other parameters. There was no significant change in PWV in patients treated with MTX (from 8.87 ± 1.91 to 8.41 ± 2.17, p = 0.29). No significant change in AIx or traditional cardiovascular risk factors was observed. Treatment with ADA significantly reduced aortic stiffness in RA patients regardless of their response to therapy. These findings imply a direct protective effect of ADA in vascular wall in RA patients.

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis

“…31,127,132,133,137,140,143,145 Notably, AIx in control groups also remained unchanged. 127,132,133,139 Similar results were found in the case-control study published after the systematic review 135 The effect of anti-TNF treatment on PWV and AIx seems inconsistent. Although most studies demonstrated therapeutic benefit on PWV (improved or stable in the anti-TNF treatment group whereas worsen in the control group), such effect was not seen on the AIx.…”

“…In a case-control study published after the systematic review, a significant decrease in PWV was also noticed in ADA 6 MTX group but not in the MTX only group. 135 Details of the anti-TNF reagents used and the control groups are listed in Table I.…”

Do anti‐tumour necrosis factor‐α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review

“…No controls. 35 18 RA Patients treated with adalimumab 40 mg SC 2 weekly for 12 weeks, compared to controls receiving methotrexate. Measurements at baseline and 12 weeks.…”

According to the Materials of the 2015/2016 New European League Against Rheumatism (Eular) Guidelines for Reducing Cardiovascular Risk in Patients With Inflammatory Arthritis: General Characterization and Discussion Problems

“…При-менение традиционных базисных противовоспалительных препаратов (БПВП), в частности метотрексата (МТ), а так-же генно-инженерных биологических препаратов (ГИБП), таких как ингибиторы фактора некроза опухоли α (ФНОα), связано со значительным снижением риска ССЗ у пациен-тов с РА [35,38,40,[42][43][44][45]. В пилотных исследованиях по-казано, что снижение активности РА коррелирует с сурро-гатными маркерами риска развития ССЗ: уменьшением толщины комплекса интима-медиа на фоне терапии тоци-лизумабом или ритуксимабом (РТМ) [46][47][48]; улучшением артериальной ригидности и жесткости аорты на фоне лече-ния МТ и ингибиторами ФНОα [49][50][51][52].…”