Effects of rituximab treatment on endothelial dysfunction, carotid atherosclerosis, and lipid profile in rheumatoid arthritis

Abstract

Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile, flow-mediated vasodilation (FMD) of the brachial artery, and common carotid intima-media thickness (ccIMT) in RA. In this study, we assessed the effects of rituximab on FMD, ccIMT, and lipid profile. Five female RA patients received two infusions of 1000 mg rituximab i.v. High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT. We also determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (Tg) levels. Assessments were performed at baseline, as well as at weeks 2, 6, and 16 after the first infusion. Rituximab (RTX) treatment resulted in a rapid and sustained improvement in FMD. The mean improvement was 30%, 22%, and 81% at weeks 2, 6, and 16, respectively. RTX had little effect on atherosclerosis within this short period of time; however, we observed 10%, 9%, and 2% decreases in ccIMT at weeks 2, 6, and 16, respectively. RTX therapy resulted in 3-11% decrease in TC, as well as 14-35% increase in HDL-C levels. Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction, as well as plasma TC and HDL-C levels. RTX may also decrease ccIMT; however, longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients.

Modulation of Autoimmunity and Atherosclerosis – Common Targets and Promising Translational Approaches Against Disease –

“…Lowering of plasma total cholesterol, raised HDL levels, and decreased intima-media thickness in the common carotid artery were also observed in the trial. 137 Although rare, anti-CD20 therapy has shown adverse effects in the form of CV events, causing patients to be withdrawn from anti-CD20 clinical trials. 138 Nevertheless, with regard to the concern over the use of anti-CD20 therapy for CVD, there is debate on whether statins decrease the efficacy of anti-CD20 agents.…”

Atherosclerosis in Patients with Rheumatoid Arthritis

“…In a study involving 49 RA patients, the atherogenic index significantly improved (~9%) after 6 months treatment with rituximab, indicating the beneficial effects on lipid profile along with improvement of disease activity [98]. Study involving small number of RA patients have also demonstrated that rituximab improves carotid atherosclerosis and endothelial function (Table 1) [99]. These data suggest the potential benefit of novel biologics in preventing CVD in RA patients.…”

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].…”

“…Применение ингибиторов ФНОα и БПВП (в основном MT) ассоциируется с увеличением концентрации ОХС, ХС ЛПНП и, в большей степени, ХС ЛПВП, что улучшает от-ношение ОХС/ХС ЛПВП [57][58][59][60][61][62][63][64][65]. В исследованиях сооб-щалось о положительном эффекте РТМ, тоцилизумаба и тофацитиниба на показатели липидного спектра крови [47,[66][67][68][69][70][71][72]. Однако общий эффект лечения этими препа-ратами проявляется в увеличении уровней липидов крови без изменений отношения ОХС/ХС ЛПВП [57,[68][69][70][71][72].…”