Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis

Deyab, Gia; Hokstad, Ingrid; Whist, Jon Elling; Småstuen, Milada Cvancarova; Agewall, Stefan; Lyberg, Torstein; Ronda, Nicoletta; Mikkelsen, Knut; Hjeltnes, Gunnbjørg; Hollan, Ivana

doi:10.1186/s13075-017-1439-1

Cited by 56 publications

(48 citation statements)

References 47 publications

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“…TNF and interleukin-6 are produced by plaque macrophages (36) and are involved in plaque evolution and destabilization (37)(38)(39)(40). Indeed, treatment with TNFi improved endothelial function in RA patients independently of inflammatory response (41). TNFi use was also associated with reduced aortic stiffness in RA independently of DAS28 change (13,42).…”

mentioning

confidence: 92%

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions

Karpouzas

Ormseth

Hernández

et al. 2020

Arthritis & Rheumatology

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Objective To evaluate whether biologic disease‐modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression. Methods In this single‐center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low‐attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham‐D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results After adjustment for the segment stenosis score, the Framingham‐D'Agostino score, and time‐varying Disease Activity Score in 28 joints using the C‐reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long‐term CVD risk (OR 0.15 [95% CI 0.04–0.60]). Noncalcified and low‐attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low‐attenuation plaque at baseline (OR 0.21 [95% CI 0.04–0.99] and OR 0.08 [95% CI 0.01–0.70], respectively), but not in those without noncalcified or low‐attenuation plaque. Per‐segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05–15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17–0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low‐attenuation plaque loss (P = 0.042). Conclusion Our findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis.

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confidence: 92%

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions

Karpouzas

Ormseth

Hernández

et al. 2020

Arthritis & Rheumatology

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“…However, the doses of methotrexate administered in these studies, between 24 and 490mg/day, are considerably higher than the doses typically prescribed in patients with autoimmune disorders, between 1 and 4mg/day. In human studies, methotrexate, singly or combined with other DMARDs, has been shown to enhance endothelial function in patients with inflammatory arthritis and rheumatoid arthritis [99][100][101].…”

Section: Methotrexate Endothelial Function Arterial Stiffness and mentioning

confidence: 99%

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

Mangoni

Tommasi

Zinellu

et al. 2019

CPD

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Increasing age is a strong, independent risk factor for atherosclerosis and cardiovascular disease. Key abnormalities driving cardiovascular risk in old age include endothelial dysfunction, increased arterial stiffness, blood pressure, and the pro-atherosclerotic effects of chronic, low-grade, inflammation. The identification of novel therapies that comprehensively target these alterations might lead to a major breakthrough in cardiovascular risk management in the older population. Systematic reviews and meta-analyses of observational studies have shown that methotrexate, a first-line synthetic disease-modifying anti-rheumatic drug, significantly reduces cardiovascular morbidity and mortality in patients with rheumatoid arthritis, a human model of systemic inflammation, premature atherosclerosis, and vascular aging. We reviewed in vitro and in vivo studies investigating the effects of methotrexate on endothelial function, arterial stiffness, and blood pressure, and the potential mechanisms of action involved. The available evidence suggests that methotrexate might have beneficial effects on vascular homeostasis and blood pressure control by targeting specific inflammatory pathways, adenosine metabolism, and 5' adenosine monophosphate-activated protein kinase. Such effects might be biologically and clinically relevant not only in patients with rheumatoid arthritis but also in older adults with high cardiovascular risk. Therefore, methotrexate has the potential to be repurposed for cardiovascular risk management in old age because of its putative pharmacological effects on inflammation, vascular homeostasis, and blood pressure. However, further study and confirmation of these effects are essential in order to adequately design intervention studies of methotrexate in the older population.

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“…Utvrđeno je da pacijenti s teškom psorijazom imaju smanjeno očekivano trajanje života te više stope kardiovaskularnog i ukupnog mortaliteta 3 20,31,35,37 . Rijetko se pojavljuju istraživanja koja navode da nema značajnog pozitivnog učinka sustavnih lijekova za psorijazu na kardiovasku-aterosklerotsku leziju 24,39 . Zaključeno je da sustavno liječenje MTX-om značajno smanjuje kardiovaskularni rizik.…”

Section: Očekivano Trajanje žIvota Kardiovaskularni Rizični čImbenicunclassified

“…Iako ovaj lijek može snižavati rizik za nastanak arterijske tromboze u pacijenata sa psorijazom, istovremeno je povezan i s hiperhomocisteinemijom koja je nepovoljni rizični čimbenik za razvoj ateroskleroze 23,37 . MTX povećava kapacitet HDL kolesterola za poticanje izbacivanja kolesterola iz pjenušavih stanica u aterosklerotskim plakovima 39 24 .…”

Section: Konvencionalno Sustavno Liječenjeunclassified

Psorijaza – vidljivi ubojica

Gašparini

Kaštelan

2019

Med. Flum. (Online)

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Sažetak. Psorijaza je jedna od najčešćih kroničnih kožnih bolesti s prevalencijom od 1,6 -3 % u općoj populaciji, stoga je ta bolest vrlo važan javnozdravstveni problem. Riječ je o upalnom imunosno posredovanom poremećaju koji se na koži očituje eritematoskvamoznim plakovima na predilekcijskim mjestima. Psorijaza nije životno ugrožavajuća bolest, ali kardiovaskularni rizični čimbenici povezani s njom mogu dovesti do letalnog ishoda. Metabolički sindrom češće se dijagnosticira u pacijenata sa psorijazom u odnosu na opću populaciju, i to ponajviše u pacijentica starijih od 40 godina koje dugo boluju od teškog oblika bolesti. Etiologija razvoja metaboličkih poremećaja nije još u potpunosti razjašnjena, ali postoje dokazi da metaboličke promjene nisu isključivo posljedica dugotrajno aktivne kožne bolesti, već da i prethode prvoj pojavi bolesti. Imunosni odgovor posredovan T-pomoćničkim (engl. T helper, Th) Th1 i Th17 limfocitima sustavno prisutan u pacijenata sa psorijazom pridonosi razvoju ili pogoršanju šećerne bolesti, arterijske hipertenzije i pretilosti. Terapija psorijaze temelji se na liječenju kožne bolesti i komorbiditeta, a prilagođena je pojedinom pacijentu. Primjena metotreksata i bioloških lijekova poput infliksimaba, adalimumaba i etanercepta povezana je s nižim stopama mortaliteta, infarkta miokarda i moždanog udara te s poboljšanjem endotelne funkcije u odnosu na pacijente liječene drugim terapijskim mogućnostima. Pristup pacijentu sa psorijazom mora biti sveobuhvatan i multidisciplinaran te uključivati liječenje psorijaze uz prevenciju, rano prepoznavanje i odgovarajuće liječenje komorbiditeta.Abstract. Psoriasis is one of the most common chronic skin diseases with the prevalence of 1.6-3% in general population, therefore it is an important public health issue. It is an inflammatory immunomediated disorder that manifests as a eritematosquamous dermatosis with plaques on predilection areas. Psoriasis is not a life-threatening disease itself, however cardiovascular risk factors connected to it may lead to a lethal outcome. Metabolic syndrome is diagnosed in patients with psoriasis more often than in general population, especially in female patients older than 40 years old with a longer and more severe form of psoriasis. Etiology of the metabolic changes is still not completely understood, although there is evidence that metabolic changes are not exclusively the result of long active disease, but can precede the first onset of symptoms. T helper (Th) Th1-and Th17-cells-mediated immunological response systemically present in psoriasis contributes to the development or deterioration of diabetes mellitus, high blood pressure and obesity. Treatment of psoriasis is based on the management of skin disease and its comorbidities adjusted to individual patient. Use of methotrexate and biological agents such as infliximab, adalimumab and etanercept has shown lower rates of mortality, myocardial infarction and stroke with improvement of endothelial function in regards to patients treated with other therapeutical o...

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Methotrexate and anti-tumor necrosis factor treatment improves endothelial function in patients with inflammatory arthritis

Cited by 56 publications

References 47 publications

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions

Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High‐Risk Lesions

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

Psorijaza – vidljivi ubojica

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