Пациенты и методы

mrj

Современная ревматология

Modern Rheumatology Journal

1996-70122310-158X

IMA-PRESS, LLC

10.14412/1996-7012-2016-1-7-14

mrj-664

Research Article

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ

ORIGINAL INVESTIGATIONS

Оценка кардиоваскулярного риска при применении ингибитора интерлейкина 1 у больных тяжелой тофусной подагрой

Assessment of cardiovascular risk from the use of an interleukin-1 inhibitor in patients with severe tophaceous gout

Елисеев

М. С.

Eliseev

M. S.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

elicmax@rambler.ru

Желябина

О. В.

Zhelyabina

O. V.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Маркелова

Е. И.

Markelova

E. I.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Новикова

Д. С.

Novikova

D. S.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Владимиров

С. А.

Vladimirov

S. A.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Корсакова

Ю. О.

Korsakova

Yu. O.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Александрова

Е. Н.

Aleksandrova

E. N.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Новиков

А. А.

Novikov

A. A.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

Насонов

Е. Л.

Nasonov

E. L.

Москва, 115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation

2016

24032016

101714

2016

Елисеев М.С., Желябина О.В., Маркелова Е.И., Новикова Д.С., Владимиров С.А., Корсакова Ю.О., Александрова Е.Н., Новиков А.А., Насонов Е.Л.

Eliseev M.S., Zhelyabina O.V., Markelova E.I., Novikova D.S., Vladimirov S.A., Korsakova Y.O., Aleksandrova E.N., Novikov A.A., Nasonov E.L.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://mrj.ima-press.net/mrj/article/view/664

Предполагается, что ингибирование интерлейкина (ИЛ) 1β может способствовать снижению риска сердечно-сосудистых заболеваний, однако механизм этого влияния изучен недостаточно.

Цель исследования – оценить влияние терапии канакинумабом на параметры структурно-функциональных свойств сосудистого русла, жесткости сосудистой стенки.

Пациенты и методы

Пациенты и методы. Проведено открытое проспективное исследование 20 больных хронической тофусной подагрой в ФГБНУ «НИИР им. В.А. Насоновой». Среди пациентов было 17 (85%) мужчин и 3 (15%) женщины. Всем больным однократно вводили канакинумаб 150 мг подкожно. Определение уровня высокочувствительного СРБ, ИЛ6, суточное мониторирование артериального давления (АД), дуплексное сканирование сонных артерий (толщина комплекса интима-медиа – КИМ), определение ригидности центральных артерий (скорость пульсовой волны в аорте – СПВА, м/с) проводили перед введением канакинумаба, на 14-й и 120-й дни после инъекции; уровень вчСРБ измеряли количественно высокочувствительным иммунотурбидиметрическим методом, концентрацию ИЛ6 определяли с использованием технологии xMAP (Human Grp I Cytokine 27-plex panel ) на анализаторе BioPlex-200 (Bio-Rad, США). Антигипертензивная, липидснижающая терапия во время исследования не изменялась. Статистический анализ осуществляли с помощью пакета прикладных программ Statistica 10.0 (StatSoft/Inc., США).

Результаты

Результаты. Медиана толщины КИМ при исследовании общей сонной артерии, исходно составлявшая 0,83 [0,71; 0,94] мм, к концу исследования снизилась до 0,74 [0,69; 0,84] мм (p=0,022). Медиана СПВА, имевшая исходное значение 14,12 [10; 17] м/с, к концу исследования снизилась до 13,1 [11; 14] м/с, но статистически недостоверно (p=0,79). Уменьшение СПВА относительно исходного уровня к концу исследования зарегистрировано у 13 (65%) пациентов: у 7 из них к концу исследования не было ни одного припухшего сустава и лишь у 5 уровень СРБ был >5 мг/л, что достоверно реже, чем у пациентов без положительной динамики этого индекса: у 6 (86%) из 7 (р=0,043). Через 14 и 120 дней динамика СПВА прямо коррелировала с изменением сывороточного уровня СРБ (p=0,012 и p=0,047 соответственно), через 14 дней – с изменением сывороточного уровня ИЛ6 (p=0,003). По результатам суточного мониторирования АД у пациентов до, через 14 и 120 дней после инъекции достоверного изменения АД не отмечалось. Средний уровень общего холестерина и триглицеридов не изменился.

Выводы

Выводы. Ингибитор ИЛ1β канакинумаб может положительно влиять на толщину КИМ и параметры артериальной жесткости. Влияние канакинумаба на структурно-функциональные свойства сосудистого русла зависит от выраженности противовоспалительного эффекта.

It is suggested that interleukin (IL)-1β inhibition may promote a reduction in the risk of cardiovascular diseases; however, the mechanism of this impact has not been adequately investigated.

Objective

Objective: to evaluate the impact of canakinumab therapy on the structural and functional properties of the vascular bed and the stiffness of the vessel wall.

Patients and methods

Patients and methods. An open-labeled prospective study was conducted in 20 patients with chronic tophaceous gout at the V.A. Nasonova Research Institute of Rheumatology. Among the patients, there were 17 (85%) men and 3 (15%) women. All the patents received a single subcutaneous injection of canakinumab 150 mg. Estimation of high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels, 24-hour blood pressure (BP) monitoring, duplex scanning of the carotid arteries (intimamedia thickness (IMT)), and determination of central artery stiffness (aortic pulse wave velocity (APWV), m/sec) were done before and 14 and 120 days after drug administration; the level of hs-CRP was quantitatively measured using a high-sensitivity immunoturbidimetric assay and the concentration of IL-6 was determined by xMAP technology (Human Grp I Cytokine 27-plex panel on a BioPlex-200 analyzer (Bio-Rad, USA). Antihypertensive lipidlowering therapy was not changed during the investigation. Statistical analysis was carried out using a package of applied Statistica 10.0 programs (StatSoft/Inc., USA).

Results

Results. Examination of the common carotid artery indicated that the median IMT that was 0.83 [0.71; 0.94] mm at baseline decreased to 0.74 [0.69; 0.84] mm by the end of the investigation (p = 0.022). The median APWV that was 14.12 [10; 17] m/sec at baseline dropped to 13.1 [11; 14] by the end of the investigation, but statistically insignificantly (p = 0.79). By the end of the investigation, there was a reduction in APWV as related to the baseline level in 13 (65%) patients: 7 of them had not one swollen joint and only 5 patients had a CRP level of > 5 mg/l, which was significantly less frequently than that in patients without positive changes in this index: in 6 (86%) of the 7 patients (p = 0.043). There was a direct correlation of changes in APW with those in serum CRP levels (p = 0.012 and p = 0.047, respectively) after 14 and 120 days and with those in serum IL-6 concentrations following 14 days (p = 0.003). 24-hour BP monitoring showed no significant BP change in the patients after 14 and 120 days after injection. The mean level of total cholesterol and triglycerides remained unchanged.

Conclusion

Conclusion. The IL-6 inhibitor canakinumab can have a positive effect on IMT and arterial stiffness. The effect of the drug on the structural and functional properties of the vascular bed is due to the magnitude of its anti-inflammatory activity

подаграингибитор итерлейкина 1 канакинумабкардиоваскулярные заболеванияатеросклерозартериальная жесткость

goutinterleukin-1 inhibitor canakinumabcardiovascular diseasesatherosclerosisarterial stiffness

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The authors declare that there are no conflicts of interest present.