rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2019-517-522rsp-2783Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHДинамические изменения уровня N-терминального фрагмента предшественника мозгового натрийуретического пептида (NT-proBNP) у больных ревматоидным артритом на фоне терапии ингибитором рецепторов интерлейкина 6Time course of changes in the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis during therapy with an interleukin-6 receptor inhibitorГерасимоваЕ. В.GerasimovaE. V.

Герасимова Елена Владимировна.

115522, Москва, Каширское шоссе, 34А.

Elena Gerasimova.

34A, Kashirskoe Shosse, Moscow 115522.

gerasimovaev@list.ruПопковаТ. В.PopkovaT. V.

115522, Москва, Каширское шоссе, 34А.

34A, Kashirskoe Shosse, Moscow 115522.

МартыноваА. В.MartynovaA. V.

115522, Москва, Каширское шоссе, 34А.

34A, Kashirskoe Shosse, Moscow 115522.

ЧеркасоваМ. В.CherkasovaM. V.

115522, Москва, Каширское шоссе, 34А.

34A, Kashirskoe Shosse, Moscow 115522.

НовиковаД. С.NovikovaD. S.

34A, Kashirskoe Shosse, Moscow 115522.

Научно-исследовательский институт ревматологии им. В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation201915112019575517522Copyright © Герасимова Е.В., Попкова Т.В., Мартынова А.В., Черкасова М.В., Новикова Д.С., 20192019Герасимова Е.В., Попкова Т.В., Мартынова А.В., Черкасова М.В., Новикова Д.С.Gerasimova E.V., Popkova T.V., Martynova A.V., Cherkasova M.V., Novikova D.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2783

Цель исследования – изучить влияние  терапии ингибитором рецепторов  интерлейкина 6 тоцилизумабом (ТЦЗ)  на динамику  уровня N-терминального фрагмента  предшественника мозгового натрийуретического пептида В-типа (NT-proBNP) у пациентов с ревматоидным артритом (РА) в течение 12-месячного периода наблюдения.

Материал и методы

Материал и методы. Обследован  31 пациент с РА (26 женщин  и 5 мужчин) с неэффективностью и/или непереносимостью базисных противовоспалительных препаратов  (БПВП); медиана возраста составила 54 [45; 61] года; продолжительности болезни – 110 [62; 168] мес; DAS28 – 6,2 [5,1; 7,1]; SDAI – 35,0 [23,9; 51,0], CDAI – 30,0 [21,0; 42,0], все больные были серопозитивны по ревматоидному фактору (РФ),  84% – по антителам к циклическому цитруллинированному пептиду (АЦЦП). Внесуставные  проявления выявлялись  у 54% больных. В исследование не включались  пациенты  с РА, имеющие  хроническую сердечную недостаточность. У больных РА обнаружена  высокая частота традиционных факторов  риска сердечно-сосудистых заболеваний (ССЗ):  артериальная гипертензия – у 75%, дислипидемия – у 61%, курение – у 17%, избыточная масса тела – у 61%, отягощенная наследственность по ССЗ – у 36%, гиподинамия – у 68% больных. Ишемическую болезнь сердца диагностировали у 11% пациентов. В 45% случаев отмечена неэффективность  трех и более БПВП, в 55% – непереносимость предшествовавшей терапии БПВП. Пациенты получали ТЦЗ по 8 мг/кг каждые 4 нед: 39% – в виде монотерапии, 61% – в комбинации с метотрексатом (МТ), медиана дозы 20 [18; 25] мг/нед.  Оценка  уровня NT-proBNP проведена  у всех пациентов с РА до начала терапии и после 12 мес лечения ТЦЗ.

Результаты и обсуждение

Результаты и обсуждение. Через 12 мес после назначения ТЦЗ у 54% пациентов отмечалась ремиссия  заболевания (DAS28 <2,6), у 46% – низкая  активность  (2,6≤ DAS28 <3,2), выявлено  снижение  медианы DAS28 с 6,2 [5,1; 7,1] до 2,7 [1,5; 3,3] (р<0,01),  СОЭ с 38 [24; 54] до 8 [4; 16] мм/ч  (р<0,01),  уровня СРБ с 27 [10; 49] до 0,5 [0,2; 0,7] мг/л (р<0,01) и NT-proBNP с 75,8 [43,0; 100,7] до 37,8 [25,1; 78,5] пг/мл  (р=0,01), хотя частота обнаружения его повышенных значений (≥100 пг/мл)  не изменилась (13%). Обнаружена  корреляция ΔNT-proBNP  с ΔСОЭ (r=0,43;  p<0,05) и с ΔСРБ (r=0,46;  p<0,05). Связи между ΔNT-proBNP, индексами активности РА, РФ и АЦЦП крови не было. Уровень NT-proBNP у больных, получающих монотерапию ТЦЗ и комбинацию  ТЦЗ+МТ, существенно  не различался.

Заключение

Заключение. После 12 мес лечения на фоне подавления активности РА выявлено  снижение  уровня NT-proBNP  как при монотерапии ТЦЗ,  так и при использовании комбинации ТЦЗ с МТ. Снижение концентрации NT-proBNP ассоциировалось с уменьшением острофазовых  показателей (уровня СРБ и СОЭ). Контроль активности РА приводит к снижению повреждающего  действия воспаления на миокард.

Objective

Objective: to investigate the impact of therapy with the interleukin-6 receptor inhibitor tocilizumab (TCZ) on the time course of changes in N-terminal pro-brain  natriuretic  peptide (NT-proBNP) levels in patients with rheumatoid arthritis (RA) during a 12-month follow-up period.

Subjects and methods

Subjects and methods. 31 RA patients (26 women and 5 men) with an inadequate  response and/or intolerance  to disease-modifying antirheumatic drugs (DMARDs) were included. Their median age was 54 [45; 61] years; the disease duration – 110 [62; 168] months; DAS28 – 6.2 [5.1; 7.1]; SDAI – 35.0 [23.9; 51.0], and CDAI – 30.0 [21.0; 42.0]. All the patients were seropositive for rheumatoid  factor (RF),  84% – for anti-cyclic citrulinated  peptide (anti-CCP) antibodies. Extra-articular manifestations were found in 54% of patients. Patients with chronic heart failure were notincluded. The RA patients were found to have a high frequency of traditional  risk factors for cardiovascular diseases (CVD): hypertension  (75%), dyslipidemia (61%), smoking (17%), overweight (61%), a family history of CVD (36%), and hypodynamia (68%). Coronary heart disease was diagnosed in 11% of patients. The inefficacy of three or more NSAIDs was noted in 45% of cases; intolerance  to previous therapy with NSAIDs was observed in 55%. The patients received TCZ at a dose of 8 mg/kg every 4 weeks: 39% received TCZ alone; 61% – in combination  with methotrexate (MTX), the MTX median dose was 20 [18; 25] mg/week. The level of NT-proBNP was measured before and 12 months after TCZ therapy.

Results and discussion

Results and discussion. After 12 months of treatment with TCZ 54% of patients had disease remission (DAS28 <2.6), 46% – low disease activity (DAS28 <3.2). Median DAS28 value decreased from 6.2 [5.1; 7.1] to 2.7 [1.5; 3.3] (p<0.01), erythrocyte sedimentation rate (ESR) – from 38 [24; 54] to 8 [4; 16] mm/h (p<0.01), C-reactive  protein (CRP)  – from 27 [10; 49] to 0.5 [0.2; 0.7] mg/L (p<0.01) and NT-proBNP – from 75.8 [43.0; 100.7] to 37.8 [25.1; 78.5] pg/l (p=0.01), although the frequency of its increased values (≥100 pg/ml)  remained unchanged  (13%). There was a correlation of ΔNT-proBNP with ΔESR (r=0.43;  p<0.05) and with ΔCRP (r=0.46;  p<0.05). No association was found between ΔNT-proBNP, RA activity measures, RF, and anti-CCP. The level of NT-proBNP in patients treated with TCZ alone and in combination  with MTX did not differ considerably.

Conclusion

Conclusion. After 12 months of treatment to suppress RA activity, there was a decrease in NT-proBNP levels when TCZ was used alone and in combination with MTX. The lower concentration of NT-proBNP was associated with a reduction  in acute phase measures (CRP and ESR). Control  of RA activity results in the reduced damaging effect of inflammation on the myocardium.

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