<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mrj</journal-id><journal-title-group><journal-title xml:lang="ru">Современная ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Modern Rheumatology Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1996-7012</issn><issn pub-type="epub">2310-158X</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14412/1996-7012-2020-2-69-75</article-id><article-id custom-type="elpub" pub-id-type="custom">mrj-1010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL INVESTIGATIONS</subject></subj-group></article-categories><title-group><article-title>Очень ранний клинический ответ при лечении ингибитором янус-киназ тофацитинибом у больных активным ревматоидным артритом: динамика боли и элементов центральной сенситизации</article-title><trans-title-group xml:lang="en"><trans-title>A very early clinical response to treatment with the Janus kinase inhibitor tofacitinib in patients with active rheumatoid arthritis: the dynamics of pain and central sensitization elements</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каратеев</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Karateev</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Андрей Евгеньевич Каратеев</p><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>Andrey Evgenyevich Karateev</p><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><email xlink:type="simple">aekarat@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Филатова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Filatova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Погожева</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Pogozheva</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Амирджанова</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Amirdzhanova</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Насонов</surname><given-names>Е. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Nasonov</surname><given-names>E. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А119991, Москва, ул. Трубецкая, 8, стр. 2</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 1155228, Trubetskaya St., Build. 2, Moscow 119991</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лила</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Lila</surname><given-names>A. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кафедра ревматологии ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования»</p><p>115522, Москва, Каширское шоссе, 34А125993, Москва, ул. Баррикадная, 2/1, стр. 1 </p></bio><bio xml:lang="en"><p>Department of Rheumatology, Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia</p><p>34A, Kashirskoe Shosse, Moscow 1155222/1, Barrikadnaya St., Build. 1, Moscow 125993 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мазуров</surname><given-names>В. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Mazurov</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>191015, Санкт-Петербург, Кирочная ул., 41</p></bio><bio xml:lang="en"><p>41, Kirochnaya St., Saint Petersburg 191015</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дё</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>De</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>191015, Санкт-Петербург, Кирочная ул., 41</p></bio><bio xml:lang="en"><p>41, Kirochnaya St., Saint Petersburg 191015</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Баранов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Baranov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>150000, Ярославль, ул. Революционная, 5</p></bio><bio xml:lang="en"><p>5, Revolyutsionnaya St., Yaroslavl 150000</p></bio><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лапкина</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lapkina</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>150000, Ярославль, ул. Революционная, 5</p></bio><bio xml:lang="en"><p>5, Revolyutsionnaya St., Yaroslavl 150000</p></bio><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лукина</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Lukina</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>111123, Москва, шоссе Энтузиастов, 86</p></bio><bio xml:lang="en"><p>86, Shosse Entuziastov, Moscow 111123</p></bio><xref ref-type="aff" rid="aff-6"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кирюхина</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kiryukhina</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>105203, Москва, ул. Нижняя Первомайская, 70</p></bio><bio xml:lang="en"><p>70, Nizhnyaya Pervomayskaya St., Moscow 105203</p></bio><xref ref-type="aff" rid="aff-7"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Давидьян</surname><given-names>С. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Davidyan</surname><given-names>S. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>105203, Москва, ул. Нижняя Первомайская, 70</p></bio><bio xml:lang="en"><p>70, Nizhnyaya Pervomayskaya St., Moscow 105203</p></bio><xref ref-type="aff" rid="aff-7"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сальникова</surname><given-names>Т. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Salnikova</surname><given-names>T. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>300035, Тула, ул. Ф. Энгельса, 58</p></bio><bio xml:lang="en"><p>58, F. Engels St., Tula 300035</p></bio><xref ref-type="aff" rid="aff-8"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Самигуллина</surname><given-names>Р. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Samigullina</surname><given-names>R. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>191015, Санкт-Петербург, Кирочная ул., 41</p></bio><bio xml:lang="en"><p>41, Kirochnaya St., Saint Petersburg 191015</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чакиева</surname><given-names>Д. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Chakieva</surname><given-names>D. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>191015, Санкт-Петербург, Кирочная ул., 41</p></bio><bio xml:lang="en"><p>41, Kirochnaya St., Saint Petersburg 191015</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Марусенко</surname><given-names>И. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Marusenko</surname><given-names>I. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>185910, Петрозаводск, проспект Ленина, 33</p></bio><bio xml:lang="en"><p>33, Lenin Prospect, Petrozavodsk 185910</p></bio><xref ref-type="aff" rid="aff-9"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Семагина</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Semagina</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>443095, Самара, ул. Ташкентская, 159</p></bio><bio xml:lang="en"><p>159, Tashkentskaya St., Samara 443095</p></bio><xref ref-type="aff" rid="aff-10"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Семченкова</surname><given-names>М. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Semchenkova</surname><given-names>M. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Смоленск, ул. Крупской, 28</p></bio><bio xml:lang="en"><p>28, Krupskaya St., Smolensk 214019</p></bio><xref ref-type="aff" rid="aff-11"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Давыдова</surname><given-names>А. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Davydova</surname><given-names>A. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>350086, Краснодар, ул. 1 Мая, 167</p></bio><bio xml:lang="en"><p>167, First May St., Krasnodar 350086</p></bio><xref ref-type="aff" rid="aff-12"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Калинина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kalinina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Волгоград, ул. Павших борцов, 1</p></bio><bio xml:lang="en"><p>1, Pavshikh Bortsov St, Volgograd 400131</p></bio><xref ref-type="aff" rid="aff-13"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.A. Nasonova Research Institute of Rheumatology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University , Ministry of Health of Russia (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>ФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Yaroslavl State Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru"><institution>ГБУЗ г. Москвы «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы</institution><country>Россия</country></aff><aff xml:lang="en"><institution>A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-7"><aff xml:lang="ru"><institution>ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.I. Pirogov National Medical and Surgical Center, Ministry of Heath of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-8"><aff xml:lang="ru"><institution>ГУЗ Тульской области «Тульская областная клиническая больница»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Tula Regional Clinical Hospital</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-9"><aff xml:lang="ru"><institution>ФГБОУ ВО «Петрозаводский государственный университет» Минобрнауки России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Petrozavodsk State Medical University, Ministry of Education and Science of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-10"><aff xml:lang="ru"><institution>ГБУЗ «Самарская областная клиническая больница им. В.Д. Середавина»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.D. Seredavin Samara Regional Clinical Hospital</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-11"><aff xml:lang="ru"><institution>ФГБОУ ВО «Смоленский государственный медицинский университет» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Smolensk State Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-12"><aff xml:lang="ru"><institution>ГБУЗ «Научно-исследовательский институт – Краевая клиническая больница №1 им. проф. С.В. Очаповского»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Prof. S.V. Ochapovsky Territorial Clinical Hospital One, Research Institute</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-13"><aff xml:lang="ru"><institution>ФГБОУ ВО «Волгоградский государственный медицинский университет» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Volgograd State Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>30</day><month>05</month><year>2020</year></pub-date><volume>14</volume><issue>2</issue><fpage>69</fpage><lpage>75</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Каратеев А.Е., Филатова Е.С., Погожева Е.Ю., Амирджанова В.Н., Насонов Е.Л., Лила А.М., Мазуров В.И., Дё А.Ю., Баранов А.А., Лапкина Н.А., Лукина Г.В., Кирюхина Н.А., Давидьян С.Ю., Сальникова Т.С., Самигуллина Р.Р., Чакиева Д.С., Марусенко И.М., Семагина О.В., Семченкова М.Ю., Давыдова А.Ф., Калинина Е.В., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Каратеев А.Е., Филатова Е.С., Погожева Е.Ю., Амирджанова В.Н., Насонов Е.Л., Лила А.М., Мазуров В.И., Дё А.Ю., Баранов А.А., Лапкина Н.А., Лукина Г.В., Кирюхина Н.А., Давидьян С.Ю., Сальникова Т.С., Самигуллина Р.Р., Чакиева Д.С., Марусенко И.М., Семагина О.В., Семченкова М.Ю., Давыдова А.Ф., Калинина Е.В.</copyright-holder><copyright-holder xml:lang="en">Karateev A.E., Filatova E.S., Pogozheva E.Y., Amirdzhanova V.N., Nasonov E.L., Lila A.M., Mazurov V.I., De A.Y., Baranov A.A., Lapkina N.A., Lukina G.V., Kiryukhina N.A., Davidyan S.Y., Salnikova T.S., Samigullina R.R., Chakieva D.S., Marusenko I.M., Semagina O.V., Semchenkova M.Y., Davydova A.F., Kalinina E.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://mrj.ima-press.net/mrj/article/view/1010">https://mrj.ima-press.net/mrj/article/view/1010</self-uri><abstract><p>Ингибиторы янус-киназ (ЯК) блокируют внутриклеточные сигнальные пути, отвечающие за синтез провоспалительных цитокинов и медиаторов, которые, в свою очередь, вызывают активацию болевых рецепторов и развитие центральной сенситизации (ЦС). Предполагается, что ингибиторы ЯК могут быстро устранять боль и уменьшать выраженность ЦС.Цель исследования – оценить влияние ингибитора ЯК тофацитиниба (ТОФА) на выраженность боли и признаки ЦС у больных активным ревматоидным артритом (РА) через 7 и 28 дней после начала терапии.Пациенты и методы. Исследуемую группу составили 39 больных РА (средний возраст 50,9±11,1 года, 79,5% женщин), DAS28 – 5,8±0,6. Из них 89,7% были серопозитивными по ревматоидному фактору, 82,0% получали метотрексат и 18,0% – лефлуномид. Всем пациентам был назначен ТОФА 5 мг 2 раза в день в связи с неэффективностью или непереносимостью генно-инженерных биологических препаратов. Оценивались выраженность боли с помощью опросника BPI (Brief Pain Inventory), наличие невропатического компонента боли (НКБ) с помощью опросника PainDETECT и признаков ЦС с помощью опросника CSI (Central Sensitization Inventory) в первые 4 нед после назначения ТОФА.Результаты и обсуждение. Пациенты исходно испытывали умеренную или выраженную боль (в среднем 5,33±2,51 по числовой рейтинговой шкале – ЧРШ, включенной в BPI), 53,8% имели признаки ЦС (CSI ≥40), 17,9% – признаки НКБ (PainDETECT &gt;18). Уже через 7 дней после начала приема ТОФА отмечалось статистически значимое снижение интенсивности боли в среднем до 4,06±2,2 по ЧРШ (р=0,01) и на 29,4±17,9% по оценке анальгетического эффекта терапии пациентом (BPI), а также выраженности ЦС – уменьшение значения CSI в среднем до 35,9±11,2 (р=0,01). Через 28 дней эффект усилился: наблюдалось снижение уровня боли по ЧРШ до 2,32±1,57 (р&lt;0,001), боли по оценке анальгетического эффекта терапии пациентом до 43,6±29,6%, медианы значения PainDETECT до 2,5 [0; 8,7] (р&lt;0,001), показателя CSI в среднем до 26,4±13,9 (р&lt;0,001). Серьезных неблагоприятных реакций не отмечено. ТОФА обладает быстрым анальгетическим эффектом, что позволяет рассматривать его как средство выбора при проведении патогенетической терапии у больных активным РА с выраженной болью, особенно при наличии признаков ЦС и вторичной фибромиалгии. Несомненно, требуются большие по масштабу длительные контролируемые исследования с более широким кругом оцениваемых параметров для уточнения лечебного потенциала ТОФА у этой категории пациентов. Ограничением настоящего исследования явился его открытый наблюдательный характер.Заключение. Использование ингибитора ЯК ТОФА позволяет достичь быстрого анальгетического эффекта, в том числе за счет влияния на ЦС и НКБ.</p></abstract><trans-abstract xml:lang="en"><p>Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of &gt;18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p&lt;0.001), in pain according to the patient's assessment of the analgesic effect of therapy to 43.6±29.6%; in the median PainDETECT score to 2.5 [0; 8.7] (p&lt;0.001); and in CSI scores to an average of 26.4±13.9 (p &lt;0.001). No serious adverse reactions were noted.TOFA has a rapid analgesic effect, which allows it to be considered as a chooser for pathogenetic therapy in patients with active RA and severe pain, especially in the presence of CS signs and secondary fibromyalgia. Undoubtedly, large-scale, long-term controlled studies with a wider range of estimated parameters are required to clarify the therapeutic potential of TOFA in this patient category. The limitation of this investigation was its open observer design pattern.Conclusion. The use of the JK inhibitor TOFA can achieve a rapid analgesic effect, inter alia due to its effect on CS and NPC.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>ревматоидный артрит</kwd><kwd>хроническая боль</kwd><kwd>центральная сенситизация</kwd><kwd>тофацитиниб</kwd><kwd>эффективность</kwd><kwd>безопасность</kwd></kwd-group><kwd-group xml:lang="en"><kwd>rheumatoid arthritis</kwd><kwd>chronic pain</kwd><kwd>central sensitization</kwd><kwd>tofacitinib</kwd><kwd>efficacy</kwd><kwd>safety</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Статья спонсируется компанией «Пфайзер». Спонсор участвовал в разработке проекта исследования и поддержке исследовательской программы, а также принятии решения о представлении статьи для публикации.</funding-statement><funding-statement xml:lang="en">This article has been supported by Pfizer. The sponsor has participated in the development of the investigation project and supported the investigation program, as well as in the decision to submit the article for publication.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, редактор. Российские клинические рекомендации. Ревматология. Москва: ГЭОТАР-Медиа; 2017. 446 с.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2017. 446 p.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Лила АМ. Ревматоидный артрит: достижения и нерешенные проблемы. Терапевтический архив. 2019; 91(5):4-7.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Lila AM. Rheumatoid arthritis: achievements and unresolved problems. Terapevticheskii arkhiv. 2019;91(5):4-7. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ. Новые подходы к фармакотерапии ревматоидного артрита: тофацитиниб. Научно-практическая ревматология. 2014;52(2):209-21. doi: 10.14412/1995-4484-2014-209-221</mixed-citation><mixed-citation xml:lang="en">Nasonov EL. New approaches to pharmacotherapy of rheumatoid arthritis: tofacitinib. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2014; 52(2):209-21. (In Russ.). doi: 10.14412/1995-4484-2014-209-221</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Авдеева АС, Лила АМ. Эффективность и безопасность тофацитиниба при иммуновоспалительных ревматических заболеваниях (часть I). Научно-практическая ревматология. 2020; 58(1):62-79. doi: 10.14412/19954484-2020-62-79</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Avdeeva AS, Lila AM. Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I). Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2020; 58(1):62-79. (In Russ.). doi: 10.14412/19954484-2020-62-79</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018 Jun;10(5-6): 117-27. doi: 10.1177/1759720X18776224. Epub 2018 May 19.</mixed-citation><mixed-citation xml:lang="en">Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018 Jun;10(5-6): 117-27. doi: 10.1177/1759720X18776224. Epub 2018 May 19.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Salaffi F, Giacobazzi G, Di Carlo M. Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets-A Focus on the JAK-STAT Pathway. Pain Res Manag. 2018 Feb 7;2018:8564215. doi: 10.1155/2018/8564215. eCollection 2018.</mixed-citation><mixed-citation xml:lang="en">Salaffi F, Giacobazzi G, Di Carlo M. Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets-A Focus on the JAK-STAT Pathway. Pain Res Manag. 2018 Feb 7;2018:8564215. doi: 10.1155/2018/8564215. eCollection 2018.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Коротаева ТВ, Логинова ЕЮ. Результаты изучения клинической эффективности и безопасности тофацитиниба в лечении псориатического артрита. Современная ревматология. 2019;13(2):112-8. doi: 10.14412/1996-7012-20192-112-118</mixed-citation><mixed-citation xml:lang="en">Korotaeva TV, Loginova EYu. Results of studying the clinical efficacy and safety of tofacitinib in the treatment of psoriatic arthritis. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2019;13(2):112-8. (In Russ.). doi: 10.14412/1996-7012-20192-112-118</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Wang TS, Tsai TF. Tofacitinib in psoriatic arthritis. Immunotherapy. 2017 Nov;9(14): 1153-63. doi: 10.2217/imt-2017-0087. Epub 2017 Oct 2.</mixed-citation><mixed-citation xml:lang="en">Wang TS, Tsai TF. Tofacitinib in psoriatic arthritis. Immunotherapy. 2017 Nov;9(14): 1153-63. doi: 10.2217/imt-2017-0087. Epub 2017 Oct 2.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Guler MA, Celik OF, Ayhan FF. The important role of central sensitization in chronic musculoskeletal pain seen in different rheumatic diseases. Clin Rheumatol. 2020 Jan; 39(1):269-74. doi: 10.1007/s10067-01904749-1. Epub 2019 Aug 24.</mixed-citation><mixed-citation xml:lang="en">Guler MA, Celik OF, Ayhan FF. The important role of central sensitization in chronic musculoskeletal pain seen in different rheumatic diseases. Clin Rheumatol. 2020 Jan; 39(1):269-74. doi: 10.1007/s10067-01904749-1. Epub 2019 Aug 24.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Neblett R, Hartzell MM, Mayer TG, et al. Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory. Pain Pract. 2017 Feb;17(2):166-75. doi: 10.1111/papr.12440. Epub 2016 Mar 15.</mixed-citation><mixed-citation xml:lang="en">Neblett R, Hartzell MM, Mayer TG, et al. Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory. Pain Pract. 2017 Feb;17(2):166-75. doi: 10.1111/papr.12440. Epub 2016 Mar 15.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Chiarotto A, Viti C, Sulli A, et al. Cross-cultural adaptation and validity of the Italian version of the Central Sensitization Inventory. Musculoskelet Sci Pract. 2018 Oct;37:20-8. doi: 10.1016/j.msksp.2018.06.005. Epub 2018 Jun 15.</mixed-citation><mixed-citation xml:lang="en">Chiarotto A, Viti C, Sulli A, et al. Cross-cultural adaptation and validity of the Italian version of the Central Sensitization Inventory. Musculoskelet Sci Pract. 2018 Oct;37:20-8. doi: 10.1016/j.msksp.2018.06.005. Epub 2018 Jun 15.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Латышева НВ. Коморбидные заболевания у пациентов с хронической мигренью. Дисс. докт. мед. наук. Москва; 2020. 260 с.</mixed-citation><mixed-citation xml:lang="en">Latysheva NV. Comorbid diseases in patients with chronic migraine. Diss. doct. med. sci. Moscow; 2020. 260 p.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Perez-Baos S, Gratal P, Barrasa JI, et al. Inhibition of pSTAT1 by tofacitinib accounts for the early improvement of experimental chronic synovitis. J Inflamm (Lond). 2019 Jan 29;16:2. doi: 10.1186/s12950-019-0206-2. eCollection 2019.</mixed-citation><mixed-citation xml:lang="en">Perez-Baos S, Gratal P, Barrasa JI, et al. Inhibition of pSTAT1 by tofacitinib accounts for the early improvement of experimental chronic synovitis. J Inflamm (Lond). 2019 Jan 29;16:2. doi: 10.1186/s12950-019-0206-2. eCollection 2019.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">McGarry T, Orr C, Wade S, et al. JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammatory Mediators in Rheumatoid Arthritis. Arthritis Rheum. 2018 Dec;70(12): 1959-70. doi: 10.1002/art.40569. Epub 2018 Oct 27.</mixed-citation><mixed-citation xml:lang="en">McGarry T, Orr C, Wade S, et al. JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammatory Mediators in Rheumatoid Arthritis. Arthritis Rheum. 2018 Dec;70(12): 1959-70. doi: 10.1002/art.40569. Epub 2018 Oct 27.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Garbers C, Aparicio-Siegmund S, RoseJohn S. The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol. 2015 Jun;34:75-82. doi: 10.1016/j.coi.2015.02.008. Epub 2015 Mar 6.</mixed-citation><mixed-citation xml:lang="en">Garbers C, Aparicio-Siegmund S, RoseJohn S. The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol. 2015 Jun;34:75-82. doi: 10.1016/j.coi.2015.02.008. Epub 2015 Mar 6.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kojima H, Inoue T, Kunimoto H, Nakajima K. IL-6-STAT3 signaling and premature senescence. JAKSTAT. 2013 Oct 1; 2(4):e25763. doi: 10.4161/jkst.25763. Epub 2013 Jul 22.</mixed-citation><mixed-citation xml:lang="en">Kojima H, Inoue T, Kunimoto H, Nakajima K. IL-6-STAT3 signaling and premature senescence. JAKSTAT. 2013 Oct 1; 2(4):e25763. doi: 10.4161/jkst.25763. Epub 2013 Jul 22.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Boyce EG, Vyas D, Rogan EL, et al. Impact of tofacitinib on patient outcomes in rheumatoid arthritis – review of clinical studies. Patient Relat Outcome Meas. 2016 Jan 14; 7:1-12. doi: 10.2147/PROM.S62879. eCollection 2016.</mixed-citation><mixed-citation xml:lang="en">Boyce EG, Vyas D, Rogan EL, et al. Impact of tofacitinib on patient outcomes in rheumatoid arthritis – review of clinical studies. Patient Relat Outcome Meas. 2016 Jan 14; 7:1-12. doi: 10.2147/PROM.S62879. eCollection 2016.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Wallenstein GV, Kanik KS, Wilkinson B, et al. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016 May-Jun; 34(3):430-42. Epub 2016 Apr 28.</mixed-citation><mixed-citation xml:lang="en">Wallenstein GV, Kanik KS, Wilkinson B, et al. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016 May-Jun; 34(3):430-42. Epub 2016 Apr 28.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebocontrolled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009 Jul;60(7):1895-905. doi: 10.1002/art.24567</mixed-citation><mixed-citation xml:lang="en">Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebocontrolled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009 Jul;60(7):1895-905. doi: 10.1002/art.24567</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Strand V, de Vlam K, СovarrubiasСobos JA, et al. Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the phase III, randomised controlled trial: OPal Beyond. RMD Open 2019;5:e000808. doi: 10.1136/rmdopen-2018-000808</mixed-citation><mixed-citation xml:lang="en">Strand V, de Vlam K, СovarrubiasСobos JA, et al. Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the phase III, randomised controlled trial: OPal Beyond. RMD Open 2019;5:e000808. doi: 10.1136/rmdopen-2018-000808</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
