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<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">rsp</journal-id><journal-title-group><journal-title xml:lang="ru">Научно-практическая ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Rheumatology Science and Practice</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1995-4484</issn><issn pub-type="epub">1995-4492</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.47360/1995-4484-2023-369-376</article-id><article-id custom-type="elpub" pub-id-type="custom">rsp-3365</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>ПЕДИАТРИЧЕСКАЯ РЕВМАТОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PEDIATRIC RHEUMATOLOGY</subject></subj-group></article-categories><title-group><article-title>Генно-инженерные биологические препараты в терапии серопозитивного ювенильного идиопатического артрита: результаты ретроспективного одноцентрового исследования</article-title><trans-title-group xml:lang="en"><trans-title>Biological therapy of seropositive juvenile idiopathic arthritis: Results of a retrospective single-center study</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0513-6826</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каледа</surname><given-names>М. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kaleda</surname><given-names>M. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><email xlink:type="simple">kaleda-mi@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1935-8585</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колхидова</surname><given-names>З. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolkhidova</surname><given-names>Z. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1842-0348</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Никишина</surname><given-names>И. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Nikishina</surname><given-names>I. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34а</p></bio><bio xml:lang="en"><p>115522, Moscow, Kashirskoye Highway, 34A</p></bio><xref ref-type="aff" rid="aff-1"/></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><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>29</day><month>06</month><year>2023</year></pub-date><volume>61</volume><issue>3</issue><fpage>369</fpage><lpage>376</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Каледа М.И., Колхидова З.А., Никишина И.П., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Каледа М.И., Колхидова З.А., Никишина И.П.</copyright-holder><copyright-holder xml:lang="en">Kaleda M.I., Kolkhidova Z.A., Nikishina I.P.</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://rsp.mediar-press.net/rsp/article/view/3365">https://rsp.mediar-press.net/rsp/article/view/3365</self-uri><abstract><p>Серопозитивный ювенильный идиопатический артрит (ЮИА) – один из наиболее редких и прогностически неблагоприятных субтипов ювенильного артрита, отличающийся повышенной частотой рефрактерности к терапии. Цель исследования – охарактеризовать терапию с использованием генно-инженерных биологических препаратов (ГИБП) у пациентов с серопозитивным ювенильным идиопатическим артритом; выявить ф акторы, влияющие на выбор ГИБП и необходимость его замены; оценить значение индекса повреждения JADI (The Juvenile Arthritis Damage Index) для прогнозирования ответа на ГИБП.Материал и методы. Проводилось ретроспективное открытое неконтролируемое нерандомизированное сплошное исследование. Диагноз серопозитивного ЮИА за период с 2010 по 2022 г. верифицирован у 92 пациентов, среди них было10,9% мальчиков. Медиана возраста дебюта ЮИА составила 12,0 [7,7; 14,0] лет. Терапия ГИБП использовалась в 89,1% случаев, в 31,7% из них – на сроке менее 1 года от дебюта. На момент назначения ГИБП медиана числа активных суставов (ЧАС) составила 15 [10; 22], скорость оседания эритроцитов (СОЭ) – 29 [18; 43 ] мм/ч, С-реактивного белка (СРБ) – 15,0 [5,3; 31,0] мг/л, внесуставные проявления выявлены у 29,0% больных. Проведен анализ факторов, которые могли бы влиять на необходимость переключения ГИБП, включая возраст дебюта, сроки верификации диагноза и начала терапии ГИБП, пол, ЧАС, позитивность по антителам к циклическому цитруллинированному пептиду (АЦЦП), уровни ревматоидного фактора (РФ), АЦЦП, СРБ и СОЭ, наличие вторичного синдрома Шегрена (СШ) на момент назначения ГИБП. С 2021 г. да в комплекс обследований включался подсчет индекса повреждения JADI у всех пациентов из исследуемой группы, поступавших в стационар (n=28; 17,9% – мальчики). Медиана возраста дебюта ЮИА среди них составила 10,5 [6,31; 13,0] года, 81,2% получали ГИБП. Проведено сопоставление индекса JADI с АЦЦП, РФ, СРБ, СОЭ, потребностью в назначении и переключении ГИБП. Результаты. В исследуемой группе пациентов 29% имели опыт применения более 1 ГИБП. В качестве первого ГИБП чаще всего использовался абатацепт (45,1%) и ингибиторы фактора некроза опухоли α (ФНО-α; 40,3%), во 2–4-й линии терапии преимущественно применялись тоцилизумаб и ритуксимаб с тенденцией к их более частому назначению в последние годы. Основная причина переключения с одного ГИБП на другой – вторичная неэффективность терапии, у 4,9% пациентов – серьезные нежелательные реакции (НР). В целом НР, не требующие отмены терапии, зафиксированы у 24,6% пациентов. Пациенты, получавшие более 1 ГИБП, имели несколько более высокую концентрацию РФ и АЦЦП и статистически значимо более высокий уровень СРБ. JADI-A составлял в среднем 2,39; JADI-A&gt;0 имели 50% пациентов, 92,8% из которых получали ГИБП с опытом назначения более 1 ГИБП у 28,6% из них. Выявлена прямая корреляция индекса JADI с АЦЦП, СОЭ и СРБ. Выводы. Серопозитивный ЮИА характеризуется высокой потребностью в назначении ГИБП, которое ассоциируется с JADI-А&gt;0. Выбор конкретного ГИБП определяется, в первую очередь, наличием системных проявлений или вторичного СШ. У пациентов с высоким уровнем суррогатных показателей активности (особенно СРБ) с учетом высокого риска вторичной неэффективности ингибиторов ФНО-α в качестве препарата выбора может рассматриваться тоцилизумаб. Мы не выявили влияния позитивности по АЦЦП на выбор или частоту замены ГИБП. Обращала на себя внимание тенденция к более высокой концентрации РФ и АЦЦП у пациентов, получавших более одного ГИБП. Установлена корреляция индекса JADI с уровнями АЦЦП, СРБ и СОЭ, что позволяет говорить о необходимости более раннего назначения ГИБП у данной категории пациентов с целью избежать необратимых изменений и повысить эффективность терапии. Применение ГИБП имело приемлемый профиль безопасности.</p></abstract><trans-abstract xml:lang="en"><p>Seropositive juvenile idiopathic arthritis (JIA) is one of the rarest and most unfavorable subtypes of juvenile arthritis, characterized by an increased frequency of inefficacy of therapy. Objective – to characterize biologic therapy in patients with seropositive JIA, to identify factors influencing the choice of a biological agents (BA) and the need to replace it, to evaluate the value of the JADI damage index for predicting the response to BA.Material and methods. The diagnosis of seropositive JIA for the period from 2010 to 2022 was verified in 92 patients, 10.9% were boys. The median age of JIA onset in the study group was 12.0 [7.7; 14.0] years. BA were prescribed to 89.1% of patients in the study group, 31.7% of them for a period of less than 1 year from the onset. The median number of active joints at the time of BA initiation was 15 [10; 22], median ESR – 29 [18; 43] mm/h, CRP – 15.0 [5.3; 31.0] mg/l. Extra-articular manifestations at the time of prescribing BA occurred in 29.0% of patients. The analysis of factors that could influence the need to switch BA was carried out: age of onset, timing of diagnosis verification and initiation of BA, gender, the number of active joints at the start of BA, ACCP positivity, RF, ACCP, ESR and CRP values – at the time of BA appointment, the presence of secondary Sjögren’s syndrome. Since 2021, the complex of examinations included the calculation of the JADI (The Juvenile Arthritis Damage Index) damage index in all patients from the study group who were admitted to the hospital (28 in total; 17.9% – boys). The median age of JIA onset among them was 10.5 [6.31; 13.0] years, 81.2% received BA. The JADI index was compared with the ACCP, RF, CRP, ESR and the need to prescribe and switch BA. The design of the study was a retrospective, open-label, non-randomized, uncontrolled study. Results. In the study group of patients, 29% had experience with more than 1 BA. Abatacept (45.1%), TNF-inhibitors (40.3%) were most often used as the first BA; tocilizumab and rituximab were predominantly used in the 2nd–4th line of therapy, with a trend towards their more frequent prescription in recent years. The main reason for switching from one BA to another is the secondary failure of therapy, 4.9% of patients have serious adverse reactions (AE). In general, AEs that did not require discontinuation of therapy were recorded in 24.6% of patients. Patients who received more than 1 BA had relatively higher values of RF, ACCP and significantly higher CRP. The mean value of JADI-A was 2.39 points, 50% of patients had significant JADI-A scores, 92.8% of whom received BA with experience of more than 1 prescription of BA in 28.6% of them. A direct correlation of the JADI index with ACCP, ESR and CRP was revealed. Conclusions. Seropositive JIA is characterized by a high need for prescribing BA, the frequency of prescribing BA is associated with significant indicators of the JADI damage index. The choice of a specific BA is determined, first of all, by the presence of systemic manifestations or secondary Sjögren’s syndrome. In patients with high surrogate measures of activity (especially CRP), given the high risk of secondary failure of TNF-inhibitors, tocilizumab in the first line of therapy may be considered as the preferred choice. Our data did not reveal an effect of ACCP positivity on the preferred choice or frequency of BA replacement. Attention was drawn to the trend towards higher RF and ACCP values in patients treated with more than one BA. A correlation was established between the JADI index and ACCP, ESR, and CRP, which indirectly leads to the conclusion that it is necessary to prescribe BA earlier in this category of patients in order to avoid permanent damage and increase the effectiveness of thera py. The use of BA had an acceptable safety profile.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>серопозитивный ювенильный идиопатический артрит</kwd><kwd>генно-инженерные биологические препараты</kwd><kwd>индекс повреждения JADI</kwd><kwd>ревматоидный фактор</kwd><kwd>детский возраст</kwd></kwd-group><kwd-group xml:lang="en"><kwd>seropositive juvenile idiopathic arthritis</kwd><kwd>biologics</kwd><kwd>JADI damage index</kwd><kwd>rheumatoid factor</kwd><kwd>childhood</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование проводилось в рамках выполнения фундаментального научного исследования по теме «Выявление клинических фенотипов и прогнозирование вариантов течения аутоиммунных и аутовоспалительных ревматических заболеваний детского возраста» FURS-2022-0001 (регистрационный номер в ЕГИСУ 1021051302580-4).</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">Ravelli A, Martini A. 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