vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v21i3.2429vsp-2946Research ArticleКЛИНИЧЕСКОЕ НАБЛЮДЕНИЕCLINICAL OBSERVATIONSОпыт долгосрочного (9 лет) применения тоцилизумаба у пациентки с ювенильным артритом с системным началом: клиническое наблюдениеExperience of Long-Term (9 Years) Administration of Tocilizumab in Female Patient with Systemic Onset Juvenile Arthritis: Case Studyhttps://orcid.org/0000-0002-0513-6826КаледаМ. И.KaledaMaria I.

Каледа Мария Игоревна - кандидат медицинских наук, старший научный сотрудник лаборатории ревматических заболеваний детского возраста ФГБНУ НИИР им. В.А. Насоновой.

115522, Москва, Каширское шоссе, д. 34А,  тел.: +7 (495) 109-29-10

Moscow

kaleda-mi@yandex.ruhttps://orcid.org/0000-0003-1842-0348НикишинаИ. П.NikishinaIrina P.

115522, Москва, Каширское шоссе, д. 34А

Moscow

https://orcid.org/0000-0001-6183-8630ПачкорияТ. Н.PachkoriaTamara N.

115522, Москва, Каширское шоссе, д. 34А

Moscow

Научно-исследовательский институт ревматологии имени В.А. НасоновойРоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation202214072022213265272Copyright © Каледа М.И., Никишина И.П., Пачкория Т.Н., 20222022Каледа М.И., Никишина И.П., Пачкория Т.Н.Kaleda M.I., Nikishina I.P., Pachkoria T.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2946Обоснование

Обоснование. Ювенильный артрит с системным началом — хроническое заболевание детского возраста, тяжесть которого обусловлена системными проявлениями, высоким риском развития таких осложнений, как синдром активации макрофагов и интерстициальное поражение легких, а также стойкого полиартрита с выраженными функциональными нарушениями. Терапия генно-инженерными биологическими препаратами существенно улучшила прогноз у этих пациентов, однако в реальной клинической практике остается немало вопросов о возможностях успешной коррекции терапии с целью поддержания длительной ремиссии.

Описание клинического случая. Представлено описание результатов длительного (9 лет) применения тоцилизумаба у пациентки с ранним дебютом ювенильного артрита с системным началом. Показано, что контроль над активностью заболевания может быть достигнут путем коррекции дозы препарата и интервалов между инфузиями.

Заключение

Заключение. Тоцилизумаб существенно улучшает жизненный прогноз у пациентов с ювенильным артритом с системным началом при хорошем профиле безопасности такого лечения.

Background

Background. Systemic onset juvenile arthritis is a chronic disease of childhood. Its severity is determined by systemic manifestations, high risk of complications, such as macrophage activation syndrome, interstitial lung disease, and persistent polyarthritis with severe functional disorders. Genetically engineered biological drugs administration significantly improves the prognosis in these patients, thus, there are many questions about the possibilities of successful treatment correction in order to maintain long-term remission in real clinical practice.

Clinical case description. The results of long-term (9 years) administration of tocilizumab in female patient with early onset of systemic onset juvenile arthritis are presented. It has been shown that control over disease activity can be achieved via adjusting the drug dosage and the intervals between infusions.

Conclusion

Conclusion. Tocilizumab significantly improves prognosis of patients with systemic onset juvenile arthritis at good safety profile of this treatment.

тоцилизумабювенильный артрит с системным началомдетинейтропенияклинический случайtocilizumabsystemic onset juvenile arthritischildrenneutropeniaclinical caseПодготовка рукописи выполнена в рамках финансирования фундаментальной научной темы № 1021051302580-4 в ФГБНУ НИИР им. В.А. НасоновойThe manuscript was prepared within the financing of the fundamental scientific topic № 1021051302580-4 in V.A. Nasonova Research Institute of RheumatologyReferencesQuartier P. Systemic Juvenile Idiopathic Arthritis/Pediatric Still’s Disease, a Syndrome but Several Clinical Forms: Recent Therapeutic Approaches. J Clin Med. 2022;11(5):1357. doi: https://doi.org/10.3390/jcm11051357Quartier P. Systemic Juvenile Idiopathic Arthritis/Pediatric Still’s Disease, a Syndrome but Several Clinical Forms: Recent Therapeutic Approaches. J Clin Med. 2022;11(5):1357. doi: https://doi.org/10.3390/jcm11051357Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol. 2006;2(1):28–34. doi: https://doi.org/10.1038/ncprheum0084Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol. 2006;2(1):28–34. doi: https://doi.org/10.1038/ncprheum0084Martini A, Ravelli A, Avcin T, et al. Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019;46(2):190–197. doi: https://doi.org/10.3899/jrheum.180168Martini A, Ravelli A, Avcin T, et al. Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019;46(2):190–197. doi: https://doi.org/10.3899/jrheum.180168Erkens R, Esteban Y, Towe C, et al. Pathogenesis and Treatment of Refractory Disease Courses in Systemic Juvenile Idiopathic Arthritis: Refractory Arthritis, Recurrent Macrophage Activation Syndrome and Chronic Lung Disease. Rheum Dis Clin N Am. 2021;47(4):585–606. doi: https://doi.org/10.1016/j.rdc.2021.06.003Erkens R, Esteban Y, Towe C, et al. Pathogenesis and Treatment of Refractory Disease Courses in Systemic Juvenile Idiopathic Arthritis: Refractory Arthritis, Recurrent Macrophage Activation Syndrome and Chronic Lung Disease. Rheum Dis Clin N Am. 2021;47(4):585–606. doi: https://doi.org/10.1016/j.rdc.2021.06.003Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2010;70(5):747–754. doi: https://doi.org/10.1136/ard.2010.134254Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2010;70(5):747–754. doi: https://doi.org/10.1136/ard.2010.134254Ruperto N, Brunner HI, Quartier P, et al. Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med. 2012;367(25):2396–2406. doi: https://doi.org/10.1056/NEJMoa1205099Ruperto N, Brunner HI, Quartier P, et al. Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med. 2012;367(25):2396–2406. doi: https://doi.org/10.1056/NEJMoa1205099De Benedetti F, Brunner HI, Ruperto N, et al. Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med. 2012;367(25):2385–2395. doi: https://doi.org/10.1056/NEJMoa1112802De Benedetti F, Brunner HI, Ruperto N, et al. Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med. 2012;367(25):2385–2395. doi: https://doi.org/10.1056/NEJMoa1112802Yokota S, Itoh Y, Morio T, et al. Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. 2016;75(9):1654–1660. doi: https://doi.org/10.1136/annrheumdis-2015-207818Yokota S, Itoh Y, Morio T, et al. Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. 2016;75(9):1654–1660. doi: https://doi.org/10.1136/annrheumdis-2015-207818Horneff G, Schulz AC, Klotsche J, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017;19(1):256. doi: https://doi.org/10.1186/s13075-017-1462-2Horneff G, Schulz AC, Klotsche J, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017;19(1):256. doi: https://doi.org/10.1186/s13075-017-1462-2Баранов А.А., Алексеева Е.И., Денисова Р.В. и др. Ретроспективный анализ эффективности и безопасности тоцилизумаба у больных тяжелым системным ювенильным идиопатическим артритом: 12 месяцев наблюдения // Вопросы современной педиатрии. — 2013. — Т. 12. — № 2. — С. 26–34. — doi: https://doi.org/10.15690/vsp.v12i2.617Baranov AA, Alekseeva EI, Denisova RV, et al. Retrospective Analysis of Efficacy and Safety ofTocilizumab Treatment in Children with Severe Systemic Juvenile Idiopathic Arthritis: 12-month Follow-up. Voprosy sovremennoi pediatrii — Current Pediatrics. 2013;12(2):26–34. (In Russ). doi: https://doi.org/10.15690/vsp.v12i2.617Каледа М.И., Никишина И.П. Эффективность и безопасность тоцилизумаба у детей с системным вариантом ювенильного артрита в клинической практике // Научно-практическая ревматология. — 2015. — Т. 53. — № 2. — С. 204–213. — doi: https://doi.org/10.14412/1995-4484-2015-204-213Kaleda MI, Nikishina IP. Efficacy and safety of tocilizumab in children with systemic juvenile arthritis in clinical practice. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(2):204–213. (In Russ). doi: https://doi.org/10.14412/1995-4484-2015-204-213Костик М.М., Исупова Е.А., Чикова И.А. и др. Оценка эффективности и безопасности терапии тоцилизумабом пациентов с системной формой ювенильного идиопатического артрита: результаты ретроспективного наблюдения // Современная ревматология. — 2017. — Т. 11. — № 4. — С. 30–39. — doi: https://doi.org/10/14412/1996-7012-2017-4-30-39Kostik MM, Isupova EA, Chikova IA, et al. Evaluation of the efficiency and safety of tocilizumab therapy in patients with systemic-onset juvenile idiopathic arthritis: results of a retrospective follow-up. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2017;11(4):30–39. (In Russ). doi: https://doi.org/10/14412/1996-7012-2017-4-30-39Benedetti F, Ruperto N, Brunner H, et al. A6: Tapering and Withdrawal of Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis in Inactive Disease: Results From an Alternative Dosing Regimen in the TENDER Study. Arthritis Rheum. 2014;66(S3):S8–S9. doi: https://doi.org/10.1002/art.38417Benedetti F, Ruperto N, Brunner H, et al. A6: Tapering and Withdrawal of Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis in Inactive Disease: Results From an Alternative Dosing Regimen in the TENDER Study. Arthritis Rheum. 2014;66(S3):S8–S9. doi: https://doi.org/10.1002/art.38417Klein A, Klotsche J, Hügle B, et al. Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry. Rheumatology (Oxford). 2020;59(9):2287–2298. doi: https://doi.org/10.1093/rheumatology/kez577Klein A, Klotsche J, Hügle B, et al. Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry. Rheumatology (Oxford). 2020;59(9):2287–2298. doi: https://doi.org/10.1093/rheumatology/kez577Алексеева Е.И., Валиева С.И., Бзарова Т.М. и др. Клинический случай применения тоцилизумаба у пациента с системным ювенильным идиопатическим артритом // Педиатрическая фармакология. — 2016. — Т. 15. — № 4. — С. 390–394. — doi: https://doi.org/10.15690/pf.v13i4.1613Alekseeva EI, Valieva SI, Bazarova ТM, et al. Clinical Case: Treating Systemic Juvenile Idiopathic Arthritis with Tocilizumab. Voprosy sovremennoi pediatrii — Pediatricheskaya farmakologiya. 2016;15(4):390–394. (In Russ). doi: https://doi.org/10.15690/pf.v13i4.1613Аксёнов А.В., Ивановская Е.А. Опыт успешного применения тоцилизумаба у ребенка с системным вариантом ювенильного идиопатического артрита // Доктор.Ру. — 2021. — Т. 20. — № 3. — С. 70–72. — doi: https://doi.org/10.31550/1727-23782021-20-3-70-72Aksenov AV, Ivanovskaya EA. Successful Use of Tocilizumab in a Child with Systemic Juvenile Idiopathic Arthritis. Doctor.Ru. 2021;20(3):70–72. (In Russ). doi: https://doi.org/10.31550/1727-2378-2021-70-72Каледа М.И. Генно-инженерная биологическая терапия системного варианта ювенильного артрита в клинической практике: дис. … канд. мед. наук. — М.; 2015. — 184 с.Kaleda MI. Genno-inzhenernaya biologicheskaya terapiya sistemnogo varianta yuvenil’nogo artrita v klinicheskoi praktike. [dissertation]. Moscow; 2015. 184 p. (In Russ).Алексеева Е.И., Ломакина О.Л., Валиева С.И. и др. Особенности течения и стационарного лечения детей с системным ювенильным идиопатическим артритом: первые результаты анализа общероссийского регистра Союза педиатров России // Вопросы современной педиатрии. — 2015. — Т. 14. — № 6. — С. 661–673. — doi: https://doi.org/10.15690/vsp.v14i6.1474Alekseeva YeI, Lomakina ОL, Valieva SI, et al. Characteristics of the Disease Progression and Hospital Treatment of Children with Systemic Juvenile Idiopathic Arthritis: First Results from the Analysis of the All-Russian Register of the Union of Pediatricians of Russia. Voprosy sovremennoi pediatrii — Current Pediatrics. 2015;14(6):661–673. (In Russ). doi: https://doi.org/10.15690/vsp.v14i6.1474Nada DW, Moghazy A, Allam AE, et al. Short-Term Outcomes and Predictors of Effectiveness of Tocilizumab in Systemic Juvenile Idiopathic Arthritis: A Prospective Cohort Study. Front Med (Lausanne). 2021;8:665028. doi: https://doi.org/10.3389/fmed.2021.665028Nada DW, Moghazy A, Allam AE, et al. Short-Term Outcomes and Predictors of Effectiveness of Tocilizumab in Systemic Juvenile Idiopathic Arthritis: A Prospective Cohort Study. Front Med (Lausanne). 2021;8:665028. doi: https://doi.org/10.3389/fmed.2021.665028Шингарова М.Ш., Алексеева Е.И., Бзарова Т.М., и др. Влияние тоцилизумаба на состояние костной ткани у пациентов с системным ювенильным идиопатическим артритом: результаты ретроспективного исследования серии случаев // Педиатрическая фармакология. — 2016. — Т. 13. — № 6. — С. 560–564. — doi: https://doi.org/10.15690/pf.v13i6.1669Shingarova MS, Alexeeva EI, Bzarova TM, et al. The Effect of Tocilizumab on the Condition of Bone Tissue of Patients with Systematic Juvenile Idiopatic Arthritis: Results of a Series of Cases Retrospective Study. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2016;13(6):560–564. (In Russ). doi: https://doi.org/10.15690/pf.v13i6.1669)De Benedetti F, Rubio-Perez N, Salazar CD, et al. A45: Neutropenia with tocilizumab treatment is not associated with increased infection risk in patients with polyarticular-course juvenile idiopathic arthritis. Arthritis Rheum. 2014;66(S3):S67–S68. doi: https://doi.org/10.1002/art.38461De Benedetti F, Rubio-Perez N, Salazar CD, et al. A45: Neutropenia with tocilizumab treatment is not associated with increased infection risk in patients with polyarticular-course juvenile idiopathic arthritis. Arthritis Rheum. 2014;66(S3):S67–S68. doi: https://doi.org/10.1002/art.38461Каледа М.И., Никишина И.П., Шаповаленко А.Н. и др. Феномен нейтропении на фоне терапии тоцилизумабом у пациентов с ювенильным идиопатическим артритом // Научно-практическая ревматология. — 2017. — Т. 55. — № 6. — С. 662–667. — doi: https://doi.org/10.14412/1995-4484-2017-662-667Kaleda MI, Nikishina IP, Shapovalenko AN, et al. The phenomenon of neutropenia during tocilizumab therapy in patients with juvenile idiopathic arthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(6):662–667 (In Russ.). doi: https://doi.org/10.14412/1995-4484-2017-662-667Kostik MM, Dubko MF, Masalova VV, et al. Successful treatment with tocilizumab every 4 weeks of a low disease activity group who achieve a drug-free remission in patients with systemic-onset juve nile idiopathic arthritis. Pediatr Rheumatol Online J. 2015;13:4 doi: https://doi.org/10.1186/1546-0096-13-4Kostik MM, Dubko MF, Masalova VV, et al. Successful treatment with tocilizumab every 4 weeks of a low disease activity group who achieve a drug-free remission in patients with systemic-onset juve nile idiopathic arthritis. Pediatr Rheumatol Online J. 2015;13:4 doi: https://doi.org/10.1186/1546-0096-13-4Yan X, Tang W, Zhang Z, et al. Tocilizumab in Systemic Juvenile Idiopathic Arthritis: Response Differs by Disease Duration at Medication Initiation and by Phenotype of Disease. Front Pediatr. 2021;9:735846. doi: https://doi.org/10.3389/fped.2021.735846Yan X, Tang W, Zhang Z, et al. Tocilizumab in Systemic Juvenile Idiopathic Arthritis: Response Differs by Disease Duration at Medication Initiation and by Phenotype of Disease. Front Pediatr. 2021;9:735846. doi: https://doi.org/10.3389/fped.2021.735846Shenoi S, Nanda K, Schulert GS, et al. Physician practi ces for withdrawal of medications in inactive systemic juvenile arthritis, Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey. Pediatr Rheumatol Online J. 2019;17(1):48. doi: https://doi.org/10.1186/s12969-019-0342-5Shenoi S, Nanda K, Schulert GS, et al. Physician practi ces for withdrawal of medications in inactive systemic juvenile arthritis, Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey. Pediatr Rheumatol Online J. 2019;17(1):48. doi: https://doi.org/10.1186/s12969-019-0342-5Каледа М.И., Никишина И.П., Костарева О.М. Оптимизация схем лечения системного варианта ювенильного артрита с коррекцией режимов внутривенного введения тоцилизумаба по данным наблюдательного ретроспективного исследования // Научно-практическая ревматология. — 2019. — Т. 57. — № 2. — С. 229–234. — doi: https://doi.org/10.14412/1995-4484-2019-229-234Kaleda MI, Nikishina IP, Kostareva OM. Optimization of systemic juvenile arthritis treatment regimens with correction of tocilizumab intravenous administration according to data of observational retrospective study. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2019;57(2):229–234 (In Russ). doi: https://doi.org/10.14412/1995-4484-2019-229-234]Malattia C, Ruperto N, Pederzoli S, et al. Tocilizumab may slow radiographic progression in patients with systemic or polyarticularcourse juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials. Arthritis Res Ther. 2020;22(1):211. doi: https://doi.org/10.1186/s13075-020-02303-yMalattia C, Ruperto N, Pederzoli S, et al. Tocilizumab may slow radiographic progression in patients with systemic or polyarticularcourse juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials. Arthritis Res Ther. 2020;22(1):211. doi: https://doi.org/10.1186/s13075-020-02303-y

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