Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022; 21: 88-92
Криопирин-ассоциированный периодический синдром с оценкой эффективности и безопасности терапии анакинрой: опыт одного Центра
https://doi.org/10.24287/1726-1708-2022-21-1-88-92Аннотация
Целью данного исследования явилось проведение анализа клинических, лабораторных и молекулярно-генетических данных 20 пациентов (9 мальчиков и 11 девочек) с диагнозом «криопирин-ассоциированный периодический синдром (CAPS)» с оценкой эффективности и безопасности терапии 6 пациентов ингибитором рецептора интерлейкина-1 – анакинрой. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Родители пациентов дали согласие на использование информации, в том числе фотографий детей, в научных исследованиях и публикациях. Возраст манифестации симптомов CAPS составил от 0 до 27 месяцев (медиана – 2 месяца). В клинических проявлениях преобладали лихорадка, сыпь, поражение центральной нервной системы, опорно-двигательного аппарата. Во время приступа у всех 20 пациентов было отмечено повышение острофазовых белков крови. Во всех случаях у больных выявлена гетерозиготная мутация в гене NLRP3 с наибольшей частотой локализации в 3-м экзоне (17/20). Терапия анакинрой была инициирована 6/20 больным. У всех 6 пациентов на фоне терапии анакинрой отмечена стабилизация состояния, у 5/6 больных – лекарственная ремиссия.
Список литературы
1. Козлова А.Л., Бурлаков В.И., Нестеренко З.А., Блудова В.О., Райкина Е.В., Варламова Т.В. и др. Клинический пример терапии ингибитором рецептора ИЛ-1 – анакинрой у пациента с криопирин-ассоциированным периодическим синдромом. Педиатрия сегодня 2021; 7 (19): 5.
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3. Козлова А.Л., Першин Б.С., Варламова Т.В., Щербина А.Ю. Опыт диагностики и лечения больных с криопирин-ассоциированным периодическим синдромом. Вопросы современной педиатрии 2015; 14 (2): 292–7. DOI: 10.15690/vsp.v14i2.1301
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6. Prieur A.M., Griscelli C., Lampert F., Truckenbrodt H., Guggenheim M.A., Lovell D.J., et al. A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J Rheumatol Suppl 1987; 66: 57–68.
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9. Hoffman H.M. Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opin Biol Ther 2009; 9: 519–31.
10. Dinarello C.A., Simon A., van der Meer J.W. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012; 11: 633–52.
11. Sibley C.H., Plass N., Snow J., Wiggs E.A., Brewer C.C., King K.A., et al. Sustained response and prevention of damage progression in patients with neo- natal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and fiveyear outcomes. Arthritis Rheum 2012; 64: 2375–86.
12. Инструкция по медицинскому применению препарата Кинерет® (анакинра) ЛП-006746-030221. [Электронный ресурс] URL: Государственный реестр лекарственных средств (rosminzdrav.ru)
13. Piram M., Koné-Paut I., Lachmann H.J., Frenkel J., Ozen S., Kuemmerle-Deschner J., et al. Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis 2014; 73 (12): 2168–73.
14. Kullenberg T., Löfqvist M., Leinonen M., Goldbach-Mansky R., Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford) 2016; 55 (8): 1499–506. DOI: 10.1093/rheumatology/kew208
15. Kuemmerle-Deschner J.B., Wittkowski H., Tyrrell P.N., Koetter I., Lohse P., Ummenhofer K., et al. Treatment of Muckle–Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther 2013; 15: R64.
Pediatric Hematology/Oncology and Immunopathology. 2022; 21: 88-92
Cryopyrin-associated periodic syndrome assess the efficacy and safety of anakinra therapy: a single center experience
https://doi.org/10.24287/1726-1708-2022-21-1-88-92Abstract
The aim of this study was to analyze the clinical, laboratory and molecular genetic data of 20 patients (9 boys, 11 girls) diagnosed with cryopyrin-associated periodic syndrome (CAPS) with an assessment of the efficacy and safety of therapy in 6 patients with an inhibitor of the interleukin-1 receptor – anakinra. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. The patients' parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications. The age of CAPS manifestation ranged from 0 to 27.0 months (median – 2 months). The clinical manifestations were dominated by fever, rash, lesions of the central nervous system, musculoskeletal system. During the attack, all 20 patients had an increase acute phase proteins of blood. All patients had heterozygous mutation in the NLRP3 gene, with the highest frequency of localization in exon 3 (17/20). 6/20 patients were initiated on anakinra therapy. All 6 patients who have been treated of anakinra enough to assess the effect of the treatment, drastic improvement of the condition was noted, but only in 5/6 patients achieved full remission.
References
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2. Caso F., Rigante D., Vitale A., Lucherini O.M., Costa L., Atteno M., et al. Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and therapeutic issues. Int J Rheumatol 2013; 2013: 513782. DOI: 10.1155/2013/513782
3. Kozlova A.L., Pershin B.S., Varlamova T.V., Shcherbina A.Yu. Opyt diagnostiki i lecheniya bol'nykh s kriopirin-assotsiirovannym periodicheskim sindromom. Voprosy sovremennoi pediatrii 2015; 14 (2): 292–7. DOI: 10.15690/vsp.v14i2.1301
4. Lachmann H.J., Quartier P., So A., Hawkins P.N. The emerging role of interleukin-1 beta in autoinflammatory diseases. Arthritis Rheum 2011; 63: 314–24.
5. Goldbach-Mansky R., Dailey N.J., Canna S.W., Gelabert A., Jones J., Rubin B.I., et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med 2006; 355: 581– 92.
6. Prieur A.M., Griscelli C., Lampert F., Truckenbrodt H., Guggenheim M.A., Lovell D.J., et al. A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients. Scand J Rheumatol Suppl 1987; 66: 57–68.
7. Ogura Y., Sutterwala F.S., Flavell R.A. The inflammasome: first line of the immune response to cell stress. Cell 2006; 126: 659–62.
8. Hawkins P.N., Lachmann H.J., McDermott M.F. Interleukin-1-receptor antagonist in the Muckle– Wells syndrome. N Engl J Med 2003; 348: 2583–4.
9. Hoffman H.M. Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opin Biol Ther 2009; 9: 519–31.
10. Dinarello C.A., Simon A., van der Meer J.W. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012; 11: 633–52.
11. Sibley C.H., Plass N., Snow J., Wiggs E.A., Brewer C.C., King K.A., et al. Sustained response and prevention of damage progression in patients with neo- natal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and fiveyear outcomes. Arthritis Rheum 2012; 64: 2375–86.
12. Instruktsiya po meditsinskomu primeneniyu preparata Kineret® (anakinra) LP-006746-030221. [Elektronnyi resurs] URL: Gosudarstvennyi reestr lekarstvennykh sredstv (rosminzdrav.ru)
13. Piram M., Koné-Paut I., Lachmann H.J., Frenkel J., Ozen S., Kuemmerle-Deschner J., et al. Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis 2014; 73 (12): 2168–73.
14. Kullenberg T., Löfqvist M., Leinonen M., Goldbach-Mansky R., Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatology (Oxford) 2016; 55 (8): 1499–506. DOI: 10.1093/rheumatology/kew208
15. Kuemmerle-Deschner J.B., Wittkowski H., Tyrrell P.N., Koetter I., Lohse P., Ummenhofer K., et al. Treatment of Muckle–Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther 2013; 15: R64.
