Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children72710.24287/1726-1708-2023-22-2-92-97ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИExperience with the use of Hizentra, an immunoglobulin preparation for subcutaneous administration, in patients with primary immunodeficiency diseasesОпыт применения иммуноглобулина для подкожного введения Хайцентра у пациентов с первичными иммунодефицитамиhttps://orcid.org/0000-0002-9399-6534AvedovaA. Ya.АведоваА. Я.
Russian Federation

Asmik Ya. Avedova, allergist-immunologist

Immunology Department

Moscow

Асмик Яковлевна Аведова, врач-аллерголог-иммунолог

отделение иммунологии

117997

ул. Саморы Машела, 1

Москва

asya.avedova95@mail.ruhttps://orcid.org/0000-0001-9857-4456RodinaYu. А.РодинаЮ. А.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-9078-8206YukhachevaD. V.ЮхачеваД. В.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-1267-9957BurlakovV. I.БурлаковВ. И.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-9083-4783DeripapaE. V.ДерипапаЕ. В.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-3113-4939ShcherbinaA. Yu.ЩербинаА. Ю.
Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России08072023222929729012023Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/727

   Immunoglobulin replacement therapy is the gold standard of treatment for patients with antibody deficiencies.

   We aimed to investigate the efficacy and safety of replacement therapy with subcutaneous immunoglobulin (SCIG) Hizentra in patients with primary immunodeficiencies.

   This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All patients and / or their legal representatives gave informed consent for this treatment. In our study, 12 patients under 18 years of age with various forms of primary immunodeficiencies who had previously received intravenous immunoglobulin were switched to SCIG treatment to receive weekly infusions of Hizentra. Therapy SCIG was administered weekly at a dose of 0.1–0.15 g/kg by rapid push infusion. All patients received Hizentra for at least 3 months. None of the patients included in the study developed severe infections. Immunoglobulin G levels in blood after 3 months of SCIG therapy were significantly higher compared to those achieved on previous intravenous immunoglobulin therapy. There were no severe adverse events associated with Hizentra administration. Our study demonstrated Hizentra to be effective and safe for the treatment of children with various forms of primary immunodeficiencies.

   Заместительная терапия препаратами иммуноглобулинов является базовой терапией у пациентов с дефектом антителообразования.

   Основной целью данной работы является оценка эффективности и безопасности заместительной терапии подкожным иммуноглобулином (ПКИГ) Хайцентра у пациентов с первичным иммунодефицитом (ПИД).

   Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Все пациенты и / или их законные представители подписали информированное согласие на проведение данного лечения. В исследование были включены 12 пациентов в возрасте до 18 лет с различными видами ПИД, ранее получавшие терапию внутривенным иммуноглобулином. Терапия ПКИГ проводилась еженедельно в дозе 0,1–0,15 г/кг за 1 введение путем подкожной инфузии с использованием техники введения “rapid push” («быстрые толчки»). Все пациенты получали терапию препаратом Хайцентра на протяжении не менее 3 мес. По результатам данного исследования не было зафиксировано ни одного случая развития тяжелого инфекционного процесса на терапии ПКИГ, концентрация иммуноглобулина G в крови через 3 мес терапии ПКИГ оказалась достоверно выше в сравнении с таковой на терапии внутривенным иммуноглобулином. Тяжелых нежелательных явлений на фоне терапии Хайцентра не отмечено. Применение препарата Хайцентра у детей с различными видами ПИД продемонстрировало безопасность и высокую эффективность.

primary immunodeficiencysubcutaneous immunoglobulinHizentraefficacysafetyпервичный иммунодефицитподкожный иммуноглобулинХайцентраэффективностьбезопасностьNot specifiedНе указано1. Picard C., Bobby Gaspar H., Al-Herz W., Bousfiha A., Casanova J. L., Chatila T., et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 2018; 38 (1): 96–128.Picard C., Bobby Gaspar H., Al-Herz W., Bousfiha A., Casanova J. L., Chatila T., et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 2018; 38 (1): 96–128.2. Bousfiha A., Jeddane L., Picard C., Al-Herz W., Ailal F., Chatila T., et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 2020; 40 (1): 66–81.Bousfiha A., Jeddane L., Picard C., Al-Herz W., Ailal F., Chatila T., et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 2020; 40 (1): 66–81.3. Mahlaoui N., Jais J., Brosselin P., Mignot C., Beaurain B., Brito C., et al. Prevalence of Primary Immunodeciencies in France is underestimated. J Allergy Clin Immunol 2017; 140 (6): 1731–3.Mahlaoui N., Jais J., Brosselin P., Mignot C., Beaurain B., Brito C., et al. Prevalence of Primary Immunodeciencies in France is underestimated. J Allergy Clin Immunol 2017; 140 (6): 1731–3.4. Bonilla F. A., Barlan I., Chapel H., Costa-Carvalho В. Т., Cunningham-Rundles С., Teresa de la Morena M., et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 2016; 4 (1): 38–59.Bonilla F. A., Barlan I., Chapel H., Costa-Carvalho В. Т., Cunningham-Rundles С., Teresa de la Morena M., et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract 2016; 4 (1): 38–59.5. Gardulf A., Hammarstrom L. Subcutaneous administration of immunoglobulins: what are the advantages? Clin Immunother 1996; 6 (2): 108–16.Gardulf A., Hammarstrom L. Subcutaneous administration of immunoglobulins: what are the advantages? Clin Immunother 1996; 6 (2): 108–16.6. Shrestha P., Karmacharya P., Wang Z., Donato A., Joshi A. Y. Impact of IVIG vs. SCIG on IgG trough level and infection incidence in primary immunodeficiency diseases: A systematic review and meta-analysis of clinical studies. World Allergy Organ J 2019; 12 (10): 100068.Shrestha P., Karmacharya P., Wang Z., Donato A., Joshi A. Y. Impact of IVIG vs. SCIG on IgG trough level and infection incidence in primary immunodeficiency diseases: A systematic review and meta-analysis of clinical studies. World Allergy Organ J 2019; 12 (10): 100068.7. Eltan S., Keskin O., Deveci M. Safety, efficiency, and treatment satisfaction in children with primary immunodeficiency receiving subcutaneous immunoglobulin treatment. North Clin Istanb 2022; 9 (3): 228–34.Eltan S., Keskin O., Deveci M. Safety, efficiency, and treatment satisfaction in children with primary immunodeficiency receiving subcutaneous immunoglobulin treatment. North Clin Istanb 2022; 9 (3): 228–34.8. Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs 2007; 21 (2): 105–16.Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs 2007; 21 (2): 105–16.9. Latysheva E., Rodina Yu., Sizyakina L., Totolian A., Tuzankina I. Efficacy and safety of octanorm (cutaquig®) in adults with primary immunodeficiencies with predominant antibody deficiency: a prospective, open-label study. Immunotherapy 2020; 2 (5): 299–309.Latysheva E., Rodina Yu., Sizyakina L., Totolian A., Tuzankina I. Efficacy and safety of octanorm (cutaquig®) in adults with primary immunodeficiencies with predominant antibody deficiency: a prospective, open-label study. Immunotherapy 2020; 2 (5): 299–309.10. Wasserman R. L. Hizentra for the treatment of primary immunodeficiency. Expert Rev Clin Immunol 2014; 10: 1293–307.Wasserman R. L. Hizentra for the treatment of primary immunodeficiency. Expert Rev Clin Immunol 2014; 10: 1293–307.11. [Electronic resource]. URL: https://esid.org/Working-Parties/RegistryWorking-Party/Diagnosis-criteria. Accessed 03. 24. 2023.[Electronic resource]. URL: https://esid.org/Working-Parties/RegistryWorking-Party/Diagnosis-criteria. Accessed 03. 24. 2023.12. Смирнова И. Н. Фармакоэкономический анализ заместительной терапии внутривенным иммуноглобулином у пациентов с первичными дефектами гуморального звена иммунитета / И. Н. Смирнова [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2016. – 15 (1): 66–71.Смирнова И. Н. Фармакоэкономический анализ заместительной терапии внутривенным иммуноглобулином у пациентов с первичными дефектами гуморального звена иммунитета / И. Н. Смирнова [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2016. – 15 (1): 66–71.13. Мухина А..А. Заместительная терапия препаратами иммуноглобулинов у пациентов с первичными иммунодефицитами в Российской Федерации / А. А. Мухина [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2020. – 19 (4 приложение): 18–29.Мухина А..А. Заместительная терапия препаратами иммуноглобулинов у пациентов с первичными иммунодефицитами в Российской Федерации / А. А. Мухина [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2020. – 19 (4 приложение): 18–29.14. Sarı G., Güven Bilgin B., Yılmaz E., Aytac G., Edeer Karaca N., Aksu G., Kutukculer N. Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder. Eur Ann Allergy Clin Immunol 2021; 53 (4): 177–84.Sarı G., Güven Bilgin B., Yılmaz E., Aytac G., Edeer Karaca N., Aksu G., Kutukculer N. Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder. Eur Ann Allergy Clin Immunol 2021; 53 (4): 177–84.15. Anderson-Smits C., Park M., Bell J., Mitchell S., Hartley L., Hawe E. Subcutaneous immunoglobulin use in immunoglobulin-naive patients with primary immunodeficiency: a systematic review. Immunotherapy 2022; 14 (5): 373–87.Anderson-Smits C., Park M., Bell J., Mitchell S., Hartley L., Hawe E. Subcutaneous immunoglobulin use in immunoglobulin-naive patients with primary immunodeficiency: a systematic review. Immunotherapy 2022; 14 (5): 373–87.16. Kobayashi R. H., Mandujano J. F., Rehman S. M., Kobayashi A. L., Geng B., Atkinson T. P., et al. Treatment of children with primary immunodeficiencies with a subcutaneous immunoglobulin 16.5 % (cutaquig® [octanorm]). Immunotherapy 2021; 13 (10): 813–24.Kobayashi R. H., Mandujano J. F., Rehman S. M., Kobayashi A. L., Geng B., Atkinson T. P., et al. Treatment of children with primary immunodeficiencies with a subcutaneous immunoglobulin 16.5 % (cutaquig® [octanorm]). Immunotherapy 2021; 13 (10): 813–24.17. Jolles S., Rojavin M., Lawo J., Nelson R. Jr., Wasserman R., Borte M., et al. Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials. J Clin Immunol 2018; 38 (8): 864–75.Jolles S., Rojavin M., Lawo J., Nelson R. Jr., Wasserman R., Borte M., et al. Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials. J Clin Immunol 2018; 38 (8): 864–75.18. Hagan J. B., Fasano M. B., Spector S., Wasserman R. L., Melamed I., Rojavin M. A., et al. Efficacy and safety of a new 20 % immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol 2010; 30 (5): 734–45.Hagan J. B., Fasano M. B., Spector S., Wasserman R. L., Melamed I., Rojavin M. A., et al. Efficacy and safety of a new 20 % immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol 2010; 30 (5): 734–45.19. Borte M., Krivan G., Derfalvi B., Gonzalez-Quevedo T., Grimbacher B., Jolles S., et al. Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20 %: a Phase II/III study in Europe in patients with primary immunodeficiencies. Clin Exp Immunol 2017; 187 (1): 146–59.Borte M., Krivan G., Derfalvi B., Gonzalez-Quevedo T., Grimbacher B., Jolles S., et al. Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20 %: a Phase II/III study in Europe in patients with primary immunodeficiencies. Clin Exp Immunol 2017; 187 (1): 146–59.20. Suez D., Stein M., Gupta S., Hussain I., Melamed I., Paris K., et al. Efficacy, safety, and pharmacokinetics of a novel human immune globulin subcutaneous, 20 % in patients with primary immunodeficiency diseases in North America. J Clin Immunol 2016; 36 (7): 700–12.Suez D., Stein M., Gupta S., Hussain I., Melamed I., Paris K., et al. Efficacy, safety, and pharmacokinetics of a novel human immune globulin subcutaneous, 20 % in patients with primary immunodeficiency diseases in North America. J Clin Immunol 2016; 36 (7): 700–12.21. Shabaninejad H., Asgharzadeh A., Rezaei N., Rezapoor A. A comparative study of intravenous immunoglobulin and subcutaneous immunoglobulin in adult patients with primary immunodeficiency diseases: a systematic review and meta-analysis. Expert Rev Clin Immunol 2016; 12 (5): 595–602.Shabaninejad H., Asgharzadeh A., Rezaei N., Rezapoor A. A comparative study of intravenous immunoglobulin and subcutaneous immunoglobulin in adult patients with primary immunodeficiency diseases: a systematic review and meta-analysis. Expert Rev Clin Immunol 2016; 12 (5): 595–602.22. Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs 2007; 21 (2): 105–16.Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs 2007; 21 (2): 105–16.