COVID-19 and other infectious diseases can exacerbate the course of paroxysmal nocturnal hemoglobinuria (PNH). The efficacy and safety of the Gam-COVID-Vac vaccine in patients with PNH has not been adequately studied. A retrospective, observational, cohort, non-comparative study was performed to assess the course of COVID-19 as well as the safety and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study included data from 52 patients with PNH aged 18 to 75 years, 38 of whom received background therapy with eculizumab (Elizaria^®) between March 2020 and January 2022. COVID-19 was diagnosed according to the results of PCR testing. The patients were divided into two groups for comparison of the incidence of COVID-19. Group 1 included non-vaccinated patients with PNH, and Group 2 included patients vaccinated prior to the onset of COVID-19. According to vaccination, patients were subdivided into non-vaccinated and vaccinated groups without signs of previous COVID-19 at the beginning of the analyzed period, and patients vaccinated half a year or more after recovery from COVID-19. Testing for anti-SARS-CoV-2 IgG levels was carried out in patients with PNH in the year after their COVID-19. Tests for anti-SARS-CoV-2 RBD IgG levels were performed on vaccinated patients. In total, 28 (53.8%) of the enrolled patients had COVID-19, including asymptomatic forms in 7 (25%) and mild forms in 16 (57%) patients. A total of 22 (42.3%) patients were fully vaccinated with Gam-COVID-Vac, of which 13 (25%) patients were vaccinated without the signs of previous SARS-CoV-2infection, and 9 (17.3%) patients were vaccinated after COVID-19. The number of patients who had COVID-19 was about two times higher in Group 1 (non-vaccinated; 24) (61.5%), whereas in Group 2 (vaccinated), the number of patients with COVID-19 was only 4 (30.8%). The proportion and number of patients who did not have COVID-19 was higher in the group of vaccinated patients (9; 69.2%) than in the group of non-vaccinated patients (15; 38.5%) (p = 0.054). In patients who had been infected with COVID-19, maximum concentrations of anti-SARS-CoV-2 IgG were observed 2–3 months after the acute infection phase, followed by a gradual decline by month 9–10. The mean RBD IgG concentration was higher in the group of patients who had been infected by COVID-19 than in the group of patients without COVID-19 (p = 0.047). Therapy type, including eculizumab, did not have a significant impact on RBD IgG titers (p > 0.05). Hospitalization was required in five (18%) patients, all of whom had breakthrough hemolysis and severe lung damage on CT scans. After the first dose, adverse events (AEs) were reported in 41% of the patients (body temperature increased in 18%; headache in 13.6%; and pain in joints in 4.5%; colitis exacerbation was observed in 4.5%). After the second dose, no AEs were reported. The performed study suggests the possible efficacy and demonstrates the safety of Gam-COVID-Vac (Sputnik V) for the prophylaxis of COVID-19 in patients with PNH who experience immunosuppression due to target therapy.

Введение. Первичная иммунная тромбоцитопения (ИТП) — это аутоиммунное заболевание, проявляющееся снижением уровня тромбоцитов и сопровождающееся повышенным риском кровотечений. Выбор стратегии лечения при резистентности к первой линии терапии остается сложной задачей. В последнее десятилетие у таких пациентов применяются агонисты рецептора тромбопоэтина (аТПОр). Непрямые сравнительные исследования свидетельствуют о преимуществе аватромбопага при неэффективности альтернативного аТПОр в предшествующих линиях лечения ИТП. Цель исследования: оценить возможность достижения и сохранения тромбоцитарного ответа (ТО) при применении аватромбопага во второй и последующих линиях терапии ИТП у пациентов с резистентностью к другим аТПОр. Материалы и методы. Терапия была проведена 17 пациентам с диагнозом первичной ИТП: 8 (48%) мужчин и 9 (52%) женщин. Медиана возраста на момент начала терапии составила 51 год (от 18 до 79 лет). Ранее 12 (70%) пациентов получили более 3 линий терапии, в том числе 15 (88%) больных — 2 аТПОр. Результаты. Медиана длительности терапии составила 29 (от 5 до 78) недель. В процессе лечения аватромбопагом ТО был достигнут у 14 (82%) больных, из них полный тромбо­цитарный ответ (ПТО) — у 8 (47%) пациентов, частичный тромбоцитарный ответ (ЧТО) — у 4 (23%) и минимальный тромбоцитарный ответ (МТО) — у 2 (11%). Ко времени анализа данных ТО сохранялся у 9 (52%) пациентов. Заключение. В настоящей работе были проанализированы результаты применения аватромбопага у пациентов с ИТП, резистентной к предшествующим линиям лечения. Полученные данные продемонстрировали его высокую эффективность, в том числе у больных, получивших более 3 линий терапии. Introduction. Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet counts and increased bleeding risk. Selecting a treatment strategy in cases of resistance to first-line therapy remains challenging. In the last decade, thrombopoietin receptor agonists (TPO-RAs) have been used in such patients. Indirect comparative studies suggest an advantage for avatrombopag when an alternative TPO-RA has failed in prior ITP treatment lines. Aim: to evaluate the feasibility of achieving and maintaining platelet response (РR) with avatrombopag in second- and subsequent-line ITP therapy in patients resistant to other TPO-RAs. Materials and Methods. Avatrombopag therapy was administered to 17 patients diagnosed with primary ITP — to 8 (48%) men and 9 (52%) women. Median age at avatrombopag initiation was 51 (18–79) years. Twelve patients (70%) had previously received more than 3 lines of therapy, including 15 (88%) patients who had received 2 TPO-RAs. Results. Median therapy duration was 29 (5–78) weeks. During therapy, РR was achieved in 14 (82%) patients, of whom 8 (47%) achieved complete platelet response (CРR), 4 (23%) achieved partial platelet response (PРR), and 2 (11%) achieved minimal platelet response (MРR). At data analysis, РR was maintained in 9 (52%) patients. Conclusion. This study analyzed the results of avatrombopag use in patients with ITP resistant to prior treatment lines. The data demonstrated its high efficacy, including in patients who had received more than 3 lines of therapy.