Aim. To study the quality of life in patients with chronic immune thrombocytopenia (ITP) in the process of romiplostim therapy and to assess the efficacy and safety of this drug in real-world setting. Materials & Methods. The study enrolled adult patients with the confirmed chronic ITP diagnosis and indications for romiplostim therapy. Clinical parameters, RAND SF-36 and FACT-Th6 quality of life as well as FACIT-Fatigue scores were evaluated prior to romiplostim administration vs. 3, 6, and 12 months after the treatment onset. Patient satisfaction checklist was also administered at all study points after the start of therapy. The clinical efficacy of romiplostim was analyzed along with assessing response and time to response. To study the quality of life and fatigue changes, the Generalized Estimating Equation (GEE) method was used during the observation period. Significant fatigue changes were determined and compared in terms of the perception differences from patient’s and physician’s perspective. Results. The study enrolled 60 chronic ITP patients treated with romiplostim in the real-world setting (mean age 51.9 years, 70 % women). The median thrombocyte count prior to romiplostim therapy was 18.5 × 109/L (interquartile range 10.8–22.3 × 109/л). On the enrollment date, 90 % of patients showed hemorrhagic syndrome. Overall response to romiplostim therapy was 98.3 % (complete response was achieved in 93.3 % of patients). After 6 months of therapy, 89.5 % of patients preserved response. After 3 months of therapy, hemorrhagic syndrome was eliminated in 81 % of patients, after 6 months the same was achieved in 93 % of patients. The median time to response was 4.4 weeks (95% confidence interval 3.6–5.3 weeks). Adverse events of grades 1/2 associated with romiplostim were reported in 6.7 % of patients. On romiplostim therapy, pronounced positive changes in quality of life were shown by all scales of the general questionnaire SF-36 and the targeted questionnaire FACT-Th6 (p < 0.001). The clearest improvements were observed in role-physical and role-emotional functioning. Already after 3 months of therapy, a considerable fatigue reduction was observed and sustained for the next 6 and 12 months of romiplostim administration (p < 0.001). During the therapy, the proportion of patients with fatigue impacting various aspects of functioning became considerably smaller. The vast majority of patients (85 %) were satisfied with the treatment. Discrepancies between patients’ and physicians’ evaluations of fatigue were also identified during the treatment. Conclusion. The results of the present multi-center observational study demonstrate high efficacy and safety of romiplostim for chronic ITP patients in the real-world setting. Romiplostim therapy yields considerable quality of life improvement and fatigue reduction. To optimize the patient monitoring system and patient-centered ITP treatment in the real-world setting, it is advisable to use the standardized questionnaires assessing quality of life and fatigue.

Background. The national observational program MPN-QoL-2020 was focused on quality of life (QoL) and symptoms in patients with classical Ph-negative myeloproliferative neoplasms (MPNs) in the Russian Federation, as well as on the perception of the disease and treatment from the patient's and physician's perspective. Aim. To evaluate QoL in patients with different MPNs using new standardized questionnaires, to assess the most common symptoms and their impact on QoL in patients with myelofibrosis (MF), polycythemia vera (PV) and essential throm-bocythemia (ET), and to characterize the perception of the disease and treatment concerns from patients' perspective and their treating physicians' perspective. Materials & Methods. In total 1100 patients with MPNs (MF: n = 355, PV: n = 408, and ET: n = 337; mean age 58 ± 14 years; 61 % women) and 100 hematologists (mean age 42 ± 12 years; 85 % women) from 37 medical centers in 8 Federal districts of the Russian Federation participated in the study. All the patients filled out symptom assessment tool (MPN10), QoL questionnaire for patients with hematological nancies (HM-PRO) and patient's survey checklist; physicians filled out physician's survey checklist and patient record for each patient included in the study. Results. For the first time in Russia in a representative population of MPN patients in the real-world setting, QoL and symptom profiles in patients with different MPNs were characterized and symptom impact on the daily living of MPN patients was identified. MPN patients exhibited QoL impairment: noticeable detriments in physical and emotional functioning, as well as in eating and drinking regimen were found, social functioning was less impaired. More than one third of MPN patients had significant QoL impairment. The vast majority of patients experienced fatigue: 92.6 % MF patients, 83.7 % PI patients, and 82 % ET patients. Symptom prevalence severity differed across different MPNs. Top disease-related symptoms to be resolved were identified from patient's and physician's perspective. Discrepancies in the attitudes of MPN patients and their treating physicians to various aspects regarding the disease and its treatment were found as well as issues needed to be improved in the patient-physician communication were identified. Conclusion. The results of national research program MPN-QoL-2020 allowed to identify the areas of QoL impairment and symptom burden in MPN patients in Russia, to verify areas of concern related to the disease and its treatment in patients with different MPNs, as well as to highlight the unmet needs in this patients' population in our country. The outcomes of the study may contribute to establishing recommendations for improving/maintaining QoL in patients with MPNs and to developing measures aimed to raise awareness of this patients' population about the disease and its treatment.

Актуальность. Национальная наблюдательная программа МПН-КЖ-2020 была направлена на получение данных об особенностях качества жизни и симптомов, а также восприятия болезни и лечения при классических Ph-негативных миелопролиферативных новообразованиях (МПН) в Российской Федерации с точки зрения пациентов и врачей. Цель. При использовании новых стандартизованных опросников изучить качество жизни пациентов с различными МПН, дать характеристику наиболее распространенным симптомам и их влиянию на качество жизни больных миелофиброзом (МФ), истинной полицитемией (ИП) и эссенциальной тромбоцитемией (ЭТ), охарактеризовать восприятие проблем, связанных с заболеванием и лечением, с точки зрения самих пациентов и их лечащих врачей-гематологов. Материалы и методы. В исследование включено 1100 пациентов с Ph-негативными МПН (355 — с МФ, 408 — с ИП и 337 — с ЭТ; средний возраст пациентов 58 ± 14 лет, 61 % женщин). В исследовании также участвовали 100 врачей-гематологов (средний возраст 42 ± 12 лет, 85 % женщин) из 37 ЛПУ в 8 федеральных округах РФ. В рамках исследования пациенты однократно заполняли специальный опросник для оценки симптомов МПН (MPN10), специальный опросник качества жизни у онкогематологических больных (HM-PRO), а также опросный лист пациента. Гематологи однократно заполняли опросный лист врача, а также «карту пациента» на всех включенных ими в исследование больных МПН. Результаты. В условиях реальной клинической практики впервые в России получены данные об особенностях качества жизни пациентов с Ph-негативными МПН, профиле симптомов при разных вариантах МПН и степени их влияния на повседневную жизнь. Больные МПН имеют нарушения качества жизни, которые в большей степени касаются физического и эмоционального функционирования, а также режима приема пищи и питья, в меньшей — социального функционирования. Более чем у 1/3 больных с Ph-негативными МПН зарегистрировано значительное нарушение качества жизни. У подавляющего большинства пациентов отмечается слабость: при МФ — у 92,6 %, при ИП — у 83,7 %, при ЭТ — у 82 %. Профили актуальных симптомов и их выраженность отличаются при разных МПН. Определены симптомы, более всего требующие коррекции с точки зрения пациентов и врачей. Установлены расхождения в оценках пациентов и их лечащих врачей в отношении к заболеванию и проводимому лечению, а также аспекты, нуждающиеся в улучшении при взаимодействии пациент-врач. Заключение. Результаты, полученные в рамках национальной наблюдательной программы МПН-КЖ-2020, позволили выявить особенности нарушений качества жизни больных МПН в России. Определен спектр специфических проблем, связанных с заболеванием и лечением, которые характерны для этих пациентов. Кроме того, актуализированы неудовлетворенные потребности этой категории пациентов в нашей стране. Результаты программы МПН-КЖ-2020 могут использоваться при подготовке рекомендаций по улучшению/поддержанию качества жизни пациентов с Ph-негативными МПН и для разработки мероприятий, направленных на повышение осведомленности больных МПН о заболевании и его лечении.

Relevance. In accordance with the guidelines on the clinical investigation of clotting factor VIII products of the European Medicines Agency and guidelines on pharmacovigilance of the Eurasian Economic Union, after registration of a new drug, it is recommended to study its efficacy and safety on a large population of patients in a standard medical practice to clarify and identify new data.Materials and methods. In a prospective, multicenter, open-label, uncontrolled observational study, the efficacy and safety of the domestic recombinant B-domain deleted blood clotting factor FVIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) in patients with moderate and severe hemophilia A in the context of standard medical practice (study protocol number CI-51/15). Patients received the drug in terms of standard medical practice for the purpose of prophylactic treatment or on demand treatment. For prophylactic treatment Octofactor was administered to patients according to the instructions for medical use in a single dose of 20–40 IU/kg every 2–3 days. In the case of bleeding a single dose of Octofactor was calculated taking into account the severity and localization of bleeding in accordance with the instructions for medical use. The results of the treatment were analyzed for a period of 52 ± 2 weeks. The main parameter for evaluating the efficacy was the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor. Additional parameters for evaluating the efficacy included: the severity of spontaneous bleeding arising during the prophylactic treatment; the number of injections and the total dose of the Octofactor to stop 1 episode of bleeding; the amount of Octofactor used during the entire observation period (52 ± 2 weeks) and for 1 month both for prophylaxis and for stopping the bleeding that occurred; an indicator of the efficacy of therapy on the scale for determining the response to treatment of acute hemarthrosis (World Federation of Hemophilia, WFH).Results.According to the results of the screening survey 237 male patients aged from 19 to 78 years old (mean age 35.2 ± 11.1 years) with moderate and severe hemophilia A (FAS-population) were included in the study. The efficacy of therapy was evaluated in 202 patients who underwent all the planned procedures during the observation period (PP-population). 193 (95.5 %) patients received prophylactic treatment, 9 (4.5 %) patients received on-demand treatment. Evaluation of the efficacy of treatment was carried out on the basis of basic and additional parameters. The main parameter for evaluating the efficacy – the frequency of spontaneous bleeding that occurred within 48–72 hours after the administration of the Octofactor – was 52 ± 2 weeks within 1.4 ± 2.9 cases. At the same time, the proportion of spontaneous bleeding that occurred within 48–72 hours after administration of the Octofactor preparation was 45.2 % of the total number of spontaneous bleeding and 15.6 % of the total number of all bleeding in patients who received prophylactic treatment. Among 608 spontaneous bleeding that occurred in patients receiving prophylactic treatment, 287 (47.2 %) of the bleeding were mild, 289 (47.5 %) were moderate and 32 (5.3 %) were heavy. Of the 275 spontaneous bleeding that occurred within 48–72 hours after administration of the study drug for prophylactic purposes, 117 (42.5 %) episodes were mild, 146 (53.1 %) were moderate, and 12 (4.4 %) were severe. With prophylactic administration the average single dose of the Octofactor was 2036.3 ± 884.7 IU, or 27.3 ± 11.2 IU/kg, in the treatment of bleeding occured during prophylactic treatment – 2227.7 ± 1087 IU, in the treatment of bleeding in patients receiving the drug only on demand – 2280.7 ± 1037.2 IU. The average monthly intake of the drug by one patient in prophylactic treatment was 19.75 ± 9.75 thousand IU, while the average monthly consumption of the drug for preventing bleeding from one patient was 17.16 ± 9.13 thousand IU for stopping bleeding against the background prevention – 3.87 ± 3.97 thousand IU. One patient who received on-demand treatment had an average monthly average of 13.47 ± 13.46 thousand IU of the Octofactor preparation. For stopping 1 bleeding, on average, 1.7 ± 1.7 injections of the Octofactor preparation were required, in the prophylactic treatment group – 1.8 ± 1.8, and in the on-demand treatment group – 1.5 ± 1.1. In the overwhelming majority of cases, patients of both groups showed excellent and good response to all treatment of acute hemarthrosis on the scale of the WFH on all visits, the reaction was moderate in a few episodes, and only in 1 case of acute hemarthrosis there was no response to the drug administration. The safety of therapy was evaluated in 228 patients who received at least 1 Octofactor administration during the study (mITT-population). There were 66 adverse events in 40 patients, 10 of them were associated with the use of the drug, the most significant of which were the formation of inhibiting antibodies to FVIII in low titer (1.5 U) in 1 patient and the development of allergic reactions in 2 patients.Conclusions.Under the conditions of standard medical practice the efficacy and safety of Octofactor was confirmed for both prophylactic treatment and on-demand bleeding treatment in adult patients with severe and moderate hemophilia A.

Background & Aims. The article presents results of two observational, prospective, multicenter studies “Quality of Life, Symptom Profile, and Adherence to Treatment in Adult Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Receiving Dasatinib” (20122015) and “Quality of Life and Symptom Profile in Imatinib-Resistant or Intolerant Patients with Chronic Myeloid Leukemia” (2011-2014). Methods. Data of 107 patients with chronic myeloid leukemia in chronic phase were involved in the real-world analysis - 32 newly diagnosed patients on first-line treatment with dasatinib or after yearly switch to dasatinib after ima-tinib treatment failure and 75 imatinib-resistant or intolerant patients on second-line treatment with dasatinib. Treatment effectiveness and safety of dasatinib were assessed during first- and second-line dasatinib treatment using clinical outcomes as well as quality of life and symptom profile assessment. Results. The real-world data obtained during observational study in limited population of CML patients conform the results of clinical trials devoted to evaluation of treatment efficacy and safety of dasatinib treatment in first- and second-line treatment and demonstrate the importance of patient-reported outcomes. Patient's quality of life improved within 12 months of the first-line dasatinib therapy according to the following scales: role physical functioning, pain, vitality, social functioning and role emotional functioning. The most pronounced and clinically significant improvement was observed for the role emotional functioning (51.1 vs. 68.9). During the second-line dasatinib treatment, stabilization of quality of life parameters was registered for the following scales: vitality, social functioning, mental health, and pain. Significant improvement of the Integral Quality of Life Index was observed (p < 0.05). Positive dynamics of relevant symptoms was registered. The symptom severity decreased during both the first- and second-line therapy. Conclusion. Quality of life and symptom assessment in CML patients contribute to a better disease control in accordance with the principles of risk-adaptive therapy.