Orphan drugs for the pathogenetic treatment of rаre diseases in the drug registry

Introduction. Despite the high cost of life-threatening rаre diseases, not all expensive drugs for the pathogenetic treatment of orphan diseases are included in the list of vital and essential drugs. Aim. Analysis of drugs for pathogenetic treatment of diseases included in the orphan drugs lists, in order to determine the specific names not included in the list of vital and essential drugs (VET List) for medical use in 2019. Materials and methods. From the standards of medical care for rare diseases included in the Decree of the Government of the Russian Federation of April 26, 2012 № 403 and the order of the government of the Russian Federation of December 10, 2018 № 2738-p allocated 62 international non-patented  names of drugs. The data obtained from the relevant INN in the State register of drugs of the Russian Ministry of health of was analyzed. Results. 90 % of the drugs are reference, 34 % interchangeable, 81 % of the considered included in the VET List for 2019. The remaining 19 % is not necessary and therefore does not have a registered selling price. Summary. Analysis of orphan drug lists revealed the absence of some of the expensive drugs in the VET List, which makes it impossible to control the maximum selling prices of the manufacturer by the government

Use of unlicensed drugs and off-label drug use: focus on COVID-19

Introduction. In a crisis, like the COVID-19 outbreak, the strategy of experimental drug use in clinical practice increases the availability of potentially effective drugs that have not yet proven the opposite for patients with life-threatening diseases, despite the fact that such use is «off-label» for unregistered indications. The choice of drugs for «off-label» use is most difficult when a large potential benefit justifies higher risks, because the use of drugs for unapproved indications increases the frequency of adverse drug reactions and thereby reduces their clinical value. Goal. Clinical and pharmacological analysis of the «off-label» features of drug use for etiotropic and pathogenetic therapy of COVID-19, description of new opportunities for state registration of medicines in the fight against a new coronavirus infection. Materials and methods. From the Russian temporary guidelines for the treatment of COVID-19 were identified 14 international non-generic names (INN) of drugs. We analyzed the data obtained for the corresponding INN in the State register of medicines of the Ministry of health of the Russian Federation. Results. There is a widespread violation of the requirements of various sections of the current instructions for the medical use of the considered drugs, which requires additional analysis of real-word data. Conclusions. For this purpose, we can use thematic reports, patient registers, and active post-marketing pharmacovigilance

Quantitative and qualitative evaluation of the use of nonsteroidal anti-inflammatory drugs in the Russian Federation over 10 years

Relevance. Studies devoted to the assessment of consumption, as well as to the issues of pharmacosafety of nonsteroidal anti-inflammatory drugs, are limited at the national level in the Russian Federation. The study of these issues will determine the general trends of consumption and prescription of this group of drugs.Aim. To assess the consumption pattern of NSAIDs in the Russian Federation in the period from 2010 to 2020.Methods. Information was searched using data from the state register of drugs (GRLS) as well as national database downloads (automated information system of Roszdravnadzor; AIS RZN). To estimate the consumption of the main INN from the group of NSAIDs for the period 2010–2020 the information on the sales volume of all trade names, sold for sale in the Russian Federation was unloaded from the database of IQVIA Solutions Ltd. and analyzed.Results. The analysis showed that the first place by total amount of consumption was occupied by acetylsalicylic acid (5 953 058 854); second place — paracetamol (4 635 122 085); third place — ibuprofen (3 230 415 088); fourth place — metamizole (4 172 344 008); fifth place — ketorolac (91 617 809,04); sixth — nimesulide (69 761 7481,8). The claimed INNs showed a slightly different distribution when calculating the DDDs/P (patient-year) totals, namely, in descending order, nimesulide, ketorolac, ibuprofen, acetylsalicylic acid, paracetamol, and methamisole.Conclusion. The indicated levels of consumption do not correlate with the data of the national database “Pharmacovigilance”, which indicates insufficient post-marketing monitoring of the safety profiles of the indicated medicines

Health-economic analysis of tocilizumab in patients with rheumatoid arthritis and systemic juvenile arthritis

Rationale. Rheumatoid arthritis (RA) and systemic juvenile arthritis (sJA) are the most frequent rheumatic diseases in adults and adolescents, consequently. Biologics disease modifying antirheumatic drugs (bDMARDs) are eff ective in treatment of RA and s JA. Aim. To perform health-economic analysis of tocilizumab for subcutaneous and intravenous injections in patients with RA and sJA comparing to TNF-α inhibitors. Materials and methods. Cost-minimizing analysis was used from the perspective of healthcare system (accounting for direct medical costs) with the modelling horizon — 1 year. We included into the model cost of RA and sJA bDMARDs, cost of adverse events correction and costs of laboratory and instrumental diagnostic. Results. Cost minimizing ratio of tocilizumab (subcutaneous form) in RA patients comparing to adalimumab (Humira), сertolizumab pegol, golimumab were 111 536; 129 094; 85 244 RUR, consequently favour to tocilizumab. Tocilizumab was less costly comparing to adalimumab (Humira), certolizumab pegol, golimumab by 12.8, 14.5, 10,0 %, consequently. Cost minimizing ratio of tocilizumab in RA patients comparing to adalimumab (Dalibra), etanercept, infl iximab (Remicade) were 40 497; 54 355; 28 419 RUR in favour to comparators. Tocilizumab was more costly comparing to adalimumab (Dalibra) etanercept, infl iximab (Remicade) by 5.6; 7.7; 3.9 %, consequently. Cost minimizing ratio of tocilizumab in sJA patients comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) were 6 535 234; 478 297 and 323 263 RUR. Tocilizumab was less costly comparing to kanakinumab, adalimumab (Humira) and adalimumab (Dalibra) by 93.3; 50.6 and 41.1 %, consequently. Conclusions. Tocilizumab is economically reasonable comparing to others TNF-α inhibitors in patients with RA and sJA

Factors associated with adverse outcome among hospitalized patients with moderate to severe COVID-19

Aims. To consider factors associated with adverse outcome among hospitalized patients with moderate and severe COVID-19.Materials and methods. Data from 345 case histories of adult patients hospitalized with moderate to severe COVID-19 were analyzed in a single-center retrospective study. Characteristics by sex, age, number of days from disease onset to admission to hospital, duration of hospitalization, duration of disease, population characteristics by medical history of comorbidities and self-medication, outcome of hospitalization and medical technologies used in hospital conditions were given for the whole cohort of patients. All parameters were analyzed using descriptive statistics methods. Qualitative variables are given in absolute (n) and relative (%) values with 95% confidence interval. Continuous variables were presented as median and quartiles. Risk factors for mortality were determined across groups using the χ2  criterion and odds ratio.Results. There was no demonstrated effect of gender, degree of pulmonary tissue lesions on computed tomography data, or time of initiation of respiratory support on disease outcome. At the same time, the age older than 65 years as well as neoplasms, type 2 diabetes mellitus, dementia, Stage 3 arterial hypertension, chronic heart failure, coronary heart disease, myocardial infarction and stroke history, chronic obstructive pulmonary disease, bronchiectatic disease, urogenital diseases were the predictors of unfavorable outcome in patients with moderate and severe COVID-19 form. Prehospital use of antiplatelet agents, direct and indirect oral anticoagulants, drugs affecting the renin-angiotensin system, systemic glucocorticosteroids, antibiotics, antiviral drugs, and analgesics was associated with a decrease in the mortality rate in patients with moderate-to-severe COVID-19, as well as timely use of pronposition and transfer to intensive care unit.Conclusions. Our findings are partially consistent with previous reports on the effect of risk factors on COVID-19 outcomes

Систематический обзор данных реальной клинической практики при COVID-19: неинтервенционные исследования

Introduction. As defined by the Food and Drug Administration, real-world data (RWD) is data related to a patient's health and/or health care delivery, usually collected from various sources as part of real-world clinical practice research.Objective: to describe the feasible and the most sought-after designs of non-interventional real-world clinical practice trials that provide evidence for the efficacy and safety of drug administration in the therapy of novel coronavirus infection.Material and methods. A search strategy for the terms “COVID-19 AND real-life”, “COVID-19 AND real-data”, “COVID-19 AND real-world” was developed to extract articles published between December 1, 2020 and March 12, 2021 from the databases: PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov database.Results. The search yielded 137 non-repetitive articles, 32 of them were included in the review. All randomized clinical trials (pragmatic and simplified large ones), studies of the effectiveness of laboratory diagnostic methods, medical triage, social distancing and other sanitary and epidemiological measures to cope with the epidemic were excluded.Conclusion. High-quality, non-randomized RWD studies can enhance the external validity of registration randomized clinical trials by complementing them with a broader range of indicators, which is essential in supporting medical and public health decision-making in the COVID-19 pandemic. Введение. По определению, данному Food and Drug Administration, данные реального мира (англ. real-world data, RWD) – это данные, относящиеся к состоянию здоровья пациента и/или оказанию медицинской помощи, обычно собираемые из различных источников в рамках исследований реальной клинической практики.Цель: описание возможных и наиболее востребованных дизайнов неинтервенционных исследований реальной клинической практики, которые позволяют получить сведения об эффективности и безопасности применения лекарственных средств в терапии новой коронавирусной инфекции.Материал и методы. Для извлечения статей, опубликованных с 1 декабря 2020 г., по 12 марта 2021 г., в рамках литературного обзора разработана стратегия поиска по терминам “COVID-19 AND real-life”, “COVID-19 AND real-data”, “COVID-19 AND real-world” в базе данных медицинских публикаций PubMed/MEDLINE, Кокрейновской базе данных систематических обзоров, а также базе данных клинических исследований СlinicalТrials.gov.Результаты. Было найдено 137 публикаций, из них 32 статьи вошли в обзор. Исключены все рандомизированные клинические испытания (прагматические и упрощенные большие), исследования эффективности методов лабораторной диагностики, медицинской сортировки, социального дистанцирования и других санитарно-эпидемиологических мер по сдерживанию эпидемии.Заключение. Высококачественные нерандомизированные исследования в рамках RWD способны усилить внешнюю валидность регистрационных рандомизированных клинических испытаний, дополнив их более широким спектром показателей, что имеет существенное значение при поддержке принятия решений в области медицины и общественного здравоохранения в условиях пандемии COVID-19.

Анализ социально-экономического бремени спинальной мышечной атрофии в Российской Федерации

Introduction. Spinal muscular atrophies (SMA) are clinically and genetically heterogeneous congenital orphan diseases that lead to progressive spinal motoneurons degeneration and loss of their function. There are 4 types of SMA with type I being the most severe. SMA patients need lots of services (medical, social etc.) throughout their life and the cost of the care has never been calculated in Russia before.Aim. The study aims to calculate the socio-economic burden of SMA in the Russian Federation for direct medical procedures and indirect costs before the introduction of pathogenetic therapy and after its implementation. The assessment of the impact of pathogenetic therapy on the dynamics of the socio-economic burden of SMA in the Russian Federation was performed.Materials and methods. The data from patient-reported SMA registry, insurance medical companies, epidemiological, and rehabilitation care data were compiled into the model. The authors accounted for direct medical (diagnostics, drugs, surgery, orthopedics, rehabilitation, and family) and nonmedical expenditures including indirect (loss of GDP) costs. Characteristics of the patient population have been taken from the national SMA register. The sources of costs data included governmental healthcare and insurance companies’ tariffs, price lists of commercial companies, clinics, and laboratory services. The modeling time horizon was 5 years. The two following calculation scenarios were evaluated: 1) none of the patients with SMA receive pathogenic therapy 2) the share of pathogenic therapy is stable during the time horizon at the current level.Results. National SMA register contains the information about 998 patients; 21% of them have SMA I type. In the first scenario, the total social-economic burden of SMA in Russia was 2.37 billion RUR/year (2.38 million RUR/patient/year); the share of in-patient care and rehabilitation were 30.8% and 32.3%, respectively. SMA type I burden was 1.6 billion RUR/year (1.5 million RUR/patient/year). In the second scenario, the total SMA burden was 5.4 billion RUR/year, the highest share of pathogenetic therapy was 43%.Conclusion. The SMA economic burden in Russia is significant and growing along with the increase in the share of pathogenic therapy, but this growth should be compensated by lowering other direct and indirect costs.Введение. Спинальные мышечные атрофии (СМА) - это клинически и генетически разнородная группа орфанных заболеваний, характеризующихся прогрессивной дегенерацией мотонейронов и потерей их функции. Выделяют четыре типа СМА, из которых тип I является наиболее неблагоприятным. Пациенты со СМА в течение жизни нуждаются как в разнообразной медицинской так и социальной помощи, суммарные затраты на которую ранее в РФ не рассчитывались.Цель. Расчет социо-экономического бремени СМА в РФ для все, популяции пациентов с учетом прямых медицинских, прямых немедицинских и непрямых затрат до момента внедрения патогенетической терапии и после ее внедрения. Оценка влияния патогенетической терапии на динамику социально-экономического бремени СМА в РФ.Материалы и методы. При расчетах бремени СМА использовали информацию из реестра пациентов, системы ОМС и социального обеспечения граждан в РФ. При оценке бремени учитывали прямые медицинские затраты (диагностика, лекарственное и хирургическое лечение, реабилитация), прямые немедицинские затраты (выплата пособий), а также непрямые затраты (недополученный ВВП). Характеристика популяции пациентов была взята из негосударственного реестра пациентов со СМА в РФ. Источником информации о ценах служили: тарифы ОМС и высокотехнологичной медицинской помощи, прайс-листы коммерческих клиник, лабораторий и поставщиков медицинских изделий. Горизонт моделирования - 5 лет. Расчеты были выполнены по двум сценариям: 1) до момента внедрения в практику патогенетической терапии; 2) при текущем уровне охвата патогенетической терапией.Результаты. Реестр содержит информацию о 998 пациентах со СМА, из которых 21% - СМА I типа. В сценарии 1 бремя СМА в РФ составило 2,37 млрд руб./год. (2,38 млн руб./пац./год) наибольшую долю затрат составляли затраты на стационарную медицинскую помощь (30,8%) и реабилитацию (32,3%). Бремя СМА I типа составило 1,6 млрд руб./год. (1,5 млн руб./пац. /год). В сценарии 2 бремя СМА в РФ составило 5,4 млрд руб./год. (5,4 млн руб./пац./год), доля затрат на патогенетическую терапию была наибольше, (43%).Заключение. Бремя СМА в РФ является существенным по мере расширения доступа пациентов к патогенетической терапии. Бремя СМА будет возрастать, однако при этом рост затрат на патогенетическую терапию должен сопровождаться снижением других прямых и непрямых затрат