Treatment of chronic hepatitis C by cepeginterferon alpha-2b in combination to ribavirin

Aim of investigation. Comparative study of efficacy and safety of Algeron in dozes of 1,5 and 2,0 mkg/kg and PegIntron in combination to ribavirin within combined mode of treatment of patients with chronic hepatitis C (CHC) with subsequent assessment of therapeutic doze of Algeron.Material and methods. In open randomized «noninferiority» clinical study of II–III phase 150 previously untreated by interferon adult CHC patients (genotypes 1, 2, 3) were randomized in three medical groups: Algeron 1,5 mkg/kg, Algeron 2,0 mkg/kg and active control group — PegIntron 1,5 mkg/kg. All patients received ribavirin 800-1400 mg/day for 24-48 wks in relation to genotype. Early virologic response (EVR) rate was used as a primary endpoint of efficacy. Intentto-treat the analysis was applied at rating of obtained results.Results. The comparative analysis has demonstrated, that EVR at the 12-th week in group of Algeron 1,5 mkg/kg was observed in 100 % of patients with genotypes 2/3 and in 88,5% of patients with genotype 1. In Algeron 2,0 mkg/kg group it was registered at 95,7 and 92,6 % of patients respectively, in control group – in 95,5 and 82,1% (р> 0,05 in comparison of all scores between groups). As no distinctions in Algeron efficacy were revealed, at more favorable safety profile of low doze, the therapeutic doze of 1,5 mkg /kg/wk has been chosen. After the first 12 wks of treatment all patients of the 1-st and 2-nd groups received Algeron in the chosen doze of 1,5 mkg/kg up to termination of the treatment course. Therefore the response at the end of treatment (direct virologic response, DVR) and sustained virologic response (SVR) were estimated for patients of the 1-st and 2-nd groups in common (n=100). Among patients with HCV 2/3 genotypes, receiving Algeron, DVR was observed in 93,6%, in control group – in 81,8%, in patients with the 1-st virus genotype — in 83 and 71,4 % of cases respectively (р>0,05 at comparison of all scores between groups). In patients with 2/3 genotypes HCV, at Algeron therapy, SVR was reached in 83 % of cases, in PegIntron group — in 81,8 %. In patients with the 1-st virus genotype it was observed in 67,9 and 57,1 % respectively (p> 0,05). The adverse events were registered during treatment by Algeron, in dose-dependent manner, however their frequency had did not exceed that in patients receiving standard PegIntron dozes.Conclusions. Study results prove high efficacy and safety of Algeron in suppression of hepatitis C virus replication and allow to recommend its application at previously untreated patients with CHC in a doze of 1,5 mkg/kg/wk for 24-48 wks in relation to genotype HCV

Efficacy of pegylated interferon alfa-2b «Algeron» in the treatment of chronic hepatitis C

Aim of the study. To compare efficacy and safety of Algeron 1.5 and 2.0 μg/kg with PegIntron in combination with ribavirin in the treatment of chronic hepatitis C and to determine therapeutic dose of Algeron.Materials and Methods. 150 adult treatment-naive patients with HCV (all genotypes)were randomized into 3 groups. In the two main groups the patients received Algeron in the dosage of 1.5 or 2.0 μg/kg/week, in the active control group – PegIntron 1.5 μg/kg/week in combination with ribavirin. Primary efficacy endpoints were rapid and early virologic response (RVR and EVR).Results. Comparative analysis of virologic response rate after 4th and 12th weeks of the therapy and biochemical response did not show any statistically significant differences between the groups. RVR was observed in 64% and 56% of patients receiving Algeron 1.5 and 2.0 μg/kg, respectively, in the PegIntron group – in 66% (mITTanalysis, p>0,05).The frequency of EVR in Algeron groups after 12 weeks of treatment (regardless of a dose – 1.5 or 2.0 μg/kg) was 94%, in the reference group (PegIntron) – 88% (p>0,05). RVR and EVR rate analysis according to HCV genotype also did not showed statistically significant differences between the groups. Safety profiles of Algeron and PegIntron were similar. The complex assessment of the efficacy and safety allowed to make the conclusion about the optimal therapeutic dose of Algeron, equal to 1.5 μg/kg/week.Conclusions. Results of the study provide evidence of the high efficacy and safety of Algeron for suppression of HCV replication and make it possible to recommend Algeron 1.5 μg/kg weekly in combination with ribavirin for the treatment of chronic hepatitis C in treatment-naÏve patients for 24–48 weeks depending on the HCV genotype

Treatment of the chronic hepatitis C complicated by mixed cryoglobulinemia with direct-acting antiviral agents

The aim of the study was to evaluate clinical, immunologic and anti-viral efficacy of antiviral therapy (АVT) with drugs of the direct antiviral action (DAA) of the chronic hepatitis C (CHC) complicated with secondary mixed cryoglobulinemia in small cohort of patients. Patients and methods: The cohort consisted of 12 patients with CHC (without signs of a coinfection of HIV, a hepatitis B virus) complicated with mixed cryoglobulinemia (criocrit more than 5% and presence of cryoglobulinemia-related symptoms). Standard DAA based therapy was indicated in all patients: 2 cases daclatasvir and asunaprevir, 3 cases daclatasvir and sofosbuvir and 7 cases Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir. Results: Anti-viral response at 12 and 24 weeks was found in 91,6% (11/12) treated patients. In one case (on the daclatasvir and asunaprevir) resistance to both drugs developed. Clinical response was confirmed in 83% – 10/12 (25% – the complete response, 58% – the partial response). Despite of anti-viral response kidney damage persisted in 2 patients without apparent improvement. There was one lethal outcome at 25th week since the beginning of treatment because of bilateral pneumonia and thromboembolism in patient with kidney involvement treated with steroids and cytostatics. In 25% of patients total elimination of cryoglobulins was confirmed by the end of AVT and in 75% dramatic decrease of criocrit was found. Conclusion: We confirmed good virologic, clinical and immunologic response and safety of AVT with DDA in patients with HCV induced crioglobulinemia, especially when using schemes with a high genetic barrier (daclatasvir and sofosbuvir, Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir).Цель: изучить вирусологическую клиническую и иммунологическую эффективность противовирусной терапии (ПВТ) хронического гепатита С (ХГС), осложнённого развитием вторичной cмешанной криоглобулинемии с использованием препаратов прямого противовирусного действия (ППД) в условиях реальной клинической практики. Материалы и методы: в исследование включено 12 больных ХГС (без ко-инфекции ВИЧ, вирусом гепатита В), осложнённым развитием смешанной криоглобулинемии с криокритом более 5% и наличием клинических проявлений криоглобулинемии. Проводилась терапия препаратами ППД: 2 пациента получали даклатасвир и асунапревир, 3 пациента – даклатасвир и софосбувир и 7 пациентов – Дасабувир; Омбитасвир+Паритапревир+Ритонавир. Результаты: среди всех включённых в исследование пациентов устойчивый вирусологический ответ на 12-й и 24-й неделях наблюдения отмечен у 91,6% (11/12). У 1 пациентки (на схеме даклатасвир и асунапревир) развилась резистентность к обоим препаратам. Клиническая эффективность составила 83% – 10/12 (25% – полный ответ, 58% – частичный ответ). Два пациента с тяжёлой нефрологической патологией, достигнув УВО, клинического ответа со стороны почек не достигли. В случаях частичного ответа чаще всего персистировали (с положительной тенденцией) нефрологические симптомы. Летальных исходов в ходе терапии и в периоде 24-недельного наблюдения не было. Один пациент умер на 25-й неделе наблюдения от двусторонней пневмонии на фоне тромбоэмболии мелких ветвей лёгочной артерии, осложнившей патогенентическую терапию преднизолоном и цитостатиками, назначенную в связи с отсутствием клинического ответа на ПВТ со стороны почек. Иммунологическая эффективность: у 25% пациентов произошла элиминация криоглобулинов уже к моменту завершения ПВТ, у 75% – снижение уровня криокрита. Заключение: полученные данные демонстрируют вирусологическую, клиническую и иммунологическую эффективность и безопасность ПВТ ППД, особенно при использованием схем с высоким генетическим барьером (даклатасвир и софосбувир, Дасабувир; Омбитасвир+Паритапревир+Ритонавир)

Эффективность и безопасность тройной терапии с использованием рекомбинантного интерлейкина-1β, рекомбинантного интерферона-α и рибавирина у пациентов с хроническим гепатитом C, инфицированных генотипом 1, с отсутствием ответа на предшествующее лечение инт

To assess the efficacy and safety of an experimental course of antiviral therapy with recombinant IL-1β in combination with recombinant interferon-α2b and ribavirin in patients with chronic hepatitis C infected with genotype 1 hepatitis C virus in lacking the virologic response to previous dual therapy pegIFN-α or standard IFN-α and ribavirin has been formed by a group of 50 patients. All patients were treated with recombinant IL-1β – 10 subcutaneous injection at a dose of 0.005 mg/kg every other day, the course of 3 weeks, with 5 courses, recombinant IFN-α2b – subcutaneous injections of 3 million IU every other day for 48 weeks. Ribavirin 1000–1200 mg per day (depending on body weight) for 48 weeks. The duration of follow-up after the end of therapy was 24 weeks. Estimated sustained virologic response (SVR). Comparison of SVR according to the version of virologic response in primary treatment showed that the use of the pilot treatment scheme is most effective at relapse (63%) than in the «null-responders» (33%) and partial (23%) responses to the preceding treatment. In the present study did not reveal a single case of serious adverse events or unexpected adverse events. Thus, the inclusion of proven safety of recombinant IL-1β in the scheme of antiviral therapy in combination with standard interferon-α and ribavirin in patients with chronic hepatitis C, and demonstrated the effectiveness of using recombinant IL-1β (in combination with standard interferon-α and ribavirin), especially in patients with recurrent HCV-infection.С целью оценки эффективности и безопасности экспериментального курса противовирусной терапии рекомбинантным ИЛ-1β в комбинации с рекомбинантным интерфероном-α

Ранний вирусологический ответ при использовании препарата цепэгинтерферона альфа-2b в комбинации с рибавирином в терапии хронического гепатита С

Algeron (cepeginterferon alfa-2b) is a new pegylated form of interferon alfa containing linear polyethylene glycol (molecular weight 20 kDa). Pharmacokinetic profile of Algeron allows once weekly administration. In phase II–III study 150 treatment-naive patients with compensated liver function were randomized into 3 groups: Algeron 1,5 μg/kg/week, Algeron 2,0 μg/kg/week, and a reference group of PegIntron 1.5 μg/kg/week in combination with ribavirin 800– 1400 mg/day. Comparative ITT -analysis of early virologic response (EVR) showed absence of differences between groups in frequency of EVR. In Algeron groups (regardless of a dose – 1,5 or 2,0 μg/kg) EVR was observed in 94%, in PegIntron group – – in 88% of patients. Complete EVR (HCV RNA≤15 I I U/mL) was recorded in 88% and 84% of patients receiving Algeron 1,5 and 2,0 μg/kg, respectively, in the reference group – – in 84% of patients. There were no statistically significant differences between groups where patients received Algeron in different doses and the reference group, with or without genotype stratification. Adverse events occurring during the treatment with Algeron are dose-dependent; however, their frequency is no more than in patients receiving standard doses of PegIntron. Based on the absence of differences in efficacy and more favorable safety profile of a lower dose of the study drug, the therapeutic dose of Algeron was selected to be 1,5 μg/kg/week.Альгерон (цепэгинтерферон альфа 2b) – инновационный препарат пегилированного интерферона-альфа, содержащий линейную ююмолекулу полиэтиленгликоля молекулярной массой 20 кДа. Фармакокинетический профиль Альгерона позволяет вводить препарат 1 раз в неделю. В рамках клинического исследования фазы 150 ранее не применявших препаратов интерферона пациентов с хроническим гепатитом С были рандомизированы в 3 группы терапии: Альгерон 1,5 мкг/кг/нед, Альгерон 2,0 мкг/кг/нед и группу сравнения – ПегИнтрон 1,5 мкг/кг/нед в комбинации с рибавирином 800– 1400 мг/сут. Сравнительный анализ продемонстрировал отсутствие различий в достижении раннего вирусологического ответа (РВО) между группами. В группах пациентов, получавших Альгерон (независимо от вводимой дозы – 1,5 или 2,0 мкг/кг), РВО наблюдался в 94% случаев, в группе ПегИнтрона – в 88% случаев. Полный РВО (HCV РНК ≤15 МЕ/мл) зарегистрирован у 88% и 84% пациентов, получавших Альгерон в дозах 1,5 и 2,0 мкг/кг соответственно, в группе сравнения – у 84% участников. Анализ частоты наличия РВО, в том числе в зависимости от генотипа вируса гепатита С, не выявил статистически значимых отличий между группами. Нежелательные явления, наблюдавшиеся в процессе лечения Альгероном, были дозозависимыми, однако их частота не превышала таковую при использовании стандартных доз ПегИнтрона. На основании отсутствия различий в эффективности при более благоприятном профиле безопасности низкой дозы исследуемого препарата была выбрана терапевтическая доза Альгерона, равная 1,5 мкг/кг/нед

Safety and efficacy of telaprevir in treatment of a chronic hepatitis C in patients of the Russian population included in early access program study

Aim of investigation. HEP3002 is the international early access program of efficacy and safety estimation of telaprevir in combination to peginterferon alpha and ribavirin for patients with severe fibrosis or liver cirrhosis caused by hepatitis C virus (HCV) genotype 1. Efficacy and safety of this therapeutic mode were evaluated in intermediate analysis on 16-th week of treatment in 153 patients from Russia who have already reached the 16-th week of treatment or potentially can do so.Material and methods. The study has prospectively included 153 HCV infected patients (genotype 1), with bridging fibrosis or compensated liver cirrhosis who received treatment by telaprevir in combination to peginterferon-alpha and ribavirin for 12 wks with subsequent 12-or 36-week rate of antiviral therapy (AVT) by peginterferon alpha and ribavirin in relation to virologic response and fibrosis severity. Analysis has been carried out for intention to treat (ITT) populations with application of 16-th week AVT data.Results. Total of 153 patients have completed 12-week course of triple therapy and 4-week course of peginterferon-alpha and ribavirin treatment (48% cirrhotic patients, 97% – HCV-1b). The level of HCV RNA was undetectable both at the 4-th week, and at the 12-th week (extended rapid virologic response) in 42 (75%) of 56 previously untreated patients, in 34 (89%) of 38 with relapses after previous treatment, in 4 (57%) of 7 with previous incomplete response, in 22 (52%) of 42 with the previous zero response and in 7 (70%) of 10 with previous virologic breakthrough. Sustained virologic response was achieved in 73 (80%) of patients available for analysis (n=91). Most frequent adverse events of the 2-4 degrees, related to telaprevir, were anemia (63 patients, 41%), thrombocytopenia (15 patients, 10%) and skin rash (7 patients, 5%). For anemia treatment in 50 (33%) patients the doze of ribavirin has been reduced, erythropoietin was prescribed to 12 (8%) to patients and no blood transfusion was required; 10 (7%) patients have ahead of schedule stopped course of treatment by telaprevir in connection with development of anemia (6), thrombocytopenia (2) and occurrence of skin rash (2).Conclusion. In 153 patients with severe liver fibrosis caused by hepatitis C virus (genotype 1), on background of triple AVT with telaprevir high level of immediate virologic response and low level of the preterm treatment discontinuation was marked

Эффективность и безопасность пангенотипной противовирусной терапии хронического гепатита С в реальной клинической практике: данные наблюдений в трех клинических центрах Санкт-Петербурга

   The aim of the analysis was to describe the results of administration of pan-genotype antiviral therapy (glecaprevir / pibrentasvir, GLE / PIB) in real-world setting in three clinical centers in St. Petersburg within the city program for the treatment of chronic hepatitis C.   Materials and methods. A retrospective analysis of the GLE / PIB usage of in the period from 2019 to 2022 within the city program for the treatment of chronic hepatitis C in St. Petersburg was carried out.   Results. The analysis included 464 patients treated in three clinical centers of St. Petersburg: St. Petersburg State Medical Institution “Clinical Infectious Diseases Hospital named after S. P. Botkin”, St. Petersburg State Medical Institution “Center for the Prevention and Control of AIDS and Infectious Diseases” and the Clinic of Infectious Diseases of the Military Medical Academy named after S. M.Kirov”. Overall 452 out of 464 patients (97 %) achieved SVR12. According to the duration of treatment, SVR12 rates were the following: 8 weeks – 97.7 % (419 / 429), 12 weeks – 92.9 % (26 / 28) and 16 weeks – 100 % (7 / 7). The effectiveness according to fibrosis stage was as follows: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-A, B) – 94 % (118 / 125). SVR12 according to HCV genotypes and subtypes was the following: genotype 1b – 100 % (63 / 63), genotype 1a – 91 % (21 / 23), genotype 1 unspecified – 100 % (23 / 23), genotype 2 – 98 % (50 / 51), genotype 3 – 97 % (292 / 301). In patients with an indeterminate genotype, the efficacy was 100 % (7 / 7). Antiviral therapy was well tolerated, there were no cases of discontinuation of therapy, as well as cases of the development of serious adverse events.   Conclusion. GLE / PIB has demonstrated high effectiveness in the real-world setting in patients infected with prevalent genotypes of HCV, including those with genotype 3 and compensated liver cirrhosis. The results of our analysis fully correspond to the data obtained earlier in clinical trials andreal-world setting.   Цель: анализ результатов применения пангенотипной комбинации глекапревир / пибрентасвир в реальной клинической практике в Санкт-Петербурге на базе 3 клинических центров в рамках городской программы по лечению хронического гепатита С.   Материалы и методы. Проведен ретроспективный анализ результатов использования комбинации глекапревир / пибрентасвир в период с 2019 по 2022 г.г в рамках городской программы по лечению хронического гепатита С в Санкт-Петербурге.   Результаты. В анализ были включены 464 пациента, проходивших лечение в 3 клинических центрах Санкт-Петербурга: Клиническая инфекционная больница им. С. П. Боткина, Центр по профилактике и борьбе со СПИД и инфекционными заболеваниями и клиника инфекционных болезней Военно-медицинской академии им. С. М. Кирова. В общей когорте 452 из 464 пациентов (97 %) достигли УВО12. В зависимости от продолжительности лечения были получены следующие показатели УВО12: 8 недель – 97,7 % (419 / 429), 12 недель – 92,9 % (26 / 28) и 16 недель – 100 % (7 / 7). Эффективность в зависимости от стадии фиброза была следующей: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-А, B) – 94 % (118 / 125). Значения УВО12 у пациентов с различными генотипами и субтипами ВГС распределились следующим образом: генотип 1b – 100 % (63 / 63), генотип 1a – 91 % (21 / 23), генотип 1 неуточненный – 100 % (23 / 23), генотип 2 – 98 % (50 / 51), генотип 3 – 97 % (292 / 301). У пациентов с неопределенным генотипом эффективность составила 100 % (7 / 7). Противовирусная терапия переносилась хорошо, не было случаев отмены терапии, а также случаев развития серьезных нежелательных явлений.   Заключение. Комбинация глекапревир / пибрентасвир продемонстрировала высокую эффективность лечения в реальной клинической практике у пациентов со всеми генотипами вируса гепатита С, в том числе с генотипом 3 и компенсированным циррозом печени. Показатели УВО12, полученные в данном анализе, в полной мере соответствуют данным клинических исследований и реальной клинической практике, опубликованным ранее

ОПТИМИЗАЦИЯ ЛЕЧЕНИЯ ХГС 1 ГЕНОТИПА В РОССИИ - ВЗГЛЯД КЛИНИЦИСТА

In primary HCV patints, Simeprevir as a component of combined antiviral therapy provides for stavle virological responces in 80,4% of cases vs. 50% in control (QUEST-1+QUEST-2).У первичных больных хроническим гепатитом С (ХГС) симепревир в составе комбинированной (противовирусной терапии) ПВТ обеспечивает устойчивый вирусологический ответ (УВО) в 80,4% случаев (в контроле - 50%, QUEST-1+QUEST-2)

Treatment of the chronic hepatitis C complicated by mixed cryoglobulinemia with direct-acting antiviral agents

The aim of the study was to evaluate clinical, immunologic and anti-viral efficacy of antiviral therapy (АVT) with drugs of the direct antiviral action (DAA) of the chronic hepatitis C (CHC) complicated with secondary mixed cryoglobulinemia in small cohort of patients. Patients and methods: The cohort consisted of 12 patients with CHC (without signs of a coinfection of HIV, a hepatitis B virus) complicated with mixed cryoglobulinemia (criocrit more than 5% and presence of cryoglobulinemia-related symptoms). Standard DAA based therapy was indicated in all patients: 2 cases daclatasvir and asunaprevir, 3 cases daclatasvir and sofosbuvir and 7 cases Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir. Results: Anti-viral response at 12 and 24 weeks was found in 91,6% (11/12) treated patients. In one case (on the daclatasvir and asunaprevir) resistance to both drugs developed. Clinical response was confirmed in 83% – 10/12 (25% – the complete response, 58% – the partial response). Despite of anti-viral response kidney damage persisted in 2 patients without apparent improvement. There was one lethal outcome at 25th week since the beginning of treatment because of bilateral pneumonia and thromboembolism in patient with kidney involvement treated with steroids and cytostatics. In 25% of patients total elimination of cryoglobulins was confirmed by the end of AVT and in 75% dramatic decrease of criocrit was found. Conclusion: We confirmed good virologic, clinical and immunologic response and safety of AVT with DDA in patients with HCV induced crioglobulinemia, especially when using schemes with a high genetic barrier (daclatasvir and sofosbuvir, Dasabuvir;Ombitasvir+Paritaprevir+Ritonavir)

Efficacy and safety of triple therapy with recombinant interleukin-1β, recombinant interferon-α and ribavirin in patients with chronic hepatitis C, genotype 1 infection, the non-responders to previous treatment with interferon and ribavirin

To assess the efficacy and safety of an experimental course of antiviral therapy with recombinant IL-1β in combination with recombinant interferon-α2b and ribavirin in patients with chronic hepatitis C infected with genotype 1 hepatitis C virus in lacking the virologic response to previous dual therapy pegIFN-α or standard IFN-α and ribavirin has been formed by a group of 50 patients. All patients were treated with recombinant IL-1β – 10 subcutaneous injection at a dose of 0.005 mg/kg every other day, the course of 3 weeks, with 5 courses, recombinant IFN-α2b – subcutaneous injections of 3 million IU every other day for 48 weeks. Ribavirin 1000–1200 mg per day (depending on body weight) for 48 weeks. The duration of follow-up after the end of therapy was 24 weeks. Estimated sustained virologic response (SVR). Comparison of SVR according to the version of virologic response in primary treatment showed that the use of the pilot treatment scheme is most effective at relapse (63%) than in the «null-responders» (33%) and partial (23%) responses to the preceding treatment. In the present study did not reveal a single case of serious adverse events or unexpected adverse events. Thus, the inclusion of proven safety of recombinant IL-1β in the scheme of antiviral therapy in combination with standard interferon-α and ribavirin in patients with chronic hepatitis C, and demonstrated the effectiveness of using recombinant IL-1β (in combination with standard interferon-α and ribavirin), especially in patients with recurrent HCV-infection