RU2429877C1 - Method of treating chronic viral hepatitis c - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: method includes daily introduction of ribavirin, and also introduction of interferon daily or every second day and introduction of interleukin-1 within periodic courses three-four weeks each which include introduction of interleukin-1 every second day with an interval of five to nine weeks. ^ EFFECT: use of the invention enables higher clinical effectiveness in chronic viral hepatitis C, providing a sparing dose regimen of interleukin-1 and reducing probability of side effects. ^ 1 ex

Description

The invention relates to medicine, namely to methods for treating patients with chronic viral hepatitis C, mainly patients who have not responded to therapy with interferon and ribavirin.

Currently, the practice of treating chronic viral hepatitis C uses therapy based on the use of interferon, including in combination with drugs that enhance its therapeutic effect, in particular, such as ribavirin or thymosin [RU 94022480].

Therapy based on the use of interferon is quite effective and provides a steady-state virological response rate in the treatment of patients at the level of 40-60%.

However, as practice shows, some patients do not respond to interferon therapy.

This is due to the fact that hepatitis C viruses have a specialized defense mechanism against interferons, based on the ability of viruses to synthesize various proteins that mimic the function of cellular proteins. The appearance of these proteins in infected cells leads to the blocking of the activation signal from interferon receptors necessary to trigger antiviral protection [Cell. 1992. Vol. 71, p. 5-7; J. Virology. 1999. V.73, No. 10, p. 8469-8475].

As studies of recent years have shown, the use of interleukin-1 in the treatment of chronic viral hepatitis C is very promising [see, for example, g. Clinical prospects of gastroenterology, hepatology. 2006, No. 5; WO 2010009762].

Interleukin-1 is a broad-spectrum immunostimulant, has antiviral activity against hepatitis C virus due to direct interferon-independent action using innate antiviral immunity activation systems, induces the synthesis of endogenous interferon, an antiviral mediator that can enhance the antiviral effect, and also promotes the abolition of the blocking effect of hepatitis C virus on the biological activity of interferon.

As the closest analogue, the authors selected a method for the treatment of chronic hepatitis C described in [WO 2010009762, examples 2, 3].

This method of treatment involves daily administration of interleukin-1 and ribavirin and periodic (1 time per week) administration of interferon.

The use of interferon and ribavirin in combination with interleukin-1 improves the effectiveness of the method under consideration.

The task of the invention is to expand the arsenal of methods for treating patients with chronic viral hepatitis C, involving the introduction of interferon, ribavirin and interleukin-1.

The essence of the invention lies in the fact that in the method of treating chronic viral hepatitis C, including daily administration of ribavirin, as well as the introduction of interferon and the introduction of interleukin-1, according to the invention, interferon is administered daily or every other day, and interleukin-1 is administered in periodic courses of three to four weeks each, as part of the course, the introduction of interleukin-1 is carried out every other day, with a break between courses of five to nine weeks.

The above-mentioned duration of treatment and the schedule for the administration of interferon, ribavirin and interleukin-1 were selected based on the studies conducted by the authors. At the same time, the dynamics of the condition of patients with chronic viral hepatitis C who were given the indicated drugs during periodic monitoring of the viral load was studied.

A significant feature of the proposed method is that it provides for the background of the introduction of interferon and ribavirin, the periodic introduction of interleukin-1 in several periodic courses with significant intervals between them, which provides a more sparing regimen for the administration of interleukin-1 and a decrease in the likelihood of side effects that may occur with its introduction.

Interferon in the claimed method is understood to mean interferons of type I and III, in particular, recombinant or synthesized interferon alpha, interferon beta, interferon omega, interferon-gamma, as well as their biological analogues or derivatives, for example pegylated interferon.

Under interleukin-1 in the present method refers to natural or recombinant interleukin-1, in particular interleukin-1 alpha, interleukin-1 beta and other members of the family of interleukin-1.

As testing of the proposed method showed, after treatment, the absence of viral load was observed in 60-80% of patients.

Thus, the implementation of the proposed method achieves high efficiency in the treatment of patients with chronic viral hepatitis C.

The method is implemented as follows.

Patients with chronic viral hepatitis C are treated by administering therapeutically effective amounts of interferon, ribavirin and interleukin-1.

Interferon is administered parenterally daily or every other day.

Ribavirin is administered orally daily.

Interleukin-1 is administered parenterally in periodic courses of three to four weeks each, as part of the course, interleukin-1 is administered every other day, with a break between courses of five to nine weeks.

The possibility of implementing the proposed method is shown in the example of a specific implementation.

Example.

A group of patients of 36 people was treated using the proposed method.

The group included patients with chronic viral hepatitis C infected with the genotype I of the virus who did not have a virological response during the previous therapy with pegylated or standard interferon and ribavirin. The duration of infection averaged 4.7 ± 1.1 years. The increase in ALT activity was 1.5-6 times higher than normal. The viral load was more than 10 ⁶ copies / ml.

The viral load was judged by the serum HCV RNA, which was determined by real-time polymerase chain reaction using the AmpliSens HCV - Monitor - FRT test system manufactured by TsNIIEMZRF (Russia) using an iCycler device from BioRad (USA) , as well as the indicator of HCV RNA in lymphocytes, which was determined using the commercial Ampli-Sens HCV FRT test systems.

Patients were given subcutaneous injections of the drug Interferon Interal-P at a dose of 3 million ME, the drug Ribavirin Vero-Ribavirin was administered orally at a dose of 1000 mg per day (for body weight less than 75 kg) and 1200 mg per day (for body weight more than 75 kg), and also carried out subcutaneous injections of the drug interleukin-1 beta Betaleikin at a dose of 0.005 μg / kg

Interal-P was administered every other day for 48 weeks.

Vero-ribavirin was administered daily in two divided doses for 48 weeks.

Betaleikin was administered as follows.

1st, 2nd, 3rd weeks — Betaleikin’s first course was administered,

4th, 5th, 6th, 7th, 8th weeks (five weeks) - a break,

9th, 10th, 11th weeks - the second course of Betaleikin's administration was carried out,

12th, 13th, 14th, 15th, 16th weeks (five weeks) - a break,

17th, 18th, 19th weeks - carried out the third course of Betaleikin's administration,

20th, 21st, 22nd, 23rd, 24th weeks (five weeks) - a break,

25th, 26th, 27th weeks - carried out the fourth course of Betaleikin's introduction,

28th, 29th, 30th, 31st, 32nd, 33rd, 34th, 35th, 36th weeks (9 weeks) - a break,

37th, 38th, 39th weeks - the fifth course of Betaleikin's administration was carried out.

After 12, 24, 48 weeks, the viral load was monitored.

As a result of the treatment, the absence of viral load was detected in 68% of patients.

Claims (1)

A method of treating chronic viral hepatitis C, including daily administration of ribavirin, as well as the introduction of interferon and the introduction of interleukin-1, characterized in that interferon is administered daily or every other day, and interleukin-1 is administered in periodic courses of three to four weeks each, as part of the course the introduction of interleukin-1 is carried out every other day, while the interval between courses is from five to nine weeks.