What is affinity purified antibodies. Shy obscurantism
Active substance
Affinity purified antibodies to human interferon gamma
Release form, composition and packaging
◊ Lozenges from white to almost white, flat-cylindrical, with a notch and chamfer; MATERIA MEDICA is inscribed on the flat side with a notch, ANAFERON is inscribed on the other flat side.
* applied to lactose monohydrate in the form of a water-alcohol mixture with a content of not more than 10 -15 ng / g of the active form of the active substance.
Excipients: lactose monohydrate - 0.267 g, microcrystalline cellulose - 0.03 g, magnesium stearate - 0.003 g.
20 pcs. - cellular contour packings (1) - packs of cardboard.
20 pcs. - cellular contour packings (2) - packs of cardboard.
20 pcs. - cellular contour packings (5) - packs of cardboard.
pharmachologic effect
With prophylactic and therapeutic use, the drug has an immunomodulatory and antiviral effect. Efficacy has been experimentally and clinically established against influenza viruses, parainfluenza, herpes simplex viruses types 1 and 2 (labial herpes,), other herpes viruses (chicken pox, infectious mononucleosis), enteroviruses, tick-borne encephalitis virus, rotavirus, coronavirus, calicivirus, adenovirus , respiratory syncytial (PC virus). The drug reduces the concentration of the virus in the affected tissues, affects the system of endogenous interferons and associated cytokines, induces the formation of endogenous "early" interferons (IFN α / β) and interferon gamma (IFN γ).
Stimulates humoral and cellular immune response. It increases the production of antibodies (including secretory IgA), activates the functions of T-effectors, T-helpers (Tx), normalizes their ratio. Increases the functional reserve of Tx and other cells involved in the immune response. It is an inducer of a mixed Tx1- and Tx2-type immune response: it increases the production of Tx1 cytokines (IFN-γ, IL-2) and Tx2 (IL-4, 10), normalizes (modulates) the balance of Tx1 / Tx2 activities. Increases the functional activity of phagocytes and natural killer cells (NK cells). Has antimutagenic properties.
Pharmacokinetics
The sensitivity of modern physico-chemical methods of analysis (gas-liquid chromatography, high-performance liquid chromatography, chromatography-mass spectrometry) does not allow assessing the content of the active components of Anaferon in biological fluids, organs and tissues, which makes it technically impossible to study pharmacokinetics.
Indications
- prevention and treatment of acute respiratory viral infections (including influenza);
- complex therapy of infections caused by herpes viruses (, chicken pox, labial herpes, genital herpes);
- complex therapy and prevention of recurrence of chronic herpes infection, incl. labial and genital herpes;
- complex therapy and prevention of other acute and chronic viral infections caused by tick-borne encephalitis virus, enterovirus, rotavirus, coronavirus, calicivirus;
- as part of the complex therapy of bacterial infections;
- complex therapy of secondary immunodeficiency states of various etiologies, incl. prevention and treatment of complications of viral and bacterial infections.
Contraindications
- increased individual sensitivity to the components of the drug.
Children and persons under 18 years of age are shown the use of the drug.
Dosage
The drug is taken orally, not during a meal. The tablet should be kept in the mouth until completely dissolved.
ARVI, influenza, intestinal infections, herpesvirus infections, neuroinfections
On the 1st day, take 8 tab. according to the following scheme: 1 tab. every 30 minutes in the first 2 hours (only 5 tablets for 2 hours), then during the same day take 1 more tablet. 3 times at regular intervals. On the 2nd day and then take 1 tab. 3 times / day until complete recovery.
If there is no improvement on the 3rd day of treatment with the drug for acute respiratory viral infections and influenza, you should consult a doctor.
IN epidemic season with preventive purpose the drug is taken daily 1 time / day for 1-3 months.
Genital herpes
At acute manifestations of genital herpes the drug is taken at regular intervals according to the following scheme: 1-3 days - 1 tab. 8 times / day, then - 1 tab. 4 times / day for at least 3 weeks.
For prevention of recurrence of chronic herpesvirus infection- 1 tab. / day. The recommended duration of the prophylactic course is determined individually and can be up to 6 months.
When using the drug for treatment and prevention of immunodeficiency states, in the complex therapy of bacterial infections- take 1 tablet / day.
If necessary, the drug can be combined with other antiviral and symptomatic agents.
Side effects
Allergic reactions and manifestations of increased individual sensitivity to the components of the drug are possible.
Overdose
Cases of overdose have not been registered to date. In case of accidental overdose, dyspeptic symptoms are possible due to the excipients included in the preparation.
Dosage form: lozenges Compound:Active ingredients:
Antibodies to gamma human interferon affinity purified - 0.003 g *
Excipients: lactose monohydrate 0.267 g, microcrystalline cellulose 0.03 g, magnesium stearate 0.003 g.
* are applied to lactose monohydrate in the form of a water-alcohol mixture with a content of not more than 10 15 ng / g of the active form of the active substance.
Description: Flat-cylindrical tablets, with a risk and a chamfer, from white to almost white. MATERIA MEDICA is inscribed on the flat side with a notch, and ANAFERON is inscribed on the other flat side. Pharmacotherapeutic group:Immunomodulators. Antivirals ATX:With prophylactic and therapeutic use, the drug has an immunomodulatory and antiviral effect. Efficacy has been experimentally and clinically established against influenza viruses, parainfluenza, herpes simplex viruses types 1 and 2 (labial herpes, genital herpes), other herpes viruses (chicken pox, infectious mononucleosis), enteroviruses, tick-borne encephalitis virus, rotavirus, coronavirus, calicivirus , adenovirus, respiratory syncytial (PC virus). The drug reduces the concentration of the virus in the affected tissues, affects the system of endogenous interferons and associated cytokines, induces the formation of endogenous "early" interferons (IFNa / β) and interferon gamma (IFNγ).
Stimulates humoral and cellular immune response. It increases the production of antibodies (including secretory IgA), activates the functions of T-effectors, T-helpers (Tx), normalizes their ratio. Increases the functional reserve of Tx and other cells involved in the immune response. It is an inducer of a mixed Tx1 and Tx2 type of immune response: it increases the production of Tx1 (IFNγ, IL-2) and Tx2 (IL-4, 10) cytokines, normalizes (modulates) the balance of Tx1 / Tx2 activities. Increases the functional activity of phagocytes and natural killer cells (NK cells). Has antimutagenic properties.
Indications:Prevention and treatment of acute respiratory viral infections (including influenza).
Complex therapy of infections caused by herpes viruses (infectious mononucleosis, chicken pox, labial herpes, genital herpes).
Complex therapy and prevention of recurrence of chronic herpesvirus infection, including labial and genital herpes.
Complex therapy and prevention of other acute and chronic viral infections caused by tick-borne encephalitis virus, enterovirus, rotavirus, coronavirus, calicivirus.
Use as part of the complex therapy of bacterial infections.
Complex therapy of secondary immunodeficiency states of various etiologies, including prevention and treatment of complications of viral and bacterial infections.
Contraindications:Increased individual sensitivity to the components of the drug.
Children and persons under 18 years of age are shown the use of the drug Anaferon for children.
Pregnancy and lactation:The safety of Anaferon in pregnant women and during lactation has not been studied. If necessary, taking the drug should take into account the risk/benefit ratio. Dosage and administration:inside. At one time - 1 tablet (keep in the mouth until completely dissolved - not during meals).
SARS, influenza, intestinal infections, herpesvirus infections, neuroinfections. Treatment should be started as early as possible - when the first signs of an acute viral infection appear according to the following scheme: in the first 2 hours, the drug is taken every 30 minutes, then during the first day three more doses are taken at regular intervals. From the second day onwards, take 1 tablet 3 times a day until complete recovery.
If there is no improvement, on the third day of treatment with the drug for acute respiratory viral infections and influenza, you should consult a doctor.
In the epidemic season, for prophylactic purposes, the drug is taken daily 1 time per day for 1-3 months.
Genital herpes. In acute manifestations of genital herpes, the drug is taken at regular intervals according to the following scheme: 1-3 days - 1 tablet 8 times a day, then 1 tablet 4 times a day for at least 3 weeks.
For the prevention of recurrence of chronic herpes infection - 1 tablet per day. The recommended duration of the prophylactic course is determined individually and can be up to 6 months.
When using the drug for the treatment and prevention of immunodeficiency conditions, in the complex therapy of bacterial infections - take 1 tablet per day.
If necessary, the drug can be combined with other antiviral and symptomatic agents.
Side effects:When using the drug according to the indicated indications and in the indicated dosages, no side effects were detected.
Manifestations of increased individual sensitivity to the components of the drug are possible.
Overdose:Cases of overdose have not been registered to date.
In case of accidental overdose, dyspeptic symptoms are possible due to the excipients included in the preparation.
Interaction:Cases of incompatibility with other drugs have not yet been identified.
If necessary, the drug can be combined with other antiviral, antibacterial and symptomatic agents.
Special instructions:The composition of the drug includes lactose monohydrate, and therefore it is not recommended to prescribe it to patients with congenital galactosemia; glucose malabsorption syndrome or with congenital, lactase deficiency. Release form / dosage:Lozenges. Package: 20 tablets in a blister pack made of PVC film and aluminum foil. 1,2 or 5 blister packs together with instructions for medical use are placed in a cardboard pack. Storage conditions:At a temperature not higher than 25 °C.
5, 7
1 FGBOU DPO RMANPO of the Ministry of Health of Russia, Moscow, Russia
2 FGBOU VO Russian National Research Medical University named after. N.I. Pirogov of the Ministry of Health of Russia, Moscow, Russia
3 GBOU VPO "First Moscow State Medical University named after I.I. THEM. Sechenov” Ministry of Health of the Russian Federation, Moscow, Russia
4 NSMU of the Ministry of Health of Russia, Novosibirsk
5 Belarusian State Medical University, Minsk, Republic of Belarus
6 ME "17th city children's clinical clinic", Minsk, Republic of Belarus
7 ME "13th city children's clinical clinic", Minsk, Republic of Belarus
Introduction: the diversity of respiratory viruses and the immaturity of the immune system in children determine the search for an effective and safe broad-spectrum antiviral drug for the treatment of acute respiratory viral infections (ARVI) in the pediatric population.
Purpose of the study: to study the effect of release-active antibodies to interferon gamma (RA antibodies to IFNγ ) for various acute respiratory viral infections, including influenza.
Material and methods: The randomized controlled trial included 569 outpatients aged 3 to 12 years with influenza/ARVI during the first day from the onset of the disease. Verification of the pathogen in nasopharyngeal samples was carried out by real-time RT-PCR (real-time PCR). Patients were randomized into 2 groups (1:1) and received as part of complex therapy (antipyretics, expectorants, mucolytics, decongestants) Anaferon for children or placebo. The duration of treatment was 5 days, observation - 14 days. As a primary criterion for effectiveness, the average duration of the disease was assessed. In patients with detected influenza viruses, the viral load was additionally assessed on the 3rd, 5th and 7th days of observation.
Research results: ITT analysis included data from 498 patients (n=258, Anaferon group for children; n=240, placebo group). Pathogens were identified: influenza A virus - in 80 (16.1%), influenza B - in 24 (4.8%), rhinovirus - in 74 (14.9%), respiratory syncytial virus - in 39 (7, 8%), metapneumovirus - in 36 (7.2%), parainfluenza - in 25 (5.0%), adenovirus - in 22 (4.4%); in 208 patients (41.8%) no viruses were detected. The use of Anaferon for children contributed to a reduction in the duration of the disease (4.6±1.4 days) compared with the placebo group (4.9±1.3 days), p=0.0242 and a decrease in viral load (viral RNA concentration for influenza A viruses /V on the 7th day of observation was 2.1±2.4 versus 4.0±1.5, p=0.0011).
Conclusion: it has been proven that the inclusion of Anaferon for children in the complex therapy of acute respiratory viral infections in children provides a faster recovery and more effective elimination of influenza A / B viruses from the nasopharyngeal mucosa. A limitation of this study is the lack of information on influenza vaccination.
Keywords: influenza, acute respiratory viral infections, children, antiviral therapy, gamma interferon, randomized placebo-controlled trial, Anaferon.
For citation: Zaplatnikov A.L., Blokhin B.M., Geppe N.A., Kondyurina E.G., Sukalo A.V., Voitovich T.N. Results of an international multicenter study of release-active antibodies to interferon gamma in the treatment of influenza and acute respiratory viral infections in children // BC. Medical review. 2019. No. 8. pp. 18-24
An international multicenter study of release-active antibodies against interferon gamma for flu and acute respiratory viral infections in children
A.L. Zaplatnikov 1 , B.M. Blokhin 2, N.A. Geppe 3, E.G. Kondyurina 4 , A.V. Sukalo 5,6 , T.N. Voytovich 5.7
1 Russian Medical Academy of Continuous Professional Education, Moscow
2 Pirogov Russian National Research Medical University, Moscow
3 Sechenov University, Moscow
5 Belarusian State Medical University, Minsk, Belarus
6 17th City Children Outpatient Department, Minsk, Belarus
7 13th City Children Outpatient Department, Minsk, Belarus
background: the diversity of respiratory viruses and immaturity of immune system in children require an effective and safe broad-spectrum antiviral agent for acute viral respiratory infections in children.
aim: to study the effect of release-active antibodies to interferon gamma on the course of various acute respiratory viral infections including flu.
Patients and Methods: 569 outpatients aged 3–12 years with flu / acute respiratory viral infection within the first few days of illness were enrolled in this randomized controlled study. Causative agent was verified by real-time PCR in nasopharyngeal swabs. The patients were randomized (1:1) to receive complex treatment (expectorants, mucolytic agents, decongestants, and Anaferon for children) or placebo. Treatment duration was 5 days, follow-up was 14 days. The primary efficacy endpoint was the average duration of disease. In patients with verified influenza virus, viral load was measured on days 3, 5, and 7 of the follow-up.
Results: ITT analysis included 498 patients (Anaferon for children group, n=258; placebo group, n=240). Influenza A virus was identified in 80 patients (16.1%), influenza B virus in 24 patients (4.8%), rhinovirus in 74 patients (14.9%), respiratory syncytial virus in 39 patients (7.8%), metapneumovirus in 36 patients (7.2 %), parainfluenza virus in 25 patients (5.0%), and adenovirus in 22 patients (4.4%). In 208 patients (41.8%), no viruses were identified. Anaferon for children has reduced the duration of disease (4.6±1.4 days in the study group and 4.9±1.3 days in placebo group, p=0.0242) and viral load (on day 7 of the follow-up, RNA concentrations of influenza A and B viruses were 2.1±2.4 and 4.0±1.5, respectively, p=0.0011).
Conclusion: Anaferon for children in the complex treatment of acute respiratory viral infections in children has provided more rapid recovery and more effective eradication of influenza A and B viruses from nasopharyngeal mucosa. The limitation of this study was the lack of the information on flu vaccination.
keywords Key words: flu, acute respiratory viral infections, children, antiviral treatment, interferon gamma, randomized placebo-controlled study, Anaferon.
For quote: Zaplatnikov A.L., Blokhin B.M., Geppe N.A. et al. An international multicenter study of release-active antibodies against interferon gamma for flu and acute respiratory viral infections in children. RMJ. medical review. 2019;8:19–24.
The article presents the results of an international multicenter study evaluating the effectiveness of release-active antibodies to interferon gamma in the treatment of influenza and acute respiratory viral infections in children.
Introduction
Influenza and other acute respiratory viral infections (ARVI) are the most common diseases in the child population. Annual outbreaks of acute respiratory viral infections are caused by respiratory viruses of 5 groups, including more than 300 subtypes, which determines a variety of clinical symptoms, on the one hand, and the complexity of etiotropic therapy and vaccination, on the other. The most severe forms of respiratory infections are caused by influenza viruses. Of particular danger are pandemic strains of the influenza virus. Other SARS caused by various respiratory viruses are also characterized by high contagiousness, the formation of mixed infections and the development of secondary bacterial complications.
Etiotropic therapy for ARVI is quite difficult to carry out, since the choice of a doctor is limited to neuraminidase inhibitors active against influenza viruses, and drugs whose antiviral effect is mediated by interferon-inducing or other primary effect. In recent years, it is endogenous interferon inducers that have become the drugs of choice for the treatment of influenza and other acute respiratory viral infections in outpatient practice, which is primarily due to the ability to provide an antiviral response against a wide range of pathogens.
It is known that the key cytokine of the antiviral immune response is interferon gamma (IFNγ); its cellular effects are diverse and include regulation of viral antigen recognition, participation in antigen processing and antigen presentation, activation of microbicidal effector functions, influence on leukocyte migration, integration of functions of other cytokines, etc. . Targeted action on IFNγ and target-associated receptors is a distinctive feature of Anaferon for children, created by Materia Medica Holding LLC based on antibodies to IFNγ. The most important effect of the drug in the treatment of influenza and other acute respiratory viral infections is the adequate production of endogenous interferons, including IFNγ and IFNα / β, which in most cases ensures a mild or abortive course of a viral infection.
The antiviral activity of Anaferon for children during therapeutic, prophylactic and therapeutic administration has been proven in a series of preclinical studies under conditions of infection of experimental animals with influenza viruses, including influenza A (H1N1)
pdm09 . Therapeutic efficacy has been demonstrated in randomized clinical trials, which involved more than 11 thousand children aged 1 month. and older with respiratory infections caused by various respiratory viruses.
Purpose of the study: obtaining additional data on the therapeutic efficacy of Anaferon for children, taking into account the etiology of acute respiratory viral infections, as well as data on its effect on the rate of elimination of influenza viruses from the nasopharyngeal mucosa.
Material and methods
A multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial was conducted at 29 outpatient centers in the Russian Federation, Belarus, and Ukraine from October 2014 to April 2018 during the seasonal rise in incidence.
The study included children of both sexes aged 3 to 12 years with clinical manifestations of influenza/ARVI during the first day from the onset of the disease.
Inclusion criteria were: a clinically established diagnosis of SARS (body temperature at least 38 °C at the time of examination, symptom severity ≥4 points: at least 1 general symptom ≥2 points and 1 symptom of the nose / throat / chest ≥2 points or more symptoms severity ≥1 point), the first 24 hours from the onset of influenza/ARVI manifestations, the possibility of starting therapy within a day from the onset of the first symptoms of SARS.
Exclusion Criteria were: the presence of indications for hospitalization or the appointment of antibacterial drugs, suspicion of initial manifestations of diseases that have symptoms similar to ARVI (other infectious diseases, influenza-like syndrome at the onset of systemic connective tissue diseases), primary or secondary immunodeficiency, a history of oncological and autoimmune diseases, polyvalent allergy, intolerance to any component of the drugs used in the treatment, malabsorption syndrome, exacerbation or decompensation of a chronic disease, taking prohibited concomitant drugs for 1 month. prior to inclusion in the study, as well as a mental disorder or alcohol/drug abuse of the patient's parents/adoptive parents.
The design of the study is presented in detail in Table 1. After signing the informed consent form, screening procedures were carried out, including: collection of complaints and anamnesis, physical examination, collection of nasopharyngeal biosamples for rapid diagnosis of influenza and subsequent detection of respiratory virus antigens, registration of influenza/ARVI symptoms.
The results of an objective examination were noted in the primary documentation, the severity of influenza/ARVI symptoms was recorded in points in an individual registration card. Parents (legal representatives) of the patient were given a diary and instructed how to fill it out. It noted the values of axillary body temperature (daily in the morning and evening) and the severity of the main symptoms of SARS in points (from 0 to 3). Based on the severity of each of the symptoms, during the subsequent statistical processing of the data, the total influenza/ARVI severity score was calculated, which included body temperature, general symptoms, and symptoms from the nose / throat / chest, converted into points (Table 2).
Express diagnostics of influenza was carried out according to the results of a qualitative immunochromatographic study of a nasal swab, which makes it possible to determine the presence of influenza A/B antigens within 10 minutes. In patients with a positive rapid influenza test, a nasopharyngeal swab was taken for subsequent real-time quantitative polymerase chain reaction (PCR) with real-time reverse transcription (real-time RT-PCR), which allows determining the viral load (concentration of influenza A / B viral RNA log 10 copies/mL) in nasal and throat swab specimens.
In patients with a negative rapid test for influenza, a qualitative PCR was performed to detect and identify other pathogens of acute respiratory viral infections (RNA of respiratory syncytial virus, metapneumovirus, parainfluenza viruses types 1, 2, 3 and 4, coronaviruses, rhinoviruses, adenovirus and bocavirus DNA).
If the inclusion criteria were met and there were no non-inclusion criteria at visit 1 (day 1), the patient was randomized into 1 of 2 groups: patients of the 1st group took Anaferon for children according to the following scheme: inside, without food, 1 tablet per dose, in the first 2 hours every 30 minutes, then until the end of the day 3 more times at regular intervals, from the 2nd to the 5th day - 1 tablet 3 rubles / day. Duration of therapy - 5 days. Patients of the 2nd group received a placebo, similar in appearance and organoleptic properties to the study drug, according to the regimen of Anaferon for children for 5 days. This study used a double-blind placebo control. The patient and the physician were not informed about the prescribed study therapy (Anaferon for children or placebo) until the study was completed and the database was closed.
Patients of both groups could receive symptomatic therapy for ARVI and influenza, based on accepted standards of treatment, including expectorants, mucolytics, nasal decongestants, if necessary, detoxification therapy, with the development of bacterial complications of influenza/ARVI, antibacterial drugs. The following antipyretics have been approved for fever > 38.5°C (or 38.0°C in patients with chronic lung, heart, or nervous system disease): paracetamol 120 mg/ml, ibuprofen 100 mg/5 ml, metamizole sodium (to provide emergency care for hyperthermia that is not controlled by paracetamol / ibuprofen, parenterally). Permitted antipyretics were given to parents at the first visit. Other antipyretics, all antivirals (except the study drug), immunostimulants and immunosuppressants, immune sera and immunoglobulins, vaccines, anticancer drugs were prohibited.
The observation period was 14 days. A total of 5 visits were made: visits on days 1, 3, 5 and 7 at the medical center or at home and delayed telephone contact with the doctor on day 14 to ask parents about the patient's condition, the presence / absence of bacterial complications the use of antibacterial drugs.
Performance criteria (primary and secondary points)
The primary efficacy criterion was the average duration of the disease until the resolution of ARI symptoms (temperature ≤37.2 °C and the absence or total severity of all ARI symptoms ≤2 points). Secondary endpoints were: the proportion of patients with recovery/improvement on days 2–5 of follow-up (according to the patient's diary), on days 3 and 5 of treatment (according to an objective examination by a doctor), fever dynamics (change in temperature by 2, 3, 4 and 5 days of observation compared with baseline), the proportion of patients with normalization of body temperature on days 2–5 of observation (≤37.0 °C), severity of clinical manifestations (in points) and course influenza/ARVI (according to the results of the area under the curve for the total severity index on days 1, 3, 5 and 7, according to the objective examination of the doctor, and from the 1st to the 7th day according to the patient's diary), the number of antipyretic doses drugs, dynamics of viral load, the proportion of patients in whom worsening of the disease was noted (bacterial complications, hospitalization).
Sample size determination and statistics
The estimation of the sample size for the efficiency analysis was based on the following rules and assumptions: the power of statistical tests, calculated by the formula P = (1 - β), was taken equal to 80% (the probability of correct rejection of the null hypothesis is 0.8); the probability of an error of the first kind "α" was allowed to be less than 5% (the probability of an erroneous acceptance of an alternative hypothesis was less than 0.05); the statistical tests used were two-tailed.
When calculating the sample size, it was assumed that the difference between the average duration of the disease in the Anaferon for children group and in the placebo group would be at least 0.5 days, and the standard deviation in both groups would not exceed 2 days.
Based on the rules and assumptions described above, the minimum required size for each of the groups (Anaferon for children and Placebo) was 254 people. Based on an in-study dropout rate of 10% and a screening dropout rate of 20%, enrollment of at least 672 patients was agreed.
Data processing and all statistical calculations for this protocol were carried out using the SAS 9.4 statistical package. To compare the proportions (percentages) in 2 groups, frequency analysis was used: Fisher's exact test; modification of the χ 2 test for multiple comparisons (Cochran - Mantel - Hensel; CMH χ 2). The applicability of the Cochran-Mantel-Haenszel test was tested using the Breslow-Day test. To compare changes in indicators in 2 groups, a two-way covariance analysis (Mixed Procedure in SAS) was used, factors - group (2 levels) and visit (4 levels), covariate - visit 1 (1 level). The Kruskal-Wallace test was used to analyze continuous variables.
Characteristics of the study groups
The period of inclusion of patients in the study was from October 8, 2014 to April 16, 2018. A total of 569 patients were included and randomized in the study (Total set), 290 - to the 1st group (Anaferon for children) and 279 - to the 2nd group (placebo). Data from 71 patients were not included in the efficacy analysis for various reasons: erroneous inclusion of a patient who did not meet the inclusion criteria (n=14, group 1; n=15, group 2), significant deviation from the protocol (n=16, 1 -th group; n=23, 2nd group), the need to prescribe drugs that are unacceptable for use in this study (n=1, 2nd group), the inability or refusal of the parent/adoptive parent of the patient to follow the requirements of the protocol (n= 2, 1st group). Thus, the sample for efficacy analysis consisted of 498 patients (n=258, group 1; n=240, group 2). All patients who received at least 1 dose of study drug (n=569) were included in the safety analysis.
The average age of patients whose data were included in the analysis of efficacy in the study group was 6.8±2.7 years, in the comparison group - 6.7±2.7 years. Boys were 53.2%, girls - 46.8%. Patients of both groups did not differ in age (p=0.5920) and gender (p=0.6537).
35.3% of patients in the Anaferon group for children and 35.7% of the placebo group had concomitant diseases, including diseases of the musculoskeletal system (13.2% and 14.9%, respectively), respiratory diseases, including allergic diseases and ENT pathology (11.2% and 6.2%), congenital, hereditary and genetic diseases (9.7% and 12.0%), eye diseases (5.8% and 5.4%), diseases of the nervous system (5.8% and 5.0%), chronic foci of infection (3.5% and 5.0%, respectively). Frequency analysis (Fischer's exact test) showed that the groups did not differ in the number of patients who had comorbidities and conditions.
At inclusion, all study participants had clinical manifestations typical of influenza/ARVI: fever in combination with other general (intoxication) and respiratory symptoms. The severity of the symptoms of the disease varied widely, since the etiology of SARS and local damage to the respiratory tract was different. The mean body temperature at inclusion in the study was 38.5±0.4 0 C in both groups; the average values of the initial total score of general symptoms - 5.9±2.7 in the 1st group and 5.9±2.9 in the 2nd group (p=0.8377); symptoms from the nose / throat / chest - 5.1±3.0 and 5.3±3.0, respectively (p=0.5462).
Research results
The frequency of detection of various respiratory viruses in nasopharyngeal samples of patients in both groups is shown in Figure 1. Influenza A / B viruses were detected in 19% of children in the 1st group and in 21.3% of patients in the 2nd group (p = 0.5762). Of the other ARVI pathogens, rhinovirus, respiratory syncytial virus, metapneumovirus and adenovirus were most often detected. The frequency of detection of pathogens of influenza and other acute respiratory viral infections in both groups had no significant differences. In 43% of patients in the Anaferon pediatric group and 40.4% of patients in the placebo group, no viruses were detected in nasopharyngeal samples, which is consistent with the results of studies in which the frequency of detection of viral antigens in nasopharyngeal samples using similar reagent kits for real-time RT-PCR did not exceeded 50%. In accordance with the protocol, the data of all patients with clinically diagnosed ARVI were included in the analysis, regardless of the result of real-time RT-PCR.
In both groups, the majority of patients were prescribed approved concomitant medications, mainly antipyretic (>45% of participants) and irrigation-elimination therapy (>70%). Antibacterial drugs of systemic action were prescribed to 2.7% of children in the Anaferon for children group and 4.6% of children in the placebo group. Frequency analysis (Fischer's exact test) showed no differences between groups in the frequency of use of concomitant medications (p=0.18).
Performance analysis
primary endpoint. Evaluation of the results for the primary endpoint showed that the use of RA AT to IFNγ in addition to symptomatic therapy for influenza/ARVI leads to a significant reduction in the duration of the disease, which lasted from 4.4 to 4.8 days in 95% of children (mean value 4.6 ±1.4 days), which was significantly shorter than in the placebo group (4.9±1.3, p=0.0242, Kruskal-Wallace test).
secondary endpoints. An analysis of the effectiveness of secondary endpoints confirmed the benefits of using Anaferon for children. According to the patient's diary, on the 3rd day of treatment, 9.7% of children had an improvement in the symptoms of the disease, which was about 2 times more than in the placebo group (4.6%). On the 4th day, the percentage of children with resolution of ARI symptoms in the 1st group was 23.6%, on the 5th day - 41.5%; (against 16.7% and 35.0%, respectively, in the 2nd group). Analysis using the Cochran - Mantel - Hensel test showed that for all 5 days of treatment with Anaferon for children, the proportion of children with resolution of ARI symptoms was significantly higher than on the background of placebo therapy (p = 0.0026) (Fig. 2).
According to an objective examination by a doctor, 12% of the children in the study group showed resolution of ARI symptoms on the 3rd day of treatment with Anaferon for children, in 45% - on the 5th day, while in the comparison group the proportion of children with recovery/improvement on the 3rd day th day was 6.7%, on the 5th day - 37.5%. The total number of children with recovery/improvement on days 3 and 5, according to the Cochran-Mantel-Haenszel test, also indicated a significant efficacy of the study drug compared to placebo (p = 0.0127).
On the 3rd day of treatment with Anaferon, body temperature values (37.4±0.8), total scores of general symptoms (2.0±2.2) and symptoms from the nose / throat / chest (4.4±2, 9), as well as the total score of all symptoms (7.0±4.6) were lower than in patients of the 2nd group, where the body temperature on the 3rd day was 37.5±0.8, the total score of general symptoms - 2.6±2.8, catarrhal symptoms - 4.8±2.7, total score of all symptoms - 8.1±4.8. According to the patient's diary, the maximum therapeutic effect of Anaferon for children was manifested at the same time (on the 2nd–4th days). As a result of the treatment of RA with antibodies to IFNγ, the severity of the course of influenza/ARVI was significantly less, which was confirmed by the analysis using the "area under the curve" (AUC) model for the total indices of symptoms of the disease according to the objective examination (p = 0.0233) and the data of the patient's diary (p=0.0084).
Additional analysis of nasopharyngeal samples by real-time RT-PCR in patients with a positive rapid test for influenza A/B showed that the viral load was significantly lower during treatment with RA antibodies to IFNγ. Moreover, the dynamics of the decrease in viral load in the study group is shown both separately and in total for influenza A/B viruses (Fig. 3).
Security Analysis
In total, during the period of treatment and observation, 77 adverse events (AEs) were noted in 56 patients, including 31 AEs in 26 (9.0%) patients of the 1st group and 46 AEs in 30 (10.7%) participants of the 2nd group. Various infections were most frequently recorded, including bronchitis (3 in group 1 and 4 in group 2), acute otitis media (4 and 5, respectively), exacerbations of chronic diseases (adenoiditis, pyelonephritis). Gastrointestinal disorders (nausea, diarrhea) were noted in 1.7% of children in group 1 and in 3.6% of children in group 2 (p=0.20). Statistical analysis (Fisher's exact test) showed no significant differences between the number of patients with AE in both groups (p=0.57). The severity of most AEs was mild (48.4% of cases in group 1 and 50.0% in group 2) and moderate (48.4% and 47.8%, respectively); 2 AEs (in the 1st group - intestinal colic, in the 2nd group - nausea) are regarded as severe. A causal relationship of AEs with the study drug was absent (87.1% in group 1 and 84.8% in group 2) or was unlikely (12.9% and 15.2%). In both cases of serious AEs, there was no relationship with taking the drug.
During the study, there were no cases of interaction of the study drug with drugs of various classes, including non-steroidal anti-inflammatory drugs, analgesics, decongestants, antibiotics, bronchodilators, inhaled corticosteroids, muco- and secretolytics.
Treatment with RA antibodies to IFNγ was well tolerated by patients. The mean value of the compliance index was close to 100%.
The discussion of the results
The study proved that the use of Anaferon for children leads to more successful treatment and faster recovery of patients with influenza/ARVI. The positive effect of the drug on the severity of all symptoms, including fever, a decrease in the severity of the course of the disease, as well as a more effective elimination of influenza A / B viruses from the nasopharyngeal mucosa indicate the advantages of including Anaferon for children in the complex of symptomatic therapy for influenza / SARS.
The results of the clinical study confirm the data of previous studies and the experience of clinical practice showing the effectiveness of Anaferon for children in the treatment of influenza and other acute respiratory viral infections.
The advantages of this study are a multicenter double-blind design, sufficient duration (3 epidemic seasons) and the number of participants from different countries.
A limitation of this study was the lack of data on previous vaccination of patients.
Conclusion
Thus, a double-blind, placebo-controlled, randomized clinical trial in the general population of children with a variety of concomitant diseases proved that the inclusion of RA antibodies to IFNγ in the complex therapy of ARVI and influenza contributes to rapid improvement and faster recovery and ensures effective elimination of influenza A / B viruses from nasal mucosa. Anaferon for children is effective and safe in the treatment of influenza/ARVI in children.
Conflict of interest
Anaferon for children is a commercial drug manufactured and sold by LLC NPF Materia Medica Holding. Zaplatnikov A.L., Blokhin B.M., Geppe N.A., Kondyurina E.G., Sukalo A.V., Voitovich T.N. received a research grant from NPF Materia Medica Holding LLC to conduct clinical trials.
Source of financing
The study was funded by a grant from NPF Materia Medica Holding LLC (Moscow, Russia). Statistical analysis and running costs for item processing were provided by OOO NPF Materia Medica Holding.
The study was registered with clinicaltrials.gov (NCT02072174).
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Does Ergoferon help against influenza and other diseases, than some T-lymphocytes look like sentinels, while others look like killers, what are interferons and why, most likely, nothing bad will happen to you with an overdose of Ergoferon, the site found out.
In rainy weather, it is easy to catch a cold even in summer, and now pharmacy visitors are starting to pay attention to antiviral drugs again. One of the leaders in sales in Russian pharmacies, positioning itself as a means for "treatment of influenza and SARS in full", according to analysts of the pharmaceutical market DSM Group, is Ergoferon, which entered the top twenty among all drugs, and as an antiviral is second only to Ingavirin and Kagocel .
Unlike the previous heroes of the “What are we being treated for” column, as many as four completed studies are devoted to Ergoferon, registered in the register of the Ministry of Health, however, it is often equated with drugs with unproven effectiveness. Let's see who is right here.
From what, from what
The instruction to Ergoferon reports that the drug works due to three components: antibodies to interferon gamma, histamine and CD4. The fact that histamine is associated with inflammation - the body's response to damage or foreign substances - we talked about in a note about Suprastin, but let's dwell on the other components in a little more detail.
These beautiful "ribbons", as if created for rhythmic gymnastics, depict the structural elements of a protein molecule. Interferons are released in the body in response to invading viruses and other infections. These substances were discovered by accident, when scientists in the middle of the last century noticed that laboratory mice that fell ill due to one virus did not become infected with a second one immediately after that. It turned out that interferons signal the cells around to be on the alert, not to stick out and prepare for a siege. True, since many molecules in our body have a far from one function, it is necessary to intervene in the work of the immune system with great care.
The interferon-gamma in question is one of the most classic "immune" interferons. It is produced by T-helpers - lymphocytes, the "sentinel" of our immunity, which notice the intruder and call for help a whole army of other cells to deal with it. To be more precise, these are T-helpers of the first type, which, releasing gamma-interferon, call for help their "brothers" - T-killers, who kill infected fellows in the body (as well as cancer cells) in order to prevent the infection from spreading.
T-helpers and some other cells of the immune system wear "breastplates" - CD4 receptors (cluster of differentiation 4). These proteins are partly immersed in the membrane, partly sticking out. They help the T-cell receptor (TCR) “pick up” what other cells show them on the “screening”, when sentinel-T-helpers go around their possessions, checking if the inhabitants of the body are hiding a “prohibition” like a virus or some wrong proteins behind its membrane.
So, the active ingredients of Ergoferon, as it has long been established, are associated with immunity. There are treatments associated with the introduction of interferons. The combination of these words with the word “antibodies” sounds even better, which in the brain of the majority also lies on the shelf “immunity”.
The Magic of Numbers
Antibodies do help the immune system work, but only if they need to neutralize or poison a virus or bacterium. But they're designed to bind to... the molecules in our immune system that it uses to protect itself. That is, their goal is to block the "communication" of immunity cells and "plug" their hooks needed to pick up and check what they are shown during the inspection. Will it do any harm?
To understand this, it is worth considering how many active ingredients are contained in the preparation. Let's remember the school chemistry course and count.
According to the instructions for Ergoferon, each of the three medicinal components-antibodies in the preparation contains 0.006 g. We will take the approximate atomic mass of the antibody as 150 kilodaltons (this number is obtained by dividing the total mass of all antibody atoms by 1/12 of the mass of a carbon atom). This value is numerically equal to the molar mass, showing how many grams are contained in one mole of a substance. This unit of measurement shows the ratio of grams and molecules. That is, in one mole of antibodies to CD4 there will be 150,000 grams. Manufacturers took 0.006 g, which means we are dealing with 4 * 10 -8 moles.
6.022 * 10 23 mol -1 - how many atoms, molecules or ions are contained in the amount of a substance equal to one mole. So, in 4 * 10 -8 mol we will find 4 * 10 -8 6,022 10 23 \u003d 24.088 * 10 15 molecules of the active substance. It is several orders of magnitude less than in a drop of water, but still a lot (water, whatever one may say, has much smaller molecules).
Instructions for Ergoferon on the website of the drug
But what kind of asterisks are next to each 0.006 in the instructions? We read a footnote written in small print: “The monohydrate is applied to lactose in the form of a mixture of three active water-alcohol dilutions of the substance, diluted 100 12, 100 30, 100 50 times, respectively.”
Universal breedings
So our 24,088*1015 "anti-CD4 affinity purified antibodies" were diluted 1*10100 times on their way to the tablet. When dividing, the degrees are subtracted, and we get 24.088 * 10 -85. That is, at such a concentration, out of 1 * 10 85 molecules of what the Ergoferon tablet was anointed with, only 24 would be the active ingredient. But there is a small problem: there are only about 10 80 particles in the visible Universe. In order to meet 24 anti-CD4 antibody molecules at such a concentration, one would have to make one hundred thousand observable Universes, entirely consisting of the “active component” of Ergoferon.
Unfortunately, even in the five tablets that manufacturers recommend taking in the first two hours after the onset of acute symptoms, you are unlikely to be lucky to meet them.
It must be admitted that the other two antibodies - to human interferon gamma and to histamine - are less diluted, but still present in no less homeopathic concentrations. For example, in the most “dense” version (human gamma-interferon), one molecule must still get into the observed ergoferon Universe. The main and, perhaps, rather curious additional question in this entertaining chemical puzzle is the question of who breeds whom.
That is why an overdose of the drug, as his website honestly reports, does not threaten anything special. If you eat a huge number of tablets, you can earn only "dyspeptic symptoms due to the fillers included in the drug." To enhance the effect, you can also eat a cardboard box: cellulose, for example, in tablets is five times more than the active substance would be up to hundreds of dilutions.
And the most important filler is lactose monohydrate, a derivative of the usual "milk sugar". It will only harm people with lactose intolerance. Ultra-high dilutions, sugar balls… Doesn't it remind you of anything? Usually such drugs are called homeopathy, but the manufacturer did not mention this either on the site or in the studies.
In the lists (not) appeared
In the terminological framework of evidence-based medicine, homeopathy is a pseudoscientific method of treatment that has nothing to do with evidence-based medicine and has not proven its superiority over placebo.
However, in order for the Ministry of Health to register a drug as a medicine, it needs to pass clinical trials (although the requirements for them in Russia are often lower than in most developed countries). There are four completed and three ongoing studies on the approved clinical trial registry.
There are more than eight articles in the PubMed database of medical research. The first link leads us to the journal Antiviral Research, which is in English and has an impact factor approaching 5, which is not bad for a medical scientific journal.
The impact factor is an indicator that reflects the frequency of citation of articles in a scientific journal for a certain period (usually two years). For example, for one of the largest medical journals, The Lancet, the impact factor is 44.0, while the average for good journals is 4.
In the course of the study, physicians compared the effectiveness of Ergoferon and Anaferon against rhinoviruses in vitro and in mice. The article says that thanks to Ergoferon, the body releases more interferon-beta, and interferon-gamma, on the contrary, less, but not significantly. Normally, interferon-beta is produced in large quantities by fibroblasts, and one of these types is used in drugs for the treatment of multiple sclerosis, so it is not entirely clear how this, together with a decrease in the concentration of interferon-gamma, should help against influenza. The article does not indicate in what concentration Ergoferon was used (maybe not in homeopathic) and in what it was dissolved, but it is indicated that the drug manufacturers financed the study.
I checked the effect of antibodies to CD4 on human leukocytes. But here we are talking not only about the whole person, but also about a substance that is too diluted to be present in Ergoferon tablets.
The next test was already carried out on humans. According to the manufacturers, it was randomized, double-blind and controlled, and the drugs were administered automatically through a telephone answering machine.
A double-blind, randomized, placebo-controlled method is a method of clinical drug research in which subjects are not privy to important details of the study being conducted. “Double blind” means that neither the subjects nor the experimenters know who is being treated with what, “randomized” means that the distribution into groups is random, and placebo is used to show that the effect of the drug is not based on autosuggestion and that this medicine helps better than a tablet without active substance. This method prevents subjective distortion of the results. Sometimes the control group is given another drug with already proven efficacy, rather than a placebo, to show that the drug not only treats better than nothing, but also outperforms analogues.
However, it should be understood that, at least, patients could easily distinguish what they were taking: everyone received either the already known antiviral drug Oseltamivir (Tamiflu) twice a day, or Ergoferon - according to a more complex regimen. In addition, patients were given antipyretics (non-steroidal anti-inflammatory drugs) and other basic flu medications. But to assess the quality of treatment, they chose mainly subjective indicators: not the death of viruses, but patients' reports of well-being. The most objective criterion was a decrease in temperature (but do not forget that both groups used antipyretics). The study involved 158 people.
All co-authors, except for one, either received a grant from Materia Medica Holding (manufacturers of Ergoferon) or work there (and one even is the head of the company), which indicates the possibility of bias in the results. The conclusion is that Ergoferon is in no way inferior to Oseltamivir.
Another study again talks about the effectiveness of Ergoferon compared to Tamiflu, but this time in mice. Here they are again injected with four milliliters, the concentration is again not specified.
And now a little surprise: all these studies were carried out in 2016-2017, while the drug began to be sold already in 2011.
Too "sighted" statistics
But there are three studies that made it to PubMed earlier: in 2011, 2012 and 2014. All of them are published in the peer-reviewed Russian journal "Antibiotics and Chemotherapy" in Russian. The impact factor of this journal is 0.426 (according to the RSCI), and for obvious reasons there is no international citation.
He talks about the study of the effect of Ergoferon on "optimization of therapy for influenza and SARS", conducted in just one medical center on 100 patients. The authors honestly admit that it was open, not blind. This leaves a loophole for the deliberate or accidental influence of doctors on the result (for example, prescribing Ergoferon to patients who give more hope for a speedy recovery). According to its results, the drug significantly contributes to a faster treatment than when taking a placebo, but the risk of error and bias is too high here (and let's not forget the concentration of the active substance in tablets, which is not very conducive to effectiveness).
The second study, comparing the effectiveness of Ergoferon and Tamiflu, included a total of 52 patients from eight medical centers. The study was not double-blind, and the drugs themselves, the pills and regimens of which differ, would be difficult to confuse. The only way to "blind" him is to give one group Tamiflu at the same time as a placebo that looks and is taken like Ergoferon, and vice versa, but the doctors did not do this.
The third study was a multicenter, double-blind, placebo-controlled, and randomized study. It tested how Ergoferon helps treat influenza in children. It included 162 participants from 13 health centers. This study also evaluates recovery by “improvement” (a rather vague criterion, you must admit), but in this case, the placebo and drug regimen is the same there, which can be called the dignity of the study. Body temperature was also used there, and antipyretics were also used. The observations were carried out according to the patient's diary and the doctor's examination, and according to the second indicator, the effectiveness of Ergoferon and placebo was almost equivalent. By the way, the third study was conducted on the liquid form of Ergoferon, but the article does not indicate in what proportion the drug was diluted.
The low concentration of the active substance, as well as the fact that the substance itself, even if it got into a tablet, should play more for viruses than for immunity (“like is treated with like”), makes Ergoferon a classic homeopathic remedy, although on the packaging it is not specified at all.
They argue about homeopathy for a long time, breaking spears, but it should be remembered that official science cannot recognize as a medicine something in which the molecule of the active substance, according to the manufacturer, has not even been. Homeopaths sue their opponents (for example, Vokrug Sveta magazine), trying to prove that their drugs work, but with carefully collected statistics and correct research methods, sugar balls do not work better than placebo. If the reader has a vivid imagination, he might as well believe in the healing powers of raspberry jam tea. Compared to cellulose, which is much more in a tablet than the active ingredient, it is at least more pleasant to use it during a cold, and folk remedies known to everyone and falsification of scientific research at the Presidium of the Russian Academy of Sciences warn against taking homeopathic remedies for the treatment of influenza, tuberculosis, childhood diarrhea , malaria and other serious diseases.
Few people would think of treating tuberculosis or malaria with homeopathy, but with influenza and diarrhea, everything is much less obvious. Moreover, in all three incomplete studies of Ergoferon on the website of the Ministry of Health, we are talking about them, and in the instructions these two diagnoses appear as indications for use.
"Anaferon for children" is one of the many products of the "Materia Medica" company, which can be bought without a prescription at any pharmacy. I am sure that the reader has heard about this remedy for colds, flu and other acute respiratory diseases, and maybe even treated it.
The description of this “drug” says that it contains active components - “antibodies to human gamma interferon affinity purified - 0.003 g”. Further in small print: "active form with a content of not more than 10-16 (ten to minus sixteenth) ng / g of active ingredient." A nanogram is one billionth of a gram, and if you multiply all these numbers and take into account the mass of the tablet, it turns out that it should not contain even one molecule of any antibodies to interferon or other active substance. For 200 rubles, a concerned parent buys his child 20 tablets, consisting of excipients: lactose monohydrate (0.267 g), microcrystalline cellulose (0.03 g) and magnesium stearate (0.003 g). In other words, you buy milk sugar at a price of 37,400 rubles per kilogram.
The company calls its drugs "release-active". They are sold exclusively in Russia (and a number of CIS countries), Mexico, Mongolia and Vietnam. And only the Russians spend several billion rubles a year on them. Someone will decide that if the drugs did not work, they would not be so popular! But it's very easy to explain.
While conscientious drug manufacturers need to find new active ingredients, produce them and conduct expensive clinical studies, sugar merchants have only one significant item of expenditure - advertising. Therefore, praise for the preparations of the "Materia Medica" can be found everywhere: from newspapers to central television channels. Now imagine that someone believes such advertising and begins to treat the flu or a cold with sugar. In most cases, the disease will go away on its own (as in a joke: with treatment, a cold goes away in a week, without treatment in seven days). In this case, the patient may mistakenly assume that the drug helped him. He does not know that even without the miraculous medicine he would have recovered just as quickly. Therefore, some people will continue to be treated with Anaferon, sincerely confident that the drug helps them. Well, we will not hear the voices of those who still could not overcome the disease.
Due to the complex dynamics of well-being in many diseases, it is very difficult for a person to understand which remedy works and which does not. Especially if it is based solely on personal experience. Let me explain with an example I used in the book Defense Against the Dark Arts:
“In 2011, The New England Journal of Medicine published an article comparing the effectiveness of four approaches for treating asthma: the bronchodilator drug Salbutamol, placebo inhalation, sham acupuncture, and no treatment. Each patient was treated with all four approaches separately, in random order. Objective spirometry data (volume and speed of breathing) showed that the drug helps, while the other three approaches are equally ineffective. However, according to the subjective feelings of patients, all three methods of active therapy helped equally well compared to no treatment at all.
This is why carefully designed clinical trials involving large numbers of patients are needed to understand which drugs work and which do not.
Of course, there are a lot of companies selling empty shells and taking advantage of the aforementioned ignorance of citizens. And it would be strange to single out only one “Materia Medica”. Those who wish can familiarize themselves with the list of popular drugs that do not have proven effectiveness. But scientists are outraged not only by misleading patients, but also by the fact that their manufacturing company is trying to promote dubious “release activity” research and pass it off as science.
Most of the "scientific" articles devoted to the release-active preparations of "Materia Medica" were published in the domestic journal, included in the list of the Higher Attestation Commission - "Bulletin of Experimental Biology and Medicine". Director of the company, Corresponding Member of the Russian Academy of Sciences Oleg Epshtein in 2003 became the author of 49 articles (!) in this journal. They all appeared under the cover of a special issue that Epstein also edited. Soon he defended his doctorate.
A detailed critique of the “release activity” phenomenon can be found in the article “The Epstein Challenge” by Nikita Khromov-Borisov and Mikhail Arkhipov. Criticisms of some of Epstein's work have also been published in international peer-reviewed scientific journals, such as with medical chemist Evgenia Dueva in the Journal of Medical Virology. But today I will limit myself to just a few quotes from Oleg Epshtein's article "The Phenomenon of Release Activity and the Hypothesis of "Spatial" Homeostasis", which will probably shock any biologist. For the rest, I will explain that an absolutely meaningless combination of real and invented terms will follow below.
"... We believe that the genome does not generate a new physical entity -" field ", but integrates the body into a supramolecular" ether ", which provides the structural basis for the integral regulation of the body." "The genetic code of any individual is not just the primary sequence of nucleotides, but their unique integral (holographic) spatial organization, which has its own set of subtle - supramolecular - vibrational characteristics." “DNA transmitted from generation to generation is capable of preserving general species spatial parameters in its oscillatory structure and, in fact, provides a “connection” of the future organism to the general species spatial matrix that has evolved at the supramolecular level.”
In some ways, this is reminiscent of the arguments of another well-known figure of pseudoscience - Pyotr Garyaev, the author of the concept of the "wave genome", spreading the idea that the mat destroys DNA. Alas, as was shown in the article by psychologist Gordon Pennycock and his colleagues from the University of Waterloo “On the perception and recognition of pseudo-deep nonsense”, people easily mistake science-like meaningless reasoning (obtained even with the help of a random quote generator) for something reasonable. This, apparently, is the calculation.
On its website, Materia Medica claims to have thirty completed clinical trials. Under the same names as in the State Register of Medicines, 20 of them are registered on the American website clinicaltrials.gov. Nine of them are considered completed, but only one of them has results. There are two possible explanations for the lack of results for the remaining completed studies. Either these results did not pass proper quality control and did not satisfy independent experts, or the authors wanted to hide the results from the regulator.
In the completed study with the results presented, it is only stated that the effectiveness of Ergoferon (another antiviral “release-active” drug of Materia Medika) is comparable to the effectiveness of Oseltamivir (aka Tamiflu). But this hardly speaks of the effectiveness of Ergoferon. The fact is that Oseltamivir was recently downgraded from the list of essential drugs by the World Health Organization to the category of “auxiliary drugs”. It turned out that initially the manufacturer did not provide all the research data, but only a part, thereby significantly overestimating the effectiveness of the drug. The sample size used in the Materia Medica study is small, so it could only reveal very large differences between Ergoferon and Tamiflu, and they may not be due to the fact that Tamiflu, if better than sugar, then not much. In addition, the experimenters and patients knew who was getting which drug, which means that the study was not blind and clean.
The skewed reporting of clinical research data is a common practice of sugar-based drug manufacturers. I will quote the website of the Boiron company, which produces Oscillococcinum:
“On the Cochrane Evidence-Based Medicine website, you can find blind, randomized, placebo-controlled trials of a range of homeopathic medicines showing positive results. In particular, Oscillococcinum appears there with a meta-analysis of six RCTs (randomized controlled trials), being one of only 5 cold medicines mentioned (in addition to Remantadine, Amantadine, Zanamivir and Oseltamivir).”
But if you are not too lazy and open the mentioned meta-analysis on the Cochrane website, then you can read the following:
“Overall, the presentation of study results was insufficient and therefore many aspects of the test methods and results were at an unclear risk of bias. In this regard, we assessed the quality of this evidence/evidence as generally low, therefore it is not possible to draw firm conclusions regarding the use of Oscillococcinum for the prevention or treatment of influenza and influenza-like illnesses.
Here it must be clarified that Oscillococcinum in composition is also sugar, which is sold under the guise of a cure for flu and colds. The active substance in it is an extract from the liver of a duck, which was serially diluted two hundred times one hundred times. This is an even more incredible dilution than the antibodies in Anaferon. The liver of one duck would be enough to treat all the people on our planet with Oscillococcinum until the Sun swallows it. Moreover, even a trillionth of this liver will not be used up by that time. However, "Materia Medica" has a drug for alcoholism - "Proproten-100", where the active substance is applied to lactose after dilution of 10-1991 ng / g. So the battle of sugar titans is almost equal.
The law does nothing to prevent this state of affairs. The general pharmacopoeial monograph "OPS dosage forms for homeopathic medicinal products", in accordance with the requirements of which, according to the federal law "On the Circulation of Medicines" (Federal Law No. 61-FZ of April 12, 2010, current version of December 28, 2017), the drug contains the following indulgence: "In the event that the degree of dilution of the active ingredient does not allow to determine the authenticity or quantitative content, the quality of the drug is evaluated by excipients." I am sure that high-quality sugar is used in these products.
In these incredible dilutions (allegedly enhancing the effectiveness of the remedy) is the whole essence of homeopathy (not to be confused with phytotherapy - herbal treatment). But if "Oscillococcinum" is openly called a homeopathic remedy, then "Materia Medica" went the other way. At least two of the company's drugs (Anaferon and Impaza) were originally registered in Russia as homeopathic, but in 2009 the word "homeopathy" disappeared from their names. Therefore, we will jokingly call "release-active" preparations "shameful" homeopathy.
But the joke no longer seems so funny when you find out that such drugs are supposed to treat not only the common cold, but also tick-borne encephalitis, impotence, diabetes, joint diseases, erectile dysfunction, sleep disorders, obesity, attention deficit disorder, chronic cerebral ischemia, alcoholism, allergies, benign prostatic hypertrophy, and many other health problems.
Classical homeopathy is guided by the principle of “like cures like”: the patient is given a diluted remedy that, undiluted, causes symptoms similar to those that he experiences. In bashful homeopathy, this magical ritual is overgrown with scientism and terms from molecular biology. For example, to treat diabetes, it is necessary to dilute antibodies to insulin receptors. For the treatment of erectile dysfunction - antibodies to the enzyme NO-synthase, which produces nitric oxide - a signal molecule that causes relaxation of the smooth muscles of blood vessels. For the treatment of viral infections - the already mentioned antibodies to interferon - a molecule involved in the body's antiviral response. The funny thing is that even if the dilutions of antibodies were not so fantastic, their most likely fate, when administered orally, is simple digestion.
For all the anti-science of such principles, Epstein's logic is extremely simple. Do you want to come up with your own pseudo-scientific release-active drug and earn billions? Keep the recipe! Pick a molecule in the human body that is involved in some process related to disease. Take antibodies to it and dilute them many, many times, apply on a sugar ball and eat. For example, HIV enters the cells of the immune system by interacting with certain receptors on their surface. We take antibodies to these receptors, dilute them - and the cure for HIV is ready! A cure for cancer? No problem! Often in cancer cells, the gene encoding the p53 protein breaks down - it limits cell division when their DNA is damaged. So, we need antibodies to it. It remains only to cure old age with antibodies to telomerase, an enzyme that lengthens the ends of chromosomes that shorten in the cells of an aging organism.
The fact that release-active drugs are registered and sold in Russia, alas, speaks of a deep crisis in the domestic healthcare system and the need to revise the criteria for drug approval. When the Commission on Combating Pseudoscience and Falsification of Scientific Research issued a memorandum on the pseudoscience of homeopathy, the Ministry of Health announced plans to create a special expert group that would consider the objections raised. Such a group was never created - in any case, the members of the Commission for Combating Pseudoscience did not hear anything about it. We fear that the inaction of the Ministry of Health may be due to the fact that the influence of sugar pill manufacturers turned out to be too great.
On the other hand, the Ministry of Education and Science of the Russian Federation has recently awarded Materia Medica with an "Antipremium" for spreading pseudoscience. This is not the first scandal involving this company. In 2017, under a flurry of angry letters from scientists and students, the organizers of the Day of the Biologist (a traditional holiday of the Faculty of Biology of Moscow State University) withdrew the invitation of the representatives of Materiya Medika with the following words: “Your comments awakened the spirit of justice in the team, we checked the information and came to a collective decision, which the administration also supported that the performance of a company with such a reputation at the Faculty of Biology is unacceptable.”
It's good that at least someone opposes the magic of the XXI century, posing as science and medicine. Every patient has the right to know if a drug is proven to work or if it is a dummy that, according to current scientific understanding, cannot work. The Commission to Combat Pseudoscience is a public organization that does not have funding, so it is difficult for us to oppose something to the advertising power of homeopaths and “shameful homeopaths”. All hope is that readers themselves will tell their friends and relatives about this problem. Only together we can defeat bashful obscurantism.
This article was written by me for the popular science publication "Attic". Original:
