What are 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 in shape, with a notch and a chamfer; on the flat side with a mark there is the inscription MATERIA MEDICA, on the other flat side there is the inscription ANAFERON.
* applied to lactose monohydrate in the form of a water-alcohol mixture containing no 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. - contour cell packaging (1) - cardboard packs.
20 pcs. - contour cell packaging (2) - cardboard packs.
20 pcs. - contour cell packaging (5) - cardboard packs.
pharmachologic effect
When used prophylactically and therapeutically, the drug has an immunomodulatory and antiviral effect. Experimentally and clinically established effectiveness against influenza viruses, parainfluenza, herpes simplex viruses types 1 and 2 (labial herpes), other herpes viruses (varicella, 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 the humoral and cellular immune response. 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 Th2-type immune response: it increases the production of Th1 (IFN γ, IL-2) and Th2 (IL-4, 10) cytokines, normalizes (modulates) the balance of Th1/Th2 activities. Increases the functional activity of phagocytes and natural killer cells (NK cells). Has antimutagenic properties.
Pharmacokinetics
The sensitivity of modern physicochemical methods of analysis (gas-liquid chromatography, high-performance liquid chromatography, gas chromatography-mass spectrometry) does not allow assessing the content of the active components of the drug 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 (chickenpox, labial herpes, genital herpes);
- complex therapy and prevention of relapses of chronic herpesvirus 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 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.
The use of the drug is indicated for children and persons under 18 years of age.
Dosage
The drug is taken orally, not during meals. The tablet should be kept in the mouth until completely dissolved.
ARVI, influenza, intestinal infections, herpesvirus infections, neuroinfections
On the 1st day take 8 tablets. according to the following scheme: 1 tab. every 30 minutes in the first 2 hours (total 5 tablets in 2 hours), then during the same day take another 1 tablet. 3 times at equal intervals. On the 2nd day and further, take 1 tablet. 3 times a 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 for preventive purposes 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 tablet. 8 times/day, then 1 tablet. 4 times/day for at least 3 weeks.
For prevention of relapses of chronic herpes virus infection- 1 tablet/day. The recommended duration of the preventive course is determined individually and can reach 6 months.
When using the drug for treatment and prevention of immunodeficiency conditions, in 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
No cases of overdose have been reported to date. In case of accidental overdose, dyspepsia may occur due to the excipients included in the drug.
Dosage form: lozenges Compound:Active components:
Antibodies to human interferon gamma, affinity purified - 0.003 g*
Excipients: lactose monohydrate 0.267 g, microcrystalline cellulose 0.03 g, magnesium stearate 0.003 g.
* applied to lactose monohydrate in the form of a water-alcohol mixture containing no more than 10-15 ng/g of the active form of the active substance.
Description: Tablets are flat-cylindrical, scored and chamfered, from white to almost white. On the flat side with a mark there is the inscription MATERIA MEDICA, on the other flat side there is the inscription ANAFERON. Pharmacotherapeutic group:Immunomodulators. Antiviral agents ATX:When used prophylactically and therapeutically, the drug has an immunomodulatory and antiviral effect. Experimental and clinical efficacy has been established against influenza viruses, parainfluenza, herpes simplex viruses types 1 and 2 (labial herpes, genital herpes), other herpes viruses (varicella, 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 the humoral and cellular immune response. 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 Th1 and Th2 type of immune response: it increases the production of Th1 (IFNγ, IL-2) and Th2 (IL-4, 10) cytokines, normalizes (modulates) the balance of Th1/Th2 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 relapses 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 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 advised to use the drug Anaferon for children.
Pregnancy and lactation:The safety of Anaferon in pregnant women and during lactation has not been studied. If it is necessary to take the drug, the risk/benefit ratio should be taken into account. Directions for use and dosage:Inside. For one dose - 1 tablet (keep in mouth until completely dissolved - not during meals).
ARVI, influenza, intestinal infections, herpesvirus infections, neuroinfections. Treatment should begin 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 24 hours three more doses are taken at equal 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.
During the epidemic season, for prophylactic purposes, the drug is taken daily once a day for 1-3 months.
Genital herpes. For acute manifestations of genital herpes, the drug is taken at regular intervals according to the following scheme: days 1-3 - 1 tablet 8 times a day, then 1 tablet 4 times a day for at least 3 weeks.
To prevent relapses of chronic herpesvirus infection - 1 tablet per day. The recommended duration of the preventive course is determined individually and can reach 6 months.
When using the drug for the treatment and prevention of immunodeficiency conditions, in 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 for the indicated indications and in the indicated dosages, no side effects were identified.
Manifestations of increased individual sensitivity to the components of the drug are possible.
Overdose:No cases of overdose have been reported to date.
In case of accidental overdose, dyspepsia may occur due to the excipients included in the drug.
Interaction:No cases of incompatibility with other drugs have been identified to date.
If necessary, the drug can be combined with other antiviral, antibacterial and symptomatic agents.
Special instructions:The drug contains lactose monohydrate, and therefore is not recommended for use in patients with congenital galactosemia; glucose malabsorption syndrome or congenital lactase deficiency. Release form/dosage:Lozenges. Package: 20 tablets each in a blister pack made of polyvinyl chloride film and aluminum foil. 1, 2 or 5 blister packs along with instructions for medical use are placed in a cardboard pack. Storage conditions:At a temperature not higher than 25 °C.
5, 7
1 Federal State Budgetary Educational Institution of Further Professional Education RMANPE of the Ministry of Health of Russia, Moscow, Russia
2 Federal State Budgetary Educational Institution of Russian National Research Medical University named after. N.I. Pirogov Ministry of Health of Russia, Moscow, Russia
3 State Budgetary Educational Institution of Higher Professional Education “First Moscow State Medical University named after. THEM. Sechenov" Ministry of Health of the Russian Federation, Moscow, Russia
4 Federal State Budgetary Educational Institution of Higher Education NSMU of the Ministry of Health of Russia, Novosibirsk
5 Belarusian State Medical University, Minsk, Republic of Belarus
6 UZ “17th City Children’s Clinical Clinic”, Minsk, Republic of Belarus
7 UZ "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 ) on the course of 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 using the real-time RT-PCR method. Patients were randomized into 2 groups (1:1) and received Anaferon for children or placebo as part of complex therapy (antipyretics, expectorants, mucolytics, decongestants). The duration of treatment was 5 days, observation - 14 days. The primary efficacy criterion was the average duration of the disease. In patients with identified influenza viruses, the viral load was additionally assessed on days 3, 5 and 7 of observation.
Research results: The ITT analysis included data from 498 patients (n=258, Anaferon group for children; n=240, placebo group). The following 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 to the placebo group (4.9±1.3 days), p=0.0242 and a decrease in the viral load (viral RNA concentration for influenza A viruses /B 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 ARVI in children ensures 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, interferon gamma, randomized placebo-controlled trial, Anaferon.
For quotation: Zaplatnikov A.L., Blokhin B.M., Geppe N.A., Kondurina 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 // RMZh. 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 effective and safe broad-spectrum antiviral agent for acute respiratory viral 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 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 information on flu vaccination.
Keywords: flu, respiratory acute viral infections, children, antiviral treatment, interferon gamma, randomized placebo-controlled study, Anaferon.
For citation: 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. R.M.J. Medical Review. 2019;8:19–24.
The article presents the results of an international multicenter study assessing 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 pediatric population. Annual outbreaks of ARVI 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 vaccine prevention, on the other. The most severe forms of respiratory infections are caused by influenza viruses. Pandemic strains of the influenza virus pose a particular danger. Other acute respiratory viral infections caused by various respiratory viruses are also highly contagious, the formation of mixed infections and the development of secondary bacterial complications.
Etiotropic therapy for ARVI is quite difficult to carry out, since the doctor’s choice 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 inducers of endogenous interferons 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 the functions of other cytokines, etc. Targeted effects on IFNγ and target-associated receptors are a distinctive property of the drug 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 the viral infection.
The antiviral activity of Anaferon for children during therapeutic, prophylactic and therapeutic-prophylactic administration was proven in a series of preclinical studies in conditions of infection of experimental animals with influenza viruses, including influenza A (H1N1)
pdm09. Therapeutic effectiveness was 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 effectiveness of Anaferon for children, taking into account the etiology of ARVI, 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 clinical trial in parallel groups was conducted at 29 outpatient centers in the Russian Federation, Belarus and Ukraine between October 2014 and April 2018 during the seasonal increase 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 ARVI (body temperature of at least 38 °C at the time of examination, severity of symptoms ≥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, the possibility of starting therapy within 24 hours from the onset of the first symptoms of ARVI.
Non-inclusion criteria were: the presence of indications for hospitalization or the prescription of antibacterial drugs, suspicion of initial manifestations of diseases with 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 allergies, intolerance to any component of the drugs used in treatment, malabsorption syndrome, exacerbation or decompensation of a chronic disease, taking prohibited concomitant medications for 1 month. before inclusion in the study, as well as mental disorder or alcohol/drug abuse of the patient's parents/adoptive parents.
The study design is presented in detail in Table 1. After signing the informed consent form, screening procedures were carried out, including: collection of complaints and anamnesis, objective 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 the objective examination were noted in the primary documentation, the severity of influenza/ARVI symptoms was recorded in points in the individual registration card. The patient's parents (legal representatives) were given a diary and given instructions on 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 ARVI in points (from 0 to 3). Based on the severity of each symptom, during subsequent statistical processing of the data, a total score of severity of influenza/ARVI was calculated, which included body temperature values, general symptoms and symptoms of the nose/throat/chest, converted into points (Table 2).
Express diagnosis of influenza was carried out based on the results of a qualitative immunochromatographic study of a nasal swab, which allows one to determine the presence of influenza A/B virus antigens within 10 minutes. In patients with a positive rapid test result for influenza, a nasopharyngeal swab was taken for subsequent 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 pharyngeal swab samples.
In patients with a negative result of a rapid test for influenza, 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, DNA of adenovirus and bocavirus).
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 regimen: orally, without meals, 1 tablet per dose, in the first 2 hours every 30 minutes, then until the end of the day 3 more times at equal intervals, from days 2 to 5 - 1 tablet 3 times a 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 taking Anaferon for children for 5 days. This study used a double-blind placebo control. The patient and physician were not informed about the assigned 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, and, if necessary, detoxification therapy; in the event of the development of bacterial complications of influenza/ARVI, antibacterial drugs. For body temperature > 38.5 °C (or 38.0 °C for patients with chronic diseases of the lungs, heart or nervous system), the following antipyretics were allowed: paracetamol 120 mg/ml, ibuprofen 100 mg/5 ml, metamizole sodium (for emergency care for hyperthermia that cannot be controlled with paracetamol/ibuprofen, parenterally). Approved antipyretics were given to parents at the first visit. Other antipyretics, all antivirals (except for the study drug), immunostimulants and immunosuppressants, immune serums and immunoglobulins, vaccines, and antitumor drugs were prohibited.
The observation period was 14 days. A total of 5 visits were conducted: visits on days 1, 3, 5 and 7 at a medical center or at home and a delayed telephone contact with a doctor on the 14th day to interview parents about the patient’s condition and the presence/absence of bacterial complications. , use of antibacterial drugs.
Performance criteria (primary and secondary points)
The primary criterion for effectiveness 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 observation (according to the patient’s diary), on days 3 and 5 of treatment (according to an objective examination by a physician), dynamics of fever (change in temperature by 2, 3, 4 and 5 days of observation compared to the initial value), the proportion of patients with normalization of body temperature on the 2–5 days of observation (≤37.0 °C), the severity of clinical manifestations (in points) and course influenza/ARVI (based on the area under the curve for the total severity index on days 1, 3, 5 and 7, according to an objective examination by a doctor, and from days 1 to 7 according to the patient’s diary), number of antipyretic doses drugs, dynamics of the viral load, the proportion of patients who experienced worsening of the disease (bacterial complications, hospitalization).
Sample size determination and statistics
The sample size estimate for the effectiveness analysis was based on the following rules and assumptions: the power of statistical tests, calculated using the formula P = (1 - β), was assumed to be 80% (the probability of correctly rejecting the null hypothesis is 0.8); the probability of a type I error “α” was allowed less than 5% (the probability of erroneously accepting an alternative hypothesis was less than 0.05); the statistical tests used were two-sided.
When calculating the sample size, it was assumed that the difference between the average duration of the disease in the Anaferon children's 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 of each group (Anaferon for children and Placebo) was 254 people. With a study attrition rate of 10% and a screening attrition rate of 20%, a minimum of 672 patients were agreed to be included.
Data processing and all statistical calculations for this protocol were carried out using the SAS 9.4 statistical package. To compare proportions (percentages) in 2 groups, frequency analysis was used: Fisher's exact test; modification of the χ 2 test for multiple comparisons (Cochran-Mantel-Haenszel; CMH χ 2). The applicability of the Cochran-Mantel-Haenszel test was checked using the Breslow-Day test. To compare changes in indicators in 2 groups, a two-factor analysis of covariance was used (Mixed Procedure in SAS), 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 for including patients in the study was from October 8, 2014 to April 16, 2018. A total of 569 patients were included and randomized into the study (Total set), 290 into group 1 (Anaferon for children) and 279 into group 2 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 - group; n=23, 2nd group), the need to prescribe drugs to the patient that are unacceptable for use in this study (n=1, 2nd group), the inability or refusal of the patient’s parent/adoptive parent to comply with 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). The safety analysis included data from all patients who received at least 1 dose of study drug (n=569).
The average age of patients whose data were included in the effectiveness analysis in the study group was 6.8±2.7 years, in the comparison group - 6.7±2.7 years. There were 53.2% boys, 46.8% girls. Patients in both groups did not differ in age (p=0.5920) and gender (p=0.6537).
35.3% of patients in the Anaferon children’s group and 35.7% in 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 (Fisher's exact test) showed that the groups did not differ in the number of patients with recorded comorbidities and conditions.
All study participants at inclusion 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 ARVI and local damage to the respiratory tract was different. The average body temperature upon 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 were 5.9±2.7 in group 1 and 5.9±2.9 in group 2 (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 of both groups is presented in Figure 1. Influenza A/B viruses were detected in 19% of children in group 1 and in 21.3% of patients in group 2 (p = 0.5762). Among other pathogens of ARVI, rhinovirus, respiratory syncytial virus, metapneumovirus and adenovirus were most often detected. The frequency of detection of influenza and other acute respiratory viral infections in both groups did not have significant differences. In 43% of patients in the Anaferon children's group and 40.4% of patients in the placebo group, viruses were not 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 was not exceeded 50%. In accordance with the protocol, the analysis included data from all patients with clinically diagnosed ARVI, regardless of the result of real-time RT-PCR.
In both groups, the majority of patients were prescribed approved concomitant medications, mainly antipyretics (>45% of participants) and irrigation-elimination therapy (>70%). Systemic antibacterial drugs were prescribed to 2.7% of children in the Anaferon children's group and 4.6% of children in the placebo group. Frequency analysis (Fisher'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 end point showed that the use of RA antibodies to IFNγ in addition to symptomatic treatment of influenza/ARVI leads to a significant reduction in the duration of the disease, which in 95% of children lasted from 4.4 to 4.8 days (average 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. Analysis of effectiveness for 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 symptoms of the disease, which was approximately 2 times more than in the placebo group (4.6%). On the 4th day, the percentage of children with resolution of ARI symptoms in group 1 was 23.6%, on the 5th day - 41.5%; (versus 16.7% and 35.0%, respectively, in group 2). Analysis using the Cochran-Mantel-Haenszel test showed that for all 5 days of treatment with Anaferon for children, the proportion of children with resolution of ARI symptoms was significantly greater than during placebo therapy (p = 0.0026) (Fig. 2).
According to an objective examination by a doctor, 12% of children in the study group showed resolution of ARI symptoms on the 3rd day of treatment with Anaferon for children, 45% - on the 5th day, while in the comparison group the proportion of children with recovery/improvement on the 3rd day the 1st 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 effectiveness of the study drug compared to placebo (p = 0.0127).
On the 3rd day of treatment with Anaferon, the values of body temperature (37.4±0.8), total scores of general symptoms (2.0±2.2) and symptoms of 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 group 2, where 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 manifested itself in the same time frame (on days 2–4). As a result of treatment of RA with antibodies to IFNγ, the severity of influenza/ARVI was significantly less, which was confirmed by analysis using the “area under the curve” (AUC) model for the total indices of disease symptoms according to an objective examination (p = 0.0233) and data from the patient’s diary (p=0.0084).
Additional analysis of nasopharyngeal samples using real-time RT-PCR in patients with a positive rapid test for influenza A/B showed that during RA treatment with antibodies to IFNγ, the viral load was significantly lower. 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
A total of 77 adverse events (AEs) were noted in 56 patients during the treatment and observation period, including 31 AEs in 26 (9.0%) patients of group 1 and 46 AEs in 30 (10.7%) patients. 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) did not show significant differences between the number of patients with AEs 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 (intestinal colic in group 1, nausea in group 2) were assessed as severe. There was no cause-and-effect relationship between the AE and the study drug (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 connection with 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 of RA with anti-IFNγ antibodies was well tolerated by patients. The average compliance rate 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, reduction in the severity of the disease, as well as more effective elimination of influenza A/B viruses from the nasopharyngeal mucosa indicate the advantages of including the drug Anaferon for children in the complex of symptomatic treatment of influenza/ARVI.
The results of the clinical study confirm the data of previous studies and clinical experience showing the effectiveness of the drug Anaferon for children in the treatment of influenza and other acute respiratory viral infections.
The advantages of this study are the 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 the patients' previous vaccination history.
Conclusion
Thus, a double-blind, placebo-controlled, randomized clinical trial in the general population of children with various concomitant diseases proved that the inclusion of RA antibodies to IFNγ in the complex therapy of ARVI and influenza promotes rapid improvement and faster recovery and ensures effective elimination of influenza A/B viruses with nasopharyngeal mucosa. The drug 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 produced and sold by LLC NPF Materia Medica Holding. Zaplatnikov A.L., Blokhin B.M., Geppe N.A., Kondurina 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 article processing were provided by NPF Materia Medica Holding LLC.
The study was registered on clinicaltrials.gov (NCT02072174).
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Does Ergoferon help against the flu and other diseases, why are some T-lymphocytes like sentinels and others like killers, what are interferons and why, if you overdose on Ergoferon, most likely nothing bad will happen to you, the site found out.
In rainy weather, it is not difficult to catch a cold even in summer, and now pharmacy visitors are beginning to again pay attention to antiviral drugs. One of the leaders in sales in Russian pharmacies, positioning itself as a means for “the treatment of influenza and ARVI in full,” according to pharmaceutical market analysts DSM Group, is Ergoferon, which is among the top twenty among all drugs, and as an antiviral it is second only to Ingavirin and Kagocel .
Unlike the previous heroes of the “What are we being treated with” column, as many as four completed studies, registered in the Ministry of Health registry, are devoted to Ergoferon, but it is often equated to drugs with unproven effectiveness. Let's figure out who is right here.
From what, from what
The instructions for Ergoferon state that the drug works thanks to three components: antibodies to interferon gamma, histamine and CD4. We talked about the fact that histamine is associated with inflammation - the body's reaction to damage or foreign substances - in a note about Suprastin, but we will 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 became 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 alert, keep their heads down and prepare for a siege. True, since many molecules in our body have more than one function, interfering with the work of the immune system must be done with great caution.
The interferon-gamma in question is one of the most classic “immune” interferons. It is produced by T-helpers - lymphocytes, “sentinels” of our immunity, which notice the intruder and call for help an entire army of other cells to deal with him. To be more precise, these are T-helper cells of the first type, which, releasing gamma interferon, call for help from their “brothers” - T-killers, which kill infected fellow members of the body (as well as cancer cells) to prevent the infection from spreading.
T-helpers and some other immune cells wear “breastplates of distinction” - CD4 receptors (cluster of differentiation 4). These proteins are partially immersed in the membrane and partially stick out. They help the T cell receptor (TCR) “pick up” what other cells show them during the “inspection” when sentinel T-helpers walk around their possessions, checking whether the inhabitants of the body are hiding “forbidden” things like a virus or some abnormal proteins behind its membrane.
So, the active ingredients of Ergoferon, as has long been established, are associated with immunity. There are treatment methods associated with the administration of interferons. The combination of these words with the word “antibodies” sounds even better, which in the majority of people’s brains also lies on the “immunity” shelf.
The magic of numbers
Antibodies do help the immune system work, but only if they need to neutralize or poison a virus or bacteria. But they are designed to bind to... the molecules our immune system uses to protect itself. That is, their goal is to block the “communication” of immune cells and “plug” their hooks, which are needed to pick up and check what they are shown during the inspection. Will this cause harm?
To understand this, it is worth considering how many active ingredients are contained in the drug. Let's remember the school chemistry course and do the math.
According to the instructions for Ergoferon, the drug contains 0.006 g of each of the three medicinal antibody components. Let us take the approximate atomic mass of the antibody as 150 kilodaltons (this number is obtained if we divide the total mass of all atoms of the antibody by 1/12 the mass of a carbon atom). This value is numerically equal to the molar mass, which shows how many grams are contained in one mole of a substance. This unit of measurement shows the ratio of grams to 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 an amount of substance equal to one mole. This means that in 4*10 –8 mole we find 4*10 –8 6,022 10 23 = 24.088*10 15 molecules of the active substance. Several orders of magnitude less than in a drop of water, but still quite a lot (water, whatever one may say, has much smaller molecules).
Instructions for Ergoferon on the drug’s website
But what are the asterisks next to each 0.006 in the instructions? We read the footnote written in small print: “Lactose monohydrate is applied to lactose in the form of a mixture of three active aqueous-alcoholic dilutions of the substance, diluted respectively 100 12, 100 30, 100 50 times.”
Ecumenical breedings
So our 24,088 * 10 15 pieces of “affinity purified anti-CD4 antibodies” were diluted 1 * 10 100 times on the way to the tablet. When dividing, the powers are subtracted, and we get 24.088 * 10 –85. That is, at such a concentration, out of 1*10 85 molecules of what was anointed on the Ergoferon tablet, only 24 would be the active substance. But there is a small problem: there are only about 10 80 particles in the visible Universe. 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 enough to encounter them.
It must be admitted that the other two antibodies - to human interferon gamma and to histamine - are less diluted, but are still present in no less homeopathic concentrations. For example, in the “dense” version (human interferon gamma), one molecule must still enter the observable ergoferon Universe. The main and, perhaps, rather interesting additional question in this entertaining chemical problem is the question of who is breeding whom.
That is why an overdose of the drug, as its website honestly reports, does not threaten anything special. If you eat a huge number of tablets, you can only get “dyspeptic symptoms caused by the fillers included in the drug.” To enhance the effect, you can also snack on a cardboard box: cellulose, for example, in tablets is five times more than the active substance would be in hundreds of dilutions.
And the most important filler is lactose monohydrate, a derivative of ordinary “milk sugar”. It will only harm people with lactose intolerance. Ultra-high dilutions, sugar balls... Doesn’t remind you of anything? Usually such drugs are called homeopathy, but the manufacturer did not note this in any way either on the website or in the studies.
Not on the lists
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 undergo clinical trials (although the requirements for them in Russia are often lower than in most developed countries). The registry of approved clinical trials includes four completed and three ongoing studies.
There are more articles in the PubMed medical research database - as many as eight. The first link takes us to the journal Antiviral Research, English-language and with an impact factor approaching 5, which is not bad for a medical scientific journal.
Impact factor is an indicator that reflects the frequency of citations of articles in a scientific journal over a certain period (usually two years). For example, one of the largest medical journals, The Lancet, has an impact factor of 44.0, while the average for good journals is 4.
During the study, doctors compared the effectiveness of Ergoferon and Anaferon against rhinoviruses in vitro and in mice. The article says that thanks to Ergoferon, the body secretes more interferon-beta, and interferon-gamma, on the contrary, less, but not significantly. Typically, beta interferons are produced in large quantities by fibroblasts, and one type is used in drugs to treat multiple sclerosis, so it is not entirely clear how this, together with reducing the concentration of gamma interferons, should help against the flu. The article does not indicate in what concentration Ergoferon was used (maybe not in homeopathic) and in what it was dissolved, but it does indicate that the manufacturers of the drug financed the study.
I checked the effect of antibodies to CD4 on human leukocytes. But here we are not only talking about the whole person, but also about a substance that is too diluted to be present in Ergoferon tablets.
The next test was carried out on humans. According to the manufacturers, it was randomized, double-blind, controlled, and the drugs were administered automatically via a telephone answering machine.
A double-blind, randomized, placebo-controlled method is a method of clinical drug research in which the subjects are not privy to important details of the study. “Double blind” means that neither the subjects nor the experimenters know who is being treated with what, “randomized” means that the assignment to groups is random, and placebo is used to show that the effect of the drug is not based on self-hypnosis and that This medicine helps better than a tablet without active ingredients. This method prevents subjective distortion of the results. Sometimes the control group is given another drug with proven effectiveness, rather than a placebo, to show that the drug not only treats better than nothing, but is superior to its analogues.
However, it is worth understanding that at least the patients could easily distinguish what they were taking: each 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 drugs for basic treatment of influenza. 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). 158 people took part in the study.
All co-authors, except one, either received a grant from Materia Medica Holding (manufacturers of Ergoferon) or work there (and one is even 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 another small surprise: all these studies were carried out in 2016-2017, while the drug began to be sold in 2011.
Too “sighted” statistics
But there are three studies that hit PubMed earlier: in 2011, 2012 and 2014. All of them were published in the peer-reviewed Russian journal “Antibiotics and Chemotherapy” in Russian. The impact factor of this journal is 0.426 (according to the Russian Science Citation Index), and for obvious reasons there is no international citation.
Describes a study of the effect of Ergoferon on “optimizing the treatment of influenza and acute respiratory viral infections,” conducted in just one medical center on 100 patients. The authors honestly admit that it was open and not blind. This leaves a loophole for doctors to deliberately or accidentally influence the outcome (for example, prescribing Ergoferon to patients who show more hope for a speedy recovery). According to its results, the drug significantly promotes faster treatment than when taking a placebo, but the risk of error and bias here is too great (and let’s not forget about the concentration of the active substance in tablets, which is not very effective).
The second study, which compared 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 tablets and dosage regimen of which are different, would be difficult to confuse. The only way to “blind” him was to give one group Tamiflu at the same time as a placebo, which looks and is taken like Ergoferon, and vice versa, but the doctors did not do this.
The third study was multicenter, double-blind, placebo-controlled, and randomized. It tested how Ergoferon helps treat influenza in children. It included 162 participants from 13 medical centers. This work also evaluates recovery by “improvement” (a rather vague criterion), but in this case the placebo and drug regimens are the same, which can be called an advantage of the study. There the criterion of body temperature was also used, and antipyretics were also used. Observations were carried out according to the patient's diary and a 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 did 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 were included in the tablet, would have to play more for viruses than for immunity (“like is treated with like”), makes Ergoferon a classic homeopathic drug, although on the packaging this is not indicated in any way.
They argue about homeopathy for a long time, breaking spears, but it should be remembered that official science cannot recognize as a medicine something that the molecule of the active substance, according to the manufacturer, has not even been in. Homeopaths start lawsuits with their opponents (for example, with the magazine “Around the World”), trying to prove that their drugs work, but with carefully collected statistics and correct research methods, sugar balls work no better than a placebo. If the reader has a vivid imagination, he may just as well believe in the healing powers of tea with raspberry jam. Compared to cellulose, of which there is much more in a tablet than the active ingredient, using it during a cold is at least more pleasant, 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, and 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 unfinished studies of Ergoferon on the website of the Ministry of Health, this is exactly what they are talking about, and in the instructions these two diagnoses are listed as indications for use.
“Anaferon for children” is one of the many drugs from Materia Medica, 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 been treated with it.
The description of this “medicine” says that it contains active components - “affinity-purified antibodies to human interferon gamma - 0.003 g.” Further in small print: “active form containing no more than 10-16 (ten to the minus sixteenth) ng/g of active substance.” 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 purchase 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. Moreover, Russians alone spend several billion rubles a year on them. Someone will decide that if the drugs didn’t work, they wouldn’t 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 traders have only one significant expense - advertising. Therefore, praise for the drugs of Materia Medica can be found everywhere: from newspapers to central television channels. Now imagine that someone believes such advertising and begins to treat flu or cold with sugar. In most cases, the disease will go away on its own (as in the 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 doesn’t 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 defeat 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 Defense Against the Dark Arts:
“In 2011, The New England Journal of Medicine published an article comparing the effectiveness of four approaches to 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 velocity measurements of breathing) showed that the drug was helpful, while the other three approaches were 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.”
That's why carefully designed clinical trials involving large numbers of patients are needed to understand which drugs work and which don't.
Of course, there are a lot of companies selling dummies and taking advantage of the aforementioned ignorance of citizens. And it would be strange to single out only the Materia Medica. Those interested can familiarize themselves with the list of popular drugs that have no proven effectiveness. But the indignation of scientists is due not only to misleading patients, but also to the fact that their manufacturing company is trying to promote dubious “release activity” studies and pass them off as science.
Most of the “scientific” articles devoted to the release-active drugs of Materia Medica were published in the domestic journal included in the list of the Higher Attestation Commission - “Bulletin of Experimental Biology and Medicine”. The director of the company, corresponding member of the Russian Academy of Sciences Oleg Epshtein in 2003 became the author of 49 articles (!) in this magazine. All of them were published under the cover of a special issue, which was also edited by Epstein. Soon he defended his doctorate.
A detailed criticism of the phenomenon of “release activity” can be read in the article by Nikita Khromov-Borisov and Mikhail Arkhipov, “Epstein’s Challenge.” International peer-reviewed scientific journals have also published criticism of some of Epstein's work, for example with medicinal chemist Evgenia Dueva in the Journal of Medical Virology. But today I will limit myself to just a few quotes from Oleg Epstein’s article “The phenomenon of release activity and the hypothesis of “spatial” homeostasis,” which will probably shock any biologist. For the rest, I’ll explain that what follows is an absolutely meaningless combination of real and fictitious terms.
“...We believe that the genome does not generate a new physical entity - a “field”, but integrates the organism into a supramolecular “ether”, which provides the structural basis for the integral regulation of the organism.” “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 species-wide spatial parameters in its vibrational structure and, in fact, ensures the “connection” of the future organism to the species-wide spatial matrix that has evolved at the supramolecular level.”
In some ways, this is reminiscent of the reasoning of another famous figure of pseudoscience - Pyotr Garyaev, the author of the concept of the “wave genome”, who spreads the idea that swearing 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 scientific, 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 studies. 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 were considered completed, but only one of them presented results. There may be two explanations for the fact that results were not presented for the remaining completed studies. Either these results did not undergo proper quality control and did not satisfy independent experts, or the authors wanted to hide the results from the regulator.
The completed study with the presented results states only that the effectiveness of Ergoferon (another antiviral “release-active” drug from Materia Medica) is comparable to the effectiveness of Oseltamivir (aka Tamiflu). But this hardly speaks about the effectiveness of Ergoferon. The fact is that Oseltamivir was recently downgraded from the list of essential drugs according to the World Health Organization to the category of “auxiliary drugs”. It turned out that the manufacturer did not initially provide all the research data, but only part of it, 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 there may not be any due to the fact that Tamiflu, even if it is better than sugar, then not by much. In addition, the experimenters and patients knew who was receiving which drug, which means the study was not blinded and unblinded.
Misrepresenting clinical trial data is a common practice among manufacturers of sugar-based drugs. I will quote the website of the Boiron company, which produces Oscillococcinum:
“On the Cochrane Society of Evidence-Based Medicine website you can find blind, randomized, placebo-controlled studies on a number 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 mentioned anti-cold drugs (besides Remantadine, Amantadine, Zanamivir and Oseltamivir).”
But if you are not too lazy and open the mentioned meta-analysis on the Cochrane website, you can read the following:
“Overall, the reporting of study results was poor and therefore many aspects of the test methods and results had an unclear risk of bias. Accordingly, we assessed the quality of this evidence to be generally low and therefore it is not possible to draw clear conclusions regarding the use of Oscillococcinum for the prevention or treatment of influenza and influenza-like illnesses.”
Here it is necessary to clarify that Oscillococcinum, in composition, is also sugar, which is sold under the guise of a medicine for the flu and colds. The active substance in it is an extract from duck liver, which was diluted two hundred times in succession. This is an even more incredible dilution than the antibodies in Anaferon. The liver of one duck would be enough to treat all people on our planet with Oscillococcinum until the Sun absorbs 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 a dilution of 10-1991 ng/g. So the battle between the sugar titans is almost equal.
The law does not prevent this state of affairs in any way. The general pharmacopoeial article “Dosage forms of the General Pharmacopoeia for Homeopathic Medicines”, in accordance with the requirements of which, according to the Federal Law “On the Circulation of Medicines” (Federal Law dated April 12, 2010 No. 61-FZ, current edition dated December 28, 2017), such the drug contains the following concession: “In the event that the degree of dilution of the active component does not allow one to determine the authenticity or quantitative content, the quality of the drug is assessed by the excipients.” I am sure that the sugar used in these products is high quality.
These incredible dilutions (supposedly enhancing the effectiveness of the drug) are the whole essence of homeopathy (not to be confused with herbal medicine - herbal treatment). But if Oscillococcinum is openly called a homeopathic remedy, then Materia Medica took a different path. At least two of the company's drugs (Anaferon and Impaza) were initially registered in Russia as homeopathic, but in 2009 the word “homeopathy” disappeared from their names. Therefore, as a joke, we will call “release-active” drugs “shameful” homeopathy.
But the joke no longer seems so funny when you find out that such drugs are supposed to treat not only colds, but also tick-borne encephalitis, impotence, diabetes, joint diseases, erectile dysfunction, sleep disorders, obesity, attention deficit disorder, chronic cerebral ischemia, alcoholism, allergies, benign prostate hypertrophy, and also solve many other health problems.
Classical homeopathy is guided by the principle of “like cures like”: the patient is prescribed a diluted drug that, in undiluted form, causes symptoms similar to those he experiences. In shy homeopathy, this magical ritual is overgrown with science and terms from molecular biology. For example, to treat diabetes, antibodies to insulin receptors must be diluted. For the treatment of erectile dysfunction - antibodies to the enzyme NO synthase, which produces nitric oxide - a signaling 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.
Despite all the unscientific nature of such principles, Epstein’s logic is extremely simple. Do you want to come up with your own pseudoscientific release-active drug and make billions? Keep the recipe! Select a molecule in the human body that is involved in some process that is related to disease. Take antibodies to it and dilute them many, many times, apply to a sugar ball and eat. For example, HIV penetrates 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. This means that antibodies to it are needed. All that remains is to cure old age with antibodies to telomerase, an enzyme that lengthens the ends of chromosomes, which shorten in the cells of an aging body.
The fact that release-active drugs are registered and sold in Russia, alas, indicates a deep crisis in the domestic healthcare system and the need to revise the criteria for drug approval. When the Commission to Combat 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 - at least, 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 has turned out to be too great.
But the Ministry of Education and Science of the Russian Federation recently awarded Materia Medica an “Anti-Premium” for disseminating pseudoscience. This is not the first scandal involving this company. In 2017, under a barrage of angry letters from scientists and students, the organizers of Biologist Day (a traditional holiday of the Faculty of Biology of Moscow State University) withdrew the invitation of representatives of Materia Medica with the following words: “Your comments awakened a spirit of justice in the team, we checked the information and came to a collective decision that 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 is speaking out against the magic of the 21st century posing as science and medicine. Every patient has the right to know whether a drug has proven effectiveness or is a dud that, according to modern scientific ideas, cannot work. The Commission to Combat Pseudoscience is a public organization that does not have funding, so it is difficult for us to do anything against the advertising power of homeopaths and “shameful homeopaths.” Our only hope is that readers themselves will tell their friends and relatives about this problem. Only together can we defeat shameful obscurantism.
This article was written by me for the popular science publication “Attic”. Original:
