FNO blockers. Tumor necrosis factor-a - a new target for anti-inflammatory therapy in rheumatoid arthritis

Antipyretics for children are prescribed by a pediatrician. But there are emergency situations for fever when the child needs to be given medicine immediately. Then the parents take responsibility and use antipyretic drugs. What is allowed to give to infants? How can you bring down the temperature in older children? What medicines are the safest?

TNF-α (tumor necrosis factor alpha) plays a key role in starting and maintaining inflammatory process in rheumatoid arthritis (RA). Suppression of TNF activity leads to a decrease in the synthesis of inflammatory mediators in the body, due to which the necessary therapeutic effect in the treatment of the disease.

One of the disadvantages of therapy with TNF-α inhibitors is the high cost. However, this method of treatment also has significant advantages: proven effectiveness; safety; persistence of the achieved remission.

Consider use of TNF-α inhibitors in clinical practice on the example of a drug widely used over the past 10 years in the United States, Canada and European countries called etanercept. This TNF inhibitor is designed for subcutaneous administration, which allows patients with RA to avoid costly and lengthy hospitalizations.

Etanercept is used in the treatment of moderate-to-moderate rheumatoid arthritis. high activity inflammatory process. The drug has a stimulating effect on the TNF-α receptors present in the patient's body. As a result, receptors more actively capture excess TNF-α, thereby reducing its concentration, which leads to a decrease in the inflammatory process.

Like other TNF-α inhibitor drugs, etanercept differs significantly in its pharmacological action from immunosuppressants also used in some RA treatment regimens. Immunosuppressants affect almost the entire immune system, while TNF-α inhibitors are active against specific targets, which are specific sites in the pathogenesis of rheumatoid arthritis.

The results of etanercept studies showed that the new medicinal product- TNF inhibitor - leads to a significant decrease in the severity of the symptoms of the disease, the achievement of persistent and long-term remissions. Etanercept can be used both as monotherapy for RA (treatment with this drug alone) and as part of complex treatment. TNF inhibitors can be combined with non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (methotrexate), glucocorticoids (GCs), and pain medications.

Etanercept is given by injection under the skin. "Injections" are performed twice a week. Possible injection zones: under the skin of the shoulder, anterior abdominal wall or thigh. Hospitalization of patients for treatment with a TNF inhibitor is not required, injections can be made nurse in the treatment room of the clinic or at home.

It should be noted that the use of TNF inhibitors may be accompanied by certain undesirable effects: fever, diarrhea, abdominal pain, leukopenia (decrease in the number of leukocytes), headache, dizziness, respiratory disorders. In addition, local reactions sometimes occur at the injection site ( pruritus, and rashes).

It has not been established with certainty what effect TNF-α inhibitors have on the protective function of the immune system. Therefore, patients receiving etanercept should be warned that the use of the drug can potentially provoke infection with various infections. Etanercept should not be used to treat patients with impaired immune system, because in this case, patients may develop serious infectious diseases, which are fraught with sepsis and death. Etanercept is also contraindicated in patients with certain heart conditions (the drug can lead to severe cardiovascular failure). TNF-α inhibitors are not intended for the treatment of RA without the participation of a physician.

The introduction of TNF-α inhibitors into wide clinical practice can be considered one of the greatest advances in medicine in the treatment of RA in recent decades. The use of this group of drugs makes it possible to achieve remission of the disease or a significant decrease in the activity of the inflammatory process, even in patients who were resistant (not sensitive) to other types of basic antirheumatic therapy. The use of TNF-α inhibitors for the treatment of RA significantly slows down the progression of the destruction (destruction) of the affected joints, which is confirmed by x-ray methods.

Introduction. To date, five tumor necrosis factor (TNF) blocker drugs: infliximab (infliximab), etanercept (etanercep), adalimumab (adalimumab), sortolizumab pegol (certolizumab pegol) and golimumab (golimumab) are suitable for the treatment of rheumatoid arthritis.

The study evaluated the efficacy and safety of TNF blockers in rheumatoid arthritis (RA) and indirectly compared all five blockers by combining the results of randomized clinical trials.

Materials and methods. A systematic literature review of databases was conducted: MEDLINE, SCOPUS (including EMBASE), Cochrane Community Libraries, and search engines on scientific materials. Only articles on double-blind, randomized trials of TNF blockers versus placebo, with or without concomitant methotrexate, were selected.

The collected materials contained information about patients and their treatment, control groups, results, study methods, and possible sources of bias. Patient inclusion criteria: age at least 16 years and diagnosed rheumatoid arthritis according to ACR criteria (1987). A total of 6780 patients treated with TNF blockers and 3082 control patients were processed. A meta-analysis of the obtained data was carried out using the Cochrane Collaboration Review 5.0 software. The efficacy and safety of TNF blockers was analyzed across six different baseline comparisons.

Results and conclusions. A total of 41 articles from 26 randomized clinical trials were included in the systematic review and meta-analysis. Infliximab was considered 5 randomized clinical trials, 7 - etanercept, 8 - adalimumab, 3 each - dolimumab and certolizumab.

In all studies, TNF blockers showed greater efficacy than placebo, but were comparable in effect to methotrexate. Golimumab was less effective than etanercept, adalimumab, and certolizumab. The combination of TNF blockers and methotrexate was superior to either alone. Increasing doses did not improve efficacy. TNF blockers were relatively safe and the profile was comparable to methotrexate.

None of the TNF blockers has been shown to be superior in efficacy compared to other drugs in this pharmacological group, but the results of safety studies show that etanercept is the safest drug. It is interesting to note that methotrexate showed almost equal results of efficacy and safety, despite the significant difference in the cost of these drugs.

The article was prepared and edited by: surgeon

Video:

Healthy:

To provide nutrients to the proliferating synovial membrane, the formation of new blood vessels- neoangiogenesis, which ...
T cells are involved in the development of rheumatoid arthritis because they are associated with MHC class II and are present ...
Kidney damage in rheumatoid arthritis is manifested by diffuse glomerulonephritis, widespread amyloidosis with a primary lesion of the kidneys or ...
Rheumatoid arthritis (RA) has an increased mortality rate, largely due to cardiovascular disease and...
Anti-cyclic citrullinated peptide (ACCP) antibodies are a key autoantibody system in rheumatoid arthritis. The sensitivity of this...
Standard laboratory tests in rheumatoid arthritis at the initial stage are important for assessing the severity of systemic inflammation ...

For citation: Nasonov E.L. Efficacy and safety of tumor necrosis factor-a inhibitors in rheumatoid arthritis // RMJ. 2008. No. 24. S. 1602

Rheumatoid arthritis (RA) is the most common inflammatory disease of the joints, with a prevalence of about 1% in the population, and economic losses for society comparable to ischemic disease hearts. The study of RA is of general medical importance, since it creates the prerequisites for deciphering the fundamental mechanisms of development and improving the pharmacotherapy of other common human diseases (atherosclerosis, diabetes 2 types, osteoporosis, etc.), pathogenetically associated with chronic inflammation.

The treatment of RA remains one of the most difficult problems in clinical medicine. In many patients, even early initiation of mono- or combination therapy with traditional DMARDs does not always slow down the progression of joint destruction, even despite the positive dynamics of clinical indicators of inflammation activity. All this was a serious incentive to improve approaches to the pharmacotherapy of RA, based on modern medical technologies and deciphering the fundamental mechanisms of the development of rheumatoid inflammation.

Of particular importance in the pathogenesis of RA and other chronic inflammatory diseases a person is given tumor necrosis factor (TNF)-a - the most well-studied representative of the group of so-called "pro-inflammatory" cytokines. TNF-a exhibits numerous "pro-inflammatory" effects (Fig. 1), which are of fundamental importance in the immunopathogenesis of RA.

The progress of biology and medicine at the end of the 20th century expanded the possibilities of pharmacotherapy for RA. Fundamentally new anti-inflammatory drugs have been developed medicines(drugs), united under the general term "genetically engineered biological preparations" . These primarily include TNF-a inhibitors blocking biological activity of this cytokine in circulation and on cellular level: chimeric (infliximab - IFN) and human (adalimumab - ADA) monoclonal antibodies to TNF-a and etanercept (ETN) (Fig. 2), which are considered as one of the most effective drugs for the treatment of RA.

ETN is a hybrid molecule consisting of a TNF receptor (P) with a molecular weight of 75 kD, connected to the Fc fragment of Ig 1 human (Fig. 2). The dimeric structure of FNOR in the ETN molecule provides a higher affinity of the drug for TNF-a, which, in turn, determines a more pronounced competitive inhibition of TNF-a activity compared to the monomeric soluble FNOR present in biological fluids. The presence of an IgG fragment in the ETH Fc molecule contributes to a longer drug life in circulation than monomeric FNOR. ETN competitively inhibits the binding of TNF-a and TNF-b (lymphotoxin-a) to membrane FNOR, thereby abolishing the biological effect of TNF, and its effectiveness has been proven in various experimental models of inflammation, including arthritis resembling human RA.

The pharmacokinetics of ETN does not depend on the sex and age of patients, does not change during combination therapy with methotrexate (MT). There is no need for dose titration in case of kidney damage or liver failure. clinically significant drug interactions ETN with digoxin and warfarin was not noted.

The high efficacy and acceptable safety of ETN has been proven in a series of randomized placebo-controlled trials (RPCTs) and their open phase, in their meta-analysis and in the process of long-term use of the drug in real clinical practice (data from national registries). Let's consider the most important of them.

Important results were obtained in the TEMPO (Trial of Etanrecept and Methotrexate with radiological patients outcome) study, which included 682 patients with significant RA (mean duration of illness 6 years). The open phase of this study and the analysis of the results obtained are ongoing. In the controlled phase of the study, patients were randomized into 3 groups. Group 1 consisted of patients receiving ETN monotherapy, group 2 - patients receiving MT monotherapy (up to 20 mg per week), group 3 - patients receiving combination therapy of ETN and MT. It was found that the effectiveness of combination therapy (ACR, DAS, DAS28 and HAQ) and the frequency of remission was significantly higher than both ETN and MT monotherapy after 24, 52 and 100 weeks. therapy (p<0,01 во всех случаях) . Комбинированная терапия более эффективно, чем монотерапия, тормозила деструкцию суставов. Частота побочных эффектов, включая инфекционные осложнения, в сравниваемых группах больных не отличалась.

We recently analyzed the results of a 4-year follow-up of patients who continued to participate in the open-label phase of the TEMPO study, among which 55 patients added ETN to MTX, 76 patients added MTX to ETN, and 96 continued combination therapy with ETN and MTX. . At baseline, patients treated with MT or ETN monotherapy had moderate disease activity, while patients treated with combination therapy had low disease activity. By the end of the 4th year, the remission rate in patients of group 1 increased from 23.6 to 41.8% (p<0,01), у пациентов группы 2 - с 26,7 до 36,8% (p>0.05), and in patients of group 3 - from 37.6 to 50% (p<0,01).

These data convincingly indicate the high efficiency of the combination therapy of ETN and MT during long-term treatment in patients with RA, which persists and even increases by the end of the 4th year of continuous therapy. In addition, when MT is not effective enough, the addition of ETN allows to achieve a good clinical effect, which expands the therapeutic possibilities of RA pharmacotherapy in the long term.

Although MTX is regarded as the “gold standard” for RA treatment, many patients experience inadequate treatment, contraindications to treatment, or side effects that require MTX to be discontinued. In some patients, sulfasalazine (SULF), which is one of the most effective DMARDs, can be a good alternative to MT. This served as the basis for conducting an RCT ( The Etanercept Study 309 ), which included 254 patients randomized (2:1:2) into 3 groups: SULF monotherapy (n=50), ETN monotherapy (n=103) and combined ETN and SULF therapy (n=101) . Inclusion criteria for the study were high disease activity (≥6 painful and swollen joints, morning stiffness ≥45 min, ESR≥28 mm/h, CRP≥20 mg/L) despite SULF treatment. ETN monotherapy and combined ETN and SULF therapy were found to be significantly more effective than SULF monotherapy according to the ACR criteria (p<0,01). При этом различия в эффективности ЭТН и СУЛЬФ были достоверны уже через 2 нед. после начала терапии (p<0,01). Значение индекса DAS28 к 24 нед. в группе пациентов, получавших СУЛЬФ, уменьшилось на 19,6%, в то время как в группе, получавшей монотерапию ЭТН - на 48,2%, а комбинированную терапию - на 49,7%. Положительная динамика имела место и в отношении параметров качества жизни (p<0,01), причем эти различия были достоверны уже через 2 нед. лечения. Частота побочных эффектов, таких как головная боль, тошнота астения, была несколько выше в группе больных, получавших комбинированную терапию (p<0,05), в то время как инфекционных осложнений и инъекционных реакций - у пациентов, получавших монотерапию ЭТН (p<0,05).

In an open prospective study by O`Dell J.R. et al. evaluated the effectiveness of combination therapy for ETN with the most commonly used DMARDs, such as SULF (n=50), hydroxychloroquine (n=50), and intramuscular gold salts (n=19), in patients who failed monotherapy with these drugs. In all groups of patients, there was a significant decrease in clinical activity according to the ACR20, 50 and 70 criteria (by 24 and 48 weeks) without a significant difference between the groups. In general, a clinical response according to ACR20 was observed by 24 weeks. in 67%, and by 48 weeks. - in 54% of patients. The incidence of side effects was similar to those obtained in other studies, the rate of treatment interruption due to side effects was 9%.

Of undoubted interest are the data of Finckh A. et al. who performed a detailed analysis of a cohort of patients treated with TNF-a inhibitors and other DMARDs (Swiss Clinical Quality Management in Rheumatoid Arthritis database). A total of 1218 patients (out of 2097 included in the database) were included in the analysis, among which 842 received TNF-α inhibitors in combination with MTX (31% ETN), 260 in combination with leflunomide (32% ETN) and 116 with other DMARDs (45% ETN). At the same time, there were no significant differences between the compared groups of patients both in terms of the duration of treatment, efficacy (clinical and radiological), and the frequency of side effects.

These data indicate the potential for monotherapy with ETN (when it is impossible to prescribe MTX) or combination therapy with MTX and other DMARDs.

Given the current concept of RA pharmacotherapy associated with early aggressive treatment of DMARDs, including biological agents, combined with careful evaluation of efficacy aimed at achieving remission, studies regarding the use of ETN in early RA are of particular interest (Table 1).

More recently, a multicenter international study COMET (Combination of methotrexate and etanercept) was completed, which included patients (n = 542), with early (duration 3 months - 2 years) active (DAS28> 3.2 and an increase in ESR> 28 mm/hour of RA or CRP>20 mg/l) who did not receive MTX. At the same time, 92% of patients had high disease activity (DAS28>5.1). Patients were randomized into 2 groups. The first included 274 patients who received ETN (50 mg/week) and MT, and the second included MT only. Depending on the effect (number of painful and swollen joints), the dose of MT was increased to 20 mg/week. within 8 weeks, starting with 7.5 mg / week. The duration of treatment was 52 weeks. The results obtained are summarized in Table 2. By the end of the study, remission occurred in 50% of patients receiving combined therapy with ETN and MTX and only in 28% of patients receiving MTX monotherapy (p<0,0001), а низкая активность - соответственно у 64 и 41% пациентов (p<0,001). Хороший/умеренный ответ по критериям EULAR отмечен у 94% получавших комбинированную терапию и у 80% пациентов, получавших монотерапию (p<0,001). При этом различия в эффективности лечения были высокодостоверны в течение всего периода наблюдения, начиная со 2 нед. Важно, что среди получавших комбинированную терапию и имевших хороший/умеренный ответ по критериям ЕULAR к 12-й неделе, у 94% пациентов эффект сохранялся до 24 нед. При этом среди пациентов, не отвечающих на комбинированную терапию к 12-й нед., у 54% развился хороший/умеренный эффект (EULAR) к 24 нед., а у 27% - клиническая ремиссия. У пациентов с высокой активностью отсутствие рентгенологического прогрессирования имело место у 80% в группе комбинированной терапии и у 59% получавших монотерапию МТ (p<0,0001). Комбинированная терапия существенно превосходила монотерапию по влиянию на параметры качества жизни (HAQ)

Despite the fact that RA most often affects middle-aged people, 10-33% of patients with RA are older than 65 years. However, data regarding the efficacy and safety of TNF-a inhibitors in older patients are limited, as these patients are generally not included in RCTs. Fleischman R.M. et al. retrospectively analyzed the results of several RCTs and open studies, which included 1128 patients, 197 (17%) of them over 65 years of age. There were no significant differences in the efficacy and toxicity of ETG therapy in the compared groups. Thus, after the first year of therapy, the ACR20 response occurred in 69% of patients under 65 years of age and in 66% of patients over 65 years of age, ACR50 - in 40% of patients in both groups, and ACR70 - in 17%. The frequency of side effects was similar. Thus, efficacy and tolerability of ETN treatment in elderly patients was very good during 6 years of follow-up .

In another study by the same group of authors, patients from the TEMPO study were also included in the analysis. As in the previous analysis, there were no differences in efficacy depending on the age of the patients. After 6 months the effect according to ACR20/50/70 was 70%, 45%/15% in patients older than 65 years, and 65%/39%/1% in patients younger than 65 years, and after 72 months. respectively 79%/47%/11% and 73%/53%/29%. The tolerability of therapy and the frequency of side effects in the elderly and young people were similar.

Given the data on the high incidence of comorbidities in patients with RA, which can have a significant impact on the prognosis, the RPCT conducted by Weisman M.H. is of undoubted interest. et al. . This study (16 weeks) specifically examined the impact of comorbidities on the safety of ETN treatment. The study included 535 patients with at least one comorbid disease (diabetes mellitus, COPD, recent pneumonia or recurrent infections). It was found that in the group treated with ETN, there is a small statistically non-significant increase in the incidence of severe side effects (8.6% vs 5.9%) in patients with diabetes (RR=1.34) and COPD (RR=1.58) . The incidence of infectious complications was similar (43.4 on placebo vs 39.8% on ETN). Thus, the presence of comorbid diseases does not significantly affect the safety of ETN treatment and is not a contraindication for its use.

Recently, Klareskog L. et al. analyzed the results of long-term use of ETN in patients participating in the open phase studies of this drug in the United States and Europe. In total, the analysis included 2054 patients with early and advanced RA, refractory to DMARDs (9763 patient-years), who took ETN for 3-10 years. It has been established that the effectiveness of ETN is maintained for a long time: ACR20 - 70-76% of patients, ACR50 - 48-58% and ACR70 - 31-37%.

Treatment tactics

According to the recommendations, ETN should be prescribed at a dose of 25 mg 2 times a week, which ensures optimal pharmacokinetic characteristics of the drug. However, later it was shown that ETN can be used at a dose of 50 mg once a week. . With the ineffectiveness of ETN in a standard dose, increasing the dose (50 mg 2 times a week) does not lead to an increase in the effect.

In terms of optimizing RA therapy using ETN (including from the point of view of pharmacoeconomic prospects), the study of Kavanaugh A. et al. , which retrospectively analyzed the data of the TEMPO study in order to clarify the possible timing of the development of the effect during the treatment of ETN. According to the authors, during the treatment of ETN and MT, there is an increase in the number of "responders" to therapy by 24 weeks. compared with 12 weeks: 37.5% of patients on ACR20, 46.8% on ACR50 and 51.1% on ACR70. Thus, to make a decision on the tactics of treating ETN, it is advisable not earlier than after 24 weeks. therapy.

With the expansion of the use of TNF-a inhibitors in clinical practice, the question of the tactics of managing patients who “do not respond” to treatment with TNF-a inhibitors becomes more and more relevant. The materials of observational studies and national registries of genetically engineered biological products indicate that if INF is ineffective, switching to ETN (switch) allows obtaining a clinical effect in patients with primary and secondary inefficiency or avoiding the development of side effects in patients who have reason for discontinuation of treatment were toxic reactions.

However, according to a prospective study by Finckh A. et al., anti-B cell therapy (rituximab) is more effective than switching to another TNF-a inhibitor (including ETN), especially if this is due to ineffectiveness. TNF-a inhibitors. These data are in good agreement with RCTs that provide convincing evidence of high efficacy of rituximab in patients not responding to treatment with TNF-a inhibitors. Based on a detailed analysis of the totality of available evidence, the NICE panel currently does not recommend switching TNF-a inhibitors and favors rituximab.

Side effects

In general, ETN is well tolerated even with long-term use, and the frequency of treatment interruption due to side effects according to RCTs and open studies does not differ from comparison groups, with the exception of injection reactions, which develop more often during ETN treatment. They usually occur in the first months of therapy, last 3-5 days, but rarely cause interruption of treatment. Obviously, ETN does not cause infusion reactions, which is an advantage of this drug compared to INF, which is administered intravenously.

There was no increase in the frequency of side effects when prescribing ETN in the dose range from 10 mg and 25 mg 2 times a week. up to 50 mg 1 time per week. and duration of therapy (up to 9 years), which is similar to that in patients who received the drug for 1 year.

However, an analysis of the results of the use of ETN and other TNF-a inhibitors in real clinical practice drew attention to the problem of rare side effects, the main of which are an increase in the risk of infectious complications, including tuberculosis, and opportunistic infections, malignant neoplasms (lymphoma), autoimmune syndromes, demyelinating diseases of the nervous system, congestive heart failure and some others. They are considered class-specific side effects of all TNF-a inhibitors. However, the positive effects of TNF-a inhibitors significantly outweigh the disadvantages of therapy associated with toxicity. In addition, the severe course of RA, which is an indication for the appointment of TNF-a inhibitors, is associated with an unfavorable life prognosis, including due to an increased risk of infectious and cardiovascular complications. Traditional DMARDs can also cause adverse reactions with greater frequency and adverse effects than TNF-a inhibitors.

Infectious complications

Analysis of data from observational and post-registration studies indicates an increased risk of bacterial infections during treatment with TNF-a inhibitors (Table 3), especially during the first 6 months. treatment with these drugs. At the same time, according to a number of studies, the risk of developing infectious complications is higher during treatment with INF than with ETN.

From the point of view of the safety of treatment with TNF-a inhibitors, the development of tuberculosis is of particular clinical importance, which is primarily associated with the reactivation of latent tuberculosis infection. At the same time, it was found that the risk of developing tuberculosis infection during ETG treatment is significantly lower than that of INF and ADA.

For example, according to the British Biological Registry, which includes 9882 patients treated with TNF-a inhibitors (5265 patients - ETN, 3569 patients - INF and 2511 patients - ADA) and 2883 patients treated with standard DMARDs, TB infection was diagnosed in 29 patients ( all received TNF-a inhibitors). When compared with ETN (RR = 1.0), the risk of developing tuberculosis was 2.84 for INF and 3.53 for ADA. Disseminated tuberculosis developed in 1 patient treated with INF and 4 patients treated with ADA.

Similar results were obtained in a multicenter prospective 3-year study ( RATIO ) conducted in France, according to which the overall incidence of tuberculosis during treatment with TNF-a inhibitors was 39.3/100,000 patient-years, which was significantly higher than in the population - 8.7/100,000 patient-years. At the same time, during ETN treatment, the infection rate was only 6.6/100,000 patient-years, while with INF and ADA it was 71.5/100,000 patient-years. Preliminary analysis showed that risk factors for TB included age (RR=1.04), residence in endemic areas (RR=7.2), and use of INF and ADA compared to ETN (RR=10.05; p=0.006 and RR=8.63; p=0.02, respectively).

It is believed that the development of tuberculosis soon after the appointment of TNF-a inhibitors is associated with the reactivation of a latent infection, and at a later time - with the primary infection with mycobacterium. During treatment with INF, tuberculosis develops earlier (on average after 12-32 weeks) than ETN (on average after 18-79 weeks). In another study, it was shown that in patients treated with INF, 43% of cases of tuberculosis infection developed during the first 90 days of treatment, while only 10% of patients treated with ETN.

There are few studies on the effect of TNF-a inhibitors on the course of infection with hepatitis B and C virus. It is believed that TNF-α inhibitors can, on the one hand, slow down the clearance of the hepatitis B virus, but, on the other hand, suppress liver inflammation caused by the hepatitis C virus. There is evidence of a beneficial effect of ETN (in combination with interferon-a and ribavirin) on the course of hepatitis C virus infection. However, in HCV carriers treated with ETN (and other TNF-a inhibitors), liver enzyme levels should be monitored more closely.

Demyelinating diseases

An association between treatment with TNF-a inhibitors and the development of demyelinating diseases of the nervous system is highly probable, although not rigorously proven. Among 77,152 patients treated with ETN, 17 cases of demyelinating diseases were identified, which is 31 cases per 100,000 patient-years, while in the general population the incidence of this pathology is 4-6 cases per 100,000 patient-years. . Therefore, the appointment of TNF-a inhibitors in patients with a history of demyelinating diseases is not recommended.

The cardiovascular system

Given the fundamental role of TNF-a in the development of heart failure, 2 RCTs (RENAISSANCE and RECOVER studies) were conducted to evaluate the effectiveness of ETN in this pathology. Both studies showed a slight trend towards increased mortality in patients treated with ETN. However, when summarizing the results of these studies (the RENEWAL study), there was no association between ETN treatment, the risk of mortality and the development of decompensation. Thus, although the role of TNF inhibitors (with the exception of high-dose IFN) in the development of heart failure has not been proven, in patients with heart failure or a decrease in left ventricular ejection fraction, it is recommended to prescribe ETN with caution and avoid prescribing high doses of TNF-α inhibitors.

Another aspect of this problem is associated with a high risk of developing early atherosclerotic vascular disease and related complications (myocardial infarction and stroke) in RA. In this regard, attention is drawn to the data that against the background of treatment with TNF-a inhibitors (including ETN), there is a decrease in the risk of developing cardiovascular accidents, primarily in patients who “respond” to treatment with these drugs.

Hepatotoxicity

The risk of hepatoxic reactions during treatment with TNF-a inhibitors is minimal, with most cases described against the background of taking INF. According to the analysis of the CORDONA database, there was no association between ETN treatment and an increase in liver enzymes, while a 2.5-fold increase in the risk of this complication was noted with the use of INF and ADA.

cytopenia

The development of cytopenia is extremely rare, but is the basis for monitoring the number of leukocytes, especially in combination therapy with ETN and myelotoxic drugs.

Autoimmune reactions

Against the background of treatment with TNF-a inhibitors, the development of autoimmune serological reactions (ANF, anti-DNA, antibodies to cardiolipin, nucleosomes and histone), very rarely lupus-like syndromes, is observed. In general, autoimmune reactions are significantly more likely to occur during treatment with INF than with ETN.

Malignant neoplasms

Data regarding the risk of developing malignant neoplasms (primarily lymphomas) during treatment with TNF-a inhibitors are contradictory. This is due to several circumstances. First, in RA patients who are indicated for the appointment of TNF-a inhibitors, there is an increased risk of developing lymphomas. Secondly, some drugs used in combination with TNF-a inhibitors for the treatment of RA have the ability to increase the risk of developing lymphomas.

An analysis of data from observational studies suggests that treatment with TNF-a inhibitors is associated with a small increase in the risk of melanoma and other skin malignancies (RR = 2.2 and 1.5, respectively). Thus, the issue of prescribing ETN in patients at risk of developing malignant neoplasms should be decided individually. Combination therapy with ETN and cyclophosphamide is not recommended as it may increase the risk of tumor development.

Thus, the huge evidence base obtained in the course of numerous RCPIs, the open phase of these studies and national registries, indicates the high efficacy and acceptable safety of ETN in RA, which dictates the need for an early registration and widespread use of this drug in Russia.

Literature
1. Nasonov E.L. Rheumatoid arthritis as a general medical problem. Therapist. Archive 2004; 5:5-7
2. Sigidin Ya.A., Lukina G.V. Rheumatoid arthritis. Moscow, ANKO, 2001, 328 pages
3. Nasonov E.L. VN Treatment of rheumatoid arthritis. Clinical guidelines. Almaz Publishing House, Moscow, 2006, 118 pages
4. Brown AK, Quin MA, Karim Z, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatiic drug-induced remission: evidence from an imaging study may explain structural progression. Arthritis Rheum 2006; 54: 3761-3673
5. Ferinstein GS. Evolving concept of rheumatoid arthritis. Nature 2003; 423:356-360
6.Beayert R; Fiers W. Tumor necrosis factor and lymphotoxin. In: Mire-Sluis AR, Thorpe R., editors. Cytokines. 1st ed. London: Academic Pr; 1998.pp. 235-60.
7. Feldman M., Brennan F., Maini R.N. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 1996; 14:397-440.
8. Nasonov EL. Pharmacotherapy of rheumatoid arthritis in the era of genetically engineered biological drugs. Therapeutic Archive, 2007, 5, 5-8
9. Nasonov E.L. Pharmacotherapy of rheumatoid arthritis - a look into the 21st century. Wedge. medicine 2005; 6:8-12
10. Nasonov EL. Treatment of rheumatoid arthritis: the current state of the problem. RMJ 2006; 14 (8); 573-577
11. Kuek A, Hazleman BL, Ostor AJK. Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J 2007; 83:251-269
12. Nasonov E.L. Tumor necrosis factor-a is a new target for anti-inflammatory therapy in rheumatoid arthritis. Wedge. Pharmacol. Therapy 2001;1:64-70
13. Nasonov E.L. Prospects for pharmacotherapy of inflammatory rheumatic diseases: monoclonal antibodies to tumor necrosis factor. RMJ, 2001, 9, 7-9.
14. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Therapeut 2008; 117:244-279
15. Mohler KM, Torrance DS, Smith CA, et al. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993;151:1548-61.
16. Dhillon S, Lyseng-Williamson KA, Scott LJ. Etanercept. A review of its use in the management of rheumatoid arthritis. Drugs 2007; 67:1211-1241.
17. Korth-Bradley JM, Rubin AS, Hanna RK, et al. The pharmacokinetics of etanercept in healthy volunteers. Ann Pharmacother. 2000;34:161-4.
18. Moreland LW, Schiff MH, Baumgartner SW et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 1999;130:478-486
19. Weinblatt ME, Kremer JM, Bankhurst AD, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340:253-9.
20. Kremer JM, Weinblatt ME, Bankhurst AD et al. Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis, continued observation. Arthritis Rheum 2003; 48: 1493-1499
21. Moreland LW, Cohen SB, Baumgartner SW, et al. Long term safety and efficact of etanercept in patients with rheumatoid arthritis. J Rheumatol 2001; 28:1238-1244
22. Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomized controlled trial. Lancet. 2004;363:675-81.
23. van der Heijde D, Klareskog L, Rodrigiez-Valvelde V, et al. Comparison of etanercept and metoptrexate, alone and combined, in the treatment of rheumatoid arthritis. Two-year clinical and radiographic results from the TEMPO study, a doble-blind, randomized trial. Arthritis Rheum 2006; 54:1063-1074
24. van der Heijde D, Klareskog L, Landewe R, et a. Disease remission and sustained halting of radiographic progression with a combination of etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 2007; 56: 3928-3939
25. Landewe R, van der Heijde D, Klareskog L, et al. Disconnect between inflammation and joint destruction after treatment with etanercept and methotrexate with radiographic and patients ourcomes. Arthritis Rheum 2006; 54: 3119-3125
26. van der Heijde D, Burmester G, Melo-Gomes J, et al. The safety and efficacy of adding etanercept to methotrexate or methotrexate to etanercept in moderately active rheumatoid arthritis patients previously treated with monotherapy. Ann Rheum Dis 2008; 67:182-188
27. Kameda H, Ueki Y, Saito K, et al. The comparison of effecacy and safety between etanercept (ETN) plus methotrexate (MT) combonation therapy and ETN monotherapy in MTX-refractory Japanese patients with rheumatoid arthritis; 24-week results frpm JESMR study. Ann Rheum Dis 2008; 67 (Suppl II): 184
28. Klareskog L, Gaubitz M, Rodriguez-Valverde V, et al. A long-term, open-label trial of the safety and efficacy of etanercept (Enbrel) in patients with rheumatoid arthritis not treated with other disease modifying antirheumatic drugs. Ann Rheum Dis 2006; 65: 1578-1584
29. van Riel PLC, Taggat AJ, Sany J, et al. Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with inadequate response to methotrexate: the ADORE study. Ann Rheum Dis 2006; 65: 1478-1483
30. van Riel PLC, Freundlich B, MacPeek D, et al. Patient-reported outcome in a trial of etanercept monotherapy versus combination therapy with etanercept and methotrexate for rheumatoid arthritis: the ADORE trial. Ann Rheum Dis 2008; 67:1104-1110
31. Combe B, Codreanu C, Fiocco U, et al. Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison. Ann Rheum Dis 2006; 65:1357-1362.
32. O'Dell JR, Petersen K, Leff R, et al. Etanercept in combination with sulfasalazine, hydroxychloroquine, or gold in the treatment of rheumatoid arthritis. J Rheumatol 2006; 33:213-218.
33 Finckh A, Dehler S, Gabay C et al. The effectiveness of leflunomide as co-therapy of TNF inhibitors in rheumatoid arthritis. A population based study. Ann Rheum Dis 2008; January 29 online.
34. Ikeda K, Cox S, Emery P. Biological therapy in early arthritis - overtreatment or the way to go? Arthritis Res Therapy 2007; 9:211
35 Machold KP, Nell VPK, Stamm TA, Smolen JS. Traditional DMARD therapy: is it sufficient: Arthritis Res Ther 2006;8:21 on lone
36 Bathon JM, Martin RW, Fleischmann RM, et al. Comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586-93.
37. Genovese MC, Bathon JM, Martin RW et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcome. Arthritis Rheum 2002; 46; 1443-1450
38. Genovese MC, Bathon JM, Fleishmann RM, et al. Long term safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol 2005; 32:1223-1242
39. Weinblatt ME, Genovese MC, Moreland LW, et al. Efficacy and safety of over 9 years of etanercept (Enbrel) therapy in North American patients with early and long-standing rheumatoid arthritis. Amer Coll Rheum. Annual Sci Meet 2006 Nov 11-15; Washington D.C. (abst)
40. Baumgartner SW, Fleischmann RM, Moreland LW, et al. Etanercept (Enbrel) in patients with rheumatoid arthritis with recent oncet versus established disease improvement in disability. J Rheumatol 2004; 31: 1532-1557
41. Emery P, Breedveld F.C., Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active early, moderate to severe rheumatoid arthritis (COMET): a randomized, double-blind, parallel treatment trial. Lancet 2008; July 16, online.
42. Moots R, Kekow J, Sato R, et al Assessment of early treatment with combination of etanercept and methotrexate on functional status among patients with active rheumatoid arthritis: the COMET trial. Ann Rheum Dis 2008; 67 (Suppl II):188
43. Breedveld F, Emery P, Ferraccioli G, et al. Clinical response and remission at 12, 24, and 52 weeks with the combination of etanercept and methotrexate in the treatment of active rheumatoid arthritis in the COMET trial. Ann Rheum Dis 2008; 67 (Suppl II): 320
44. Anis A, Zhang W, Emery P, et al. Work-related outcome in early active rheumatoid arthritis: results from the COMET trial. Ann Rheum Dis 2008; 67 (Suppl II): 79
45. Fleishman RM, Baumgartner SW, Tindall EA, et al. Response to etanercept (Enbrel) in eldery patients with rheumatoid arthritis: a retrospective analysis of clinical trial results. J Rheumatol 2003; 30:691-696.
46 Bathon JM, Fleischmann RM, van der Heijde DM, et al. Safety and efficacy of etanercept treatment in eldery subjects with rheumatoid arthritis. J Rheumatol 2006; 33:234-243.
47. Weisman MH, Paulus HE, Burch FX, et al. A placebo-controlled, randomized, double-blind study evaluating the safety of etanercept in patients with rheumatoid arthritis and concominant comorbid diseases. Rheumatology 2007; 46:1122-1125.
48. Baumgatner SW, Fleishman RM, Moreland LW et al. Etanercept (Enbrel in patients with rheumatoid arthritis with early onset versus established disease: improvement in disability. J Rheumat 2004; 31: 1532-1537
49. Keystone E, Freundlich B, Schiff M, et al. Patients with moderate rheumatoid arthritis achive better disease activity states with etanercept treatment than patients with severe rheumatoid arthritis. Ann Rheum Dis 2008; 67 (Suppl II):186.
50. Klareskog L, Moreland LW, Cohen SB, et al. Safety and efficacy of over 10 years of continuous etanercept therapy in patients with rheumatoid arthritis in North America and Europe. Ann Rheum Dis 2008; 67 (Suppl II): 175
51. Chen Y-F, Jobanputra P, Barton P, et al. A systemic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and economic of their cost-effectiveness. Helth Technol Assess 2006; 10 (42)
52. Cartlehner G, Hansen RA, Jonas BL, et al. The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis: a systemic review and metaanalysis. J Rheumatol 2006; 33: 2398-2408
53 Alonso-Ruiz A, Pijoan JI, Ansuategui E et al. Tumor necrosis factor alpha drugs in rheumatoid arthritis: a systemic review and metaanalysis of efficacy and safety. BMC musculoskeletal disorders 2008; 9:52
54. Donahue KE et al. Systemic review: comparative effectiveness and harm of disease-modifying medications for rheumatoid arthritis. Ann Intern Med 2008; 148:124-131
55. Nixon R, Bansback N, Brennan A. The efficacy of inhibiting tumor necrosis factor alpha and interleukin 1 in patients with rheumatoid arthritis: a meta-analysis and adjusted indferect comparisons. Rheumatology 2007, online
56. Zink A, Strangfeld A, Schneider M, et al. Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observation cohort study. Arthritis Rheum 2006; 54: 3399-3407
57. Hyrich KM, Symmons DPM, Watson KD, et al. Comparison of the response to infliximab or etanercept monotherapy with the response to cotherapy with methotrexate or another disease-modifying antirheumatic drug in patients with rheumatoid arthritis. Results from the BSBR. Arthritis Rheum 2006; 54: 1786-1794
58. Krisatensen LE, Saxne T, Geborek P. The LUNDEX, a new index of drug efficacy in clinical practice. Results of a five-years observational study of treatment with infliximab and etanercept among rheumatoid arthritis patients in Southern Sweden. Arthritis Rheum 2006; 54:600-606
59. Keystone EC, Schiff MH, Kremer JM, et al. Once-weekly administration of 50mg etanercept in patients with active rheumatoid arthritis: Results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;50:353-63.
60 Weinblatt ME, Schiff MH, Ruderman EM, et al. Efficacy and safety of etanercept 50 mg twice a week in patients with rheumatoid arthritis who had a suboptimal response to etanercept 50 mg once a week. Arthritis Rheum 2008; 58: 1921-1930.
61. Ariza-Ariza R, Navarro-Sarabia F, Hernandez-Cruz B, et al. Dose escalation of the anti-TNF-a agents in patients with rheumatoid arthritis. A systemic review. Rheumatology 2006
62 Kavanaugh A, Klareskog L, van der Heijde D, et al. Improvement in clinical response between 12 and 24 weeks in patients with rheumatoid arthritis on etanercept therapy with or without methotrexate. Ann Rheum Dis 5 June 2008. on line
63. Lutt JR, Deodhar A. Rheumatoid arthritis. Strategies in the management of patients showing an Inadequate response to TNFa antagonist. drug 2008; 68:591-606
64. Iannone F, Trotta F, Montecucco C, et al. Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effect. Ann Rheum Dis 2007; 66:249-252
65. Cohen G, Courvoiser N, Cohen JD, et al. The efficiency of switching from infliximab to etanercept and vice-versa in patients with rheumatoid arthritis. Clin Exp Rheumatol 2005; 23:795-800
66. Di Poi E, Perrin A, Morassi MP, et al. Switching to etanercept in patients with rheumatoid arthritis with no response to infliximab. Clin Exp Rheumatol 2007; 25:85-87
67. Haraoui B, Keystone EC, Thorne JC, et al. Clinical outcome of patients with rheumatoid arthritis after swithing from infliximab to etanercept. J Rheumatol 2004; 31:2356-2359
68. Cantini F, Niccoli L, Porciello G, et al. Switching from ingliximab or adalimumab to etanercept 500 mg/once weekly in resistant or intolerant patients with rheumatoid arthritis. Arthritis Rheum 2005; 52 (Suppl 9): S384 (abst)
69. Buch MH, Bingham SJ, Bejarano V, et al. Therapy of patients with rheumatoid arthritis: outcome of infliximab failures switching to etanercept. Arthritis Rheum 2007; 57:448-453
70. Koike T, Harigai M, Inokuma S, et al. Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: results from a large Japanese post marketing surveillance. Ann Rheum Dis 2008; 67: (Suppl II):181
71 Finckh A, Ciurea A, Brulhart L, et al. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum 2007; 56: 1417-1423
72 Finckh A, Ciurea A, Brulhart L, et al. Which subgroup of rheumatoid arthritis patients benefit most from switching tp Rituximab versus alternative anti-TNF agents after previous failure to anti-TNF agents? Ann Rheum Dis 2008; 67 (Suppl II):
73. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for theumatoid arthritis refractory to anti-tumor necrosis factor therapy. Results of multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006; 54: 2793-2806
74. Rheumatoid arthritis - adalimumab, etanercept and infliximab (sequential use). http;//www.nice.org.uk/guidance/index
75. Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 2007; 66 (Suppl III): iii2-iii22
76. Stone JH. Tumor necrosis factor-alpha inhibitors: an overview of adverse effects. UpToDate 2008, May 31, version 16.2
77. Askling J, Dixon W. The safety of anti-tumor necrosis factor therapy in rheumatoid arthritis. Curr Opin Rheumatol 2008; 20:138-144
78. Solomon DH, Lunt M, Schneeweiss S. The risk of infection associated with tumor necrosis factor an antagonist. Making sense of epidemiologic evidence. Arthritis Rheum 2008; 58:919-928
79. Kozlov RS, Yakushin SB, Nasonov EL. Infectious complications of therapy with tumor necrosis factor blockers: forewarned is forearmed. Clinical Microbiology and Antimicrobial Chemotherapy, 2006, 8:314-324
80. Kim HA, Yoo CD, Baek HJ, et al. Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population. Clin Exp Rheumatol 1998; 16:9-13.
81 Doran MF, Crowson CS, Pond GR, et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 2002; 46:2287-2293.
82. Kroesen, S, Widmer, AF, Tyndall, A, Hasler, P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford) 2003; 42:617.
83. Crum, NF, Lederman, ER, Wallace, MR. Infections associated with tumor necrosis factor-alpha antagonists. Medicine (Baltimore) 2005; 84:291.
84. Gomez-Reino, JJ, Carmona, L, Valverde, VR, et al. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 2003; 48:2122.
85. Listing, J, Strangfeld, A, Kary, S, et al. Infections in patients with rheumatoid arthritis are treated with biologic agents. Arthritis Rheum 2005; 52:3403.
86. Curtis, JR, Patkar, N, Xie, A, et al. Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 2007; 56:1125.
87. Curtis, JR, Xi, J, Patkar, N, et al. Drug-specific and time-dependent risks of bacterial infection among patients with rheumatoid arthritis who were exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 2007; 56:4226.
88. Dixon, WG, Watson, K, Lunt, M, et al. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2006; 54:2368.
89. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006; 54:628-634
90 Askling J, Fored CM, Brandt L, et al. Time-dependent increase in risk of hospitalization with infection among Swedish RA patients treated with TNF antagonists. Ann Rheum Dis 2007; 66:1339-1344.
91 Dixon WG, Symmons DP, Lunt M, et al. Serious infection following antitumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies. Arthritis Rheum 2007; 56:2896-2904.
92. Keane, J, Gershon, S, Wise, RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345:1098.
93. Brassard, P, Kezouh, A, Suissa, S. Antirheumatic Drugs and the Risk of Tuberculosis. Clin Infect Dis 2006; 43:717.
94. Wallis, RS, Broder, MS, Wong, JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004; 38:1261.
95 Wolfe F, Michaud K, Anderson J, Urbansky K. Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum 2004;50:372-9.
96 Dixon WG, Hyrich KL, Watson KD, et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the BSP biologics register (BSRBR). Ann Rheum Dis 2008; 67: (Supp II) :178
97 Askling J, Fored CM, Brandt L, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum 2005;52(7):1986-92.
98 Tubach F, Salmon D, Ravaud P, et al. The risk of tuberculosis with anti-TNF is higher with monoclonal antibodies than with the soluble receptor. Results of the French 3-year prospective ratio observation. Ann Rheum Dis 2008; 67: (Suppl II): 52
99. Guidotti, LG, Ishikawa, T, Hobbs, MV, et al. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 1996; 4:25.
100. Guidotti, LG, Ando, K, Hobbs, MV, et al. Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proc Natl Acad Sci U S A 1994; 91:3764.
101. Nelson, DR, Lim, HL, Marousis, CG, et al. Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus infection. Dig Dis Sci 1997; 42:2487.
102. Ferri C, Ferraccioli G, Ferrari D, et al. Safety of anti-tumor necrosis factor-a therapy in patients with rheumatoid arthritis and chronic hepatitis C virus infection. J Rheumatol 2008, Aug 1. online.
103. Marotte H, Fontanges E, Bailly F, et al. Etanercept treatment for three months is safe in patients with rheumatologic manifestations associated with hepatitis C virus. Rheumatology 2007; 46:97-99
104. Mohan, N, Edwards, ET, Cupps, TR, et al. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001; 44:2862.
105. Nasonov E.L., Samsonov M.Yu. New aspects of the pathogenesis of heart failure: the role of tumor necrosis factor Heart failure, 2000; 1(4): 139-143
106. Mann, D, McMurray, J, Packer, M, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the randomized etanercept worldwide evaluation (RENEWAL). Circulation 2004; 109:1594.
107. Anker, SD, Coats, AJ. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 2002; 86:123.
108. Gabriel, SE. Tumor necrosis factor inhibition: a part of the solution or a part of the problem of heart failure in rheumatoid arthritis?. Arthritis Rheum 2008; 58:637.
109. Nasonov E.L. The problem of atherothrombosis in rheumatology. Bulletin of the Russian Academy of Medical Sciences, 2003; 7, 6-10
110. Nasonov E.L. Rheumatoid arthritis - model of atherothrombosis breast cancer 2005; 13:509-512
111. Jacobsson LTH, Turesson C, Culfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005; 32:1213-1228
112. Jacobsson LTN, Turesson C, Nilsson J-A, et al. Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66:670-675
113. Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor a therapy. Results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2007; 56: 2905-2912
114. Furst DE, Sokolove J, Greenberg J, et al. Risk of elevated liver enzyme (LFTS) with THF inhibitors in rheumatoid arthritis: analysis in 6861 patients with 22552 visits. Ann Rheum Dis 2008; 67:52
115. Haraoui B, Keystone E. Musculoskeletal manifestations and autoimmune diseases related to new biologic agents. Curr Opin Rheumatol 2006; 18:96-100
116. Mongey A-B, Hess EV. Drug insight: autoimmune effects of medications - what's new? Nat Clin Pract Rheumatol 2008; 4: 136-144`
117. Georgescu, L, Quinn, GC, Schwartzman, S, Paget, SA. Lymphoma in patients with rheumatoid arthritis: association with the disease state or methotrexate treatment. Semin Arthritis Rheum 1997; 26:794.
118. Gridley, G, McLaughlin, JK, Ekbom, A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85:307.
119. Ebeo, CT, Girish, MR, Byrd, RP, et al. Methotrexate-induced pulmonary lymphoma. Chest 2003; 123:2150.
120. Wolfe, W, Michaud, K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: Analyzes from a large US observational study. Arthritis Rheum 2007; 56:2886.
121. Stone, JH, Holbrook, JT, Marriott, MA, et al. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum 2006; 54:1608.

Tumor necrosis factor alpha (TNF-ᵅ) is a 157 amino acid protein. It is the first multifunctional TFN family cytokine whose properties have been identified for the treatment of cancer. Its biological activity is regulated by TNF-alpha soluble receptors 1 and 2.

The natural effect is directly expressed by the stimulation of the production of interleukin-1, which is capable of recognizing healthy and oncological structures at the cellular level. In this regard, tumor necrosis factor-alpha affects the cancer cell through its surface.

TNF-alpha in the body is mainly produced by active macrophages, T-lymphocytes and natural killer cells of the affected tissues. It plays a key role in apoptosis and cell reproduction.

However, the influence of this natural element is closely related to the toxicity of the substance. Therefore, more effective and less toxic variants of tumor necrosis factor are currently used, for example, such as Thymosin-alpha. Oncologists are also developing ways to directly deliver the necrosis factor to the tumor, without affecting other tissues and without being included in the general circulation.

Tumor necrosis factor-alpha and cancer

To date, the influence of this element, as well as its antagonists and subsequent biological elements, on such forms of oncological lesions as:

Malignant tumors of the stomach and chest:

Tumor necrosis factor-alpha leads to the death of potentially cancerous cells.

Non-small cell lung cancer:

TNF-alpha protects the body from the effects of various pathogens, which prevents the onset of the disease.

Sarcoma and melanoma:

In these types of cancers, a particularly effective tumor necrosis factor-alpha is recombinant.

Cancer of the uterus and ovaries:

Also are sensitive to this element.

Due to its ability to destroy the blood supply of the tumor, tumor necrosis factor-alpha can also be used for clinical therapy of metastatic cancer.

Preparations

Tumor necrosis factor-alpha related to cytokines. They are able to prevent tumor activity not only by counteracting abnormal cells, but also by combining with the main cellular mechanisms. Therefore, when creating drugs, the following types of drugs are used, represented by TNF inhibitors:

Monoclonal antibodies ("Infliximab", adalimumab "Humira", rituximab, represented by the drug "Rituxan");
Recombinant proteins that include immunoglobulin domains and TNF receptors, in particular interferon-1 and 2 (etanercept "Enbrel", golimumab "Simponi").

Among the Russian drugs of the cytokine group, Refnot, Reaferon, Roferon, Intron and others stand out.

Price

The cost of drugs of the cytokinic group directly depends on the country of manufacture. Medicines of European and American origin will be much more expensive than Russian and Ukrainian ones.

However, this does not mean at all that domestic pharmaceuticals will differ from imported ones in terms of the specifics of their action. So, for example, we will direct comparative prices for packages of the drug of the same capacity of 100 yew. unit:

preparations containing monoclonal antibodies (Russia): 1 bottle - from 1500 rubles. up to 2000 rubles; 5 bottles - from 10,000 rubles. up to 12,000 rubles;
medicines with monoclonal antibodies (Ukraine): 1 bottle - from 500 UAH. up to 800 UAH; for 5 bottles the price is from 2000 UAH. up to 3500 UAH;
recombinant: the cost in Russia for one bottle is from 2000 rubles. up to 3000 rub. In Ukraine, the price is higher: from 1000 UAH. up to 1800 UAH what is associated with the need for transportation;
the price of imported products containing tumor necrosis factor-alpha per vial ranges from 1000 USD. up to 1300 USD

Where to buy tumor necrosis factor-alpha?

Preparations containing tumor necrosis factor-alpha can be purchased in almost all countries of the world. In domestic pharmacology, drugs of the cytokine group are sold in pharmacies in large cities. But in most cases, drugs are given to the patient only by prescription and pre-order.

Patients from the CIS countries can purchase a drug from a Russian manufacturer, since the price of imported drugs is many times higher.

Suppression of TNF activity leads to a decrease in the synthesis of inflammatory mediators in the body, due to which the necessary therapeutic effect in the treatment of the disease is achieved.

Are you here:
home
News

2018 Oncology. All site materials are posted for informational purposes only and cannot be the basis for making any decisions on self-treatment, including. All copyrights to materials belong to their respective owners

tumor necrosis factor

Tumor necrosis factor (TNF): determination of TNF; TNF value; treatment with anti-TNF drugs; payback security for higher efficiency

TNF is synthesized by activated macrophages and has cytotoxic, immunomodulatory, and anti-inflammatory effects.
TNF is involved in antiviral, antitumor and transplantation immunity.
In relation to some tumors, TNF has a cytostatic and cytolytic effect.
TNF stimulates macrophages.
At high concentrations, TNF can damage endothelial cells and increase microvascular permeability, causing activation of the hemostasis and complement system, followed by neutrophil accumulation and intravascular microthrombosis (DIC).
The action of TNF extends to lipid metabolism, coagulation, insulin sensitivity and endothelial health, as well as a number of other functions.
TNF inhibits the growth of tumor cells and regulates a number of metabolic processes, as well as the activity of the immune response to infectious agents, which prevents the uncontrolled use of anti-TNF drugs and raises questions about their safety.

What are the mechanisms of antitumor action of TNF:

TNF has a targeted effect on a malignant cell through TNF receptors, provoking programmed cell death or suppressing the process of division; also stimulates the production of antigens in the affected cell;
stimulates "hemorrhagic" tumor necrosis (death of cancer cells).
blocking angiogenesis - suppression of the process of growth of tumor vessels, damage to tumor vessels without harming healthy vessels.

Features of the antitumor effect of TNF:

TNF does not act on all tumor cells; Cytotoxically resistant cells themselves produce endogenous TNF and active nuclear transcription factor NF-kB.
a number of cells show a dose-dependent effect of TNF, the combined use of cytokines TNF and IFN-gamma in many cases gives a much more pronounced effect than when treated with one of these drugs;
TNF acts on tumor cells that are resistant to chemotherapy, and TNF-based therapy in combination with chemotherapy can effectively kill the affected cells.

primary and secondary immunodeficiencies;
AIDS;
severe viral infections;
severe burns, injuries;
treatment with cytostatics, immunosuppressants, corticosteroids.

DIC;
sepsis;
infectious diseases;
allergic and autoimmune diseases;
crisis of rejection of donor organs in recipients;
oncological diseases.

Instrument - Microlab Star ELISA.

Norm: up to 87 pkg / ml

Reference values: 0 - 8.21 pg/ml.

Sepsis (the content may be of a phase nature - an increase at the beginning and a decrease with a pronounced prolonged infection due to the depletion of protective mechanisms).
Septic shock.
DIC syndrome.
Allergic diseases.
The initial period in HIV-infected.
Obesity.
In the acute period of various infections.

Severe and persistent viral infections.
Oncological diseases.
AIDS.
Secondary immunodeficiency states.
Injuries, burns (severe).
Myocarditis.
Taking drugs: immunosuppressants, cytostatics, corticosteroids.

How important are the functions of TNF in the human body?

The following mechanisms of influence of TNF are distinguished:

Cytotoxic effect on both tumor cells and cells affected by viruses.
Stimulates the formation of other active substances - leukotrienes, prostaglandins, thromboxane.
It has an immunomodulatory and anti-inflammatory effect (with the activation of macrophages and neutrophils).
Increased membrane permeability.
Increased insulin resistance (an effect leading to the development of hyperglycemia, possibly due to inhibition of the activity of insulin receptor tyrosine kinase, as well as stimulation of lipolysis and an increase in the concentration of free fatty acids).
Damage to the vascular endothelium and increased capillary permeability.
Activation of the hemostasis system.

An in-depth study of the immune status in the case of a severe course of acute, chronic, infectious and autoimmune diseases.
Oncology.
Severe mechanical injuries and burns.
Atherosclerotic lesions of the vessels of the brain and heart.
Rheumatoid arthritis and collagenoses.
Chronic pathology of the lungs.

Inflammatory CD4 T cell activity

Under the conditions of interaction of macrophages with inflammatory T-cells, a more efficient fusion of phagosomes, which captured bacteria, with lysosomes, the custodians of proteolytic enzymes that destroy intracellular pathogens, is observed. The process of phagocytosis is accompanied by the so-called oxygen explosion - the formation of oxygen radicals and nitric oxide, which have bactericidal activity.

Anti-TNF therapy should not be prescribed to debilitated patients, as well as to those who have previously had an infectious disease, because. in both cases, they are at high risk of infection.

Reviews

I would like to see the bibliography

They will not present literature to you. Controversial. Not proven. Experiments.

I underwent a course of treatment with Dr. Ognevoy for psoriasis. By the way, it is quite effective. And now she is forcing the TNF to give up !! Can someone explain why and what he shows with psoriasis. Although the rate has dropped. TNF twice!! And the skin is clean

Where can you buy this drug?

where can i buy tumor necrosis factor

HYBRID POLYPEPTIDE WITH ACTIVITY α1-THYMOSIN-α-TUMORS NECROSIS FACTOR-THYMOSIN a1, METHOD FOR OBTAINING HYBRID POLYPEPTIDE WITH ACTIVITY α1-THYMOSIN- α-TUMORSNECROSIS FACTOR-THYMOSIN a1 , RECOMBINANT PLASMID DNA pThy EXPRESSING A HYBRID POLYPEPTIDE WITH ACTIVITY α1 - THYMOSIN α TUMOR NECROSIS FACTOR - THYMOSIN- a1 Patent of the Russian Federation

Anti TNF preparations

Rheumatology is a specialization of internal medicine dealing with the diagnosis and treatment of rheumatic diseases.

Drugs that are not tumor necrosis factor (TNF) inhibitors are more effective in treating patients with rheumatoid arthritis who do not respond to anti-TNF drugs, according to a clinical study published in the Journal of the American Medical Association.

Anti-TNF drugs are used worldwide to treat rheumatoid arthritis. They deactivate TNF, molecules produced by the immune system that cause inflammation. However, about a third of patients do not respond to this type of therapy.

The study involved 300 patients with rheumatoid arthritis who had an insufficient response to anti-TNF drugs.

All participants were divided into two groups. In the first group, patients received anti-TNF drugs such as adalimumab, etanercept, certolizumab, and infliximab for 52 weeks. In the second group, patients took non-TNF drugs such as tocilizumab, rituximab, and abatacept.

The results of the study showed that 54% of patients who took anti-TNF drugs and 69% of participants who took non-TNF drugs had a moderate response to treatment.

In addition, more patients taking non-TNF drugs had low levels of disease activity at 24 and 52 weeks of the study.

The researchers concluded that patients with rheumatoid arthritis who have not responded to anti-TNF drugs may benefit from non-TNF drugs.

Treatment with anti-TNF drugs: paying off safety for higher efficacy?

Tumor necrosis factor (TNF) is an extracellular protein, an inflammatory cytokine with a wide spectrum of action, which is synthesized mainly by monocytes and macrophages. Its action extends to lipid metabolism, coagulation, insulin sensitivity and endothelial health, as well as a number of other functions.

For the first time, TNF was detected in the blood serum of mice that were injected with BCG and endotoxin. It turned out that the serum of such mice has a cytotoxic effect, and further study revealed the protein responsible for the development of this effect.

In recent years, the importance of TNF has become increasingly important. Increased interest is associated with the bidirectional action of this cytokine. On the one hand, it plays an important role in the regulation of normal differentiation, growth and metabolism of various cells, and on the other hand, it acts as a mediator of pathological immunoinflammatory processes in various human diseases.

Treatment of polyarthritis

Polyarthritis is a type of arthritis in which the disease affects multiple joints. It affects people of all genders and ages and is often associated with various autoimmune disorders.

Treatment

Basic treatment of polyarthritis (prescribed by a rheumatologist);

Symptomatic treatment (aimed at pain relief).

In the second case, non-steroidal anti-inflammatory drugs (in various forms) are used, for example, brufen, indomethacin-Acri, flugalin, orthofen, roxicam. But it is worth considering the side effects, as well as contraindications to taking these drugs (for example, peptic ulcer).

Medical treatment

Non-steroidal anti-inflammatory

NSAIDs help reduce inflammation. They block the activity of prostaglandins (substances that play an important role in inflammation). They also help relieve mild to moderate pain. NSAIDs are fast-acting and often have fewer side effects than other stronger and more toxic drugs used to treat arthritis. In some cases, taking these medicines can cause indigestion, as well as the formation of ulcers.

Corticosteroids

Treatment of polyarthritis with these medicines helps to relieve inflammation, as well as suppress the immune response. Due to the fact that polyarthritis is often caused by autoimmune disorders, such as systemic lupus, these drugs are used to suppress the immune response that accompanies such disorders.

In most cases, it is corticosteroids that are first prescribed to patients with such diseases. In order to prevent steroid-induced osteoporosis, it is recommended to use, for example, bisphosphonates. These medicines often reduce pain and other symptoms much faster than other medicines.

Basic antirheumatic drugs (DMARDs)

PRPs modify the course of the disease. They can change the course of many diseases that cause polyarthritis. Due to the fact that they begin to act only 6-8 weeks after the start of administration, during this period an additional simultaneous intake of NSAIDs and corticosteroids is often prescribed. DMARDs, like corticosteroids, achieve their therapeutic effect by suppressing the immune system.

Polyarthritis is often treated with methotrexate, the same drug that is sometimes used for chemotherapy in cancer patients (at high doses). Methotrexate sometimes causes liver damage, therefore, during its use, it is necessary to regularly analyze the patient's blood in order to detect this, as well as other possible side effects, as early as possible.

The following DMARDs are also used to treat polyarthritis:

Sulfasalazine.
Hydroxychloroquine (an antimalarial drug). In 1 case, ison causes serious damage to the eyes.

Anti-TNF drugs

In many types of arthritis, including polyarthritis, tumor necrosis factor can cause inflammation. Drugs that block tumor necrosis factor are called anti-TNF drugs.

Treatment of polyarthritis requires the use of the following anti-TNF drugs:

They are administered by subcutaneous injection or intravenously. Taking anti-TNF can cause chills, joint and muscle pain, fever, increased susceptibility to infections, headaches, and other side effects in some cases.

Physiotherapy

Physiotherapy provides an opportunity to reduce pain, inflammation and swelling. This treatment of polyarthritis, such as magnetic therapy, paraffin, ozokerite therapy, ultrasound, cryotherapy, is used simultaneously with drug therapy. They make it possible to restore blood flow to joints that have been damaged, as well as slow down the process of bone loss and normalize metabolism.

It is impossible to completely eliminate this disease. In this regard, the treatment of polyarthritis is always necessary. With the help of continuous treatment, the patient will be able to maintain the quality of his life for a long time, as well as the usual level of activity and excellent well-being.

Please note: the information posted on the site is not a medical recommendation, advice or guide to action. Before using the information presented on our portal, be sure to consult your doctor!

Tumor necrosis factor - Alpha

TNF-alpha in the body is mainly produced by active macrophages, T-lymphocytes and natural killer cells of the affected tissues. It plays a key role in apoptosis and cell reproduction.

Tumor necrosis factor-alpha and cancer

To date, the influence of this element, as well as its antagonists and subsequent biological elements, on such forms of oncological lesions as:

Malignant tumors of the stomach and chest:

Tumor necrosis factor-alpha leads to the death of potentially cancerous cells.

Non-small cell lung cancer:

TNF-alpha protects the body from the effects of various pathogens, which prevents the onset of the disease.

Sarcoma and melanoma:

In these types of cancers, a particularly effective tumor necrosis factor-alpha is recombinant.

Cancer of the uterus and ovaries:

Also are sensitive to this element.

Due to its ability to destroy the blood supply of the tumor, tumor necrosis factor-alpha can also be used for clinical therapy of metastatic cancer.

Preparations

Tumor necrosis factor-alpha is a cytokine. They are able to prevent tumor activity not only by counteracting abnormal cells, but also by combining with the main cellular mechanisms. Therefore, when creating drugs, the following types of drugs are used, represented by TNF inhibitors:

Monoclonal antibodies ("Infliximab", adalimumab "Humira", rituximab, represented by the drug "Rituxan");
Recombinant proteins that include immunoglobulin domains and TNF receptors, in particular interferon-1 and 2 (etanercept "Enbrel", golimumab "Simponi").

Among the Russian drugs of the cytokine group, Refnot, Reaferon, Roferon, Intron and others stand out.

The cost of drugs of the cytokinic group directly depends on the country of manufacture. Medicines of European and American origin will be much more expensive than Russian and Ukrainian ones.

preparations containing monoclonal antibodies (Russia): 1 bottle - from 1500 rubles. up to 2000 rubles; 5 bottles - bran. dorub.;
medicines with monoclonal antibodies (Ukraine): 1 bottle - from 500 UAH. up to 800 UAH; for 5 bottles the price is from 2000 UAH. up to 3500 UAH;
recombinant tumor necrosis factor: the cost in Russia for one bottle is from 2000 rubles. up to 3000 rub. In Ukraine, the price is higher: from 1000 UAH. up to 1800 UAH what is associated with the need for transportation;
the price of imported products containing tumor necrosis factor-alpha per vial ranges from 1000 USD. up to 1300 USD

Where to buy tumor necrosis factor-alpha?

Patients from the CIS countries can purchase a drug from a Russian manufacturer, since the price of imported drugs is many times higher.

Reviews

About the drugs in this group, there are different opinions not only of cancer patients and their relatives, but also of the oncologists themselves:

Some point to the ability of drugs with tumor necrosis factor-alpha to fight cancer on their own.
Other experts confirm only the ability of cytokines to enhance the effect of traditional therapy.
Emphasis on possible side effects, especially for patients with latent viral infections, tuberculosis, cardiovascular disease and chronic liver disease.

In any case, the maximum duration of treatment with tumor necrosis factor-alpha is only 2 courses. It can be carried out at home after a thorough diagnosis and collection of tests.

There are few patient reviews of the drug, but most patients with the therapeutic use of tumor necrosis factor-alpha note an improvement in their general state of health, especially in the presence of advanced or recurrent cancer. Some, in the later stages of the development of the disease, perceive the drug as the only panacea. However, this attitude is not adequate. Even despite the positive reviews, research is still underway in world practice regarding the safety of the product.

Tumor necrosis factor-alpha is one of the newest biological weapons, which is still a lot of discussion in scientific oncology.

It is important to know:

Add a comment Cancel reply

Categories:

The information on this site is provided for informational purposes only! It is not recommended to use the described methods and recipes for the treatment of cancer on your own and without consulting a doctor!

Tumor necrosis factor (TNF): role in the body, determination in the blood, administration in the form of drugs

Tumor necrosis factor (TNF) is an extracellular protein that is practically absent in the blood of a healthy person. This substance begins to be actively produced in pathology - inflammation, autoimmunization, tumors.

In modern literature, you can find its designation as TNF and TNF-alpha. The latter name is considered obsolete, but is still used by some authors. In addition to alpha-TNF, there is another form of it - beta, which is formed by lymphocytes, but much slower than the first - for several days.

TNF is produced by blood cells - macrophages, monocytes, lymphocytes, as well as the endothelial lining of blood vessels. When a foreign antigen protein (a microorganism, its toxin, tumor growth products) enters the body, TNF reaches its maximum concentration within the first 2-3 hours.

Tumor necrosis factor does not damage healthy cells, but it has a strong antitumor effect. For the first time, such an effect of this protein was proved in experiments on mice in which regression of tumors was observed. In this regard, the protein got its name. Later studies showed that the role of TNF is not limited to the lysis of tumor cells, its action is multifaceted, it takes part not only in reactions in pathology, but is also necessary for a healthy body. At the same time, all the functions of this protein and its true essence still raise a lot of questions.

The main role of TNF is participation in inflammatory and immune responses. These two processes are closely related and cannot be separated. At all stages of the formation of the immune response and inflammation, tumor necrosis factor acts as one of the main regulatory proteins. In tumors, both inflammatory and immune processes, “controlled” by cytokines, also actively occur.

The main biological effects of TNF are:

Participation in immune reactions;
regulation of inflammation;
Influence on the process of hematopoiesis;
Cytotoxic action;
intersystem effect.

When microbes, viruses, foreign proteins enter the body, immunity is activated. TNF promotes an increase in the number of T- and B-lymphocytes, the movement of neutrophils to the site of inflammation, the "sticking" of neutrophils, lymphocytes, macrophages to the inner lining of blood vessels at the site of inflammation. An increase in vascular permeability in the area of development of the inflammatory response is also the result of the action of TNF.

The effect of tumor necrosis factor (TNF) on body cells

Tumor necrosis factor affects hematopoiesis. It inhibits the reproduction of erythrocytes, lymphocytes and white blood cells, but if hematopoiesis is suppressed for any reason, then TNF will stimulate it. Many active proteins, cytokines, have a protective effect against radiation. TNF also has this effect.

Tumor necrosis factor can be detected not only in blood, urine, but also in cerebrospinal fluid, which indicates its cross-system effect. This protein regulates the activity of the nervous and endocrine systems. The beta-type of TNF has a predominantly local effect, and the organism owes its systemic manifestations of immunity, inflammation and regulation of metabolism to the alpha-form of the cytokine.

One of the most important effects of TNF is cytotoxic, that is, cell destruction, which fully manifests itself during the development of tumors. TNF acts on tumor cells, causing their death due to the release of free radicals, reactive oxygen species and nitric oxide. Since single cancer cells are formed in any organism throughout life, healthy people also need TNF for their timely and rapid neutralization.

Transplantation of organs and tissues is accompanied by the placement of foreign antigens into the body, even if the organ is the most suitable for a set of specific individual antigens. Transplantation is often accompanied by activation of local inflammatory reactions, which are also based on the action of TNF. Any foreign protein stimulates an immune response, and transplanted tissues are no exception.

After transplantation, an increase in the content of cytokine in the blood serum can be detected, which indirectly may indicate the onset of a rejection reaction. This fact underlies research on the use of drugs - antibodies to TNF, which can slow down the rejection of transplanted tissues.

The negative effect of high concentrations of TNF can be traced in severe shock against the background of septic conditions. The production of this cytokine is especially pronounced during infection with bacteria, when a sharp suppression of immunity is combined with heart, kidney, and liver failure, leading to the death of patients.

TNF is able to break down fat and deactivate the enzyme involved in the accumulation of lipids. Large concentrations of the cytokine lead to depletion (cachexia), so it was also called cachectin. These processes cause cancer cachexia and malnutrition in patients with long-term infectious diseases.

In addition to the described properties, TNF also plays a reparative function. Following damage in the focus of inflammation and an active immune response, healing processes increase. TNF activates the blood coagulation system, due to which the zone of inflammation is delimited by means of the microvasculature. Microthrombi prevent further spread of infection. Activation of fibroblast cells and their synthesis of collagen fibers contributes to the healing of the lesion.

Determination of the level of TNF and its significance

A laboratory study of the level of TNF does not apply to frequently used tests, but this indicator is very important for certain types of pathology. The definition of TNF is shown when:

Frequent and prolonged infectious and inflammatory processes;
autoimmune diseases;
malignant tumors;
burn disease;
Injuries;
Collagenosis, rheumatoid arthritis.

An increase in the level of cytokines can serve not only as a diagnostic but also as a prognostic criterion. So, in sepsis, a sharp increase in TNF plays a fatal role, leading to severe shock and death.

For research, venous blood is taken from the patient, it is not allowed to drink tea or coffee before the analysis, only plain water is allowed. At least 8 hours in advance, you should exclude the intake of any food.

An increase in TNF in the blood is observed with:

Infectious pathology;
sepsis;
burns;
Allergic reactions;
Autoimmune processes;
multiple sclerosis;
Meningitis and encephalitis of a bacterial or viral nature;
DIC;
Graft-versus-host reactions;
Psoriasis;
Diabetes mellitus of the first type;
Myeloma and other tumors of the blood system;
Shock.

In addition to an increase, a decrease in the level of TNF is also possible, because normally it should be present, albeit in scanty amounts, to maintain health and immunity. A decrease in the concentration of TNF is typical for:

immunodeficiency syndromes;
Cancer of internal organs;
The use of certain drugs - cytostatics, immunosuppressants, hormones.

TNF in pharmacology

The variety of biological responses mediated by TNF prompted research into the clinical use of tumor necrosis factor preparations and its inhibitors. The most promising are antibodies that reduce the amount of TNF in severe diseases and prevent deadly complications, as well as a recombinant synthetic cytokine prescribed for cancer patients.

Actively used drugs analogues of human tumor necrosis factor in oncology. For example, such treatment, along with standard chemotherapy, shows high efficiency against breast cancer and some other tumors.

TNF-alpha inhibitors have anti-inflammatory effects. With the development of inflammation, there is no need to immediately prescribe drugs of this group, because in order to recover, the body itself must go through all the stages of the inflammatory process, form immunity and ensure healing.

Early suppression of natural defense mechanisms is fraught with complications, therefore, TNF inhibitors are indicated only with an excessive, inadequate response, when the body is unable to control the infectious process.

TNF inhibitor drugs - Remicade, Enbrel - are prescribed for rheumatoid arthritis, Crohn's disease in adults and children, ulcerative colitis, spondyloarthritis, psoriasis. As a rule, these drugs are not used if standard therapy with hormones, cytostatics, antitumor agents is ineffective, if it is intolerable or if there are contraindications to drugs of other groups.

Antibodies to TNF (infliximab, rituximab) suppress excessive production of TNF and are indicated for sepsis, especially with the risk of developing shock; in advanced shock, they reduce mortality. Antibodies to cytokines can be prescribed in case of long-term infectious diseases with cachexia.

Thymosin-alpha (timaktid) is classified as an immunomodulatory agent. It is prescribed for diseases with impaired immunity, infectious pathology, sepsis, for the normalization of hematopoiesis after irradiation, for HIV infection, and severe postoperative infectious complications.

Cytokine therapy is a separate direction in the treatment of oncopathology, which has been developing since the end of the last century. Cytokine preparations show high efficiency, but their independent use is not justified. The best result is possible only with an integrated approach and the combined use of cytokines, chemotherapy and radiation.

TNF-based drugs destroy the tumor, prevent the spread of metastases, and prevent recurrence after removal of tumors. When used simultaneously with cytostatics, cytokines reduce their toxic effect and the likelihood of adverse reactions. In addition, due to the favorable effect on the immune system, cytokines prevent possible infectious complications during chemotherapy.

Among TNF drugs with antitumor activity, refnot and ingaron, registered in Russia, are used. These are drugs with proven effectiveness against cancer cells, but their toxicity is an order of magnitude lower than the cytokine produced in the human body.

Refnot has a direct destructive effect on cancer cells, inhibits their division, and causes hemorrhagic tumor necrosis. The viability of a neoplasm is closely related to its blood supply, and refnot reduces the formation of new vessels in the tumor and activates the coagulation system.

An important property of refnot is its ability to enhance the cytotoxic effect of drugs based on interferon and other antitumor agents. So, it increases the effectiveness of cytarabine, doxorubicin and others, due to which a high antitumor activity of the combined use of cytokines and chemotherapeutic drugs is achieved.

Refnot can be prescribed not only for breast cancer, as indicated in the official recommendations for use, but also for other neoplasms - lung cancer, melanoma, tumors of the female reproductive system

Side effects with the use of cytokines are few, usually a short-term fever, itchy skin. The drugs are contraindicated in case of individual intolerance, pregnant women and nursing mothers.

Cytokine therapy is prescribed exclusively by a specialist, self-medication in this case is out of the question, and drugs can be purchased only by prescription. For each patient, an individual treatment regimen and combinations with other antitumor agents are developed.

Tumor necrosis factor inhibitors - modern drugs for the treatment of rheumatoid arthritis

TNF-α (tumor necrosis factor alpha) plays a key role in starting and maintaining the inflammatory process in rheumatoid arthritis (RA). Suppression of TNF activity leads to a decrease in the synthesis of inflammatory mediators in the body, due to which the necessary therapeutic effect in the treatment of the disease is achieved.

Let us consider the use of TNF-α inhibitors in clinical practice using the example of a drug called etanercept, which has been widely used over the past 10 years in the United States, Canada, and European countries. This TNF inhibitor is designed for subcutaneous administration, which allows patients with RA to avoid costly and lengthy hospitalizations.

Etanercept is used in the treatment of rheumatoid arthritis with moderate to high inflammatory activity. The drug has a stimulating effect on the TNF-α receptors present in the patient's body. As a result, receptors more actively capture excess TNF-α, thereby reducing its concentration, which leads to a decrease in the inflammatory process.

Like other TNF-α inhibitor drugs, etanercept differs significantly in its pharmacological action from the immunosuppressants also used in some RA treatment regimens. Immunosuppressants affect almost the entire immune system, while TNF-α inhibitors are active against specific targets, which are specific sites in the pathogenesis of rheumatoid arthritis.

The results of etanercept studies have shown that a new drug, a TNF inhibitor, leads to a significant reduction in the severity of symptoms of the disease, the achievement of stable and long-term remissions. Etanercept can be used both as monotherapy for RA (treatment with this drug alone) and as part of complex treatment. TNF inhibitors can be combined with non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressants (methotrexate), glucocorticoids (GCs), and pain medications.

Etanercept is given by injection under the skin. "Injections" are performed twice a week. Possible injection zones: under the skin of the shoulder, anterior abdominal wall or thigh. Hospitalization of patients for treatment with a TNF inhibitor is not required; injections can be made by a nurse in the treatment room of a polyclinic or at home.

It has not been established with certainty what effect TNF-α inhibitors have on the protective function of the immune system. Therefore, patients receiving etanercept should be warned that the use of the drug can potentially provoke infection with various infections. Etanercept should not be used in patients with weakened immune systems as in this case, patients may develop serious infectious diseases that are fraught with sepsis and death. Etanercept is also contraindicated in patients with certain heart conditions (the drug can lead to severe cardiovascular failure). TNF-α inhibitors are not intended for the treatment of RA without the participation of a physician.

News feed Spinet.ru

08.02 Is it possible to wear high heels if you have back problems?
01.02 How do bone fractures occur in the elderly
27.01 Benefit or harm from training in winter
22.01 Kinesiology taping: myths and reality
15.01 What diet is good for bones

Arthritis

Arthritis
What is arthritis
Causes
Acute purulent arthritis
gonorrheal arthritis
Chlamydial arthritis
Post-vaccination arthritis
Arthritis traumatic
Occupational arthritis
Rheumatism
Reactive arthritis
Arthritis in children
Arthralgia
Shoulder arthritis
Complications of Arthritis
DIAGNOSTICS
Diagnostics
Diagnostic methods
Early diagnosis
Laboratory diagnostics
Difficulties in diagnosis
Method of early diagnosis
The role of tumor necrosis factor in rheumatoid arthritis
The role of T cells in the development of rheumatoid arthritis
TREATMENT
Treatment of rheumatoid arthritis
Diet treatment
Cryotherapy
Hydrogen peroxide
Chondoprotectors
Diet food
Physiotherapy
Gymnastics for joints
Start treatment as early as possible
Medicines
Relieve pain at home
How is arthritis treated?
Prevent joint destruction in arthritis
Spa treatment
Folk methods
Treatment with bee venom
Use of paraffin
What is the treatment for arthritis?
Alternative Therapy for Arthritis
Use (GCS) in therapy
The role of drug therapy
Treatment of gouty arthritis
Treatment with folk methods
The use of dietary supplements in therapy
Phytotherapy in the treatment of arthritis
Tumor necrosis factor inhibitors
PREVENTION
Joints hurt
Workouts for arthritis
Aerobics
diet for arthritis

spine health ©

All information on the site is for informational purposes only. Do not use this information for self-medication. Possible contraindications. Be sure to consult your doctor.

FNO blockers. Tumor necrosis factor-a - a new target for anti-inflammatory therapy in rheumatoid arthritis

Video:

Healthy:

Related articles:

Tumor necrosis factor-alpha and cancer

Preparations

Price

Where to buy tumor necrosis factor-alpha?

tumor necrosis factor

Reviews

Anti TNF preparations

Treatment with anti-TNF drugs: paying off safety for higher efficacy?

Treatment of polyarthritis

Treatment

Medical treatment

Non-steroidal anti-inflammatory

Corticosteroids

Basic antirheumatic drugs (DMARDs)

Anti-TNF drugs

Physiotherapy

Tumor necrosis factor - Alpha

Tumor necrosis factor-alpha and cancer

Preparations

Where to buy tumor necrosis factor-alpha?

Reviews

It is important to know:

Add a comment Cancel reply

Categories:

Tumor necrosis factor (TNF): role in the body, determination in the blood, administration in the form of drugs

Determination of the level of TNF and its significance

TNF in pharmacology

Tumor necrosis factor inhibitors - modern drugs for the treatment of rheumatoid arthritis

News feed Spinet.ru

Recent topics in the forum:

Arthritis