Моноклональные антитела в лечении бронхиальной астмы

Monoclonal antibodies in the treatment of bronchial asthma

KOSYKH A. V.

Teacher, pharmacist-organizer, clinical pharmacologist

FSBEI of HE «Stavropol State Medical University» Essentuksky branch

(Russia, Essentuki)

Email: alekskosyx@mail.ru

Abstract: An innovative drug for biological therapy of bronchial asthma (BA) omalizumab (Ksolar) has become available in Russian clinical practice. The drug is a recombinant humanized monoclonal antibodies against immunoglobulin (Ig) E. Subcutaneous administration of Xolar reduces plasma levels of IgE to undetectable values ​​and inhibits early and late bronchospastic response to allergenic provocation.

Key words: monoclonal antibodies, innovative drug, bronchial asthma, Xolar, basic therapy

An innovative drug for biological therapy of bronchial asthma (BA) omalizumab (Ksolar) has become available in Russian clinical practice. The drug is a recombinant humanized monoclonal antibodies against immunoglobulin (Ig) E. Subcutaneous administration of Xolar reduces plasma levels of IgE to undetectable values ​​and inhibits early and late bronchospastic response to allergenic provocation.

In patients with chronic severe IgE-mediated asthma requiring therapy with high doses of inhaled or oral glucocorticosteroids, Xolar treatment reduces the frequency of asthma exacerbations, reduces the severity of the disease and allows, in steroid-dependent asthma, to reduce the maintenance dose of glucocorticosteroids or completely cancel them. The drug has a good safety profile. The introduction of Xolar (omalizumab) into Russian clinical practice will significantly improve the quality of medical care for patients with uncontrolled atopic BA of moderate and severe course.

The clinical efficacy of Xolar has been studied in the INNOVATE study (Investigation of Omalizumab in Severe Asthma Treatment - Omalizumab study in the treatment of severe bronchial asthma). In this randomized, placebo-controlled, double-blind study, in which only patients with severe persistent atopic asthma uncontrolled despite drug treatment took part (stage IV therapy according to the recommendations of GINA (Global Initiative for Asthma) ), evaluated the efficacy, safety and tolerability of Xolar during 28 weeks of treatment. The efficacy analysis took into account the data of 419 patients with persistent atopic asthma uncontrolled despite treatment with high doses of glucocorticosteroids and LABA in combination with other drugs for asthma control (if necessary). In addition to the ongoing treatment, patients received either Xolar by subcutaneous injection or placebo. The Xolar dose for each patient was determined according to the dose calculation table based on the initial IgE level and body weight.

The INNOVATE study demonstrated that in patients with uncontrolled severe persistent atopic asthma, the addition of Xolar to treatment (stage IV according to the GINA recommendations) leads to the following results:

• reduction in the number of clinically significant BA exacerbations by 26%;

• reducing the number of severe exacerbations by 50%;

• a significant (44%) decrease in the number of emergency medical visits (the number of hospitalizations, including admissions to intensive care units, unscheduled visits to the doctor) compared with placebo.

In the subgroup of patients who responded to treatment with omalizumab, the frequency of clinically significant exacerbations of asthma over a 28-week treatment period decreased by 60.5% compared with the placebo group (0.34 versus 0.85, p <0.001). It is especially important that the frequency of severe exacerbations of asthma in the main group decreased by 76% compared with the placebo group (0.13 versus 0.54, p <0.001).

According to a study by S.T. Holgate et al., In patients with chronic severe asthma requiring therapy with high doses of ICS or oral glucocorticosteroids, Xolarom treatment reduces the frequency of asthma exacerbations, reduces the severity of asthma, and allows for steroid-dependent asthma to reduce or even cancel the doses of systemic drugs. This treatment improves the course of other related allergic diseases.

A pooled analysis of 7 clinical trials showed that when Xolar was used in patients with severe persistent asthma (93% of all analyzed participants), the frequency of exacerbations was reduced by 38%, and the frequency of emergency visits for medical help was reduced by 47%. In another pooled analysis, including data from 6 clinical trials (1342 patients received Xolar, 1206 patients received placebo), the effect of the drug on the quality of life was assessed using the Asthma Quality of Life Questionnaire (Asthma Quality of Life Questionnaire) scale.

When Xolar was prescribed, a significantly more pronounced improvement in the quality of life on the AQLQ scales was revealed than in the placebo / control groups (1.01 versus 0.61; p <0.001), and there was also a significant difference in the number of patients who achieved a clinically significant improvement (by ≥ 0.5 points) (66.3% versus 52.4%; p <0.001). The use of Xolar in patients with severe asthma reduces the risk of death from severe exacerbations of asthma.

According to American scientists, the addition of omalizumab to ICS therapy in asthma is accompanied by an improvement in a significant proportion of patients and reduces the number of BA exacerbations by 19–75% (regardless of the use of LABA or antileukotriene agents).

In patients with severe persistent allergic asthma with elevated serum IgE levels, when prescribing omalizumab at an average dose of 450 mg every 4 weeks after 6 weeks of treatment, the number of day and night attacks of asthma is significantly reduced, as well as the frequency of exacerbations (by 82%), and the overall quality of life improves. ... The majority of doctors (82%) and patients (86%) assess the effectiveness of the drug as “excellent”.

Within a year after the appointment of omalizumab, in addition to the standard basic therapy, 49% of patients did not need oral steroids, which is 47% more than in the basic therapy group. Treatment with Xolarom allowed to reduce the need of patients for emergency drugs (short-acting beta-2-agonists) by 80%. Omalizumab improved the quality of life of AD patients by 49% compared to placebo. The drug demonstrates high efficiency and safety when used in children.

In the countries of the European Union, omalizumab is prescribed in addition to the therapy that the patient receives for severe atopic persistent asthma, while sensitization to environmental allergens has been proven, there are decreased indicators of respiratory function (forced expiratory volume in 1 second (FEV1) less than 80% ) and documented severe exacerbations while taking high doses of combined drugs.

It is rather difficult to predict the clinical efficacy of the Xolar drug, therefore the decision on the further use of the drug must be made in each specific case after 12 weeks of treatment with omalizumab, taking into account the severity of the disease before the start of drug treatment, the need for additional therapy and the dynamics of the frequency of exacerbations.

The use of anti-IgE monoclonal antibodies (omalizumab) is indicated in patients with the phenotype of chronic severe asthma, atopic severe asthma and IgE-mediated response, including those taking systemic steroids. The effectiveness of omalizumab therapy in such patients is expressed in a decrease in the frequency of exacerbations of asthma, a decrease in the severity of asthma, and a decrease in the doses of inhaled or oral glucocorticosteroids required to control the disease.

The indication for the use of Xolar (omalizumab) in Russia is the treatment of persistent atopic bronchial asthma of moderate and severe course, the symptoms of which are insufficiently controlled by the use of inhaled glucocorticosteroids, in patients aged 6 years and older.

The introduction of Xolar (omalizumab) into Russian clinical practice will significantly improve the quality of medical care for patients with uncontrolled atopic BA of moderate and severe course. Considering that in the structure of BA treatment costs the share of expenses for treatment of severe BA reaches 80% (mainly the cost of providing emergency medical care, expensive hospitalizations and long periods of disability), the use of Xolar (omalizumab) can reduce the use of health care resources and the economic burden of this severe disease.

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