Personalized targeted therapy of moderate and severe atopic asthma in Russia

Introduction. Taking into account the prevalence of asthma and especially severe atopic asthma which requires carefully selected and expensive therapy, the appearance of the domestic biosimilar omalizumab among biological therapy drugs makes the choice of treatment for this category more affordable. The article presents the results of an observational open prospective clinical trial of the omalizumab biosimilar in severe athopic asthma patients.The purpose of this study was to evaluate the efficacy and safety of the domestic production biosimilar in the real clinical practice.Materials and methods. The study involved 10 adult patients aged 19 to 55 years with a diagnosis of moderate to severe uncontrolled persistent asthma treated with mediun to high dose ICS and second&more controller (ACQ-5 ≥ 1,5, FEV1 < 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources. Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of  breath and SABA using. An  asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p >< 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment. Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety>< 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources.Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of  breath and SABA using. An  asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p < 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment.Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety

Transforming growth factors TGF- β1, TGF- β2 and TGF- β3 in the tissue of nasal polyps in different phenotypes of chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSP) is a heterogenous disease. We have earlier detected differences in severity of clinical manifestations, cellular infiltration degree shown in nasal polyps, of eosinophil-to-neutrophil ratio, efficacy of intranasal glucocorticosteroid baseline therapy, and various inflammatory patterns for several cytokines on the mRNA expression level in different phenotypes with isolated CRSP cases, CRSP associated with respiratory allergy (RA), or non-allergic bronchial asthma.The purpose of this work was to study the cytokines of TGF-â family in the tissues of nasal polyps in patients with different CRSP phenotypes. The research involved 292 patients suffering from CRSP divided into 3 phenotypic groups. Group I consisted of patients with isolated CRSP free of associated BA and/or sensitization to atopic allergens. Group II included patients with CRSP combined with respiratory allergy and was further divided into two subgroups. I.e., Group 2a comprised patients with CRSP, allergic BA (aBA), and allergic rhinitis (AR), while the patients with CRSP, AR, and non-allergic BA were placed to the group 2b. The patients suffering from CRSP complicated with non-allergic BA were allocated to the group III. The patients with hypertrophic rhinitis served as control. The levels of TGF-â1, TGF-â2, and TGF-â3 proteins (pg/mg) were measured by means of multiplex immunoassay approach in supernates of tissue homogenates from nasal polyps removed by surgery, and in posterior parts of inferior nasal conchae. The total protein level was determined in tissue supernatant, with cytokine contents recalculated for the mg/ml protein concentration for standardization of measurements.In the control group, trace concentrations of all three growth factors were detected. Significant difference in protein contents was found for the studied cytokines, depending on CRSP phenotype. The levels of TGF-â1 and TGF-â2 were statistically lower in isolated CRSP than in other groups of comorbid CRSP patients. TGF-â1 and TGF-â2 concentrations were significantly lower in CRSP + allergic BA group IIa than in CRSP + nonallergic BA and CRSP + RA groups. The amount of TGF-â3 cytokine was maximal in CRSP + non-allergic BA group III compared to the patients with isolated CRSP of group I and CRSP + non-allergic BA group 2a.Conclusions.The high level of all three TGF-â isoforms in patients with CRSP compared to the control group suggested a high potential of mucous membranes of paranasal sinuses for active tissue remodeling followed by nasal polype formation.Different mechanisms were presumed for development of local pathological process in different clinical phenotypes of CRSP, depending on the comorbid pathology, especially, BA or respiratory disorders.Minimal TGF-â1 and TGF-â2 levels were detected in isolated CRSP.The highest concentrations of TGF-â1, TGF-â2, and TGF-â3 were discovered in the patients with CRSP accompanied by non-allergic BA as compared to the groups with isolated CRSP and CRSP+allergic BA.5. Determination of TGF-â1, TGF-â2, and TGF-â3 levels can serve as an additional criterion for differentiating between the mechanisms of mucous membrane damage in local pathological process in tissues of comorbid patients with different CRSP phenotypes

Экономическая целесообразность аллерген-специфической иммунотерапии

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The role of leukotriene receptor blockers in the treatment of allergic rhinitis in combination with chronic rhinosinusitis with nasal polyps

Background. Leukotrienes play an important role in the pathogenesis of allergic rhinitis (AR) and eosinophilic type of chronic rhinosinusitis with nasal polyps (CRSwNP). There is a phenotype of CRSwNP in combination with AR, which has specifics of local inflammation.The aim of our study was to investigate the efficacy of using an antileukotriene drug in the treatment of AR in combination with CRSwNP.Materials and methods. 63 patients with AR and bilateral CRSwNP after endoscopic bilateral polypotomy were randomly divided into 2 groups. In the 1st group 32 people (age 50.28 ± 1.37 years) were prescribed a basic therapy with nasal spray of mometasone furoate at a daily dose of 400 µg in combination with montelukast 1 tab. 10 mg at night, in the 2nd group 31 people (age 50.31 ± 1, 16 years old) received only mometasone furoate monotherapy. Endoscopic examination of the nasal cavity was performed once every 3 months. The follow-up period was 1 year.Results. After 3 months in the 1st group of patients there was a recurrence of polyp growth was observed in 25% of cases, in the 2nd group in 35.5% of patients (p < 0.05). After 6 months, the number of relapses of CRSwNP decreased to 15.6% of cases in group 1 and to 22.6% in group 2 (p < 0.05). After 9 months in group 1 recurrence of NP was recorded in 12.5% of patients and nasal polyps were completely absent during endoscopic examination in 9.4% of cases, in the 2nd group, relapse was detected in 19.35% of patients (p < 0.05). 1 year after surgery, in group 1, relapse of NP was found in 12.5% of patients with AR and in 12.5% of cases was remission of the pathological process with cancellation of basic therapy. In group 2, recurrence of NP was in 16.1% of cases, there were no reasons for withdraw treatment of intranasal glucocorticosteroids in this group.Discussion. The clinical effectiveness of the addition of Montelukast to basic therapy has been reflected in a reduction in the growth rate of polyposic vegetation, the number of repeated operations and the stabilization of the flow of chronic inflammatory process.Conclusions. In the case of the clinical phenotype of AR with CRSwNP, the addition of a leukotriene receptor blocker montelukast to the basic therapy of intranasal glucocorticosteroids made it possible to improve drug control of both diseases and reduce the frequency of CRSwNP relapses

Легкая бронхиальная астма: настоящее и будущее

Mild asthma is characterized by infrequent and slight clinical manifestations and, therefore, is paid lack of attention both from patients and physicians. Physicians tend to underestimate risk of severe exacerbations including asthmatic status in patients with mild asthma. Patients with mild asthma are often poorly adherent to treatment. Also, certain difficulties are related to timely and correct diagnosis and the choice of the optimal treatment by primary care physicians who are first physicians encountering such patients. The paradoxus of asthma and use of short-acting β2-agonists (SABA) to treat chronic airway inflammation lead to excessive dependence on rescue inhalers and insufficient adherence to maintenance anti-inflammatory therapy. This could trigger acute exacerbations and even fatal outcomes in patients with mild asthma. Therefore, SABA monotherapy has to be limited. Easy-to-use questionnaires, algorithms and treatment protocols accessible for primary care physicians could improve detection of mild asthma. Favorable results of clinical trials on as-needed use of budesonide/formoterol Turbuhaler® could change the management paradigm for mild asthma regarding risk of exacerbations, control of asthma symptoms, airway inflammation, and cost-efficacy.При легком течении бронхиальной астмы (БА) часто отмечается недостаточно серьезное отношение врачей и больных к указанному заболеванию по причине редких и не причиняющих особых неудобств клинических проявлений. При БА легкой степени вероятность тяжелых обострений вплоть до астматического статуса врачами недооценивается, а у пациентов часто отмечается очень низкая приверженность назначенному лечению. Также существуют проблемы своевременного выявления, правильной диагностики и подбора адекватной терапии БА врачами первичного звена, к которым в первую очередь обращаются такие больные. Парадокс БА, лечение хронического воспалительного заболевания короткодействующими β2-агонистами (КДБА) приводит к чрезмерной зависимости от скоропомощных препаратов и недостаточной приверженности поддерживающей противовоспалительной терапии, что может явиться причиной обострений и летального исхода у пациентов с БА легкой степени. При этом лечение КДБА в виде монотерапии следует ограничить. Для улучшения диагностики и лечения БА необходимо создание доступных и удобных в реальной практике вопросников, алгоритмов и схем терапии, прежде всего для врачей первичного звена. Изменению парадигмы в лечении больных легкой БА по влиянию на риск обострения, контроль над симптомами БА, степень воспаления дыхательных путей и экономическую эффективность будут способствовать положительные результаты исследований применения Будесонид / Формотерол Турбухалер® в новом режиме по требованию

Будесонид / формотерол Турбухалер® в режиме «по потребности» при легкой бронхиальной астме: результаты исследований SYGMA-1, -2 (SYmbicort® Given as needed in Mild Asthma)

According to the modern concepts, asthma is a heterogeneous disease characterized by chronic airway inflammation and respiratory symptoms, which vary in time and intensity and manifest together with variable obstruction of the airways. Asthma is responsible for the deterioration of health status and quality of life in approximately 339 million of adult patients and children worldwide. Despite the fact that asthma is a chronic inflammatory disease, patients with asthma generally inadequately receive anti-inflammatory therapy in real clinical practice and rely on short-acting beta2-agonists (SABA) too much; this can “mimic” worsening of asthma symptoms. SABA monotherapy “on demand” does not affect chronic airway inflammation, underlying asthma occurrence and progression. As a result, such patients still have the risk of asthma exacerbation and disease progression. Therefore, the need of a new therapeutic strategy for patients with milder asthma (steps 1 and 2), which would provide anti-inflammatory treatment considering the low adherence to the regular maintenance therapy and high dependency on SABA, is obvious. Such approach has become available after the SYGMA (SYmbicort® Given as needed in Mild Asthma) trial was completed. According to the results of this trial, budesonide/formoterol 160/4.5 µg/dose as needed was superior to as needed SABA in better asthma control and decrease in severe asthma exacerbation rate by 64% (p < 0.001). Results of SYGMA 1 and 2 trials also demonstrated that budesonide/formoterol 160/4.5 µg/dose as needed was noninferior compared to regular treatment with budesonide in preventing severe asthma exacerbations while the cumulative dose of budesonide was reduced by ≥75%. Согласно современным представлениям, бронхиальная астма (БА) – это гетерогенное заболевание, характеризующееся хроническим воспалением дыхательных путей, наличием различных по времени и интенсивности респираторных симптомов, которые проявляются вместе с вариабельной обструкцией дыхательных путей. В целом БА является причиной ухудшения статуса здоровья и качества жизни примерно у 339 млн взрослых и детей. Несмотря на то, что БА является хроническим заболеванием, в основе которого лежит воспаление, в реальной клинической практике пациенты с БА получают противовоспалительную базисную терапию в недостаточном объеме, чрезмерно полагаясь на короткодействующие β2-агонисты (КДБА), применение которых может маскировать ухудшение симптомов заболевания. Монотерапия КДБА в режиме «по потребности» не оказывает влияния на хроническое воспаление дыхательных путей, лежащее в основе развития и прогрессирования БА. В результате у этих пациентов сохраняется риск обострений БА и прогрессирования заболевания. Принимая во внимание низкую приверженность пациентов базисной терапии и высокую зависимость от применения КДБА, очевидным становится факт необходимости появления новой стратегии ведения пациентов с более легким течением БА (ступени терапии I–II), при использовании которой будет учтена необходимость противовоспалительной терапии БА. Появление нового подхода стало возможным после получения результатов клинической программы SYGMA (SYmbicort® Given as needed in Mild Asthma – Симбикорт® по потребности у пациентов с легкой БА). Эффективность применения комбинации будесонид / формотерол 160 / 4,5 мкг / доза в режиме «по потребности» превосходила таковую при использовании КДБА «по потребности» в отношении контроля над симптомами БА и снижения частоты тяжелых обострений на 64 % (p < 0,001). По результатам исследований SYGMA-1 и -2 также подтверждено, что использование комбинации будесонид / формотерол 160 / 4,5 мкг / доза «по потребности» не менее эффективно предупреждает обострения БА по сравнению с регулярным приемом будесонида при снижении кумулятивной дозы будесонида не менее чем на 75 %

Место фиксированной комбинации индакатерола, гликопиррония и мометазона фуроата в терапии бронхиальной астмы. Заключение Совета экспертов Российского респираторного общества

Achieving the control of bronchial asthma (BA) in real clinical practice remains an unresolved problem, despite the expansion of therapeutic options in this area. Guidelines about when and for whom should a particular treatment be used continue to develop. Increasing of inhaled corticosteroid dose (ICS) in combination with a long-acting β2-agonist (LABA) does not always lead to the desired result, although a combined LABA-ICS inhaler could improve the course of asthma and increase adherence. The addition of tiotropium bromide to LABA-ICS requires the use of two inhalers. The targeted biological therapy is associated with the complexity of phenotyping and is possible only in specialized medical centers. Mometasone furoate, indacaterol acetate, and glycopyrronium bromide in fixed doses were combined in Breezhaler® inhaler for asthma maintenance therapy once per day. This way of treatment helps to realize full potential of maintenance inhalation therapy of bronchial asthma and to simplify the achievement of control over the disease in routine clinical practice.Достижение контроля над бронхиальной астмой (БА) в реальной клинической практике остается нерешенной проблемой, несмотря на существенное расширение терапевтических возможностей в этом направлении. Рекомендации о том, когда и для кого должны использоваться те или иные методы лечения, продолжают расширяться. При увеличении дозы ингаляционного глюкокортикостероида (иГКС) в комбинации с длительно действующим β2-агонистом (ДДБА) далеко не всегда достигается желаемый результат, хотя при использовании единого ингалятора иГКС / ДДБА может улучшиться течение БА и повыситься приверженность терапии. При добавлении тиотро-пия бромида к иГКС / ДДБА требуется использование 2 ингаляторов, а назначение таргетной биологической терапии связано со сложностью фенотипирования и возможно только в специализированных медицинских центрах. Мометазона фуроат, индакатерола ацетат и гликопиррония бромид объединены в фиксированную комбинацию, доставляемую с помощью ингалятора Бризхалер® 1 раз в день для поддерживающей терапии БА. Этот способ лечения помогает реализовать потенциал базисной ингаляционной терапии БА и упростить достижение контроля над заболеванием в повседневной клинической практике