Болезнь-модифицирующая терапия бронхиальной астмы: место омализумаба

In the past years, we have seen a paradigm shift from symptomatic to disease-modifying approach to the treatment of chronic diseases. The treatment of asthma, which is a chronic disease, is no exception to this shift. Although the available therapies for asthma have been traditionally identified as either “controllers” or “relievers”, this dichotomous classification does not address the therapeutic potential to modify the underlying disease. The disease-modifying therapy for asthma can be defined either as airway remodeling or as modifying the disease's natural course. Among the biological therapies, the disease-modifying effect of omalizumab was studied most comprehensively. Some studies of other biological therapies for severe asthma (mepolizumab, benralizumab) also addressed the airway remodeling effect. A further study of the disease-modifying therapy should help gain a deeper understanding of its potential in managing asthma.В последние годы в терапии хронических заболеваний наблюдается смена парадигмы лечения со смещением фокуса с симптом-ориентированного подхода на болезнь-модифицирующий. Бронхиальная астма (БА), которая относится к группе хронических заболеваний, не стала исключением. В настоящее время общепринятый подход к дихотомической классификации терапии БА на препараты для профилактики обострений и облегчения симптомов не позволяют отразить их болезнь-модифицирующий потенциал. Понятие «болезнь-модифицирующая терапия БА» может рассматриваться не только с позиции влияния на ремоделирование дыхательных путей (ДП), но и как возможность модифицировать естественное течение БА. Среди биологической терапии наиболее изучено болезнь-модифици-рующее действие омализумаба. Некоторые исследования применения меполизумаба и бенрализумаба направлены на оценку их влияния на ремоделирование ДП. Дальнейшее изучение вопроса болезнь-модифицирующей терапии поможет получить более полное видение ее потенциала в ведении пациентов с БА

INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р&lt;0.0001) and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58%) among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028).Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.</p

THE SLCO1B1 GENE POLYMORPHISM AND STATIN-INDUCED MYOPATHY IN RUSSIAN PATIENTS

Aim. To evaluate the risk of muscle tissue damage in patients taking statins, and usefulness of the gene SLCO1B1 typifying for the risk estimation of such an unpleasant adverse drug reaction (ADR).Material and methods. The observation of 258 patients with ischemic heart disease, taking statins, was conducted. To evaluate the credibility of causeoutcome relation “ADR – statin” the WHO classifications and criteria were used together with Naranjo algorithm.Results. The 3 groups were stratified: I – patients with muscle pain or weakness and with probable to definite chance of the cause-outcome relation (n=31); II – patients with muscle symptoms and possible or doubtful degree of credibility for causeoutcome relation (n=27); III – patients without muscle symptoms (n=200); of those into further study we included 35 subjects. Among those with muscle symptoms women were more prevalent (I group – 61,3% (19/35); (p&gt;0,05 in all groups). Mean time of hypolipidemic therapy of 1st group patients was 48,8 months (p&lt;0,0001 vs 2nd and 3rd groups). Manifecting of muscle symptomatic in a majority of patients (19/35) was during the first year of therapy (RR 2,5; p=0,0841). Average doses of statins were higher in those of the 1st group: 38,3 mg/day (p I vs II=0,0004); p I vs III=0,0139). As a result of allele SLCO1B1*5 typifying a tendency of more frequent C-allele in the 1st group was found comparing to 2nd and 3rd groups: HR I vs II 2,35 (p=0,1242); RR I vs III 2,37 (p=0,0732); RR II vs III 1,00 (p&gt;0,9999). The algorithm for statin-induced myopathy was invented.Conclusion. In patients with CHD the ADR as myopathy were found in 12% of cases. The most significant predictors: duration of hypolipidemic therapy more than12 months (RR 7,7; p=0,0002), atorvastatin usage in dose more than 40 mg per day (RR 2,67, p=0,0139). The prevalence of statin-associated muscle events was higher in women (RR 1,88, p=0,23) and carriers of allele type SLCO1B1*5 (RR 2,37; p=0,0732)