The new therapeutics of severe asthma
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monoclonal therapies for severe asthma
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The new therapeutics of severe asthma
- 2. PHENOTYPES OF ASTHMA Moore WC et al. Am J Respir Crit Care Med. 2010;181(4):315-23. Chung KF. J Intern Med 2016; 279: 192–204.
- 3. PHENOTYPES OF ASTHMA Haldar P et al. Am J Respir Crit Care Med. 2008 ; 178(3): 218–224. Chung KF. J Intern Med 2016; 279: 192–204.
- 4. Chung KF. J Intern Med 2016; 279: 192–204. PATHOGENESIS OF ASTHMA
- 5. Th2-high Asthma IL-4 IL-5 IL-13 IL-25 IL-33 TSLP Th2-low Asthma IL-1β TNF-α IL-17Allergens Irritant gases Type1 Hypersensitivity Eosinophilia Neutrophilia Better responce to ICS Less response to ICS ENDOTYPES OF ASTHMA
- 6. Dunn RM, Wechsler ME. Clin Pharmacol Ther. 2015;97(1):55-65. TARGETED THERAPY
- 7. Dunn RM, Wechsler ME. Clin Pharmacol Ther. 2015;97(1):55-65. TARGETED THERAPY
- 8. TARGETED THERAPY Chung KF. Lancet 2015; 386: 1086–96
- 9. SEVERE ASTHMA Chung KF, Wenzel S. Eur Respir J 2014;44:1378-9.
- 10. Chung KF, Wenzel SE, et al. Eur Respir J. 2014 Feb;43(2):343-73 UpToDate SEVERE ASTHMA
- 11. SEVERE ASTHMA Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2016. Available from: www.ginasthma.org
- 12. TARGETED THERAPY Chung KF, Wenzel SE, et al. E Eur Respir J. 2014 Feb;43(2):343-73.
- 13. COMORBIDITIES n % Rinitis 18 15 Gastroesophaegeal Reflux 15 12.5 Sinusitis 13 10.8 Hypertension 8 6.7 Gastric ulcus/gastritis 3 2.5 Diabetes 3 2.5 Tyroid diseases 2 1.7 ASHD/Hyperlipidemia 0 0 Anxiety disorders/depression 0 0 Stroke/serebrovascular damage 0 0 Cataract/glaucoma 0 0 Sleep apnea syndrome 0 0 Ceylan E. et al. The Relationship Between Mild Asthma Comorbidities and Systemic Inflammation, unpublished
- 14. TARGETED MONOCLONAL ANTİBODY SITUATION IgE Omalizumab IL-4Rα AMG-317 Dupilumab IL-5 Mepolizumab Reslizumab IL-5Rα Benralizumab IL-13 Lebrikizumab Tralokinumab IL-17R Bradolumab Anti-TNFα Etanercept Golimumab TARGETED THERAPY
- 16. TARGETED THERAPY Chung KF, Wenzel SE, et al. E Eur Respir J. 2014 Feb;43(2):343-73
- 17. TARGETED THERAPY / OMALIZUMAB Pelaia G. J Asthma Allergy. 2011; 4: 49–59. TTD Astım Tanı ve Tedavi Rehberi.2014. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2016. Available from: www.ginasthma.org Up To Date Omalizumab can be used patients who have below critria: • In Step 5 • Severe eosinophilic asthma who is uncontrolled with inhaled corticosteroids and/or other therapies • Sensitive to a perennial allergen which prove(s) skin prick test and/or with spesific-IgE • And total IgE should be between 30 and 1500 I.U./mL
- 18. Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations %53 and %47 respectively.
- 22. ANTI-IL-5(MEPOLIZUMAB)-CONCLUSION According to GINA 2016 guideline, mepolizumab can be used in step 5 whose asthma is severe eosinophilic and uncontrolled but only older than 12 years patients.. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2016. Available from: www.ginasthma.org
- 23. In both studies, patients receiving reslizumab had a significant reduction in the frequency of asthma exacerbations (study 1: rate ratio [RR] 0.50 [95% CI 0.37– 0.67] ; study 2: 0.41 [0.28–0.59]; both p<0.0001) compared with those receiving placebo.
- 24. Compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P=.01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P=.02) in the combined groups.
- 25. Both dose of benralizumab can decrease levels of ECP and EDN. For the combined benralizumab groups, ECP declined from a baseline mean (SD) of 26.1 (30.3) μg/L to 8.6 (9.1) μg/L at day 84, and EDN declined from 25.67 (33.80) ng/mL to 4.79 (9.87) ng/mL. Visits to the ED at week 24 were lower in the combined benralizumab groups compared with placebo (weighted rate of 2.95 vs 4.32; P = .02).
- 26. Benralizumab reduced exacerbation rates compared with placebo in the 100 mg group (0·34 vs 0·57, reduction 41%, 80% CI 11 to 60, p=0∙096) but not in the 2 mg group or the 20 mg group.
- 28. Treatment with lebrikizumab reduced the rate of asthma exacerbations, which was more pronounced in the periostin-high patients (all doses: 60% reduction) than in the periostin-low patients (all doses: 5% reduction); no dose– response was evident. Lung function also improved following lebrikizumab treatment, with greatest increase in FEV1 in periostin-high patients (all doses: 9.1% placebo adjusted improvement) compared with periostin-low patients (all doses: 2.6% placebo-adjusted improvement).
- 29. In patients in this subgroup who also had baseline serum dipeptidyl peptidase-4 (DPP-4) higher than the population baseline median, we noted additional improvements in prebronchodilator FEV1, ACQ-6, and AQLQ(S), and, in those with periostin concentrations higher than the median, we noted improvements in asthma exacerbation rate, prebronchodilator FEV1, and ACQ-6.
- 30. THE PROBLEMS OF THE NEW THERAPEUTICS Injection site reactions Nasopharyngitis Headache Anaphylaxis(rarely)
- 31. 30% - %70 Rabe KF, et al. J Allergy Clin Immunol 2004; 114: 40-7. Sekerel BE, et al. Respir Med 2006; 100: 1850-4.
- 32. WHICH BIOMARKER IS THE MOST IMPORTANT FOR THE TREATMENT FOLLOW-UP?
- 34. GRAZIE PER I’ATTENZIONE :)
Editor's Notes
- A phenotype is defined as the composite observable characteristics or traits of an organism that result from genetic as well as environmental influences. For a chronic disease such as asthma, phenotyping may be useful in providing long-term prediction of outcomes and determining specific treatments for selected phenotypes, such that these differences between individual patients can be exploited to relate to clinically meaningful outcomes. Cluster analysis of clinical and physiological features is increasingly used to define phenotypes of asthma (Table 1). In the Severe Asthma Research Program (SARP) and the UK Leicester adult cohorts, hierarchical cluster analysis of populations with a range of asthma severities was used [6, 7]. Patient clusters were either identified with minimal airflow obstruction and low disease activity, early disease onset and an atopic background or associated with adult-onset and active disease (more severe group of patients with asthma) (Table 1). Thus, age at disease onset, lung function and atopic state featured highly in these clusters or phenotypes, as also observed in cohorts from Korea and Japan [8, 9]. Clusters related to more severe disease were represented in the adult SARP cohort by individuals on high-dose ICS therapy, often combined with oral corticosteroid treatment associated with severe airflow obstruction. In the TENOR study, a cluster described in adolescents and adults was associated with aspirin sensitivity, in primarily White, female and atopic patients with late-onset asthma, and these patients were more likely to experience exacerbations [10]. The obesity component in severe asthma defined in both the SARP and Leicester cohorts has also been described in other analyses [11, 12], with obese uncontrolled and obese well-controlled clusters that differed from one another with regard to age of asthma onset, measures of asthma symptoms and control, exhaled nitric oxide concentration (FeNO) and airway hyper-responsiveness but were similar with regard to measures of lung function, airway eosinophilia and serum IgE [11]. A cluster of obese women with late-onset asthma and frequent symptoms with high healthcare use but with low sputum eosinophil counts has also been described [13].
- How is asthma severity assessed? Asthma severity can be assessed retrospectively from the level of treatment (p14) required to control symptoms and exacerbations. Mild asthma is asthma that can be controlled with Step 1 or 2 treatment. Severe asthma is asthma that requires Step 4 or 5 treatment, to maintain symptom control. It may appear similar to asthma that is uncontrolled due to lack of treatment