Brooke L. Gildon, Pharm.D., BCPS, BCPPS, AE C Associate Professor of Pharmacy Practice Southwestern Oklahoma State University College of Pharmacy Oklahoma Society of Health System Pharmacists Annual Meeting April 13, 2018 Objective Identify new recommendations in the treatment of pediatric asthma 1. Boxed warning removal ICS/LABAs 2. Tiotropium 3. Biologics benralizumab & mepolizumab 4. New inhaler devices 2
Pre Assessment Questions 1. Tiotropium, an inhaled long acting anticholinergic, is FDA approved for asthma maintenance therapy in what patient ages? 2. Name 2 biologic agents approved for children > 12 years with severe eosinophilic asthma? 3 FDA Boxed Warning Boxed warning linked to asthma related death removed from ICS/LABA combo products ICS/LABAs do not result in significantly more serious asthma related side effects than ICS alone Change based on 4 large clinical safety trials involving 41,297 patients (> 4 years of age) Products: fluticasone/salmeterol or vilanterol, mometasone or budesonide/formoterol Warning remains for LABAs alone in asthma FDA Drug Safety Communication. https://www.fda.gov/drugs/drugsafety/ucm589587.htm. Accessed March 15, 2018. 4
5 Tiotropium Inhaled long acting anticholinergic FDA approved for asthma maintenance therapy in those >6 years (2017 approval) Used as an add on therapy to ICS and/or other maintenance medications Not included in NHLBI EPR 3 (pending future update) Steps 4, 5 in GINA for those >12 years GINA=Global Initiative for Asthma Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org. Spiriva Respimat [package insert]. Ridgefield, CT.: Boehringer Ingelheim Pharmaceuticals, Inc; 2017. 6
Tiotropium Labeling FDA approved asthma dosing: Spiriva Respimat 1.25 mcg/actuation; 2 puffs once daily Soft mist delivery system Well tolerated in clinical trials Minor adverse effects (e.g., allergic rhinitis, dry mouth, headache) Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org. Spiriva Respimat [package insert]. Ridgefield, CT.: Boehringer Ingelheim Pharmaceuticals, Inc; 2017. 7 Peds Tiotropium Studies School aged children Significant improvement seen in FEV 1 response, asthma control, and risk of exacerba on 5 mcg dose may be best for changes in lung function Adolescents Significant results seen in FEV 1 response, changes in ACQ 7 scoring, and risk of exacerba on Inconsistent data regarding 5 mcg dose vs. 2.5 mcg Szefler SJ, et al. J Allergy Clin Immunol 2017: 140; 1277 1287. Hamelmann E, et al. J Allergy Clin Immunol 2016; 138: 441 50. Kerstjens H, et al. N Engl J Med 2012; 367: 1198 1207. Rodrigo GJ, et al. Ann Allergy Asthma Immunol 2015; 115: 211 216. Rodrigo GJ, et al. Pediatr Allergy Immunol 2017; 28: 573 578. ACQ=Asthma Control Questionnaire 8
Tiotropium Take Home Points Improved lung function and decreased risk of exacerbation seen in children with severe asthma 5 mcg vs 2.5 mcg daily dosing; inconsistent outcomes by dose, study, and patient age Not shown to impact outcomes such as asthma symptoms or rescue medication use Further studies needed to better define role and optimal dosing 9 Omalizumab, Mepolizumab, Benralizumab Reslizumab* *Not approved for use in pediatrics 10
Mepolizumab Interleukin 5 receptor antagonist FDA approved >12 years with severe asthma and an eosinophilic phenotype (add on therapy) Step 5 in GINA for those >12 years Reduced incidence of asthma exacerbations (53%) SubQ dosing every 4 weeks Hypersensitivity reaction possible Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org. Nucala TM (Mepolizumab) [package insert]. Philadelphia, PA: GlaxoSmithKline; 2017. Ortega HG, et al. N Engl J Med 2014; 371: 1198 207. 11 Benralizumab Interleukin 5 receptor antagonist FDA approved >12 years with severe asthma and an eosinophilic phenotype (add on therapy) Step 5 in GINA for those >12 years Reduced incidence of asthma exacerbations Showed an oral glucocorticoid sparing effect SubQ dosing every 4 weeks X 3 doses then once every 8 weeks Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org. Fasenra TM (Benralizumab) [package insert]. Wilmington, DE: AstraZeneca; 2017. Nair P, et al. N Engl J Med 2017; 376: 2448 2458. 12
Biologics Take Home Points Considered add on therapy for pediatric patients in treatment step 5 Phenotype guided treatment option (e.g., severe allergic vs eosinophilic asthma) Lack of comparison trials between agents Need more data regarding younger children Important to review patient specific factors (e.g., adherence to controller, biomarkers, comorbidities) 13 New Inhaler Devices RespiClick Respimat Ellipta RediHaler TM 14
Post Assessment Questions 1. Tiotropium, an inhaled long acting anticholinergic, is FDA approved for asthma maintenance therapy in what patient ages? Adults and children >6 years 2. Name 2 biologic agents approved for children > 12 years with severe eosinophilic asthma? Benralizumab Mepolizumab 15 Brooke L. Gildon, Pharm.D., BCPS, BCPPS, AE C Associate Professor of Pharmacy Practice Southwestern Oklahoma State University College of Pharmacy Oklahoma Society of Health System Pharmacists Annual Meeting April 13, 2018