Asthma Pharmacology Update PowerPoint Presentation

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David Young, Pharm.D. Associate Professor (Clinical) 252 Skaggs Hall 581-8510 dyoung@pharm.utah.edu Update in Asthma Care 2013

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Objectives Differentiate between the 4 stages of asthma based on current guidelines Discuss the role of combination therapy in the treatment of asthma  Discuss the role of LABA in the treatment of asthma Given a patient with poorly controlled asthma, develop a treatment plan based on level on control Counsel on the appropriate use of a metered dose inhaler (MDI) and a dry-powdered inhaler (DPI)

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I have asthma? Yes No

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I know somebody who has asthma? Yes No

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I have provided care to a patient with asthma? Yes No

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Epidemiology Affects 8% of US population 25.7 million in 2010 1:11 children 1:12 adults 8.9million office visits in 2009 1.9 million emergency room visits in 2009 479,00 hospitalizations in 2009 14.2 million missed work in 2008 http://www.cdc.gov/asthma/impacts_nation/AsthmaFactSheet.pdf accessed 9/112

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Epidemiology High cost $56 billion/year $3,300/person/year Mortality 33388 deaths in the US in 2009 http://www.cdc.gov/asthma/impacts_nation/AsthmaFactSheet.pdf accessed 9/12

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I am familiar with the most current asthma treatment guidelines? Strongly Agree Agree Neutral Disagree Strongly Disagree

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Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 4 care or higher is required. Consider consultation at step 3. Step 1 Preferred: SABA PRN Step 2 Preferred: Low dose ICS Alternative: Cromolyn, LTRA, Nedocromil or Theophylline Step 3 Preferred: Low-dose ICS + LABA OR – Medium dose ICS Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton Step 4 Preferred: Medium Dose ICS + LABA Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton Step 5 Preferred: High Dose ICS + LABA AND Consider Omalizumab for patients who have allergies Step 6 Preferred: High dose ICS + LABA + oral corticosteroid AND Consider Omalizumab for patients who have allergies Each Step: Patient Education and Environmental Control and management of comorbidities Steps 2 – 4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma 2007 NAEPP Guidelines, EPR-3 – Section 4, pg 343. Assess control STEP-WISE APPROACH TO THERAPY

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Stepping UP (EPR 3, 2007) Asthma NOT WELL CONTROLLED Review adherence, inhaler technique, environmental control, co morbid conditions Step up 1 step and reevaluate in 2-6 weeks Asthma VERY POORLY CONTROLLED Review adherence, inhaler technique, environmental control, co morbid conditions Consider short course of oral steroid Step up 1 or 2 steps and reevaluate in 2 weeks

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Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 4 care or higher is required. Consider consultation at step 3. Step 1 Preferred: SABA PRN Step 2 Preferred: Low dose ICS Alternative: Cromolyn, LTRA, Nedocromil or Theophylline Step 3 Preferred: Low-dose ICS + LABA OR – Medium dose ICS Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton Step 4 Preferred: Medium Dose ICS + LABA Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton Step 5 Preferred: High Dose ICS + LABA AND Consider Omalizumab for patients who have allergies Step 6 Preferred: High dose ICS + LABA + oral corticosteroid AND Consider Omalizumab for patients who have allergies Each Step: Patient Education and Environmental Control and management of comorbidities Steps 2 – 4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma 2007 NAEPP Guidelines, EPR-3 – Section 4, pg 343. Assess control STEP-WISE APPROACH TO THERAPY

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ICS + LABA in asthma

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ICS + LABA in asthma

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Stepping DOWN (GINA, 20011) (asthma is controlled >3months) If pt on Medium-High dose Reduce dose 50% at 3 month intervals (Evidence B) If control achieved on low dose Switch to once daily (Evidence A) If pt taking ICS + LABA Reduce ICS dose 50% + LABA (Evidence B) Once control achieved on low dose + LABA (Evidence D) Attempt to d/c LABA If pt taking ICS + other controller Reduce ICS dose 50% + other controller (Evidence D) Once control achieved on low dose + other controller (Evidence D) Attempt to d/c other controller If pt on lowest dose of controller and no symptoms for 1 year Attempt to d/c controller

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Intermittent Asthma Persistent Asthma: Daily Medication Consult asthma specialist if step 4 care or higher is required. Consider consultation at step 3. Step 1 Preferred: SABA PRN Step 2 Preferred: Low dose ICS Alternative: Cromolyn, LTRA, Nedocromil or Theophylline Step 3 Preferred: Low-dose ICS + LABA OR – Medium dose ICS Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton Step 4 Preferred: Medium Dose ICS + LABA Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton Step 5 Preferred: High Dose ICS + LABA AND Consider Omalizumab for patients who have allergies Step 6 Preferred: High dose ICS + LABA + oral corticosteroid AND Consider Omalizumab for patients who have allergies Each Step: Patient Education and Environmental Control and management of comorbidities Steps 2 – 4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma 2007 NAEPP Guidelines, EPR-3 – Section 4, pg 343. Assess control STEP-WISE APPROACH TO THERAPY

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SMART Study Design (Nelson HS et al. Chest 2006) Salmeterol Multicenter Asthma Research Trial (SMART) 28-week, multi-center, randomized, double-blind, placebo-controlled, observational surveillance trial initiated in July 1996 6163 US sites; 1316 investigators Target enrollment: ~60,000 patients >12 yrs with asthma currently using prescription asthma medications no history of previous salmeterol/formoterol use All therapy taken on outpatient basis

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SMART Study Design

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Study Endpoints Primary Endpoint Combined number of respiratory-related deaths or respiratory-related life-threatening experiences (intubation and ventilation) Secondary Endpoints Combined asthma-related deaths or life-threatening experiences Asthma-related deaths

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Demographics

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Baseline Asthma Characteristics in Caucasians and African Americans

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SMART 28-week Results RR (95% CI) SAL n PLA n 1° Endpoint Asthma Death Asthma Death or Life Threatening Experience Respiratory Death Respiratory Death or Life Threatening Experience Total N=13176 N=13179 Caucasian N=9281 N=9361 African American N=2366 N=2319 .031 .062 .125 .25 .5 4 2 1 16 8 64 32 128 2° Endpoints

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RR (95% CI) SAL n PLA n Asthma Death Asthma Death or Life Threatening Experience Respiratory Death or Life Threatening Experience SMART 28-week Results .031 .062 .125 .25 .5 4 2 1 16 8 64 32 128 3.02 (0.82-11.11) 9 3 5.61 (1.25-25.26) 11 2 1.25 (0.60-2.60) 16 13 0.88 (0.42-1.84) 13 15 Respiratory Death 2° Endpoints 1° Endpoint

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Summary of SMART Results Total Population No significant differences in the primary endpoint A significant increase (?), in secondary endpoint of asthma-related deaths was observed in patients receiving salmeterol 13 vs. 3 pts African Americans Statistically significant increase in combined respiratory and asthma-related deaths Worse asthma at baseline NO baseline ICS led to increased risk No difference in asthma-related death alone Caucasians No significant increase in primary or secondary endpoint s

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Bailey et al. Current Med Research Opinions 2008 2000

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Safety LABA (EPR 3, 2007) If asthma not sufficiently controlled with ICS alone, the option of increasing the ICS dose=to addition of LABA Based Salmeterol Multicenter Asthma Research Trial (SMART) conducted by Nelson et al. Chest 2006 High dose formoterol trial conducted by Mann et al. Chest 2007 In general do not exceed salmeterol 100mcg or 24mcg formoterol daily

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Safety LABA (FDA, 2010) Use  of a LABA alone without use of a long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated (absolutely advised against) in the treatment of asthma. LABAs should not be used in patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. LABAs should only be used as additional therapy for patients with asthma who are currently taking but are not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid.

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Safety LABA (FDA, 2010) Once asthma control is achieved and maintained, patients should be assessed at regular intervals and step down therapy should begin (e.g., discontinue LABA), if possible without loss of asthma control, and the patient should continue to be treated with a long-term asthma control medication, such as an inhaled corticosteroid. Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA, to ensure adherence with both medications.

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Weatherall et al. Thorax 2010 2000

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Leukotriene antagonists + ICS

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Budesonide/Form Maintenance + Relief Double-blind, randomized, parallel group, multi-center study N=2091 2 week run-in 1 year treatment period (all taken twice daily) 160mcg BUD (low dose)+ formoterol 4.5mcg + Terbutaline 160mcg BUD (low dose)+ formoterol 4.5mcg + RELIEF Atienza et al. Respirology 2012

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Budesonide/Form Maintenance + Relief Atienza et al. Respirology 2012

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Results (BUD/Form + RELIEF> BUD/Form + Terbutaline))  Mean daily prn inhalations -0.25 (p<0.001)  PEF 5.8 L/min (p=0.002)  FEV1 0.040 (p=0.001)  Asthma symptom score -0.08 (p=0.025)  Asthma Control Days +4.2% (p=0.005) Budesonide/Form Maintenance + Relief Atienza et al. Respirology 2012

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ICS + LABA + Relief

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Tiotropium in Uncontrolled Asthma

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http://hamptonroads.com/files/images/6161.jpg. accessed 3/08

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I can instruct a patient on how to properly use an MDI? Yes No

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MDI-technique “Is significant” Lindgren et al. Eur J Resp Dis 1987;70:93-98. 56% of patients made errors in MDI-technique which resulted in a 30% decrease in bronchodilation versus control (p<0.01) Giraud et al. Eur Resp J 2002;19:246-251 71% of patients misused MDI’s 47% due to poor coordination Asthma less stable in misusers (p<0.001) Among misusers, asthma less stable in poor coordinators (p<0.001)

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MDI technique Plaza et al. Resp 1998;65:195-198 9% of patients, 15% of nurses, and 28% of physicians showed correct MDI-technique. Interiano et al. Arch Intern Med 1993;153:81-85 65% of patients, 39% of housestaff, 82% of nurses were categorized as having “poor” MDI-technique.

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How to tell if MDI is empty Diary Do NOT float test Dose counter Short Acting Beta-2 Agonists Ventolin HFA, Proair HFA Inhaled corticosteroids Advair Diskus, Advair HFA, Alvesco, Asthmanex Twisthaler, Dulera, Flovent HFA, Pulmicort flexhaler, Symbicort

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Clinical Pearls

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Phasing out CFC containing inhalers Montreal Protocol (1989) banned CFC’s Allowed to remain on market due to “essential use” Azmacort 12/31/10 Aerobid 6/30/11 Epinephrine 12/31/11 Combivent 6/2013 Maxair autohaler 6/2013 Epinephrine (Asthmanefrine) Approved >4yrs 0.5ml (11.25mg epinephrine) via EZ Breathe Atomizer 1-3 inhalations every 3 hours prn (maximum 12 inhalations/24hr) Seek medical help if no relief in 20 minutes

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Shortened expiration inhalers

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Priming inhalers

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Upright storage Advair HFA, Ventolin HFA, Symbicort, Xopenex HFA are not affected by storage position Flovent HFA has not been studied so priming is recommended if it is stored in any position other than upright

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Conclusions Asthma is a chronic disease when improperly treated can lead to poor outcomes Successful asthma therapy requires regular assessments of symptom control and medication adherence Proper inhaler technique is critical to successful asthma therapy Asthma education requires continuous reinforcement

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Education Resources Google: Asthma Care Pharmacy Utah or http://health.utah.gov/asthma/professionals/pharmacy.htm

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