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Cme one size fits all - final

Update on Asthma And Allergy

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Cme one size fits all - final

  1. 1. HOUSEKEEPING 1. Please ensure you mute your line. * 6 to Mute. #6 to unmute. Please keep your line muted throughout the presentation. 2. If you have a question for our faculty, please submit them using the Question Panel on your computer. Questions will be noted and prioritized by the Chair. At the end of the presentation, the Chair will moderate the QnA and direct the questions to the faculty. 3. Please close all other programs running on your computer – this will help ensure the best possible experience. 4. If you have any technical issues during the program, Dave Coughlan our site moderator will support you- just send him a question in the question box or text Nadine Hollett-Banks’ cell 1.519-870-0695. Click here to submit question PC iPad Click here to submit question Asthma Management – The One Size Fits all ApproachAsthma Management – The One Size Fits all Approach Great for Socks…not for patients!Great for Socks…not for patients!
  2. 2. Asthma Management – The One SizeAsthma Management – The One Size Fits all ApproachFits all Approach Great for Socks…not for patients!Great for Socks…not for patients! Anne K. Ellis, MD MSc FRCPCAnne K. Ellis, MD MSc FRCPC Associate Professor and ChairAssociate Professor and Chair Division of Allergy & Immunology Department of Medicine, Queen’s University Twitter: @DrAnneEllis Date: Sept 22nd , 2015 Time: 12:15h
  3. 3. Disclosures Facilitator’s Name: Dr. Anne K. Ellis Grants/research support: Circassia Ltd/Adiga Life Sciences GlaxoSmithKline Novartis SunPharma Advanced Research Corporation Merck Speaker’s bureau/honoraria: Merck, Pfizer, AstraZeneca, Novartis Consulting fees: ALK Abello, Ora Inc. Advisory Boards: Merck, Novartis
  4. 4. Objectives ∗ By the end of this learning session, the attendee will be able to: ∗ Describe differences in performance characteristic of the various asthma controller therapies ∗ Develop a patient focused approach to asthma management ∗ Learn where to access educational resources for patients
  5. 5. Introduction - Asthma ∗ Chronic inflammatory lung disorder characterized by: ∗ reversible airflow obstruction ∗ airway hyperresponsiveness ∗ Presents symptomatically with dyspnea, wheeze and sensation of chest tightness
  6. 6. Barnes PJ. Clin Exp Allergy 1996;26:738-745.
  7. 7. Diagnosis of Asthma ∗ Confirmed when compatible symptom pattern is accompanied by objective measures of variable airflow obstruction ∗ Spirometry: ∗ >12% improvement in FEV1 15 mins after SABA ∗ OR >20% improvement after 10-14 days of oral prednisone ∗ OR >20% spontaneous variability ∗ Serial PEF ∗ >20% change after bronchodilation or over time ∗ Methacholine challenge ∗ 20% reduction in FEV1 with provocative concentration of methacholine Boulet L, et al. CMAJ 1999;161(11 Suppl):S1-61, Kaplan AG. CMAJ 2009;181:E210-20 FEV1: forced expiratory volume in 1 second, SABA: short-acting bronchodilator
  8. 8. Asthma – Phenotypes ∗ Eosinophilic Bronchitis ∗ Steroid-responsive ∗ Typically atopic ∗ Neutrophilic bronchitis ∗ Less steroid-responsive ∗ Smoking, viral illness, others ∗ Non-inflammatory ∗ Obesity, others
  9. 9. Allergic Asthma ∗ Allergen contact with airway mucosa in a sensitized individual results in rhinitis, conjunctivitis, and asthmatic responses ∗ Immediate allergic response maximal 15 to 30 min after allergen challenge, resolves in 1 to 3 hours ∗ ~50% of subjects develop a late-phase allergic response ∗ persistent, less reversible decrease in pulmonary function ∗ maximal in 6-12h and partially resolves within 24h
  10. 10. Late Phase Asthmatic Response
  11. 11. The Prevalence of Asthma in Canada: 1.Has increased steadily over the past 20 years 2.Is one of the highest in the world 3.Affects a large portion of the pediatric population 4.Affects nearly 3 million people in Canada 5.All of the above Polling Question: Epidemiology of Asthma in Canada Statistics Canada. Available at:Statistics Canada. Available at: Asthma Society of Canada. Available at:Asthma Society of Canada. Available at:
  12. 12. Epidemiology of Asthma in Canada ∗ Prevalence increased over past 20 years among adults until 2001 and remains one of the highest in the world ∗ 1979: 2.3% ∗ 1988: 4.9% ∗ 1994: 6.1% ∗ 2001: 8.4% ∗ 2009: 8.4% ∗ At least 12% of children have asthma Statistics Canada. Available at: Asthma Society of Canada. Available at:
  13. 13. Asthma Triggers ∗ Allergens ∗ Dust mites, mold spores, animal dander, cockroaches, pollen, indoor and outdoor pollutants, irritants (smoke, perfumes, cleaning agents) ∗ Pharmacologic agents (ASA, beta-blockers) ∗ Physical triggers (exercise, cold air) ∗ Physiologic factors ∗ Stress, GERD, viral and bacterial URI, rhinitis
  14. 14. Lung Function Declines with Frequency o Asthma Exacerbations Bai T.Bai T. Eur Respir J 2007;30:452-456Eur Respir J 2007;30:452-456 P<0.05P<0.05 AnnualchangeinFEVAnnualchangeinFEV11mL/yrmL/yr 00 ––1010 ––2020 ––3030 ––5050 ––4040 InfrequentInfrequent ExacerbationsExacerbations FrequentFrequent
  15. 15. Factors Leading to Inadequate Asthma Control ∗ Wrong diagnosis or confounding illness ∗ Incorrect choice of inhaler or poor technique ∗ Concurrent smoking ∗ Concomitant rhinitis ∗ Individual variation in treatment response ∗ Undertreatment ∗ Unintentional or intentional nonadherence Haughney J, et al. Respir Med 2008;102:1681-1693Haughney J, et al. Respir Med 2008;102:1681-1693
  16. 16. Goals of Asthma Management ∗ Achieve and maintain control of symptoms ∗ Prevent asthma exacerbations ∗ Maintain optimal pulmonary function ∗ Maintain normal activity levels (+ exercise) ∗ Avoid adverse effects from asthma medications ∗ Prevent the development of irreversible airflow obstruction ∗ Prevent asthma mortality GINA: Global Strategy for Asthma Management and Prevention, 2009GINA: Global Strategy for Asthma Management and Prevention, 2009 1717
  17. 17. What are the drugs? What are the devices?
  18. 18. Asthma Medications 1919 Treatment Effects Most common AEs Relievers Short-acting beta-2 agonists • Use on-demand only at min. dose and frequency • Tremor, palpitations, restlessness, headache, muscle cramps, nervousness Controllers Inhaled corticosteroids • For persistent asthma • Not intended as rescue med. • May take 1-2 weeks to see benefits • Local: Oral candidiasis, dysphonia, reflex cough and bronchospasm • Systemic: ↓ bone density, poor growth, adrenal gland suppression, bruising, ↑ blood sugar Leukotriene receptor antagonists • Alternative for persistent asthma and as add-on to ICS • Headaches, stomach pain, and cough Anti-IgE MAb • For moderate to severe asthma with frequent need for oral CS • Headache, malaise, anaphylaxis LemièreLemière et al. Can Respir J 200et al. Can Respir J 2004;11 Suppl A:9A-18A4;11 Suppl A:9A-18A Irwin R. Chest 2006;130(1 Suppl):41S-53SIrwin R. Chest 2006;130(1 Suppl):41S-53S
  19. 19. Asthma Medications (cont’d) Treatment Effects Most common AEs Add-on therapies Long-acting beta-2- agonists • Improves asthma control in older children and adults • Only to be used as an add-on when asthma not controlled with ICS • Not to be used as monotherapy • Tachycardia, palpitation, irritability, insomnia, muscle cramps, tremor LemièreLemière et al. Can Respir J 200et al. Can Respir J 2004;11 Suppl A:9A-18A4;11 Suppl A:9A-18A
  20. 20.
  21. 21. Canadian Thoracic Society Asthma Management Continuum LABA = long-acting beta agonistLougheed MD, et al. Can Respir J 2010; 17(1):15-24. <6 yr of age < 100 mcg/day<6 yr of age < 100 mcg/day
  22. 22. Asthma Management - Details ∗ Allergen and Irritant Avoidance ∗ Avoidance of other triggers (e.g. cold air, influenza vaccine, NSAIDs in sensitive px’s) ∗ Education, education, education ∗ Assessment of Control at each patient visit
  23. 23. I judge patient’s asthma control by: 1.Need for fast-acting beta-agonist 2.Physical activity 3.Night time symptoms 4.Exacerbations 5.Absence from work or school Polling Question: Indicators of Asthma Control Statistics Canada. Available at:Statistics Canada. Available at: Asthma Society of Canada. Available at:Asthma Society of Canada. Available at:
  24. 24. Indicators of Asthma Control Characteristic Frequency or Value Daytime symptoms < 4 days/week Night-time symptoms < 1 night/week Physical activity Normal Exacerbations Mild, infrequent Absence from work or school due to asthma None Need for a fast-acting beta-agonist < 4 doses/week FEV1 or PEF ≥ 90% personal best PEF diurnal variation† < 10% to 15% FEV1 = forced expiratory volume in 1 second; PEF = peak expiratory flow. † Diurnal variation is calculated as the highest PEF minus the lowest divided by the highest PEF multiplied by 100 for morning and night (determined over a 2-week period). Lougheed MD, et al. Can Respir J 2010; 17(1):15-24. Educate Patients That This Level of Asthma Control is Generally Achievable
  25. 25. Actual and Perceived Asthma Control in Canada: TRAC Study 100 Patients(%) Actual (based on CACG) 53% 80 60 40 20 60 47% 3% 97% 12% 88% 10% 90% Patients General practitioners Specialists Perceptions CACG = Canadian Asthma Consensus Guidelines. FitzGerald JM, et al. Can Respir J 2006; 13(5):253-9. Not controlled Controlled
  26. 26. Why Don’t Patients Take Asthma Medications as Prescribed? ∗ Most do not want to take daily medications when they feel well and have no asthma symptoms ∗ Many believe they know when they need to take their asthma medications ∗ Most use SABAs because these work quickly ∗ Many do not know or believe that poor current asthma control results in future risks SABA = short-acting beta agonist.SABA = short-acting beta agonist.
  27. 27. Short Acting Beta-Agonists (SABA) ∗ Onset of action 5 to 15min, duration ~4 hr ∗ Salbutamol (Ventolin®) ∗ MDI (100 mcg) ∗ Diskus (200 mcg) ∗ Terburtaline (Bricanyl®) ∗ Turbuhaler (500 mcg)
  28. 28. Long Acting Beta-Agonists (LABA) ∗ Black Box warning against monotherapy ∗ Only for 12 yr of age and up ∗ Salmeterol (Serevent®) ∗ Maximal dose 100 mcg/day ∗ Onset of action ~ 1 hr ∗ MDI – 25 mcg; Diskus – 50 mcg ∗ Formoterol (Oxeeze®) ∗ Maximal dose 48 mcg/day ∗ Onset of action ~ 15 min ∗ Turbuhaler – 6 mcg
  29. 29. Inhaled Corticosteroids Generic Name Formulation Doses Beclomethasone (QVAR®)*** Inhalation aerosol (MDI) 50 mcg 100 mcg Fluticasone (Flovent®) Dry powder for inhalation (Diskus**) ¥ ¥ Contains lactose/milk protein Inhalation aerosol (MDI)* 50 mcg 100mcg 250 mcg 500 mcg 50 mcg 125 mcg 250 mcg Budesonide (Pulmicort®)*** Dry powder for inhalation (Turbuhaler) 100 mcg 200 mcg Ciclesonide (Alvesco®)*** Inhalation aerosol (MDI) 100 mcg 200mcg Mometasone (Asmanex®)§ Dry powder for inhalation (Twisthaler)** 200 mcg 400 mcg ***6 yoa and up***6 yoa and up § 12 yoa and up§ 12 yoa and up**4 yoa and up**4 yoa and up*12 mo and up*12 mo and up
  30. 30. Available ICS + LABA Single-inhaler Combinations Advair® Product Monograph. GlaxoSmithKline Inc., July 2010. Symbicort® Product Monograph. AstraZeneca Canada Inc., December 2010. ZenhaleTM Product Monograph. Merck Canada Inc., January 2011. Combination Formulation Doses Fluticasone + salmeterol (Advair®) Dry powder for inhalation (Diskus¥ ) ¥ Contains lactose/milk protein Inhalation aerosol (MDI) 100 mcg/50 mcg 250 mcg/50 mcg 500 mcg/50 mcg 50 mcg/25 mcg 125 mcg/25 mcg 250 mcg/25 mcg Budesonide + formoterol (Symbicort®) Dry powder for inhalation (Turbuhaler) 100 mcg/6 mcg 200 mcg/6 mcg Mometasone + formoterol (Zenhale®) Inhalation aerosol (MDI) 50 mcg/5 mcg 100 mcg/5 mcg 200 mcg/5 mcg
  31. 31. Use of Asthma Inhalers/Meds ∗ PRN SABA alone ∗ Fixed dose ICS (and/or LTRA); PRN SABA ∗ Fixed dose ICS/LABA (± LTRA); PRN SABA ∗ At times of acute exacerbation, double or quadruple ICS dose or introduce oral CS ∗ Single inhaler Maintenance and Rescue Therapy (SMART) – Fixed dose ICS/LABA and PRN ICS/LABA* ∗ * Only effective if the LABA is formoterol due to onset of action differences ∗ * Only Health Canada approved for Symbicort®
  32. 32. ICS Safety: Key Pharmacokinetic and Pharmacodynamic Properties ICS Oral bio- availability (%) Receptor binding affinity Protein binding (%) Beclomethasone 15 53/1,345a 87 Budesonide 11 935 88 Fluticasone < 1 1,800 90 Mometasone < 1 2,200 98-99 Ciclesonide < 1 12b /1,212c 99 Key characteristics: ↑ receptor binding/potency ↑ lipophilicity ↑ plasma protein binding ↑ metabolism ↓ bioavailablity ↓ systemic exposure ↑ therapeutic index Rossi GA, et al. Pulm Pharmacol Ther 2007; 20(1):23-35. Bousquet J. Int J Clin Pract 2009; 63(5):806-19. a Relative receptor affinity for 17-beclomethasone monopropionate. b Ciclesonide. c Desisobutyryl-ciclesonide
  33. 33. Corticosteroid Trade name Daily ICS dose, mcg^ Adult (>12 years old) Low Medium High Beclomethasone dipropionate HFA QVAR† ≤250 251-500 >500 Budesonide* Pulmicort Turbuhaler‡ ≤400 401-800 >800 Ciclesonide* Alvesco§ ≤200 201-400 >400 Fluticasone Flovent MDI and spacer; Flovent Diskus¶ ≤250 251-500 >500 Mometasone Asmanex Twisthaler** 200 400 >400 Adapted from Lougheed MD, et al. Can Respir J. 2012;19:127-64. ^Comparative clinical significance has not been established What is Low Dose ICS?
  34. 34. LABA Differences: Onset of Bronchodilation **pp ≤ 0.016 vs. fluticasone + salmeterol.≤ 0.016 vs. fluticasone + salmeterol. Bernstein DI, et al. Allergy Asthma Clin Immunol 2010; 6 (Suppl 2):33.Bernstein DI, et al. Allergy Asthma Clin Immunol 2010; 6 (Suppl 2):33. 350350 MeanchangefrombaselineinFEVMeanchangefrombaselineinFEV11(mL)(mL) Minutes post doseMinutes post dose 00 300300 250250 200200 150150 100100 5050 00 55 1010 1515 2020 2525 3030 3535 4040 4545 5050 5555 6060 ** ** ** ** Mometasone + formoterol 200/10 mcg bidMometasone + formoterol 200/10 mcg bid Fluticasone + salmeterol 250/50 mcg bidFluticasone + salmeterol 250/50 mcg bid
  35. 35. ∗ Specific for CysLTR1 ∗ CysLT2 is present in the lung but appears to be confined to blood vessels ∗ Available agents: ∗ Singulair® = montelukast ∗ 4mg, 5mg and 10mg tablets, dosing is OD ∗ Accolate® = zafirlukast ∗ 20mg BID Leukotriene Receptor Antagonists (LTRA’s)
  36. 36. ∗ Montelukast is approved for use in children 1 year of age and older for asthma and 2 years of age and older for allergic rhinitis ∗ Pregnancy category B ∗ Zafirlukast approved for children 12 y and older ∗ Pregnancy category B Leukotriene Receptor Antagonists (LTRA’s)
  37. 37. Personalized Asthma Treatment ∗ Assess patient preference and ability to use device(s) ** ∗ Patients fearful of ICS, evaluate steroid alternatives for maintenance, such as LTRAs; ensure Aerochamber in use ∗ Ask patient about desire for rapid onset, and select the ICS/LABA accordingly ∗ Choose ICS with lowest bioavailability and associated with lowest risk of adverse effects but that also produces desired efficacy outcomes
  38. 38. Patient Compliance to ICS Therapy Can Prevent Asthma Deaths Suissa S, et al. N Engl J Med 2000; 343(5):332-6.Suissa S, et al. N Engl J Med 2000; 343(5):332-6. Fitted rate ratio for death from asthma as a functionFitted rate ratio for death from asthma as a function of the number of canisters of ICS used during yearof the number of canisters of ICS used during year before index date.before index date. 2.52.5 RateratiofordeathfromasthmaRateratiofordeathfromasthma 2.02.0 1.51.5 1.01.0 0.50.5 00 Number of canisters of ICS per yearNumber of canisters of ICS per year 3311 44 55 12129988 1010 111166 7700 22
  39. 39. Non-adherence to Asthma Therapy Intentional Motivation Beliefs/preferences Perceptual barriers Non-intentional Capacity and resources Practical barriers Barriers to assessing adherence: Patient and physician may prefer to avoid the subject Lack of clear, easy methods for addressing barriers to adherence Perception that little can be done? Horne R, et al. Chest 2006;130:65SHorne R, et al. Chest 2006;130:65S--72S72S 4040
  40. 40. Strategies to Improve Adherence ∗ Focus on patient education ∗ Ensure language at appropriate level ∗ Write it down ∗ Consider referral to an asthma educator ∗ Encourage self-monitoring ∗ Use a written asthma action plan ∗ Monitor adherence to medication regimen and proper inhaler techniques ∗ Combination therapy may improve complianceNational Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Expert Panel.National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Expert Panel. Guidelines for the Diagnosis and Management of Asthma Full Report 2007Guidelines for the Diagnosis and Management of Asthma Full Report 2007 Stoloff SW, et al. J Allergy Clin Immunol 2004;113:245-251Stoloff SW, et al. J Allergy Clin Immunol 2004;113:245-251 4141
  41. 41. Asthma Education Centres A link to this resource has been posted as a hand out in your control panel that you can download.
  42. 42. Unique Considerations ∗ Pediatrics ∗ Allergic Asthma
  43. 43. Pediatric Considerations ∗ Diagnostic challenge before age 5 ∗ Atopy risk factor for persistence of childhood wheeze ∗ Lower ICS doses usually sufficient ∗ Aerochambers not optional – discussion of benefits can improve adherence ∗ Adherence to oral/non-steroidal therapy often higher but must assess patient response ∗ Spirometry generally becomes reliable around age 8 to 10 to provide objective assessment of disease
  44. 44. Unique considerations – Allergic Population ∗ Allergic rhinitis and asthma often co-exist ∗ Treating rhinitis improves asthma outcomes ∗ Remember to treat with INCS as well ∗ LTRA’s indicated for both, as is omalizumab and immunotherapy ∗ Dual targets one medication: ∗ LTRAs ∗ Allergen specific immunotherapy ∗ Omalizumab
  45. 45. Biologic Therapy ∗ Omalizumab (Xolair®) ∗ Monoclonal antibody against IgE molecule ∗ Indicated for moderate to severe allergic asthma ∗ Shown to decrease hospitalizations, ER visits, and requirements for oral corticosteroids ∗ Typically given under specialist supervision (injection, risk of anaphylaxis)
  46. 46. Allergen immunotherapy ∗ Reached its 100th anniversary (Noon, 1911) ∗ Currently, subcutaneous immunotherapy (SCIT), a.k.a ‘allergy shots’ established as effective in the treatment of IgE-mediated reactions to: ∗ Hymenoptera venom ∗ Allergic rhinitis ∗ Allergic asthma
  47. 47. What is immunotherapy? ∗ Decrease allergen sensitivity via gradual administration of increasing doses of allergen extracts ∗ Advances over last 25 yrs include improved quality of extracts, better understanding of underlying immune mechanisms ∗ Modifies immune response from an allergic, inflammatory pattern to a more protective, less damaging response ∗ IT and allergen avoidance are the only treatments that modify the natural history of allergic disease, inducing remission and/or long-term cure
  48. 48. Efficacy in Asthma ∗ Confirmed in 3 meta-analyses of RCTs of specific immunotherapy for patients with allergic asthma ∗ Most recent included 75 trials involving over 3500 patients ∗ 33 dust mite ∗ 20 pollen ∗ 10 animal ∗ 2 mould ∗ 6 multiple aeroallergens Abramson et al. Cochrane Database System Rev 2009Abramson et al. Cochrane Database System Rev 2009
  49. 49. Efficacy ∗ Standardized Mean Difference in symptoms scores were best for dust mite and all pollens; overall SMD -0.72 (95% CI -0.99 to -0.44) ∗ If studies reported better, same, worse: ∗ Overall NNT = 4 to prevent one asthma deterioration ∗ Pollen NNT = 3 ∗ NNT = 5 to prevent one increase in medication requirements; NNT = 4 to prevent worsening of BHR
  50. 50. Established aspects ∗ Effective doses of allergen extract: ∗ Ragweed ∗ Timothy ∗ Birch ∗ D. pteronyssinus ∗ D. farinae ∗ Cat dander ∗ Dog dander ∗ Duration: ∗ After 5 years of SCIT, benefit generally persists ∗ If after 1-2 years at an appropriate maintenance dose, and no benefit noted, can discontinue Rx
  51. 51. Safety of Immunotherapy ∗ Local, systemic, and even fatal reactions are a recognized complication of SCIT ∗ Large local reactions not predictive of future systemic reactions (SRs) ∗ Incidence of SRs a function of: ∗ Patient sensitivity ∗ Dose ∗ Modifications to extract ∗ Systemic reactions to SCIT occur in 0.9 – 3.3% of injections with traditional schedules ∗ Rush protocols, up to 38% Nelson. J Allergy Clin Immunol 2007Nelson. J Allergy Clin Immunol 2007
  52. 52. Additional Agents/On the Horizon Ipatropium bromide (Atrovent®) 500 ug q4h PRN Tiotropium bromide (Spiriva®) 18 mg QAM Mepolizumab (Mepo®) Monoclonal anti-IL-5 antibody Other biologics?
  53. 53. Summary ∗ Asthma is a chronic disease–control inflammation to prevent symptoms ∗ Avoidance of triggers with ongoing education essential components of asthma management ∗ Review device technique/adherence whenever possible ∗ Uncontrolled asthma and severe exacerbations accelerate decline in lung function ∗ Unique considerations in allergic populations ∗ United airways; Disease modifying therapy
  54. 54. Questions? ∗ or ∗ Twitter: @DrAnneEllis