eRTD PPT on .......Home Nebulization.pptx

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1. Round Table Discussion on the Role of Home Maintenance Nebulization in COPD

2. 2 Objectives Understanding the drug and device usage in AE-COPD patients at discharge Role of nebulizers as an alternative in the long-term management of COPD at home Nebulized drugs that can be used in management of stable COPD at home

3. 3 COPD, or C hronic O bstructive P ulmonary D isease, is a progressive disease that makes it hard to breathe . Definition (GOLD-2020) GOLD ( G lobal Initiative for Chronic O bstructive L ung D isease) has defined COPD as a common , preventable and treatable disease that is characterized by - Persistent Respiratory Symptoms  Due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases Airflow limitation (many factors cause this airflow limitation) GOLD-2020

4. Presenter's Name 4 Global Scenario of COPD GOLD 2020, Lancet Respir Med. 2017 Sep;5(9):691-706; J Glob Health. 2015 Dec;5(2):020415; Respirology 2018; Global Burden of Disease Report, 2016 Prevalence: 384 Million DALYs: 63.85 Million Deaths: 3.2 Million Rank: 3 rd (Cause of Death)

5. Presenter's Name 5 Indian Scenario of COPD Prevalence: 55.3 Million DALYs: 22.37 Million Deaths: 8.48 Lakhs Rank: 2 nd (Cause of Death) Lancet Respir Med. 2017 Sep;5(9):691-706; J Glob Health. 2015 Dec;5(2):020415; Respirology 2018; Global Burden of Disease Report, 2016

6. 6 Causes/Risk Factors for COPD Smoking is the largest contributor to the COPD burden [SDI=69.4] in developed countries. However, COPD burden [SDI=58.1] due to environmental exposures is highest in developing countries 80% of COPD in India is due to non-smoking (only 20% cases are smoking). Out of 80% COPD cases, 35% are because of household pollution ( BIOMASS ) 35% are because of air pollution outside 10% are because of occupational exposure . [ rediff article 2018; GBD data 2016]

7. Presenter's Name 7 ABCD refined Assessment Tool – GOLD 2020

8. 8 Why use bronchodilator therapy in COPD? Lancet Respir Med. 2017 Jul;5(7):540-542 COPD Cause Symptoms Persistent Airflow Limitation is the principle pathology of COPD ! Caused by multiple factors, 1. Bronchoconstriction 2. Mucus hypersecretion 3. Airway remodelling 4. Reduced elastic recoil & alveolar attachments - Emphysema Bronchodilator therapy is the cornerstone in COPD Management Bronchodilators work by relaxing the smooth muscles around the airways allowing them to dilate & become larger to facilitate easier breathing Relieves the trapped air. Provides Symptomatic Relief Inflammation, Oxidative stress and Protease

9. Reflex Cholinergic tone Appears to be major reversible component of airways Obstruction In COPD Eur Respir Rev 2006; 15: 99, 32–36 9 Drug of Choice  Inhaled Anti Cholinergic Agents

10. 10 Why to use Glycopyrrolate as a bronchodilator in COPD Management Lately, various clinical trails have shown that – Glycopyrrolate, a long acting muscarinic antagonists [LAMA] DEFLATES the lungs, Glycopyrrolate binds to M3 muscarinic receptors & produces prolonged bronchodilation. Expert Rev Respir Med. 2018 Jun;12(6):447-459 Reduces breathlessness, Reduces exacerbation risk & improves quality of life in moderate to severe COPD patients . Deflation Air flow

11. 11 Following an acute exacerbation, what are the majority of your COPD patients prescribed at discharge? LABA + LAMA ICS + LABA ICS + LABA + LAMA

12. 12 What influences your drug prescription for AECOPD patients post discharge?

13. Which device is prescribed at discharge to the majority of patients post acute exacerbation of COPD? 13 pMDI with Spacer DPI BAI Nebulizer

14. 14 What is your device prescription influenced by? Factors Influencing Device Prescription Cleve Clin J Med. 2018 Feb;85(2 Suppl 1):S19-S27 J Assoc Physicians India. 2017 May;65(5):60-73 Chronic Obstr Pulm Dis. 2018; 5(2): 111–123. Cognition Manual dexterity Comorbidities Preference and outlook Age Poor eyesight Patient related Type of drugs Combination Frequency of dosing Strength of dose Side effects Large doses (if required) Drug related Severity of disease Respiratory status-lung condition Disease related Device related Ease of use Device efficacy Cost Duration of use

15. Selecting Inhalation Device should be Based on Quality Of Actuation-inhalation Coordination & PIFR ERS Annual Congress London 2016 15 It is also recommended that patient preferences for devices should be considered when prescribing an inhaler, but physicians must be cognizant that patients often overestimate their ability to handle a device correctly

16. <10% 10-20% 21-30% 31-40% >40% Don’t know In your opinion, what percentage of your AE-COPD patients would have a low PIFR (<60L/min)

17. 17 Important message: PIFR is reduced even in stable COPD patients (in outpatient settings) Discordance with prescribed inhalers was seen in 40% of COPD patients , suggesting that many COPD patients do not generate required inspiratory force to overcome prescribed DPIs resistance in the course of normal use. 2019

18. 18 Should PIFR be checked for both in- and outpatients for assessing suitability of delivery devices including nebulized therapies? Yes No

19. Role of nebulizers as an alternative in the long-term management of COPD at home

20. 20 In your opinion, what are the factors that determine the selection of COPD patients for home maintenance nebulization? Patients must be carefully screened before prescription of maintenance nebulization. More importantly, the screening should focus on the ability to use handheld inhaler devices and every effort should be made to introduce/re-introduce drug administration through handheld inhalers J Assoc Physicians India. 2017 May;65(5):60-73

21. 21 Clinical Scenarios where Maintenance Therapy with Nebulizer is Preferred in Patients with COPD Patients with inspiratory flow rates as low as 30 L/min Patients who are unwilling or find it difficult to use pMDI or DPI Patients having breath hold capacity of < 5-10 sec Patients who have cognitive impairment, muscle weakness due to age or co-morbidity COPD. 2012 Feb;9(1):58-72, J Allergy Clin Immunol Pract . 2018 May - Jun;6(3):987-995 Patients with poor hand-eye coordination

22. Selecting the Right Nebulizer 22 Feature Jet Nebulizer Ultrasonic Nebulizer Vibrating Mesh Nebulizer Power source Compressed gas or electric Electric Electric or battery Portability Limited Limited Portable Treatment time 15–20 mins 4–10 mins <1–5 mins Output rate Low Higher Highest Performance variability High Intermediate Low Cleaning Required after every use Required after several uses Required after every use Cost Very low High High Suspensions, efficiency Low Poor Variable COPD. 2012 Feb;9(1):58-72  JET NEBULIZER IS THE MOST WIDELY PREFERRED NEBULIZER

23. 23 Approved nebulized drugs in India for use in home nebulization Updated from, J Assoc Physicians India. 2017 May;65(5):60-73 Drug class Molecule Recommended use (in adults )* SABA Salbutamol/Levosalbutamol SOS in OADs SAMA Ipratropium bromide Long-term maintenance in COPD SABA+SAMA Levosalbutamol + Ipratropium bromide Salbutamol + Ipratropium bromide Long-term maintenance in COPD/ SOS in OADs LABA Arformoterol Long-term maintenance in COPD LAMA Glycopyrronium Long-term maintenance in COPD ICS+LABA Budesonide + Formoterol Long-term maintenance in OADs Mucolytics N-acetylcysteine Ambroxol Short-term adjuvant use in OADs in case of mucus hypersecretion For exact indication, posology & administration - please refer to the prescribing information available from the manufacturer of the respective products

24. 24

25. 25 What percentage of your patients are prescribed home nebulization for long-term COPD management <10% 10-20% 21-30% 31-40% >40%

26. Have you prescribed nebulized ICS-LABA to patients at discharge, post COPD exacerbation ? YES NO What % of your patients are prescribed nebulized ICS-LABA at discharge, post COPD exacerbation ? >80% 50-80% 20-50% <20%

27. 27 What has been your experience with Nebulized formoterol & budesonide in home maintenance nebulization? Efficacy Acceptability Safety Cost Technical Issues

28. 28 Int J Chron Obstruct Pulmon Dis. 2018 Dec 27;14:117-127 Nebulized formoterol group, was non-inferior to placebo with respect to safety in patients with moderate-to-severe COPD had fewer treatment withdrawals Cumulative probability of safety event (%) 12.5% 12% 10.8% 9.9% HR (90%CI)=0.83 HR (90%CI)=0.77 N = 1071 COPD patients Groups: Nebulized formoterol (20 μ g; n=541); BID Placebo (n=530); BID for 52 weeks. Nebulized LABA Reduces AE related ER visits & Hospitalization

29. 29 N=569 subjects with COPD Received twice-daily 20 μg formoterol fumarate inhalation solution for nebulization or 12 μ g formoterol fumarate DPI for 52 weeks. No effect on heart rate Heart rate No increase in QT prolongation QT-interval Long-term safety of formoterol in home nebulization in COPD patients

30. 30 Efficacy of nebulized formoterol Int J Chron Obstruct Pulmon Dis. 2018 Dec 27;14:117-127 (P<0.001) Improvement in TDI scores at month - 3 Transitional dyspnoea index (TDI) LS mean change from baseline FVC ± SEM (P<0.005)

31. 31 Respir Med. 1998 Jan;92(1):44-9. J Natl Med Assoc. 2006 Jun;98(6):851-61 Recommendations: To ascertain long-term safety in patients with OADs, it is recommended to perform a regular review (at least every 6 months) OAD patients with complicating comorbidities such as CVD and diabetes should be reviewed regularly (every 6 months) for blood glucose and cardiac parameters. No significant dose-related suppression of plasma cortisol No reports of cataract, ocular hypertension, osteoporosis in the geriatric population Long term safety of budesonide in home nebulization in COPD patients

32. YES NO Have you prescribed nebulized Glycopyrronium at discharge, post COPD exacerbation? >80% 50-80% 20-50% <20% What % of your patients are prescribed nebulized Glycopyrronium at discharge, post COPD exacerbation ?

33. 33 Pharmacological effects of Glycopyrrolate in COPD GOLD 2019; Drug Des Devel Ther . 2017 Nov 15;11:3257-3271 Prolonged bronchodilation 1 Decreases air trapping and hyperinflation 2 Improves symptoms [  breathlessness and mucous secretion] 3 Improves health related quality of life 4 Reduces exacerbations and related hospitalizations 5

34. 34 Long duration of Action - 24hr Drug Des Devel Ther . 2017 Nov 15; 11:3257-3271, Clin Ther . 2005 Apr;27(4):377-92; Int J Chron Obstruct Pulmon Dis. 2012;7:729-41 Faster onset of action [5mins] than Tiotropium [30min] More potent than Tiotropium M3 receptor selectivity Lesser oral absorption Comparative benefits of Glycopyrrolate over other anti-cholinergics

35. 35 How has been your clinical experience with nebulized Glycopyrronium till now ?

36. 36 Respir Med. 2017 Nov;132:238-250. GOLDEN 3 and 4 Trial Phase III, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety trial of 12 weeks in moderate to severe COPD patients. GOLDEN 3: n = 653, GOLDEN 4: n = 641. BID BID Placebo-adjusted values (P<0.0001) (p<0.001) BID BID Placebo-adjusted values Treatment with nebulized Glycopyrronium resulted in significant and clinically important improvements in trough FEV1 and FVC from baseline at week 12

37. 37 Glycopyrronium resulted in statistically significant improvement in health status [SGRQ scores] in GOLDEN 3 and 4 Respiratory Medicine 132 (2017) 238-250 Worsening Improvement SGRQ score at 12 weeks 50% of COPD patients receiving 25μg; BID of nebulized glycopyrrolate in GOLDEN 3 trial showed clinically significant improvement in SGRQ score (minimum clinically important difference [MCID] = - 4.056 units). GLY 25 ug Glycopyrrolate 25μg = 46.8% Glycopyrrolate 50μg = 41.7% Placebo = 34.5% The % of SGRQ Responder in GOLDEN 3 and 4

38. 1 respule, once a day, total dose :25 mcg 1 respule, twice a day, total dose: 50 mcg Any other ? Please specify 38 What is the DOSAGE REGIMEN of nebulized Glycopyrronium PRESCRIBED for the MAJORITY OF YOUR COPD patients? Duration of the therapy ?

39. The term "night-time symptoms" in COPD has not been distinctly defined in an objective sense but epidemiological data suggests that the prevalence of nocturnal symptoms and symptomatic sleep disturbance may exceed 75% in patients with COPD . The panel concluded that Night-time symptoms in COPD are prevalent and bothersome; their cause(s) are multiple and include demographic factors, such as age and obesity, pharmacotherapy, disease-specific symptoms and the presence of comorbid sleep disorders, and other medical conditions; potential long-term consequences can include lung function changes, increased exacerbation frequency, emergence or worsening of cardiovascular disease, cognitive effects, depression, impaired quality of life and increased mortality.

40. 40 Respiratory Medicine 132 (2017) 238-250; Chronic Obstr Pulm Dis. 2018 Dec 13;6(1):86-99 Nebulized Glycopyrrolate at 25 μ g; BID – shows highest numeric reduction in night-time awakening due to coughing or wheezing. [ Respiratory Medicine 132 (2017) 238-250 ] Nebulized Glycopyrrolate at 25 μ g; BID – decreases percentage of exacerbations in moderate to very severe COPD having high cardiovascular risk. GOLDEN 3 and 4 Trial – Effect on Night-time Symptoms GOLDEN 3 and 4 Trial – Effect on Exacerbation rate

41. Are there concerns regarding the cardiac safety of nebulized LAMA ? 41

42. 42 Safety of Glycopyrronium In GOLDEN 3 & 4 Treatment Emergent Adverse Events [TEAE] Cough and worsening of COPD Placebo = 52.3% GLY 25μg = 39.6% GLY 50μg = 48.2% GOLDEN 3 GOLDEN 4 Placebo = 52.4% GLY 25μg = 47.2% GLY 50μg = 53.3% TEAE were similar or less in both GLY groups in comparison to placebo Respir Med. 2017 Nov;132:238-250. The overall % of COPD patients who experienced an SAE was similar in GOLDEN 3 (4.6%) & GOLDEN 4 (4.2%) MACE: GOLDEN 3 trial: 3 subjects in nebulized GLY 50μg group GOLDEN 4 trial: None in both GLY group two subjects in the placebo group had MACE in GOLDEN 4

43. 43 Incidence of MACE Respir Med. 2017 Nov;132:251-260, Chronic  Obstr Pulm Dis. 2018 Dec 13;6(1):86-99 . GOLDEN 5: Phase III, randomized, open-label, active-controlled, parallel-group, 48-week multicenter trial in moderate to very severe COPD patients. Treatment Groups, N = 1086 Nebulized glycopyrrolate 50 μ g [n=620] BID for 48 weeks. Tiotropium 18 μ g [n=466] once daily via soft mist inhaler for 48 weeks. Incidence of Major Adverse Cardiac Events (MACE) were lower with nebulized Glycopyrronium than with tiotropium for both high and low CV risk subgroups

44. What is the most frequently prescribed nebulized drug with nebulized Glycopyrronium at discharge, post COPD exacerbation? ICS/LABA ICS SABA/SAMA Any other ?

45. 45 Data on file What % of your patients are co-prescribed with nebulized ICS/LABA at discharge, post COPD exacerbation? >80% 50-80% 20-50% <20% Based on the physico-chemical compatibility study, Glycohale respule is compatible with Foracort respule

46. 46 On what aspects of nebulization do you think the patients should be educated?

47. Advise patients to have their full supply of medication at home 1 Perform nebulization in a well ventilated room Prevent your caretaker/family member from staying inside the room during nebulization DON’T let the caretaker get too close while Nebulization is being conducted. Maintain distance of at least 6 feet from the patient . Close the door while nebulization is being undertaken. 2 DON’T share nebulizers between family members . Every nebulizer should be a single-use nebulizer 2 . Avoid air-conditioning in the room altogether 5 . DO leave the room vacant with the door closed for 30 minutes after the patient has vacated the room post-nebulization. 4 Wash the accessories as per the guide and use disinfectants like Isopropanol (70%) or Hydrogen Peroxide (3%) 4. 1 WHO Interim guidelines 2019; 2 CDC guidelines www.health.state.mn.us ; 3 https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene.html ; 4 https://www.health.qld.gov.au/data/assets/pdf_file/0038/939656/qh-covid-19-Infection-control-guidelines.pdf ; 5 www.ncdc.gov Good Nebulization Practice at HOME Setting

48. 48 All inhalation devices are equally efficacious in all types of patients provided they are used correctly Not all patients can use handheld inhalers. Hence Nebulization can be an alternative treatment modality Patients on maintenance nebulization should undergo regular review to ascertain long-term safety Selection of an appropriate inhalation device should have individualized and patient-specific approach Patients should strictly follow cleaning and maintenance recommendations Take Home Points to Remember

49. 49