sign in sign up
<<
Home , Arformoterol, Pirbuterol

COPD: Inhaled Drugs and Delivery 2016

Brian W.Carlin, MD, MAACVPR, FAARC, FCCP SleepMedicine and Lung Health Consultants Pittsburgh, Pennsylvania May 2017 Disclosures

Consultant/Independent Contractor: AstraZeneca; Boehringer-Ingelheim Pharmaceuticals; Monaghan Medical Corporation; Nonin Medical; Sunovion Pharmaceuticals, Philips

Grant/Research Support: Philips Respironics

Speakers Bureaus: Boehringer Ingelheim Pharmaceuticals; GlaxoSmithKline; Sunovion Pharmaceuticals

2 Pharmacologic Treatment Options Treatment Options for COPD

ICS + LABA and LAMA C LAMA and LABA or D or ICS + LABA and PDE-4 LAMA and PDE-4 or ≥2 or LAMA and LABA LABA and PDE-4 or LAMA and PDE-4

A LAMA B or 1 LABA LAMA and LABA or Exacerbations/y SABA and SAMA 0 mMRC 0-1 mMRC ≥2 CAT <10 CAT ≥10

ICS, inhaled ; SABA, short-acting beta2-adrenoceptor agonist; SAMA, short-acting ; mMRC = mMRC Breathlessness Scale; CAT = COPD Assessment Test

Global Initiative for Chronic (GOLD) 2016. www.goldcopd.org. Accessed 3/29/16. 4 Pharmacologic Options Anti-Inflammatory Short-Acting Long-Acting Inhaled (SAMA) Anticholinergic (LAMA) ICS + LABA Ipratropium Tiotropium,Tiotropium or aclidinium, or + umeclidinium,Aclidinium or glycopyrrolate +

Β2-Agonists (SABA) Umeclidinium Fluticasone + Β2-Agonists (LABA) Albuterol Salmeterol,Β2-Agonists or formoterol,(LABA) or Oral Levalbuterol ,Salmeterol, or orindacaterolFormoterol, (ultra), or or Metaproterenol Arformoterol, oorlodaterolIndacaterol (ultra), or PDE-4 Inhibitors LAMAOlodaterol + LABA SAMA + SABA TiotropiumLAMA + olodaterolLABA Oral Steroids Ipratropium + albuterol UmeclidiniumTiotropium + + vilanterol Prednisone IndacaterolUmeclidinium + glycopyrrolate + vilanterol Methylprednisolone Derivative: 5 Newer Therapies (continued)

Medication/Formulation Class Approved Indication

Long-term, once-daily maintenance treatment, Vilanterol/umeclidinium LABA + Dec COPD-related airflow obstruction, including bromide inhalation powder1 LAMA 2013 chronic bronchitis/emphysema

Fluticasone furoate/vilanterol ICS + May Once-daily alternative to inhalation powder2 LABA 2013 fluticasone/salmeterol, budesonide/formoterol

Aclidinium bromide inhalation July Long-term, twice-daily maintenance treatment, LAMA powder3 2012 COPD-related

1. Anoro Ellipta. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm379057.htm. Accessed 4/4/16. 2. Breo Ellipta. www.fda.gov/newsevents/newsroom/pressannouncements/ucm351664.htm. Accessed 3/29/16.. 3 Tudorza Pressair. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm313052.htm. Accessed 3/29/16. 6 Newer Therapies (continued)

Medication/Formulation Class Approved Indication

Long-term, once-daily maintenance treatment, Aug Olodaterol inhalation spray1 LABA COPD-related airflow obstruction, including 2014 chronic bronchitis/emphysema

Long-term, once-daily maintenance treatment, April LAMA COPD-related airflow obstruction, including inhalation powder2 2014 chronic bronchitis/emphysema

1. Olodaterol. http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2014/08-01-14-fda-approves-boehringer-ingelheims-striverdi-respimat-olodaterol-inhalation-spray- maintenance-treatment-copd.html. Accessed 3/29/16. 2. Umeclidinium. www.prnewswire.com/news-releases/gsk-receives-approval-for-incruse-ellipta-umeclidinium-in-the-us-for-the-treatment-of-copd- 257416481.html. Accessed 4/5/16. 7 Newer Therapies

Medication/ Class Approved Indication Formulation

Indacaterol + LAMA + Oct Long-term maintenance treatment of airflow glycopyrrolate LABA 2015 obstruction in patients with COPD inhalation powder1

Glycopyrrolate Oct Stand-alone, long-term maintenance treatment of LAMA inhalation powder2 2015 airflow obstruction in patients with COPD

Long-term, once-daily from start of maintenance Tiotropium/olodaterol LAMA + April treatment, COPD-related airflow obstruction, inhalation spray3,4 LABA 2015 including chronic bronchitis/emphysema

1. UTIBRON™ NEOHALER® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016. http://www.pharma.us.novartis.com/product/pi/pdf/utibron.pdf. 2. Seebri TM NeohalerR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016. http://pharma.us.novartis.com/product/pi/pdf/seebri.pdf. 3. Tiotropium/olodaterol. www.boehringer- ingelheim.com/news/news_releases/press_releases/2015/20_may_2015_copd.html. Accessed 3/29/16. 4. Stiolto [package insert]. Ridgefield, CT: Boehringer Ingleheim; 2015. 8 Adverse Effects of Therapy

. . Dry mouth, urinary retention, glaucoma

. Beta2-agonists . Tachycardia, palpitations, premature ventricular contractions, tremors, hypokalemia

. Inhaled . Dysphonia, thrush, systemic effects (bruising, bone density, cataract), pneumonia, local irritation

Harvey RA, et al. Pharmacology (Lippincott’s Illustrated Reviews Series). 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2012. 9 Most COPD Patients Do Not Receive Recommended Treatment

Patients not receiving recommended maintenance therapy

LAAC, long-acting anticholinergic; SAAC, short-acting anticholinergic; Ach, inhaled anticholinergic Make B et al. Int J Chron Obstruct Pulmon Dis. 2012;7:1-9. 10 INHALED DRUG DEPOSITION

. Patient inhalational flow

. Aerosol velocity

. Inhaled drug particle size Delivery Devices Inhaler Use Fink, Respir Care 2005

14 Inhaler Use Fink, Respir Care 2005 Inhaler Use Fink, Respir Care 2005

16 Inhaler Use Fink, Respir Care 2005

17 Inhaler Use Fink, Respir Care 2005 Factors That Determine Selection of Delivery System Clinical efficacy Cognitive/ Disease severity dexterity issues Need for combination Lifestyle/ therapy preference

Cost Ease of use Portability

Photo credit: www.humana.com 19 Inhaler Devices Available United States

Diskus® MDI Handihaler®

Aerolizer™ Twisthaler®

Pressair®

Ellipta® Flexhaler® Respimat® Spacer Devices 20 Inhaler Devices Available United States Small-Volume

• Select a medication delivery system/regimen that is aligned with treatment goals, patient abilities and preferences; consider costs • Train patients on proper device technique; reinforce training at each visit

21 pMDI

. HFA driven, breath-actuated . Advantages . Portable, compact . Disadvantages . Requires coordination . Shaken prior to use . Oropharyngeal deposition 22 DPI

. Single, multidose . Advantages . Portable, compact . No spacer required . Disadvantages . Inspiratory flow dependent . Poor dose reproducibility

23 Soft mist

. Single, multidose . Advantages . Portable, compact . No spacer required . Disadvantages . Newer model of use

24

. Jet, vibrating mesh, ultrasonic . Advantages . Propellant free . Slow velocity aerosol . Disadvantages . Bulky . Power sources

. Frequent cleaning 25 Individualizing Inhaled Therapy1,2

. Good hand-breath coordination required for MDIs . May not be suitable for elderly, confused, those with hand conditions (e.g., arthritis)

. Dry-powder inhalers (DPIs) do not require coordination of actuation, inhalation; easier to use than MDIs . Breath actuation may be difficult in patients with poor inspiratory effort

. Avoid changing inhaler types for individual patients

1. Vincken W et al. Prim Care Respir. 2010;19(1):10-20. 2. De Coster DA et al. Curr Respir Care Rep. 2014;3:121-132. 26 Types of Inhaler Errors

1. Device care and preparation 2. Exhalation before use 3. Timing 4. Coordination with device 5. Flow rate errors 6. Completing inhalation/breath hold 7. After care (ie, rinsing/gargling)

• Extremely high rate of device technique errors with use of chronic inhaled medications • Incorrect technique poorly perceived by patient; must be assessed by HCPs

27 Increasing Patient Adherence to COPD Treatment Adherence to Medications: Poor

. 167 patients with COPD . LABA: 54% adherencea . ICS: 40% adherence

. Patients more adherent when they perceive clinician as a lung disease expert

aAdherence measured by electronic pharmacy records to assess adherence, defined as medication possession ratio ≥0.80

Cecere LM et al. COPD. 2012;9:251-258. 29 Barriers to Treatment Adherence

. Inadequate education about COPD, therapy1 . Perceived burden of medication regimen1,2 . Device difficult to use3 . Depressed mood3 . Medication-related cost3 . Adverse effects3

1. Laforest L et al. Prim Care Resp J. 2010;19(2):148-154. 2. George J et al. Chest. 2005;128(5):3198-3204. 3. Restrepo RD et al. Int J COPD. 2008;3(3):371-384. 30 Features of Devices

. pMDIs(pressurized metered-dose inhalers) . DPIs (dry powder inhalers) . Soft-mist inhaler . Nebulizers

31 Systematic Review of Errors in Inhaler Use Sanchis, CHEST 2016 (in press)

32 Systematic Review of Errors in Inhaler Use Sanchis, CHEST 2016

. 144 articles (n = 54354 patients) . MDI errors . Co-ordination (45%) . Speed and/or depth of inspiration (44%) . No post-inhalation breath-hold (46%) . DPI errors . Incorrect preparation (28%) . No full expiration before inhalation (46%) . No post-inhalation breath hold (37%)

33 Systematic Review of Errors in Inhaler Use Sanchis, CHEST 2016

. Prevalence (technique) . Correct 31% (33-40%) . Acceptable 41% (36-47%) . Poor 31% (27-36%)

34 EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

. Evaluate the relative effects of two educational strategies in adults hospitalized with /COPD . Teach to goal . Brief verbal instruction . Randomized trial . Inhaler technique . Standardize checklists . Misuse (<75% steps or less correct) . Primary outcome – use at 30 days post discharge EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

36 EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

37 EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

38 EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

. Results . N = 120 . Women 73%, African-Americans 90% . Pre-education . TTG 92% . Brief intervention 84%

. Post-education (immediate) . TTG 11% . Brief instruction 60%

. Post-education (30 day) . TTG 54% . Brief instruction 70% EFFECTIVENESS OF INTERVENTIONS Press et al, Annals ATS 2016

. Teach to goal instruction in inhaler technique

. Did not reduce inhaler misuse at 30 days

. Associated with fewer acute care events at 30 days Pittsburgh Regional Health Initiative

. CMS innovation award grant . Readmission reduction program . Seven community hospitals . Provider educational sessions . COPD . Spirometry . Inhaled device use

41 Standardized Inhaler Training Across a COPD Care Management Program

. Nurses, RTs, pharmacists . 3 hour program . Pre-test, Post-test . Written, simulation (checklists) . Didactic session . Training session . “Instructor” . “Patient” . “Assessor(s)” . Checklists, actual device placebos

Carlin, ATS annual meeting 2017 42 Standardized Inhaler Training Across a COPD Care Management Program

43 Standardized Inhaler Training Across a COPD Care Management Program

. Written tests . 10 single best answer, multiple choice . Similar domain content (not same questions) . Results (number correct) . Pre 7.66

. Post 9.24

Carlin, ATS annual meeting 2016 44 Standardized Inhaler Training Across a COPD Care Management Program

Carlin, ATS annual meeting 2016 45 Inhaler Use Alismail et al, Respir Care 2016

46 Inhaler Use Alismail et al, Respir Care 2016

47 Common Myths About Inhaler Use

. Inhalers are so simple they need no instruction

. DPIs are easier to use than pMDIs

. Nebulizers are easier to use than inhalers

. Someone else will teach the patient if I don’t

48 Common Myths About Inhaler Use

. I know and follow the current guidelines

. Once inhaled medications are prescribed, the patient will conscientiously take them

. I teach the patient correctly, but they don’t use the inhalers right

49 Pulmonologist Survey Braman et al, ATS 2016

. Survey regarding attitudes and practices . Inhalational devices . Knowledge . 98% somewhat knowledgeable . 54% extremely knowledgeable . 70% teach patient on first visit

50 Pulmonologist Survey Braman et al, ATS 2016

. Discuss clean and store 9%

. Which patients should use a hand-held nebulizer (very knowledgeable) 31%

. Small volume nebulizers essential for some patients 56%

. Hand held nebulizers more effective than DPI/MDI (MMRC grade of 4) 63%

51 How Do I Use These Devices ?

Summary Tailoring Therapy

• Individual Presentation, Underlying Mechanisms • Individual Risk Factors  Mortality  Skin bruising  Disease progression Current  Nutritional impairment  Lung function  Neuropsychological effects  Symptoms Pharmacological  GI symptoms  Exercise tolerance  Exacerbations Options  Disability  Health status, QOL Benefits Risks

• Comorbidities  Pneumonia LABA  Tuberculosis LAMA  Osteoporosis, fractures LABA + LAMA  Muscle dysfunction LABA + ICS  Cataract LABA + LAMA + ICS  Diabetes LABA + PDE-4  Tremor  Cardiovascular events LAMA + PDE-4

Woodruff PG et al. Lancet. 2015;385(9979):1789-1798. 55 Steps to Improving Adherence

. Select best medication delivery system for patient . Provide education about COPD . Provide training on use of delivery system . Develop a rapid action plan to prevent, manage exacerbations

56 References REFERENCES

. Braman SS, Carlin BW, Dhand R, Hanania NA, Mahler DA, et al. Results of a pulmonologist survey regarding attitudes and practices with inhalation devices for COPD. Am J Respir Crit Care Med 193;2016,A7816A

. Alismail A, Song C, Terry MH, et al. Respir Care 2016;61(5):593-599.

. Press VG, Arora VM, Trela KC, et al. Effectiveness of interventions to teach metered-dose and diskus inhaler techniques. Ann Am Thor Soc 2016;13(5):816-824.

58 REFERENCES

. Roggeri A, Micheletto C. Toggeri DP. Inhalation errors due to device switch in patients with COPD and asthma: critical health and economic issues. Int J COPD 2016;11:597-602.

. Carlin BW, Kanel K, Thomas G, Campus S. Standardizing inhaler training across a COPD care management project. Am J Respir Crit Care Med 193;2016.

. Video courtesy of Paradigm Medical Communications. Monograph available at https://ce.paradigmmc.com/attendee/view_program.jsp?programCode=20117P3chNGf

. Paradigm Medical Communications: paradigmmc.com

59 Thank You !!

[email protected]