4/4/2018

1

Improving Outcomes in COPDUpdates 2018

Neil MacIntyre MD

Duke University

Durham NC

Improving Outcomes in COPD

• COPD – pathophysiology, clinical picture/impact

• Diagnosis and staging

• Evidence based management guidelines

• Barriers to implementation

. Barnes PJ. N Engl J Med. 2000;343:269-80.

4/4/2018

2

COPD spectrum

• Proximal predominant (large airways)

– mucus gland hypertrophy (cough/sputum)

– reduced respiratory drive

– airway hyper-reactivity

• Distal predominant (small airways/alveoli)

– dyspnea - active respiratory drive

– reduced DLCO

COPD spectrum

table

Emphysema Bronchitis

COPD: the clinical spectrumCOPD is a systemic disease

• Chronic airway inflammation “spills” inflammatory cytokines into the circulation

– ASCVD

– Renal insufficiency

– Neuro-myopathy

– Osteoporosis

• Cachexia, debility may be product of this

Resp Care. 2006; 51: 840-8

COPD natural history depends on tobacco exposure/sensitivity

4/4/2018

3

0.0

0.5

1.0

1.5

2.0

2.5

3.0

CoronaryHeart Disease

Stroke Other CVD COPD All OtherCauses

-59% -64% -35% +163% -7%

COPD Projected to Be the Third-Leading Cause of Death by 2020

Proportion of 1965-1998 Rate, Percentage Change in Age-Adjusted Death (US)

Global Initiative for Chronic Obstructive Lung Disease teaching slide kit. Available at: www.goldcopd.com/slides/download.ppt.

Pro

po

rtio

n o

f 19

65 R

ate

COPD: Direct Cost

$0

$2

$4

$6

$8

$10

$12

$14

$16

$18

$20

COPD

Nursing Home Care*

Home Health Care*

Physician Services

Hospital Care

Prescription Drugs

Morbidity and Mortality: 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases. NIH/NHLBI. May 2002.

†

Improving Outcomes in COPD

• COPD – pathophysiology, clinical picture/impact

• Diagnosis and staging

• Evidence based management guidelines

• Barriers to implementation

SYMPTOMSsputum

cough

dyspnea

wheezing

EXPOSURE TO RISK

FACTORS

SPIROMETRY

Diagnosis of COPD

Adapted with permission from the GOLD web site. Available at: www.goldcopd.com.

AND/

OR

SpirometryCOPD: the spirogram

Normal

Obstructed

Restricted

4/4/2018

4

Global Obstructive Lung Disease (GOLD) Consortium Staging

www.goldcopd.com

Spirometry can miss emphysema

In COPDgene, 357 of 858 smokers with normal spirometry had emphysema on CT

Symptoms/function as important as FEV1 on survival

BODE: Dyspnea, 6MWT, BMI, FEV1

GOLD 2017: Combined Assessment of COPD

• Diagnose COPD

– Spirometry not enough

– Radiology (hyperinflation, emphysema) and DLCO alternate diagnostic tools

• Two components determine severity of disease

– Symptom assessment

– Risk of exacerbations

CAT = COPD assessment test; mMRC = modified Medical Research Council.Global Initiative for Chronic Obstructive Lung Disease. 2014. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Accessed March 6, 2014.

Global Strategy for Diagnosis, Management and Prevention of COPD

Combined Assessment of COPD

Ris

k(G

OLD

Cla

ssif

icat

ion

of

Air

flo

w L

imit

atio

n)

Ris

k(E

xace

rbat

ion

his

tory

)

> 2

1

0

(C) (D)

(A) (B)

mMRC 0-1CAT < 10

4

3

2

1

mMRC > 2CAT > 10

Symptoms(mMRC or CAT score))

4/4/2018

5

GOLD 2017

1)Diagnose 2) Obstruction Severity 3) Impact

Improving Outcomes in COPD

• COPD – pathophysiology, clinical picture/impact

• Diagnosis and staging

• Evidence based management guidelines

• Barriers to implementation

GOLD Guidelines 2017Guided by impact – not physiology

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Non-pharmacologic

PatientGroup

Essential Recommended Depending on localguidelines

ASmoking cessation (caninclude pharmacologic

treatment)Physical activity

Flu vaccinationPneumococcal

vaccination

B, C, D

Smoking cessation (caninclude pharmacologic

treatment)Pulmonary rehabilitation

Physical activityFlu vaccinationPneumococcal

vaccination

© 2013 Global Initiative for Chronic Obstructive Lung Disease

Current Inhaled Medications for COPD

Medication Brand Usual Starting Dose Duration

β2-Agonists

Short-acting

Albuterol ProAir, Proventil, Ventolin 2 puffs q 4-6 hrs PRN 4-6 h

Levalbuterol Xopenex HFA 2 puffs q 4-6 hrs PRN 4-6 h

Pirbuterol Maxair Autohaler 2 puffs q 4-6 hrs PRN 5 h

Long-acting

Formoterol Foradil Aerolizer , Perforomist, Brovana

1 inhaled capsule bid 12+ h

Indacaterol Arcapta Neohaler 1 inhaled capsule daily 24+ h

Salmeterol Serevent Diskus 1 puff bid 12+ h

HFA = hydrofluoroalkane.

http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fbe6d514-9d89-48f7-80a0-d1b41983f203. Accessed April 3, 2014. Cazzola M, et al. Drugs Today. 2011;106:84-90. http://www.pdr.net/. Accessed April 3, 2014. PL Detail-Document, Inhalers for COPD. Pharmacist’s Letter/Prescriber’s Letter. August 2013.

Current Inhaled Medications for COPD Cont’d

Medication Brand Usual Starting Dose Duration

Anticholinergics

Short-acting

Ipratropium bromide Atrovent 2 puffs qid 6-8 h

Long-acting

Aclidinum Tudorza Pressair 1 puff bid 24+ h

Tiotropium bromide Spiriva Handihaler 1 inhaled capsule daily 24+ h

Combination Bronchodilators

Albuterol/ipratropium Combivent 2 puffs q 4-6 hrs PRN 4-6 h

Umeclidinum/Vilanterol Anoro Ellipta 1 puff daily 24 h

http://www.pdr.net/. Accessed April 3, 2014. Salmon M, et al. J Pharmacol Exp Ther. 2013;345(2):260-70. Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1):218-30. PL Detail-Document, Inhalers for COPD. Pharmacist’s Letter/Prescriber’s Letter. August 2013.

* NEW: Titropium/olodaterol (Stiolto)

4/4/2018

6

Current Inhaled Medications for COPD Cont’d

Medication Brand Usual Starting Dose Duration

Inhaled Corticosteroids

Budesonide Pulmicort Flexhaler 1-2 puffs bid 12 h

Fluticasone Flovent HFA 1-2 puffs bid 12 h

Beclomethasone QVAR 1-2 puffs bid 12 h

Combination Inhalers

Formoterol/Budesonide Symbicort 2 puffs bid 12 h

Fluticasone/Salmeterol Advair DiskusAdvair HFA

1 puff bid2 puffs bid

12 h

Fluticasone/Vilanterol Breo Ellipta 1 puff daily 24 h

HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4.

PL Detail-Document, Inhalers for COPD. Pharmacist’s Letter/Prescriber’s Letter. August 2013. http://www.pdr.net/. Accessed April 3, 2014. Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1):218-30.

The latest compounds and formulations - 2017

• LABAs– Oladaterol SMI (Stiverdi)

• LAMAs– Glycopyronium DPI (Seebri)

– Umeclidium DPI (Incruse)

• LABA/ICS– Formoterol/beclamethasone MDI and DPI

(Fostair)

– Formoterol/mometasone MDI (Dulera)

The latest compounds and formulations - 2018

• LAMA/LABA

– Formoterol/aclidinium DPI (Genuair)

– Formoterol/glycopyrronium MDI* (Bevespi)

– Indacaterol/glycopyronium DPI (Ultibro)

– Oladaterol/tiotropium SMI (Stiolto)

• LAMA/LABA/ICS

– “Stay tuned” – Trelegy Ellipta

* co-suspension technology

Current Oral Medications for COPDMedication Brand Usual Starting Dose Duration

Corticosteroids

Methylprednisolone 4-48mg/day depending on disease and response

12-24 h

Prednisolone 5-60mg/day depending on disease and response

12-24 h

Prednisone 5-60mg/day depending on disease and response

12-24 h

PDE4 Inhibitor

Roflumilast Daliresp One 500 mcg tablet daily 17+ h

HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4.

Using Oral Corticosteroids: a toolbox. Pharmacist’s Letter/Prescriber’s Letter. 2010;26(5):260507. http://www.pdr.net/. Accessed April 3, 2014.

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Pharmacologic Therapy(Medications in each box are mentioned in alphabetical order, and therefore not

necessarily in order of preference.)

Patient Recommended First choice

Alternative choice

ASAMA prn

orSABA prn

LAMAor

LABA or

SABA and SAMA

BLAMA

orLABA

LAMA and LABA

C

ICS + LABAor

LAMA

LAMA and LABA orLAMA and PDE4-inh. or

LABA and PDE4-inh.

D

ICS + LABAand/orLAMA

ICS + LABA and LAMA orICS+LABA and PDE4-inh. or

LAMA and LABA orLAMA and PDE4-inh.

Other Management Issues

• Oxygen– Rest/episodic– Targets? SpO2>88% correct?

• Nocturnal NIV for hypercapnia (high pressure)– Lancet Resp Med 2014; Sept 2: 298– JAMA 2017;317:2177

• Lung volume reduction procedures– Surgery vs bronchoscopic

• Action plan for AECOPD– Bronchodilators/antibiotics/steroids/hot line

4/4/2018

7

Improving Outcomes in COPD

• COPD – pathophysiology, clinical picture/impact

• Diagnosis and staging

• Evidence based management guidelines

• Barriers to implementation

Barriers

• Clinician barriers

– Proper diagnosis/staging/prescribing per guidelines

• Patient barriers

– Understanding complex medication regimens

– Adherence to treatment plans (both pharmaceutical and non-pharmaceutical)

• System barriers

– Costs of medications

– Clinical support structures

Clinical COPD Is Just The Tip Of The Iceberg

*Repeated exacerbations and hospitalizations

Mannino. MMWR Surveill Summ. 2002;51(6):1-16.

SUBCLINICAL COPD? Millions at risk

10 Million Dx2 Million “severe”

Reproduced with permission. Zaas D et al. Chest. 2004;125:106-11.

COPD Often Unrecognized During Hospitalization.

0

10

20

30

40

50

60

70

80

90

Admission

Diagnosis

Discharge

Diagnosis

Perc

enta

ge C

orr

ectl

y D

iagn

ose

dW

ith

Ob

stru

ctiv

e Lu

ng

Dis

ease

Mild Moderate Severe Very Severe

SPR Performance 2006-2012

50.0

40.0

30.0

20.0

10.0

5.0

201220112010200920082007

Spirometry: HMO

2006

0.0

45.0

35.0

25.0

15.0

Commercial

Medicaid

Medicare

HMO = health maintenance organization.

PCE Performance 2008–2012

90.0

80.0

70.0

60.0

55.0

2012201120102009

Pharmacotherapy: Corticosteroids (HMO)

2008

50.0

85.0

75.0

65.0

Commercial

Medicaid

Medicare

4/4/2018

8

PCE Performance 2008–2012

90.0

80.0

70.0

60.0

55.0

2012201120102009

Pharmacotherapy: Bronchodilators (HMO)

2008

50.0

85.0

75.0

65.0

Commercial

Medicaid

Medicare

Barriers

• Clinician barriers

– Proper diagnosis/staging/prescribing per guidelines

• Patient barriers

– Understanding complex medication regimens

– Adherence to treatment plans (both pharmaceutical and non-pharmaceutical)

• System barriers

– Costs of medications

– Clinical support structures

LABA Adherence

• N = 1014 COPD in health plan given new LABA

• Prescription filling over 1 year:

– >80% 26%

– 60-70% 14%

– 40-50% 20%

– 20-30% 21%

– <20% 19%

CHEST 2014, Abstract 12014b

Cost Differences Between Baseline and Follow-up

Asche CV, et al. Int J Chron Obstruct Pulmon Dis. 2012;7:201-209.

LAMA/LABA LABA/ICS LAMA/LABA/ICS

Why aren’t patients adherent?

• Lack of understanding of importance

– Maintenance vs rescue

• Ineffective use of devices

– Breathing maneuvers, device operation

• Costs

– The “donut hole” and drugs running several hundred $/month

49

Barriers

• Clinician barriers

– Proper diagnosis/staging/prescribing per guidelines

• Patient barriers

– Understanding complex medication regimens

– Adherence to treatment plans (both pharmaceutical and non-pharmaceutical)

• System barriers

– Costs of medications

– Clinical support structures

4/4/2018

9

System Barriers

• Access to clinicians– Priority scheduling

– Hot lines

– Home visits

– Education

• Discharge planning– Medications

– Follow-up plans

• Pulmonary rehabilitation centers

Barriers to pulm rehab

• Less than 2% of COPD patients use PR (COPD 2014; July 1)

• Why not more?

– Limited number of programs

– Cost/reimbursement issues (now CMS reimbursed)

– Logistics (transport, timing)

– Motivation

52

Clinical Support Structure

• Access to clinicians

– Hot lines

– Home visits

– Education

• Discharge planning

– Medications

– Follow-up plans

• Rehabilitation centers

Improving Outcomes in COPD

• COPD – pathophysiology, clinical picture/impact

• Diagnosis and staging

• Evidence based management guidelines

• Barriers to implementation