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Take My Breath Away COPD Update
Juliann Horne, PharmD, PhC, BCACP [email protected]
April 16, 2016
Take My Breath Away COPD Update
Juliann Horne, PharmD, PhC, BCACP
April 16, 2016
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Conflicts of Interest • Nothing to disclose
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Learning ObjecLves – Pharmacists • Describe signs and symptoms and classificaLon of chronic
obstrucLve pulmonary disease (COPD).
• Explain the role of pharmacotherapy for COPD.
• Compare and contrast recently approved pharmacotherapeuLc agents and inhaler devices for the treatment of COPD.
• Explain appropriate use of recently approved inhaler devices.
Learning ObjecLves – Technicians
• List signs and symptoms of COPD.
• List treatments and inhaler devices for COPD.
• Explain the role of pharmacotherapy for COPD.
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Outline • Background • Diagnosis & Assessment • Treatment
o Non-‐pharmacological o New evidence in pharmacotherapy
• Devices & AdministraLon
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Epidemiology • 3rd leading cause of death in the US • 12.7 million US adults esLmated to have COPD (2011) o Largely underesLmated o ~24 million U.S. adults have evidence of impaired lung funcLon o Slightly more common in women than men
• About 80% of cases due to cigare1e smoking • Financial burden (US)
o EsLmated cost: $49.9 billion (direct and indirect)
www.lung.org
COPD GOLD Guidelines 2016
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Diagnosis and Assessment
COPD Symptoms (Indicators to Consider a COPD Diagnosis)
• Over 40 years of age (generally) • Dyspnea
� Progressive � Persistent � Worse with exercise
• Chronic cough • Chronic sputum producLon • History of exposure to risk factors • Family history of COPD
Not diagnosLc but increases probability
of COPD
Perform spirometry in paLents > 40 with any other indicators
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Spirometric Assessment • Post-‐bronchodilator FEV1 %
predicted classifies severity of airflow limitaLon
In paLents with FEV1:FVC < 0.70 (70%): GOLD
Classifica?on Severity FEV1 (% predicted) Exacerba?ons per year
GOLD 1 Mild FEV1 ≥ 80% predicted ?
GOLD 2 Moderate FEV1 50 – 79% predicted 0.7-‐0.9
GOLD 3 Severe FEV1 30 – 49% predicted 1.1-‐1.3
GOLD 4 Very Severe FEV1 < 30% predicted 1.2-‐2.0
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Combined Assessment of COPD
• Symptoms • Risk • FEV1 • ExacerbaLon history
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PaLent Case • Charlie is a 58 y/o female with COPD and diabetes.
Shortness of breath when hurrying or walking uphill. Discharged from hospital 3 weeks ago for an exacerbaLon. CAT = 8. Spirometry: FEV1 68% of predicted.
• In which GOLD Combined Assessment PaLent Group does she belong?
A B
C D
Asthma-‐COPD Overlap Syndrome (ACOS)
Feature Asthma COPD
Age of Onset • Younger than 20 • Older than 40 Panern of Symptoms • Variable
• Triggers • Worse at night or early AM • DrasLc response to meds
• Good and bad days but symptoms despite meds • Chronic cough, before dyspnea
Lung FuncLon • Variable airflow limitaLon • Persistent airflow limitaLon • FEV1/FVC < 0.7
Past/Family History • Previous diagnosis or family history of asthma.
• Previous diagnosis of chronic bronchiLs or emphysema • Exposure to risk factor
Time Course • No worsening of symptoms over Lme
• Symptoms slowly progress over Lme
Chest X-‐ray • Normal • HyperinflaLon
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http://www.goldcopd.org/asthma-copd-overlap.html
Asthma-‐COPD Overlap Syndrome (ACOS)
Treatment
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Treatment Goals Reduce Symptoms Reduce Risk • Improve exercise
tolerance • Improve lung funcLon
(FEV1) • Improve quality of life
and health status
• Fewer exacerbaLons • Less disease
progression • Reduced mortality
PaLent Case • Maverick is a 63 y/o male with a 30 pack-‐year smoking history
(quit 10 years ago), past medical history significant for hypertension and COPD. VaccinaLon history: o Influenza October 2015 o Tetanus 2012 o Zoster 2012
• For which vaccines will he be due within the next 3 years?
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Non-‐Pharmacologic/ProphylacLc Therapy
• Smoking cessa?on* • Oxygen* • Annual influenza vaccinaLon • Pneumococcal vaccinaLon
o PPSV23 for all COPD paLents o PCV13 for all paLents 65 or older
• Pulmonary rehabilitaLon (for COPD group B-‐D) o Exercise, nutriLon, educaLon, smoking cessaLon, behavioral health
*Mortality benefit
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COPD Risk and Smoking CessaLon
BMJ. 1977;1:1645-8.
PaLent Case • Maverick is a 63 y/o male with a 30 pack-‐year smoking history
(quit 10 years ago), past medical history significant for hypertension and COPD. VaccinaLon history: o Influenza October 2015 o Tetanus 2012 o Zoster 2012
• For which vaccines will he be due within the next 3 years? o Annual influenza o Pneumovax now o Prevnar at 65 o No Pneumovax 2nd dose unLl 68 (5 years aser first dose)
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Pharmacologic Therapy
Overview LABA/LAMA Combo
Controversial Role of ICS
Treatment Goals – Role of Pharmacotherapy
Reduce Symptoms Reduce Risk • Improve exercise
tolerance • Improve lung
func?on (FEV1) • Improve quality of
life and health status
• Fewer exacerba?ons • Less disease
progression • Reduced mortality
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Pharmacologic Treatment Principles
• Inhaled treatment preferred
• Long-‐ac?ng bronchodilators preferred (LABA, LAMA)
• Consider combina?on of mechanisms
• Avoid cor?costeroid monotherapy
• Tailor device based on paLent characterisLcs
Inhaled Treatments for COPD
Bronchodilators
Beta2-‐agonists
Short-‐acLng (SABA)
Long-‐acLng (LABA)
AnLcholinergics
Short-‐acLng (SAMA)
Long-‐acLng (LAMA)
Inhaled corLcosteroids
(ICS)
Not to be used alone
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COPD Drugs Approved Since 2013 Drug Class Date
U?bron™ Neohaler® (indacaterol + glycopyrrolate) LABA/LAMA Oct 2015
S?olto™ Respimat® (Lotropium + olodaterol) LABA/LAMA May 2015
ProAir® RespiClick (albuterol) SABA Apr 2015
Striverdi® Respimat® (olodaterol) LABA July 2014
Incruse™ Ellipta™ (umeclidinium) LAMA May 2014
Anoro™ Ellipta™ (umeclidinium + vilanterol) LABA/LAMA Dec 2013
Breo® Ellipta™ (fluLcasone + vilanterol) ICS/LABA May 2013
www.centerwatch.com
Comparison of Inhaled Treatments
Short-‐ac?ng LABA LAMA ICS
• For paLents with occasional symptoms
• ↓ exacerbaLon rate
• Salmeterol ↓ hospitalizaLons
• Tiotropium ↓ exacerbaLon rate and hosp’ns
• Tiotropium may be > salmeterol
• ↓ symptoms & exacerbaLons
• Bronchodilator + ICS may ↓ mortality
• Response less rapid in COPD than asthma
• Adherence difficult
• No evidence for addiLon to long-‐acLng agents
• Can worsen tremor
• May precipitate arrhythmias in high risk paLents
• Dry mouth • QuesLonable
signal of ↑ CV events and mortality with ipratropium and Lotropium SMI
• Adverse effects — candidiasis — myopathy — ↑ pneumonia — ↓ bone density?
— cataracts • Withdrawal?
PROS
CONS
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IniLal Treatment
GOLD 2
GOLD 1
GOLD 3
GOLD 4
No. exacerbaLons/year
1 (not leading to hosp)
0
≥2
(or ≥ 1 leading to hosp)
SABA or SAMA PRN LABA or LAMA or SABA/
SAMA
LABA or LAMA
LABA/LAMA
LABA/ICS ± LAMA
± PDE-‐4 inhibitor or LABA/LAMA
or LAMA + PDE-‐4 inhibitor
LABA/ICS or LAMA
LABA/LAMA or LAMA + PDE-‐4 inhibitor or LABA + PDE-‐4 inhibitor
A B
C D
CAT < 10
CAT ≥ 10 (Symptoms)
Assessing Treatment Response
• Have you noLced a difference since starLng this treatment?
• If you are bener: o Are you less breathless? o Can you do more? o Can you sleep bener? o Describe what difference it has made to you.
• Is that change worthwhile to you?
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PaLent Case • Maverick (63 y/o male), newly diagnosed with COPD. • No history of exacerbaLons.
FEV1 is 60% predicted, CAT score is 12 (GOLD Group B). Symptoms are mainly dyspnea on exerLon and faLgue. No characterisLcs consistent with asthma.
• What would you recommend as iniLal treatment for Maverick? A. Combivent Respimat (SABA/SAMA) PRN
B. Spiriva Respimat (LAMA) 2 inhalaLons daily
C. SLolto Resipmat (LABA/LAMA) 2 inhalaLons daily
D. Breo Ellipta (LABA/ICS) 1 inhalaLon daily
IniLal Treatment
GOLD 2
GOLD 1
GOLD 3
GOLD 4
No. exacerbaLons/year
1 (not leading to hosp)
0
≥2
(or ≥ 1 leading to hosp)
SABA or SAMA PRN LABA or LAMA or SABA/
SAMA
LABA or LAMA
LABA/LAMA
LABA/ICS ± LAMA
± PDE-‐4 inhibitor or LABA/LAMA
or LAMA + PDE-‐4 inhibitor
LABA/ICS or LAMA
LABA/LAMA or LAMA + PDE-‐4 inhibitor or LABA + PDE-‐4 inhibitor
A B
C D
CAT < 10
CAT ≥ 10 (Symptoms)
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LABA/LAMA vs LABA/ICS • ILLUMINATE study (Lancet Respir Med 2013)
o Indacaterol/glycopyrrionium vs fluLcasone/salmeterol o PaLents without previous exacerbaLons (majority COPD Group B) o 138 mL improvement in FEV1 LABA/LAMA vs LABA/ICS @ week 26
Vogelmeier et al. Lancet Respir Med. 2013;1:51-60.
LABA/LAMA vs LABA/ICS • LANTERN study (Int J COPD 2015)
o Indacaterol/glycopyrrionium vs fluLcasone/salmeterol o PaLents with 0-‐1 exacerbaLon in previous year (Groups B and D) o Primary endpoint: FEV1; Secondary endpoint: exacerbaLons
Zhong et al. Int J COPD. 2015;10:1015–1026
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LABA/LAMA vs LABA/ICS • LANTERN study (Int J COPD 2015)
o Indacaterol/glycopyrrionium vs fluLcasone/salmeterol o PaLents with 0-‐1 exacerbaLon in previous year (Groups B and D) o Primary endpoint: FEV1; Secondary endpoint: exacerbaLons
Zhong et al. Int J COPD 2015;10:1015–1026.
Indacaterol/glycopyrronium
FluLcasone/salmeterol
LABA/LAMA vs LAMA • SPARK study (Lancet Respir Med. 2013)
o Indacaterol/glycopyrronium vs glycopyrronium vs Lotropium o GOLD Group C and D (at least 1 exacerbaLon previous year) o 12% reducLon in exacerbaLons LABA/LAMA vs Glycopyrronium o Similar adverse events in all 3 groups, most frequent: COPD worsening
Wedzicha et al. Lancet Respir Med. 2013;1(3):199-209.
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Monotherapy vs Dual BronchodilaLon
Adapted from Beeh KM, Beier J. Adv Ther. 2010;27:150-9.
Insurance Coverage LABA/LAMA Combo S?olto Respimat Anoro Ellipta U?bron Neohaler
Humana Medicare Pref Pref NC BCBS Medicare NC Pref NC Silverscript Medicare NC Pref NC Presbyterian Medicare NC Tier 4 (ST) NC AARP Medicare Pref Pref NC BCBS Centennial NC NC NC Molina Centennial NC NC NC Pres Centennial NC Pref NC UHC Centennial NC Pref NC Express Scripts Pref Pref NC
As of March 31, 2016
Pref = Preferred; NC = Not Covered; ST = Step Therapy
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PaLent Case • 69 year old female with a history of COPD, diagnosed 2 years
ago with hospital admission for exacerbaLon. History of smoking, quit 2 years ago aser exacerbaLon. No exacerbaLons within last 2 years. CAT score = 17, chronic cough and sputum. FEV1 = 52%. On Symbicort 160/4.5 mcg, 2 puffs BID.
• How should this paLent’s COPD be treated?
ICS Withdrawal Studies • COSMIC study 2005
o History of 2 or more exacerbaLons in last year o 3 month run-‐in with salmeterol/fluLcasone
• Followed by 12 months treatment with salmeterol vs salmeterol/fluLcasone o Decrease in lung funcLon (FEV1) but no change in exacerbaLon rate
• WISDOM study (NEJM 2014) o GOLD Groups C and D o 6 week run in with ICS/LABA/LAMA
• Randomized to 3-‐step withdrawal of ICS or conLnued triple therapy x 1 year o No difference in Lme to exacerbaLon (primary endpoint) o 5% decrease FEV1 (38 mL), no increase in symptoms
• Occurs over first 3 weeks, then no further decline (Magnussen et al 2016)
Wouters et al. Thorax. 2005;60(6):480-487. Magnussen et al. N Engl J Med. 2014;371(14):1285-4. Magnussen. Eur Respir J 2016; 47:651-654.
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ICS Withdrawal Studies • INSTEAD study (Eur Resp J 2014)
o Less severe COPD, no history of exacerbaLons o PaLents on at least 3 months of fluLcasone/salmeterol o Randomized to conLnued therapy or switch to indacaterol x 26 weeks o Primary outcome: FEV1 -‐ no change
• Not powered for exacerbaLons, but rate numerically lower with indacaterol than fluLcasone/salmeterol
Rossi et al. Eur Respir J 2014;44:1548–1556.
Controversial Role of ICS • European Medicines Agency
o Pharmacovigilance Risk Assessment Comminee (PRAC)
o March 18, 2016 – Results of PRAC Review of ICS • Confirmed increased risk of pneumonia with ICS in COPD
• No difference in rate of pneumonia between different ICS inhalers
• Benefits of ICS use sLll outweigh risk of pneumonia
o AwaiLng the Agency’s final stance on whether ICS are safe
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Controversial Role of ICS • From the 2016 GOLD Guidelines…
Long-‐term treatment containing inhaled corLcosteroids should not be prescribed outside their indicaLons, due to the risk of pneumonia and the possibility of an increased
risk of fractures following long-‐term exposure
Long-‐term treatment with inhaled corLcosteroids is recommended for paLents with severe and very severe
COPD and frequent exacerba?ons that are not adequately controlled by long-‐acLng bronchodilators
http://www.goldcopd.org/asthma-copd-overlap.html
Treatment: ICS, usually with long-‐acLng bronchodilator(s)
Asthma-‐COPD Overlap Syndrome (ACOS)
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PaLent Case • 69 year old female with a history of COPD, diagnosed 2 years
ago with hospital admission for exacerbaLon. History of smoking, quit 2 years ago aser exacerbaLon. No exacerbaLons within last 2 years. CAT score = 17, chronic cough and sputum. FEV1 = 52%. On Symbicort 160/4.5 mcg, 2 puffs BID.
• How should this paLent’s COPD be treated?
New Algorithm for COPD Management (Proposed)
Cooper et al. Lancet Respir Med. 2015;3:266-268.
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Devices and AdministraLon
Available Devices
MDI • Metered dose inhaler
• Difficult to coordinate breath
• Valved holding chamber helpful
• Contains propellants
DPI • Dry powder inhaler
• Requires forceful inhalaLon
SMI • Sos mist inhaler • Slow steady mist • No shaking or spacer required
Nebulizer • Not portable • Expensive • No coordinaLon of breath required
• ConLnue only if symptomaLc benefit clear
Device selecLon depends on paLent characterisLcs and cost/insurance formulary
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Dry Powder Inhalers (DPI) “All-‐In-‐One” Devices
Trade Name(s) Device Inhala?on Advair® (LABA/ICS) Serevent® (LABA)
Diskus® Quick, deep breath
Tudorza™ (LAMA) Pressair™ Breo® (LABA/ICS) Anoro™ (LABA/LAMA) Arnuity™ (ICS)
Ellipta™
Long, steady, deep breath
ProAir® (SABA) RespiClick
Ellipta™
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Insurance Coverage LAMA
Tudorza Pressair
Spiriva Handihaler
Spiriva Respimat
Incruse Ellipta
Seebri Neohaler
Humana Medicare Tier 4 (NP) Pref Pref NC NC BCBS Medicare NC Pref Pref NC NC Silverscript Medicare NC NC Tier 4 (NP) Pref NC
Presbyterian Medicare Pref Pref Pref NC NC AARP Medicare NC Pref Pref NC NC BCBS Cent NC Pref Pref Pref NC
Molina Cent Pref NC NC Pref NC
Pres Cent Pref Pref Pref NC NC UHC Cent NC NC NC Pref NC
Express Scripts Pref Pref Pref Pref NC
As of March 31, 2016
ProAir® RespiClick
OPEN INHALE CLOSE
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Dry Powder Inhalers (DPI)
Trade Name Device Inhala?on
Spiriva® (LAMA) Handihaler® Quick, deep breath
Foradil® (LABA) Aerolizer®
ArcaptaTM (LABA) NeohalerTM
“Assembly-‐Required” Devices Trade Name Device Inhala?on
Spiriva® (LAMA) Handihaler®
Quick, deep breath
Foradil® (LABA) Aerolizer®
Arcapta® (LABA) Neohaler® ULbron™ (LABA/LAMA) Neohaler®
Neohaler®
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Trade Name Device Inhala?on Combivent® (SABA/SAMA)
Respimat® Slow, deep breath Spiriva® (LAMA) SLolto™ (LABA/LAMA) Striverdi® (LABA)
Sos Mist Inhalers (SMIs) Respimat® First Time Use
Load cartridge Prime Ready to use
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Respimat® Inhaled Short-‐AcLng Bronchodilators
Drug Device Dose Frequency Dura?on of Ac?on
Albuterol ProvenLl® HFA ProAir® HFA Ventolin® HFA
MDI 1-‐2 puffs (90 mcg/puff)
every 4-‐6 hours PRN
4-‐6 hours
Albuterol ProAir®
Respiclik™ (DPI)
1-‐2 inhalaLons (90 mcg/puff)
every 4-‐6 hours PRN
4-‐6 hours
Albuterol AccuNeb®
Nebulized SoluLon
2.5 mg every 4-‐6 hours PRN
4-‐6 hours
Levalbuterol Xopenex® HFA
MDI 2 puffs (45 mcg/puff)
every 4-‐6 hours PRN
6-‐8 hours
Levalbuterol Xopenex®
Nebulized SoluLon
0.63 mg every 6-‐8 hours PRN
6-‐8 hours
SABA
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Inhaled Short-‐AcLng Bronchodilators
Drug Device Dose Frequency Dura?on of Ac?on
Ipratropium Atrovent® HFA
MDI 2 puffs (17 mcg/puff)
four Lmes daily, up to 12 puffs/day
6-‐8 hours
Ipratropium
Nebulized SoluLon
0.5 mg every 6-‐8 hours 6-‐8 hours
SAMA
SABA + SAMA Drug Device Dose Frequency Dura?on of Ac?on
Ipratropium /albuterol Combivent®
Respimat® SMI
1 inhalaLon (20 mcg/100
mcg)
every 6 hours, up to every 4 hours
6-‐8 hours
Ipratropium /albuterol Duoneb®
Nebulized SoluLon
0.5 mg/2.5 mg every 6 hours, up to every 4 hours
6-‐8 hours
Inhaled Long-‐AcLng Bronchodilators
Drug Device Dose Frequency Dura?on of Ac?on
Salmeterol Serevent®
Diskus® DPI
1 inhalaLon (50 mcg tab)
twice daily 12 hours
Formoterol Foradil®
Aerolizer® DPI
1 inhalaLon (12 mcg cap)
twice daily 12 hours
Formoterol Perforomist®
Nebulized SoluLon
20 mcg twice daily 12 hours
Arformoterol Brovana®
Nebulized SoluLon
15 mcg twice daily 12 hours
Indacaterol ArcaptaTM
NeohalerTM
DPI 1-‐2 inhalaLon (75 mcg cap)
once daily 24 hours
Olodaterol Striverdi®
Respimat® SMI
2 inhalaLons (2.5 mcg)
once daily 24 hours
LABA
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Inhaled Long-‐AcLng Bronchodilators
Drug Device Dose Frequency Dura?on of Ac?on
Tiotropium Spiriva®
Handihaler® DPI
2 inhalaLons (18 mcg cap) once daily 24 hours
Tiotropium Spiriva®
Respimat® SMI
2 inhalaLons (2.5 mcg/inh) once daily 24 hours
Aclidinium TudorzaTM
PressairTM DPI
1 inhalaLon (400 mcg tab) twice daily 12 hours
Umeclidinium IncruseTM
ElliptaTM DPI
1 inhalaLon (62.5 mcg) once daily 24 hours
Glycopyrrolate Seebri®
Neohaler® (DPI) LAMA Twice a day 12 hours
LAMA
Single Agent Inhaled CorLcosteroids
Drug Device Dose Frequency
Flu.casone propionate Flovent® HFA
MDI 1 puff (250 mcg/puff) twice daily
Flu.casone propionate Flovent®
Diskus® DPI
1 inhalaLon (50 mcg/inh) twice daily
Beclomethasone Qvar® HFA MDI 40 to 400 mcg per
day twice daily
Budesonide Pulmicort®
Flexhaler® MDI
1 puff (180 mcg/puff) twice daily
Flu.casone furoate Arnuity®
ElliptaTM DPI
1 puff (100 or 200 mcg/
puff) once daily
No single-‐agent ICS are FDA-‐approved for COPD; should be used with long-‐acLng bronchodilator
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Inhaled CombinaLon Products
Drug Device Dose Frequency Dura?on of Ac?on
Flu=casone propionate/ salmeterol Advair®
Diskus® DPI
1 inhalaLon (250/50 mcg) twice daily 12 hours
Budesonide/formoterol Symbicort® MDI 2 puff
(160/4.5 mcg) twice daily 12 hours
Flu=casone furoate/ vilanterol Breo®
ElliptaTM DPI
1 inhalaLon (100/25 mcg) once daily 24 hours
LABA/ICS
Inhaled CombinaLon Products LABA/LAMA
Drug Device Dose Frequency Dura?on of Ac?on
AnoroTM Umeclidinium/ Vilanterol
ElliptaTM DPI
1 inhalaLon (62.5/25 mcg) once daily 24 hours
SLolto™ Tiotropium/ olodaterol
Respimat® SMI
2 inhalaLons (2.5/2.5 mcg/inh) once daily 24 hours
ULbron™ Glycopyrronium/ Indacaterol
Neohaler® (DPI)
Assembly required
LABA/LAMA twice a day 12 hours
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In the Pipeline • PDE3 and PDE4 inhibitors for inhalaLon • Nucala (mepolizumab) – IL5 antagonist • Budesonide/formoterol/glycopyrronium combinaLon inhaler
Gross. COPD. 2016; 3(1): 498-502.
Summary • COPD
o GOLD combined assessment: symptoms (CAT score), FEV1, and exacerbaLon history
o Long-‐acLng bronchodilators for most paLents o Inhaled corLcosteroids only for paLents with high exacerbaLon risk
o Longer-‐acLng and combinaLon formulaLons becoming more available
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Summary • GOLD combined assessment: symptoms (CAT score), FEV1, and exacerbaLon history
• Pharmacotherapy improves symptoms and reduces risk of exacerbaLons, but no impact on mortality or lung decline
• Long-‐acLng bronchodilators for most paLents • Inhaled corLcosteroids only for paLents with high exacerbaLon risk
• Safe to withdraw ICS in non-‐exacerbators without characterisLcs of asthma
• Longer-‐acLng and combinaLon formulaLons becoming more available
QuesLons? Juliann Horne [email protected]
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References • Global Strategy for the Diagnosis, Management and Preven.on of COPD, Global
IniLaLve for Chronic ObstrucLve Lung Disease (GOLD) 2016. Available from: hnp://www.goldcopd.org/.
• American Lung AssociaLon. Chronic obstrucLve pulmonary disease (COPD) fact sheet. Updated May 2014. Accessed at hnp://www.lung.org/lung-‐disease/copd/resources/facts-‐figures/COPD-‐Fact-‐Sheet.html. Accessed on February 23, 2015.
• CenterWatch. FDA Approved Drugs for Pulmonary/Respiratory Diseases. Updated March 2015. Accessed at hnps://www.centerwatch.com/drug-‐informaLon/fda-‐approved-‐drugs/therapeuLc-‐area/18/pulmonary-‐respiratory-‐diseases. Accessed on May 8, 2015.
• Lexicomp Online®, Lexi-‐Drugs®, Hudson, Ohio: Lexi-‐Comp, Inc.; January 29, 2015. • Fletcher C, Peto R. The natural history of COPD. BMJ. 1977;1:1645-‐1648. • Gross N. COPD pipeline XXX. Chronic Obstr Pulm Dis (Miami). 2016; 3(1): 498-‐502.
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Stable COPD – IniLal Management
Pa?ent Group First Choice Second Choice
Group A SABA PRN or
SAMA PRN
LABA or
LAMA or
SABA + SAMA
Group B LABA or
LAMA
LABA + LAMA
Stable COPD – IniLal Management
*PDE-‐4 inhibitor only recommended if chronic bronchiLs present
Pa?ent Group First Choice Second Choice
Group C ICS + LABA or
LAMA
LABA + LAMA or
LAMA + PDE-‐4 inhibitor* or
LABA + PDE-‐4 inhibitor* Group D ICS + LABA
or ICS + LAMA
ICS + LABA + LAMA or
ICS + LABA + PDE-‐4 inhibitor* or
LABA + LAMA or
LAMA+ PDE-‐4 inhibitor*
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Oral Treatments for COPD • Methylxanthines (theophylline, aminophylline) o Narrow therapeuLc index, drug interacLons o Less well tolerated and less effecLve than inhaled bronchodilators
• MucolyLcs o N-‐acetylcysteine may have anLoxidant effects, could have a role in the treatment of paLents with recurrent exacerbaLons (Evidence B).
o Roflumilast (Daliresp)
Oral Treatments for COPD • PDE-‐4 inhibitor (roflumilast = Daliresp®)
o Approved February 2011 o 500 mcg PO daily o Inhibits inflammaLon by prevenLng breakdown of cAMP o Adverse effects: diarrhea, weight loss; suicide cauLon o Contraindicated in moderate to severe hepaLc insufficiency o Always use in combinaLon with at least one long-‐acLng bronchodilator
o Reduces exacerbaLons in paLents with severe COPD (FEV1 < 50% predicted, chronic bronchiLs, frequent exacerbaLons)
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REACT Trial (March 2015) • 1-‐year, double-‐blind, controlled, mulLcenter study • Inclusions
o Age 40 or older o 20 pack-‐years or more o FEV1 ≤ 50% predicted, symptoms of chronic bronchiLs, history of 2 or more
exacerbaLons in the past year, with cough and sputum o On LABA/ICS ± LAMA for 12 months
• Randomized to roflumilast/placebo + baseline inhaled therapy
• Results (n=1,945) o 15-‐20% reducLon in moderate to severe exacerbaLons o Improvements in pulmonary funcLon tests o No difference in paLent reported symptoms
Martinez et al. Lancet. 2015;385:857-66.
Spirometry Results
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Available Products by Device Medica?on MDI DPI SMI Nebulized
Albuterol ProvenLl HFA Proair HFA Ventolin HFA
AccuNeb
Levalbuterol Xopenex HFA Xopenex
Ipratropium Atrovent HFA Ipratropium
Albuterol/ Ipratropium
Combivent Respimat Duoneb
Salmeterol Serevent Diskus
Formoterol Foradil Aerolizer Perforomist
Arformoterol Brovana
Indacaterol Arcapta Neohaler
Olodaterol Striverdi Respimat
Available Products by Device Medica?on MDI DPI SMI Nebulized
Tiotropium Spiriva Handihaler Spiriva Respimat
Aclidinium Tudorza Pressair
Umeclidinium Incruse Ellipta
FluLcasone propionate
Flovent HFA Flovent Diskus
Beclomethasone Qvar HFA
Budesonide Pulmicort Flexhaler Budesonide
FluLcasone prop/salmeterol
Advair HFA Advair Diskus
Budesonide/ formoterol
Symbicort
Mometasone/ formoterol
Dulera
FluLcasone furoate/vilanterol
Breo Ellipta
Umeclidinium/ vilanterol
Anoro Ellipta
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DefiniLon • Common preventable and treatable pulmonary disease • Characterized by airflow limitaLon • Chronic inflammatory response in the airways and the lung to
noxious gases/parLcles • Usually progressive • Characterized by emphysema and chronic bronchiLs • No cure
NO CURE
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COPD Cycle COPD
Dyspnea
Immobility Social IsolaLon
Depression
Lack of Fitness
COPD & ComorbidiLes • CAD, heart failure, atrial fibrillaLon, and hypertension should
be treated according to current guidelines o In Afib, use of high doses of beta-‐agonists can make heart rate control more difficult
• Beta-‐blockers o When indicated, B-‐blocker benefits outweigh risk
o Consider B1 selecLve if possible
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Pressair Tudorza Pressair (aclidinium)
• New FDA Warning April 2015 • Based on post-‐markeLng reports
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Advair Diskus Spiriva Handihaler
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Foradil Aerolizer