Post on 12-Aug-2015
BREO ELLIPTA IN MODERATE-SEVERE COPD
Kathy Chow
Amcare Rotation
Navel Hospital Camp Pendleton
August 5, 2013
OUTLINE
Patient case Epidemiology Pathophysiology Risk factors Diagnosis COPD Classifications/Treatment Breo Ellipta and trials On the market comparisons
PATIENT CASE
57yo male presents to pharmacy clinic post ER admission of COPD exacerbation
CC SOB and recurrent hospitalizations
PMH Been to emergency department 5 times last year
and admitted twice. COPD for 10 years
SH 50 pack years, but quit 2 years ago.
PATIENT CASE
Current medications: Tiotropium 1 puff (18mcg) QD Albuterol Inhaler PRN for SOB. Oxygen while sleeping (8hrs/night)
Vital signs WNL
Labs FEV1/FVC = 0.46 Absolute FEV1 = 45% of predicted.
What changes would you make to the medication regimen?
EPIDEMIOLOGY
4th leading cause of death in the US Estimated annual treatment costs exceeding
$30 billion(health and indirect cost combined) A major cause of disability (11th leading cause
of disability worldwide) Current projections by 2020.
COPD will be the 5th leading cause of disability worldwide, behind only ischemic heart disease, major depression, traffic accidents, and cerebrovascular disease
Koda Kimble
PATHOPHYSIOLOGY
COPD DEFINITIONS
Chronic BronchitisChronic cough for at least 3 months for 2 consecutive years
Inflammation of the bronchioles (where asthma, CHF, reflux is ruled out)
EmphysemaAlveolar wall destruction and airspace enlargement
Koda Kimble
RISK FACTORS
Cigarette smoking (current or past history)Most pts have at least 20 pack year history
Cofactors Occupational dusts and chemicals Indoor and outdoor air pollutionRespiratory viruses
α1-antitrypsin deficiency(<2% with emphysema)Lack of protease inhibitor to prevent
breakdown of elastin
Koda Kimble
DIAGNOSIS
Risk factors Clinical symptoms Spirometry (gold standard) Chest X ray Pulse oximetry
Koda Kimble
COPD CLASSIFICATIONClassificatio
n Spirometry
ResultsSymptoms
Mild FEV1/FVC <0.70
FEV1 ≥80%
predicted
Minimal SOB
Moderate FEV1/FVC <0.70
50% ≤FEV1<80%
predicted
moderate or severe shortness of breath on exertion, with or without cough, or
sputum
Gold guidelines
COPD CLASSIFICATIONClassificatio
n Spirometry Results Symptoms
Severe FEV1/FVC <0.70
30% ≤FEV1 <50%
predicted
Severe shortness of breath, with or without cough, or sputum- often
with repeated exacerbations which
usually impact quality of life, reduced exercise
capacity, fatigue.
Very severe FEV1/FVC <0.70
FEV1 <30% predicted
or FEV1 <50%
predicted + chronic respiratory failure
Impaired QOL due to SOB- possible
exacerbations may even be life threatening at
times
Gold guidelines
TREATMENT
Patient
Group
First choice Alternative Choice Other possible
treatments
Mild SAAC prnor
SABA prn
LAACor
LABAor
SABAand
SAAC
Theophylline
Mod LAACor
LABA
LAAC and LABA SABA and/or SAAC
Theophylline
Gold guidelines
TREATMENTPatient Group
First choice
Alternative Choice Other possible
treatments
Severe ICS+ LABAOR
LAAC
LAAC + LABAOR
LAAC + PDE4IOR
LABA + PDE4I
SABA and/orSAAC
Theophylline
Very Severe
ICS + LABAand/orLAAC
ICS + LABA +LAACor
ICS + LABA + PDE4Ior
LAAC + LABAor
LAAC + PDE4I
Carbocysteine
SABAand/orLAAC
Theophylline
Gold guidelines
BREO ELLIPTA IN MODERATE TO SEVERE COPD
Cost per month: $267.68 Approved May 2013 MOA
Vilanterol (LABA)+ Fluticasone Furoate (ICS) half life = 24 hrs
Side Effects Nasopharyngitis (9%) URTI (7%) Oral Candidiasis (5%)
Administration Once daily dry powder inhaler Swish and spit with water after administration
Pharmacist Letter, Lexicomp, Breo Ellipta PI
BREO ELLIPTA METHODS
2 week run in period 24 week (10 clinic visits in between) 7 day telephone follow up. Multicenter, RCT, double blind, placebo
controlled Eligible subjects were then randomized
(1:1:1:1:1) FF/VI 100/25 FF/VI 50/25 FF 100ug VI 25ug, Placebo
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA INCLUSION CRITERIA
≥40 years old COPD Diagnosis Smoking history of ≥10 pack-years Post bronchodilator FEV1/FVC ≤0.7 Post bronchodilator FEV1≤70% predicted ≥2 on mMRC (modified medical research
council dyspnea scale)
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA EXCLUSION CRITERIA Asthma diagnosis Non-COPD respiratory disorders Lung volume reduction surgery within 12 months of visit 1 Clinically significant abnormal EKG Acute worsening of COPD requiring corticosteroids or
antibiotics or treatment prescribed by a physician within 6 weeks prior to visit 1
Hospitalization due to poorly controlled COPD within 12 weeks prior to visit 1
Lower respiratory tract infection requiring antibiotics within 6 weeks prior to visit 1
Long term oxygen therapy or nocturnal oxygen therapy (≥12hr/day)
Non compliance (fail to complete 4 out of 7 daily diary card, using prohibited COPD meds)
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA STATISICAL ANALYSIS
To achieve 90% power and α risk of 0.05, a sample size of at least 146 per arm was required to detect treatment difference of 100ml
ITT, all subjects were accounted for if they had at least 1 dose of the study med
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA STUDY POPULATION
Treatment 100/25ug Placebo
Start with N=206 Adverse events =14Lack of efficacy = 12Exacerbation = 12
Other dropped due to protocol deviation, lost to f/u, withdrew consent, investigator discretion
Completed n = 151
Start with N=207Adverse events n = 15Lack of efficacy n = 20Exacerbation n=17
Other dropped due to protocol deviation, lost to f/u, withdrew consent, investigator discretion
Completed n=138
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA STUDY CHARACTERISTICS
Treatment 100/25ug Placebo
Subject CharacteristicsAge = 62Male = 68%Race = White 75%, Asian 20%Current smoker = 54%Pack yr = 46Emphysema = 61%Chronic Bronchitis = 62%Pre treatment lung functions were similar.
Similar to treatment group
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA ENDPOINT
FF/VI 100/25ugImproved weighted mean FEV1 at
168 weeks by 173ml 95%CI(123-224ml) p = <0.001
Trough FEV1 by 115ml 95%CI (60-169ml) p=<0.001
All secondary endpoints were not statistically significant.
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA SAFETY OUTCOME
Adverse Event
Treatment Placebo
Nasopharyngitis
22(11%) 14(7%)
URTI 21(10%) 8(4%)
Headache 18(9%) 5(2%)
Oropharyngeal Candidiasis
6(3%) 2(<1%)
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
BREO ELLIPTA CONCLUSIONS
FF/VI provides significant sustained bronchodilation at 24 weeks with rapid onset of action and treatments were well tolerated
Longer term studies required to determined COPD exacerbations
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
ON THE MARKET…. Medication NameCost per 30 day
Doses Onset Sig Side Effects
Budesonide /Formoterol/(Symbicort)$235.53
80/4.5ug, 160/4.5ug
10-20 min BID Headache (7-11%)Nasopharyngitis (7-11%)URTI (4-11%)Oral Candidiasis (1-6%)
Salmeterol/Fluticasone Propionate(Advair Diskus)$341.81
100/50ug, 250/50ug, 500/50ug
10-20 min BID Headache (12-27%)URTI (16-27%)Pharyngitis (9-13%)Oral Candidiasis (1-4%)Throat Irritation (7-9%)
Vilanterol/Fluticasone Propionate (Breo Ellipta)$267.68
100/25ug
10-20 min QD Headache (7%)Nasopharyngitis (9%)URTI (7%)Oral Candidiasis (5%)
Lexicomp, Breo Ellipta PI, pharmacist letter
BACK TO PATIENT CASE CC
SOB and recurrent hospitalizations
PMH Been to emergency department 5 times last year and
admitted twice. COPD for 10 years
SH 50 pack years, but quit 2 years ago.
Labs FEV1/FVC = 0.46 Absolute FEV1 = 45% of predicted.
Current meds Tiotropium 1 puff (18mcg) QD Albuterol Inhaler PRN for SOB
What is the plan?
REFERENCES "Inhalers for COPD." Pharmacist Letter. Therapeutic
Research Center, Aug. 2013. Web. Aug. 2013. “Breo Ellipta Prescribing Information."
GlaxoSmithKline, 2013. Web. 28 July 2013."News & Events From Around the World." Global Initiative for Chronic Obstructive Lung Disease RSS.
03 Aug. 2013.Koda Kimble COPD Uptodate stable COPD Edward M. Kerwin “A randomized trial of fluticasone
furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. January 2013. Accessed July 2013.
Edward M. Kerwin “A randomized trial of fluticasone furoate/vilanterol (50/25ug; 100/25ug) on lung function in COPD. Supplementary online material. January 2013. Accessed July 2013.