Transcript Asthma Epidemiology in Older Adults

Cost-Utility Analysis of Long-Acting Beta Agonists
versus Leukotriene Receptor Antagonists in Older
Adults with Persistent Asthma Receiving
Concomitant Inhaled Corticosteroid Therapy
Shoroq Altawalbeh, PharmD, PhD
Assistant Professor of Clinical Pharmacy
Faculty of Pharmacy
Jordan University of Science and Technology
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Outline
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Introduction
Objectives
Methods
Results
Summary & clinical implication
Future directions
Acknowledgement
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Asthma in Older Adults
 Frequent coexistence of comorbid conditions
 Poor recall and perception of symptoms
 Depressive symptoms
 Reduced psychological and physical quality of life
 Physical disability
 Low adherence and treatment side effects
Gillman A, Douglass JA. Asia Pac Allergy 2012;2:101-8.
Lee JA, P LR, Berg JP. J Asthma 2014;51:399-404.
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Asthma Epidemiology in Older Adults
Prevalence
estimated to be
greater than
10%
Public health
concern
The population
of older adults
is increasing
rapidly
Gillman A, Douglass JA. Asia Pac Allergy 2012;2:101-8.
Song WJ, Cho SH.. Allergy Asthma Immunol Res 2015;7:431-9
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Poor Asthma Outcomes in Older Adults
Compared to younger adults:
Poor asthma control
OR = 2.18 (1.28-3.72)1
More asthma
hospitalizations
4.5 versus 2.3 hospitalization / 100,000 persons2
Half of all asthma-related deaths occurred in
individuals over 65 years old3
More asthma-related
deaths
Higher asthma-related
expenditures
$1490 vs $773 ( 50% inpatient & 35% medications)4
1-Kampe M et al.Eur Clin Respir J 2014:1:1-9
3-Stupka E, deShazo R. Am J Med 2009;122:6-11.
2-Moorman J, Rudd R, Johnson C, et al. MMWR Surveill Summ. 2007;56:1-54 5
4- Plaza V, Serra-Batlles J, Ferrer M, et al. Respiration 2000;67:65-70
Asthma Treatment; Stepwise Approach
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Asthma Treatment: The Add-on Challenge
• The latest GINA guidelines recommended:
 When asthma symptoms are not well-controlled on low dose ICS, LABA is the
first line add-on treatment. LTRA is an alternative.
• Asthma treatments are still understudied in older adults
 Excluded from clinical trials.
 Different add-on treatments were not directly compared in older adults.
• The evidence for treatment of asthma in older patients is mostly based on
research conducted in younger adults or age-pooled populations
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2014.
Gillman A, Douglass JA. Asia Pac Allergy 2012;2:101-8.
Travers J, Marsh S, Williams M, et al. Thorax 2007;62:219-23
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Long Acting Beta
Agonists
(LABA)
Add-on
Concens
 An effective asthma treatment
 Understudied in older adults
 Concerns in question:
- Asthma catastrophic events
- CV adverse events
Shrewsbury S, Pyke S, Britton M. BMJ 2000;320:1368-73.
Fish JE, Israel E, Murray JJ, et al. Chest 2001;120:423-30.
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LABA-Associated Pulmonary Concerns
(asthma-related intubations and deaths)
LABA alone or in combination with ICS versus placebo:
LABA
with/without
ICS versus
placebo
LABA +ICS
versus ICS
alone
Total
The American Journal of Medicine (2010) 123, 322-328
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LABA-Associated CV Concerns
LABA alone or in combination with ICS versus placebo:
Salpeter SR, Ormiston TM, Salpeter EE. Chest 2004;125:2309-21
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Biological Background; LABA Cardiovascular
Concerns
LABA
Hypokalaemia
Increase heart
rate
Cardiac
Arrhythmia
Heart attack
and death
Johnston SL, Edwards MR. Thorax 2009;64:739-41.
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Leukotriene Receptor
Antagonists
(LTRA)
Add-on
Concens
 An effective asthma treatment compared with
placebo and ICS alone
 Favored safety profile
 Possible role in secondary prevention of
cardiovascular diseases.
 Understudied in older adults
Bozek A, Warkocka-Szoltysek B, Filipowska-Gronska A, et al. J Asthma 2012;49:530-4.
Joos S, Miksch A, Szecsenyi J, et al. Thorax 2008;63:453-62.
Ingelsson E, Yin L, Back M. J Allergy Clin Immunol 2012;129:702-7 e2.
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Biological Background; LTRA Cardio- Protective Effect
Leukotrienes
AntiLeukotrienes
cysteinylleukotriene type
1 receptors
Inflammation
Atherosclerotic
lesions
Vasoconstriction
Back M. Cardiovasc Drugs Ther 2009;23:41-8.
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Head to Head Comparisons in Adult Based Research
(<65 years old)
 Asthma outcomes are better with ICS+LABA
compared to ICS+LTRA; less asthma exacerbations
and better pulmonary function
 CV outcomes were not compared.
Fish JE, Israel E, Murray JJ, et al. Chest 2001;120:423-30.
Lee TA, Chang CL, Stephenson JJ, et al. Curr Med Res Opin 2010;26:2851-60.
Tan H, Sarawate C, Singer J, et al. Mayo Clin Proc 2009;84:675-84.
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Head to Head Comparisons in Older Adult Based Research
(>=65 years old)
Altawalbeh SM, Thorpe CT, Zgibor JC, Kane-Gill S, Kang Y, Thorpe JM. J Am Geriatr Soc. 2016 Aug;64(8):1592-600.
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In Older Adults
Increased
LABA add-on
CV
exacerbations
LTRA add-on
Asthma
exacerbations
Increased
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Objectives:
 To estimate and compare quality-adjusted survival
and costs associated with ICS+LABA and ICS+LTRA
treatments in an older adults with asthma.
 Guide clinical decisions in older adults by combining
effectiveness, CV safety and costs in a single analysis.
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Methods:
 A Markov model was developed to estimate and
compare the incremental costs and quality-adjusted
life expectancy.
We simulated a cohort of older adults, 66 years of
age or older, who were treated for their persistent
asthma by ICS+LABA treatment, ICS+LTRA treatment,
or ICS (as a reference group).
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Reasons for using Models in Health Care:
• The purpose of a decision model is to estimate
the effects of various choices
Choice 1
Choice 2
Set of Downstream
consequences
Set of Downstream
consequences
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Fig. 1. Markov model structure. Patients transitioned through five clinical health states: healthy
without any exacerbation (well), post asthma exacerbation, post-CV exacerbation, post-asthma/CV
exacerbation, and dead. In each cycle, patients could survive or die from experiencing asthma or CV
events.
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Parameters
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Event Probabilities
• Data: Fee for Service (FFS) Medicare data files (2009-2010).
• Study design: Retrospective cohort design.
• Logistic regression models were used to obtain the adjusted
probabilities of asthma and CV hospitalizations by treatment
groups.
– Adjusting for patient ages , race/ethnicity, geographic regions ,gender,
enrollment in the low-income subsidy, disability, asthma duration
since the first diagnosis in medicare data, preexisting cardiovascular
diseases, number of comorbid conditions, and for differing lengths of
follow-up time across patient.
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Results:
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Base case results
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One-Way Sensitivity Analyses Thresholds Analyses
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Probabilistic Sensitivity Analysis
Fig. 2. Probabilistic sensitivity analysis results. The CE acceptability curve shows
probabilities of treatments being cost-effective. CE, cost-effectiveness
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Major Findings
 The cost-effectiveness of ICS+LABA treatment is
economically unfavorable in older adults when
compared with LTRA as add- on treatment.
 The extra CV risks associated with LABA treatment
compared with LTRA treatment largely offset its
superiority in controlling asthma and improving
survival, and increase the costs incurred by patients
and society.
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Clinical Implications
 Important step on the personalized medicine way
 Clinical provider should consider the risk- benefit ratio
when prescribing LABA for elderly
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In Hospital
Death Rates Among Elderly; Age: 65-84
Asthma
0.73%
Cardiac
dysrhythmias
1.01%
Congestive heart failure
3.11%
Acute myocardial infarction
6.15%
Acute cerebrovascular disease
8.97%
HCUPnet 2010
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Future Directions
• Subgroup analysis to personalize asthma treatments;
Maximize the Benefit/ Risk Ratio
Find subgroups in older adults who have the
highest CV risks from LABA treatment.
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Acknowledgement
• Kenneth J. Smith, MD, MS
Section of Decision Sciences and Clinical Systems Modeling, Department of
Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
• Joshua M. Thorpe, Ph.D., M.P.H
Department of Pharmacy and Therapeutics, School of Pharmacy, University of
Pittsburgh, Pittsburgh, PA, USA.
• Carolyn T. Thorpe, PhD, MPH
Department of Pharmacy and Therapeutics, School of Pharmacy, University of
Pittsburgh, Pittsburgh, PA, USA.
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Thank you
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