Idea Transcript
10/27/11
Update on Asthma & COPD
Disclosures
• No Pharma Consulting, Research, Lectures • NHLBI - Asthma Clinical Research Network
Stephen C. Lazarus, M.D. Division of Pulmonary & Critical Care Medicine Cardiovascular Research Institute University of California San Francisco
Primary Care Medicine: Principles & Practice San Francisco, CA October 27, 2011
Update on Asthma & COPD Asthma: • Prevalence continues to increase in the US
• ~ 1/3 of asthmatics take long-term controllers • There is a role for:
Inhaled corticosteroids Leukotriene modifiers Long-acting ß2-agonists (LABAs) Long-acting Muscarinic antagonists (LAMAs)
• Intermittent or prn treatment may work for some patients
• NHLBI AsthmaNet • NHLBI - COPD Clinical Research Network • NAEPP Coordinating Committee • NHLBI SPIROMICS
Update on Asthma & COPD COPD: • COPD is a leading cause of death worldwide, and mortality is increasing
• Exacerbations are the major complication of COPD • Exacerbations are associated with accelerated loss of lung function
• Most exacerbations are caused by infection • There are effective strategies for decreasing exacerbations
• Symptom-based management is effective
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Asthma Prevalence in the US 2001-2009
MMWR 60:647, 2011
Case #1 Your sister calls to tell you she s pregnant She s worried that her baby will have asthma because: • She has asthma • The baby s father has allergies • The baby s grand father and 2 uncles have asthma
Asthma Prevalence in the US 2001-2009 Adults
MMWR 60:647, 2011
Question #1: You tell her to: 1. Move to a farm 2. Move to the tropics 3. Take Vitamin D 4. All of the above
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Relationship Between Microbial Exposure and Probability of Asthma
2 separate studies: • PARSIFAL • N = 6,843 Bavarian Children • Mattress Dust • Vacuum Cleaner
• GABRIELA • N = 9,668 Bavarian Children • Settled Dust • Electrostatic Dust Collector
Ege et al N Engl J Med 364:701, 2011
Asthma Prevalence in the US 2001-2009 Adults
Prevalence (%)
Asthma Characteristics US 2008
Prevalence (%)
2009
MMWR 60:647, 2011
MMWR 60:647, 2011
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Case #2
Question #2: What is your next step?
• 39 year-old man with moderate asthma • Inhaled corticosteroids, ~320 mcg/day • Symptoms/rescue 2-4 days/week
1. Add a LABA 2. Add a LAMA 3. Increase inhaled corticosteroids 4. Any of the above
• Symptoms/rescue 1-2 nights/month
FDA announces new Safety Controls for LABAs in Asthma 1) LABAs are contraindicated without ICS or other controller 2) LABAs should only be used long-term in patients whose asthma cannot be controlled with other medications 3) Once asthma control is achieved, LABAs should be discontinued 4) Pediatric and adolescent patients should use combination product (LABA + ICS), to avoid monotherapy February 10, 2010
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ß-agonist Summary • Risk of SABAs appears to segregate by genotype (Arg/Arg vs haplotypes)
• LABAs have been associated with increased
risk of severe asthma exacerbations and asthma-related death
• LABAs appear to be safe when used
together with ICS (in general population)
ß-agonist Summary • NAEPP and GINA guidelines recommend LABAs as add-on therapy
• Counsel patients about poorly-controlled asthma, and consider withdrawal of LABAs in patients who are poorly controlled
• LABAs should not be used as monotherapy
FDA Requires Post-Market Safety Trials for Long-Acting Beta-Agonists (LABAs) in Asthma
FDA Requires Post-Market Safety Trials for Long-Acting Beta-Agonists (LABAs) in Asthma
• 5 Randomized, D-B Controlled Trials • ICS + LABA vs ICS
• 1 Trial in Children 4 – 11 years old
• 4 Trials in Adults and Adolescents (≥ 12)
• Duration of Treatment: 6 months • Primary endpoint: a composite of serious outcomes
- Budesonide + Formoterol - Fluticasone + Salmeterol - Mometasone + Formoterol - Formoterol (vs Fluticasone) • n = 11,700 x 4 = 46,800 patients
April 15, 2011
- Fluticasone + Salmeterol
• n = 6,200 children
- Asthma-related deaths - Intubation - Hospitalization
• Timeline: 2011 - 2017 April 15, 2011
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Alternatives to LABAs?
Tiotropium Step-Up for Uncontrolled Asthma
Peters et al. N Engl J Med 363:18, 2010
Tiotropium Step-Up for Uncontrolled Asthma
Peters et al. N Engl J Med 363:18, 2010
Tiotropium Step-Up for Uncontrolled Asthma
Peters et al. N Engl J Med 363:18, 2010
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Tiotropium Step-Up for Uncontrolled Asthma
TALC Conclusions • Tiotropium step-up therapy demonstrated
efficacy (asthma control) equivalent to a LABA (salmeterol) in patients inadequately controlled on low-dose ICS.
• Further studies are required to establish
the efficacy of tiotropium in reducing asthma exacerbations, and to establish long-term safety in patients with asthma.
Peters et al. N Engl J Med 363:18, 2010
Predictors of Response to Tiotropium Higher Cholinergic Tone (Lower Resting Heart Rate) Greater Airway Obstruction (Lower FEV1/FVC ratio) Positive Short-Acting Bronchodilator Response (Albuterol > Ipratropium) Younger Age (Asthma Control Days)
MaximizingTiotropium Responsiveness in Patients with Uncontrolled Asthma • Evaluate Asthma Control with Patient on ICS • If Uncontrolled - FEV1 < 70% pred - Symptomatic 6-7 days/wk • Perform Spirometry Before and After Albuterol • Positive Tiotropium Response More Likely if - FEV1/FVC Ratio is Low - Positive Response to Albuterol
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Asthma Characteristics US 2008
Failure to Prescribe Controller is Associated with Recurrent ED or Hospital Visits N = 6,139 Subjects (78% ED, 22% Hospitalized)
• Prescribed controllers within 180 days • Rx at Discharge vs Later • Primary Outcome: readmission
Prevalence (%)
No Controller at Discharge: • Higher risk of readmission RR 1.79 (1.42 – 2.25) • 0.8% increase with each day delay RR 1.008 (1.005 – 1.011) MMWR 60:647, 2011
Rescue Use of Beclomethasone and Albuterol in a Single Inhaler for Mild Asthma Prn BDP/S Regular BDP Regular BDP/S
Prn S
Buikema et al. ATS 2011.
Is High-Dose Fixed ICS dosing Necessary? Symptom-Guided Management as an Alternate Approach Subjects: 2760 adults and children with moderately severe asthma (mean FEV1 = 73% predicted) Budesonide/Formoterol Combination Therapy as Both Maintenance and Reliever Medication in Asthma Purpose: to compare three treatments: Bud/FM 80/4.5 2X/d + prn Terbutaline Bud 320 2x/d + prn Terbutaline Bud/FM 80/4.5 2x/d + prn Bud/FM 80/4.5 Outcomes: Time to first exacerbation; number of exacerbations Symptoms, nocturnal awakenings, AM PEF, FEV1
Papi et al. N Engl J Med 2007;356:2040-52.
O Byrne P, et al. Am J Resp Crit Care Med 2005; 171:129-136
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Time to First Exacerbation
Should all patients with asthma be treated regularly with an inhaled corticosteroid?
The IMPACT Study
O Byrne P, et al. Am J Resp Crit Care Med 2005; 171:129-136
Change in AM Peak Flow
Change in AM PEF (%)
Baseline to End Treatment 10
P=0.904
Asthma Exacerbation Rates (symptoms warranting course of oral CS) 47.8 wks Controller 0.48 wks Controller
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0
Bud
Zaf
PRN
Boushey et al N Engl J Med 352:1525-1528, 2005
Boushey et al N Engl J Med 352:1525-1528, 2005
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No Increased Risk of Pneumonia in Patients Taking Inhaled Corticosteroids Placebo HR 0.51 (0.35 – 0.74; p < 0.001)
Budesonide
Best Adjustment Strategy for Asthma in the Long Term
BASALT A study to determine if adjustment of asthma therapy based on consensus guidelines or biomarkers of airway inflammation is superior to adjustment of therapy based on symptoms in asthmatics adequately controlled with an inhaled corticosteroid alone
O Byrne et al Am J Respir Crit Care Med 183:589, 2011
BASALT: Time to Treatment Failure
Probability of Treatment Failure
l: Confidentia
ented will be pres – a t a d d e Unpublish
Presented, AAAAI, 2011
BASALT • No difference among treatment groups: – Rescue albuterol use – Symptoms (daytime or nocturnal) – ACQ – ASUI – Quality of life measures – Pre- or post-bronchodilator FEV1 Presented, AAAAI, 2011
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BASALT: FEV1
BASALT: ICS Dose • Mean Monthly Inhaled Steroid Dose – GBA 1610 ug/month – BBA 1617 ug/month – SBA 832 ug/month (p