cme one size fits all - final
TRANSCRIPT
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Asthma Management – The One Size Fits all Approach Asthma Management – The One Size Fits all Approach Great for Socks…not for patients!Great for Socks…not for patients!
Asthma Management – The One Size Asthma Management – The One Size Fits all Approach Fits all Approach
Great for Socks…not for patients!Great for Socks…not for patients!Anne K. Ellis, MD MSc FRCPCAnne K. Ellis, MD MSc FRCPCAssociate Professor and ChairAssociate Professor and ChairDivision of Allergy & ImmunologyDepartment of Medicine, Queen’s [email protected]: @DrAnneEllis
Date: Sept 22nd, 2015
Time: 12:15h
Disclosures
Facilitator’s Name: Dr. Anne K. Ellis
Grants/research support: Circassia Ltd/Adiga Life SciencesGlaxoSmithKlineNovartisSunPharma Advanced Research CorporationMerck
Speaker’s bureau/honoraria:
Merck, Pfizer, AstraZeneca, Novartis
Consulting fees: ALK Abello, Ora Inc.
Advisory Boards: Merck, Novartis
Objectives
By the end of this learning session, the attendee will be able to: Describe differences in performance characteristic of
the various asthma controller therapies Develop a patient focused approach to asthma
management Learn where to access educational resources for
patients
Introduction - Asthma
Chronic inflammatory lung disorder characterized by: reversible airflow obstruction airway hyperresponsiveness
Presents symptomatically with dyspnea, wheeze and sensation of chest tightness
Barnes PJ. Clin Exp Allergy 1996;26:738-745.
Diagnosis of Asthma
Confirmed when compatible symptom pattern is accompanied by objective measures of variable airflow obstruction
Spirometry: >12% improvement in FEV1 15 mins after SABA OR >20% improvement after 10-14 days of oral prednisone OR >20% spontaneous variability
Serial PEF >20% change after bronchodilation or over time
Methacholine challenge 20% reduction in FEV1 with provocative concentration of
methacholine
Boulet L, et al. CMAJ 1999;161(11 Suppl):S1-61, Kaplan AG. CMAJ 2009;181:E210-20
FEV1: forced expiratory volume in 1 second, SABA: short-acting bronchodilator
Asthma – Phenotypes
Eosinophilic Bronchitis Steroid-responsive Typically atopic
Neutrophilic bronchitis Less steroid-responsive Smoking, viral illness, others
Non-inflammatory Obesity, others
Allergic Asthma
Allergen contact with airway mucosa in a sensitized individual results in rhinitis, conjunctivitis, and asthmatic responses
Immediate allergic response maximal 15 to 30 min after allergen challenge, resolves in 1 to 3 hours
~50% of subjects develop a late-phase allergic response persistent, less reversible decrease in pulmonary
function maximal in 6-12h and partially resolves within 24h
Late Phase Asthmatic Response
The Prevalence of Asthma in Canada:1.Has increased steadily over the past 20 years2.Is one of the highest in the world3.Affects a large portion of the pediatric population4.Affects nearly 3 million people in Canada5.All of the above
Polling Question:Epidemiology of Asthma in Canada
Statistics Canada. Available at: Statistics Canada. Available at: www40.statcan.ca. www40.statcan.ca. Asthma Society of Canada. Available at: Asthma Society of Canada. Available at: www.asthma.cawww.asthma.ca..
Epidemiology of Asthma in Canada
Prevalence increased over past 20 years among adults until 2001 and remains one of the highest in the world 1979: 2.3% 1988: 4.9% 1994: 6.1% 2001: 8.4% 2009: 8.4%
At least 12% of children have asthmaStatistics Canada. Available at: www40.statcan.ca.
Asthma Society of Canada. Available at: www.asthma.ca.
Asthma Triggers
Allergens Dust mites, mold spores, animal dander,
cockroaches, pollen, indoor and outdoor pollutants, irritants (smoke, perfumes, cleaning agents)
Pharmacologic agents (ASA, beta-blockers) Physical triggers (exercise, cold air) Physiologic factors
Stress, GERD, viral and bacterial URI, rhinitis
Lung Function Declines with Frequency of Asthma Exacerbations
Bai T. Bai T. Eur Respir J 2007;30:452-456Eur Respir J 2007;30:452-456
P<0.05P<0.05
Ann
ual c
hang
e in
FEV
Ann
ual c
hang
e in
FEV
1 1 m
L/yr
mL/
yr 00
––1010
––2020
––3030
––5050
––4040
InfrequenInfrequentt
ExacerbationsExacerbationsFrequentFrequent
Factors Leading to Inadequate Asthma Control
Wrong diagnosis or confounding illness Incorrect choice of inhaler or poor technique Concurrent smoking Concomitant rhinitis Individual variation in treatment response Undertreatment Unintentional or intentional nonadherence
Haughney J, et al. Respir Med 2008;102:1681-1693Haughney J, et al. Respir Med 2008;102:1681-1693
Goals of Asthma Management
Achieve and maintain control of symptoms Prevent asthma exacerbations Maintain optimal pulmonary function Maintain normal activity levels (+ exercise) Avoid adverse effects from asthma medications Prevent the development of irreversible airflow
obstruction Prevent asthma mortality
GINA: Global Strategy for Asthma Management and Prevention, 2009GINA: Global Strategy for Asthma Management and Prevention, 2009 1717
What are the drugs?What are the devices?
Asthma Medications
1919
Treatment Effects Most common AEsRelievers
Short-acting beta-2 agonists
• Use on-demand only at min. dose and frequency
• Tremor, palpitations, restlessness, headache, muscle cramps, nervousness
ControllersInhaled corticosteroids • For persistent asthma
• Not intended as rescue med.
• May take 1-2 weeks to see benefits
• Local: Oral candidiasis, dysphonia, reflex cough and bronchospasm
• Systemic: bone density, poor growth, adrenal gland suppression, bruising, blood sugar
Leukotriene receptor antagonists
• Alternative for persistent asthma and as add-on to ICS
• Headaches, stomach pain, and cough
Anti-IgE MAb • For moderate to severe asthma with frequent need for oral CS
• Headache, malaise, anaphylaxis
LemièreLemière et al. Can Respir J 200 et al. Can Respir J 2004;11 Suppl A:9A-18A4;11 Suppl A:9A-18AIrwin R. Chest 2006;130(1 Suppl):41S-53SIrwin R. Chest 2006;130(1 Suppl):41S-53S
Asthma Medications (cont’d)
Treatment Effects Most common AEsAdd-on therapies
Long-acting beta-2-agonists
• Improves asthma control in older children and adults
• Only to be used as an add-on when asthma not controlled with ICS
• Not to be used as monotherapy
• Tachycardia, palpitation, irritability, insomnia, muscle cramps, tremor
LemièreLemière et al. Can Respir J 200 et al. Can Respir J 2004;11 Suppl A:9A-18A4;11 Suppl A:9A-18A
http://asthma.ca/inhalertraining.php
Canadian Thoracic Society Asthma Management Continuum
LABA = long-acting beta agonistLougheed MD, et al. Can Respir J 2010; 17(1):15-24.
<6 yr of age < 100 mcg/day <6 yr of age < 100 mcg/day
Asthma Management - Details
Allergen and Irritant Avoidance Avoidance of other triggers (e.g. cold air,
influenza vaccine, NSAIDs in sensitive px’s) Education, education, education Assessment of Control at each patient visit
I judge patient’s asthma control by:1.Need for fast-acting beta-agonist2.Physical activity3.Night time symptoms4.Exacerbations5.Absence from work or school
Polling Question:Indicators of Asthma Control
Statistics Canada. Available at: Statistics Canada. Available at: www40.statcan.ca. www40.statcan.ca. Asthma Society of Canada. Available at: Asthma Society of Canada. Available at: www.asthma.cawww.asthma.ca..
Indicators of Asthma Control
Characteristic Frequency or Value
Daytime symptoms < 4 days/week
Night-time symptoms < 1 night/week
Physical activity Normal
Exacerbations Mild, infrequent
Absence from work or school due to asthma None
Need for a fast-acting beta-agonist < 4 doses/week
FEV1 or PEF ≥ 90% personal best
PEF diurnal variation† < 10% to 15%
FEV1 = forced expiratory volume in 1 second; PEF = peak expiratory flow.†Diurnal variation is calculated as the highest PEF minus the lowest divided by the highest PEF multiplied by 100 for morning and night (determined over a 2-week period).
Lougheed MD, et al. Can Respir J 2010; 17(1):15-24.
Educate Patients That This Level of Asthma Control is Generally Achievable
Actual and Perceived Asthma Control in Canada: TRAC Study
100
Pat
ient
s (%
)
Actual(based on CACG)
53%
80
60
40
20
60
47%
3%
97%12%
88%
10%
90%
Patients Generalpractitioners
Specialists
Perceptions
CACG = Canadian Asthma Consensus Guidelines.FitzGerald JM, et al. Can Respir J 2006; 13(5):253-9.
Not controlledControlled
Why Don’t Patients Take Asthma Medications as Prescribed?
Most do not want to take daily medications when they feel well and have no asthma symptoms
Many believe they know when they need to take their asthma medications
Most use SABAs because these work quickly Many do not know or believe that poor
current asthma control results in future risks
SABA = short-acting beta agonist.SABA = short-acting beta agonist.
Short Acting Beta-Agonists (SABA)
Onset of action 5 to 15min, duration ~4 hr Salbutamol (Ventolin®)
MDI (100 mcg) Diskus (200 mcg)
Terburtaline (Bricanyl®) Turbuhaler (500 mcg)
Long Acting Beta-Agonists (LABA)
Black Box warning against monotherapy Only for 12 yr of age and up Salmeterol (Serevent®)
Maximal dose 100 mcg/day Onset of action ~ 1 hr MDI – 25 mcg; Diskus – 50 mcg
Formoterol (Oxeeze®) Maximal dose 48 mcg/day Onset of action ~ 15 min Turbuhaler – 6 mcg
Inhaled CorticosteroidsGeneric Name Formulation Doses
Beclomethasone (QVAR®)*** Inhalation aerosol (MDI) 50 mcg100 mcg
Fluticasone (Flovent®) Dry powder for inhalation (Diskus**) ¥
¥Contains lactose/milk protein
Inhalation aerosol (MDI)*
50 mcg100mcg250 mcg500 mcg
50 mcg125 mcg250 mcg
Budesonide (Pulmicort®)*** Dry powder for inhalation (Turbuhaler)
100 mcg200 mcg
Ciclesonide (Alvesco®)*** Inhalation aerosol (MDI) 100 mcg200mcg
Mometasone (Asmanex®)§ Dry powder for inhalation (Twisthaler)**
200 mcg400 mcg
***6 yoa and up***6 yoa and up § 12 yoa and up§ 12 yoa and up**4 yoa and up**4 yoa and up*12 mo and up*12 mo and up
Available ICS + LABA Single-inhaler Combinations
Advair® Product Monograph. GlaxoSmithKline Inc., July 2010.Symbicort® Product Monograph. AstraZeneca Canada Inc., December 2010.ZenhaleTM Product Monograph. Merck Canada Inc., January 2011.
Combination Formulation Doses
Fluticasone + salmeterol (Advair®)
Dry powder for inhalation(Diskus¥)
¥Contains lactose/milk protein
Inhalation aerosol (MDI)
100 mcg/50 mcg 250 mcg/50 mcg 500 mcg/50 mcg
50 mcg/25 mcg125 mcg/25 mcg250 mcg/25 mcg
Budesonide + formoterol (Symbicort®)
Dry powder for inhalation(Turbuhaler)
100 mcg/6 mcg200 mcg/6 mcg
Mometasone + formoterol (Zenhale®)
Inhalation aerosol (MDI) 50 mcg/5 mcg100 mcg/5 mcg200 mcg/5 mcg
Use of Asthma Inhalers/Meds
PRN SABA alone Fixed dose ICS (and/or LTRA); PRN SABA Fixed dose ICS/LABA (± LTRA); PRN SABA
At times of acute exacerbation, double or quadruple ICS dose or introduce oral CS
Single inhaler Maintenance and Rescue Therapy (SMART) – Fixed dose ICS/LABA and PRN ICS/LABA* * Only effective if the LABA is formoterol due to onset
of action differences * Only Health Canada approved for Symbicort®
ICS Safety: Key Pharmacokinetic and Pharmacodynamic PropertiesICS Oral bio-
availability (%)
Receptor binding affinity
Protein binding (%)
Beclomethasone 15 53/1,345a 87
Budesonide 11 935 88
Fluticasone < 1 1,800 90
Mometasone < 1 2,200 98-99
Ciclesonide < 1 12b/1,212c 99
Key characteristics:↑ receptor binding/potency↑ lipophilicity↑ plasma protein binding↑ metabolism↓ bioavailablity↓ systemic exposure
↑ therapeutic index
Rossi GA, et al. Pulm Pharmacol Ther 2007; 20(1):23-35.Bousquet J. Int J Clin Pract 2009; 63(5):806-19.
a Relative receptor affinity for 17-beclomethasone monopropionate.b Ciclesonide.c Desisobutyryl-ciclesonide
Corticosteroid Trade name
Daily ICS dose, mcg^Adult (>12 years old)
Low Medium HighBeclomethasone dipropionate HFA QVAR† ≤250 251-500 >500
Budesonide* Pulmicort Turbuhaler‡ ≤400 401-800 >800Ciclesonide* Alvesco§ ≤200 201-400 >400Fluticasone Flovent MDI and spacer; Flovent Diskus¶ ≤250 251-500 >500Mometasone Asmanex Twisthaler** 200 400 >400
Adapted from Lougheed MD, et al. Can Respir J. 2012;19:127-64.
^Comparative clinical significance has not been established
What is Low Dose ICS?
LABA Differences: Onset of Bronchodilation
**pp ≤ 0.016 vs. fluticasone + salmeterol. ≤ 0.016 vs. fluticasone + salmeterol.Bernstein DI, et al. Allergy Asthma Clin Immunol 2010; 6 (Suppl 2):33.Bernstein DI, et al. Allergy Asthma Clin Immunol 2010; 6 (Suppl 2):33.
350350M
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Minutes post doseMinutes post dose
00
300300
250250
200200
150150
100100
5050
00
55 1010 1515 2020 2525 3030 3535 4040 4545 5050 5555 6060
**
**
**
**
Mometasone + formoterol 200/10 mcg bidMometasone + formoterol 200/10 mcg bid
Fluticasone + salmeterol 250/50 mcg bidFluticasone + salmeterol 250/50 mcg bid
Specific for CysLTR1 CysLT2 is present in the lung but appears to
be confined to blood vessels Available agents: Singulair® = montelukast
4mg, 5mg and 10mg tablets, dosing is OD Accolate® = zafirlukast
20mg BID
Leukotriene Receptor Antagonists (LTRA’s)
Montelukast is approved for use in children 1 year of age and older for asthma and 2 years of age and older for allergic rhinitis Pregnancy category B
Zafirlukast approved for children 12 y and older Pregnancy category B
Leukotriene Receptor Antagonists (LTRA’s)
Personalized Asthma Treatment
Assess patient preference and ability to use device(s) **
Patients fearful of ICS, evaluate steroid alternatives for maintenance, such as LTRAs; ensure Aerochamber in use
Ask patient about desire for rapid onset, and select the ICS/LABA accordingly
Choose ICS with lowest bioavailability and associated with lowest risk of adverse effects but that also produces desired efficacy outcomes
Patient Compliance to ICS Therapy Can Prevent Asthma Deaths
Suissa S, et al. N Engl J Med 2000; 343(5):332-6.Suissa S, et al. N Engl J Med 2000; 343(5):332-6.
Fitted rate ratio for death from asthma as a function Fitted rate ratio for death from asthma as a function of the number of canisters of ICS used during year of the number of canisters of ICS used during year
before index date.before index date.
2.52.5
Rat
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1.51.5
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00
Number of canisters of ICS per yearNumber of canisters of ICS per year3311 44 55 12129988 1010 111166 7700 22
Non-adherence to Asthma Therapy
Intentional Motivation Beliefs/preferences Perceptual barriers
Non-intentional Capacity and resources Practical barriers
Barriers to assessing adherence: Patient and physician may prefer to avoid the subject Lack of clear, easy methods for addressing barriers to
adherence Perception that little can be done?
Horne R, et al. Chest 2006;130:65SHorne R, et al. Chest 2006;130:65S--72S72S 4040
Strategies to Improve Adherence
Focus on patient education Ensure language at appropriate level Write it down Consider referral to an asthma educator
Encourage self-monitoring Use a written asthma action plan Monitor adherence to medication regimen and
proper inhaler techniques Combination therapy may improve complianceNational Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Expert Panel. National Heart, Lung, and Blood Institute National Asthma Education and Prevention Program Expert Panel.
Guidelines for the Diagnosis and Management of Asthma Full Report 2007Guidelines for the Diagnosis and Management of Asthma Full Report 2007Stoloff SW, et al. J Allergy Clin Immunol 2004;113:245-251Stoloff SW, et al. J Allergy Clin Immunol 2004;113:245-251
4141
Asthma Education Centres
A link to this resource has been posted as a hand out in your control panel that you can download.
Unique Considerations
Pediatrics Allergic Asthma
Pediatric Considerations
Diagnostic challenge before age 5 Atopy risk factor for persistence of childhood wheeze Lower ICS doses usually sufficient Aerochambers not optional – discussion of benefits
can improve adherence Adherence to oral/non-steroidal therapy often higher
but must assess patient response Spirometry generally becomes reliable around age 8
to 10 to provide objective assessment of disease
Unique considerations – Allergic Population
Allergic rhinitis and asthma often co-exist Treating rhinitis improves asthma outcomes Remember to treat with INCS as well LTRA’s indicated for both, as is omalizumab and
immunotherapy Dual targets one medication:
LTRAs Allergen specific immunotherapy Omalizumab
Biologic Therapy
Omalizumab (Xolair®) Monoclonal antibody against IgE molecule Indicated for moderate to severe allergic
asthma Shown to decrease hospitalizations, ER visits,
and requirements for oral corticosteroids Typically given under specialist supervision
(injection, risk of anaphylaxis)
Allergen immunotherapy
Reached its 100th anniversary (Noon, 1911) Currently, subcutaneous immunotherapy (SCIT),
a.k.a ‘allergy shots’ established as effective in the treatment of IgE-mediated reactions to: Hymenoptera venom Allergic rhinitis Allergic asthma
What is immunotherapy?
Decrease allergen sensitivity via gradual administration of increasing doses of allergen extracts
Advances over last 25 yrs include improved quality of extracts, better understanding of underlying immune mechanisms
Modifies immune response from an allergic, inflammatory pattern to a more protective, less damaging response
IT and allergen avoidance are the only treatments that modify the natural history of allergic disease, inducing remission and/or long-term cure
Efficacy in Asthma
Confirmed in 3 meta-analyses of RCTs of specific immunotherapy for patients with allergic asthma
Most recent included 75 trials involving over 3500 patients 33 dust mite 20 pollen 10 animal 2 mould 6 multiple aeroallergens
Abramson et al. Cochrane Database System Rev 2009Abramson et al. Cochrane Database System Rev 2009
Efficacy
Standardized Mean Difference in symptoms scores were best for dust mite and all pollens; overall SMD -0.72 (95% CI -0.99 to -0.44)
If studies reported better, same, worse: Overall NNT = 4 to prevent one asthma deterioration Pollen NNT = 3
NNT = 5 to prevent one increase in medication requirements; NNT = 4 to prevent worsening of BHR
Established aspects
Effective doses of allergen extract: Ragweed Timothy Birch D. pteronyssinus D. farinae Cat dander Dog dander
Duration: After 5 years of SCIT,
benefit generally persists
If after 1-2 years at an appropriate maintenance dose, and no benefit noted, can discontinue Rx
Safety of Immunotherapy
Local, systemic, and even fatal reactions are a recognized complication of SCIT
Large local reactions not predictive of future systemic reactions (SRs)
Incidence of SRs a function of: Patient sensitivity Dose Modifications to extract
Systemic reactions to SCIT occur in 0.9 – 3.3% of injections with traditional schedules
Rush protocols, up to 38% Nelson. J Allergy Clin Immunol 2007Nelson. J Allergy Clin Immunol 2007
Additional Agents/On the Horizon
Ipatropium bromide (Atrovent®) 500 ug q4h PRN
Tiotropium bromide (Spiriva®) 18 mg QAM
Mepolizumab (Mepo®) Monoclonal anti-IL-5 antibody
Other biologics?
Summary
Asthma is a chronic disease–control inflammation to prevent symptoms
Avoidance of triggers with ongoing education essential components of asthma management
Review device technique/adherence whenever possible
Uncontrolled asthma and severe exacerbations accelerate decline in lung function
Unique considerations in allergic populations United airways; Disease modifying therapy
Questions?
[email protected] or [email protected] Twitter: @DrAnneEllis