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  • Allergen Immunotherapy and Asthma

    Linda Cox, MD, FAAAI

    ASCIA 2013 Meeting

  • Allergen Immunotherapy and Asthma

    Overview: burden/prevalence of asthma and allergic disease

    Allergen immunotherapy and asthma: is it effective?

    SCIT and SLIT efficacy

    AIT and asthma safety

    AIT as a disease modifying treatment; prevention, duration

  • The Burden & Prevalence of Allergic disease: Key Points

    Allergic rhinitis is one of the most common pediatric & adult chronic diseases

    Allergic rhinitis is a risk factor for asthma

    Up to 40% of allergic rhinitis patients will develop asthma

    Asthma is one of the most common and costly chronic pediatric illnesses

    Asthma and allergy medications only control symptoms

    Allergen immunotherapy is currently the only disease modifying treatment for allergic disease

    Disease modification may translate into significant cost-savings 2 to reduced medication use, co-morbidillnesses, progression of disease, etc.

  • World Health Organization survey regarding asthma Doctor diagnosed asthma 4.5%

    Current World Population Of 7 Billion Translates To 315 Million Individuals With Asthma.

    The prevalence of clinical asthma varied widely amongst the 70 participating countries, ranging from 1.0% in Vietnam to 21.5% in Australia, who reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing

    To et al Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC public health. 2012;12:204.

  • 0









    1 2 3 4 5 6 7 8 9 10 11 12 13

    Age (years)

    Prevalence of current wheeze from birth to age 13 years in children with any wheezing episode at school age (57 years),

    Illi S, et al. Lancet 2006

    Non-atopic n=59

    Atopic n=94

    Sensitisztion to perennial allergens developing in the fi rst 3 years of life was associated with a loss of lung function at school age. 90% non-atopic wheeze

    Perennial allergen sensitization early in life and chronic asthma in children: a birth cohort study






    Growing out of asthma

  • A Longitudinal, Population-Based, Cohort Study of Childhood Asthma Followed to Adulthood

    Purpose: To identify risk factors for persistence and relapse of asthma

    Design: Assessed 1139 children from age 9 to 26 yrs with questionnaires, PFT, bronchial challenge and allergy testing

    Seen every 2 yrs, PFT at 9,11,13,15,21 years

    Skin test 13 & 21years

    613 with complete respiratory data included in analysis

    Seare et al, NEJM 2003; 349:1414-1422

  • Seare, M et al NEJM 2003; 349:1414-1422

    613 Children Followed From Age 9 To 26 Yrs 75% Reported Wheezing On At Least One Occasion And

    51% Wheezed > One Occasion

    Sensitization to house dust mites predicted the persistence of wheezing (OR,2.41; P=0.001) and relapse (OR, 2.18; P=0.01),

  • Asthma burden of disease economic reality

    US: Asthma rates and associated costs have increased dramatically over the last thirty years. 1

    Asthma prevalence increased from 7.3% in 2001 to 8.4% in 2010, ~25.7 million2

    Estimated total direct and indirect costs to society was $56 billion in 2007

    ED and hospitalization ~58% and 64% of total direct costs


    2000 - 10: hospital costs more than tripled-$210.8 million to $748.5 million which was a 255% increase,

    1. 2. Akinbami et al Trends in asthma prevalence, health care use, and mortality in the US, 20012010. NCHS data brief, no 94.

  • Florida Asthma Stats

    From 2000 to 2005 ED costs doubled $102.3 million to $204.1 million represents a 99.6% increase

    Largest increase in total charges (and total visits) occurred among those paid for by Medicare or Medicaid (i.e., government insurer.)

  • Florida Asthma Coalition 36 Measures Only One Addresses Triggers and this does not specify allergen trigger

  • Where Does AIT Fit in the Guidelines for Allergen Immunotherapy for Asthma?

    ARIA recommendations 2010:

    SCIT: conditional recommendation in allergic asthma (moderate quality evidence)

    SLIT: conditional recommendation in allergic asthma (low quality evidence)

    GINA report 2012:

    Immunotherapy should be considered only after strict environmental avoidance and pharmacological intervention,

    including ICS

    Immunotherapy is not listed in GINA treatment steps for achieving control

    Broek et al. ARIA revision 2010. JACI 2010;126:466-76

    GINA global strategy for asthma management and prevention: updated 2012

  • 16 Partridge et al BMC pulmonary medicine. 2006;6:13.

    Compliance in Asthma is a major concern

    70% of patients adjust themselves their medication

    3415 adults with asthma in 11 countries prescribed regular maintenance therapy,

    74% of patients used short-acting 2-agonists daily and

    51% were classified by ACT as having uncontrolled asthma.

    Even patients with well-controlled asthma reported an average of 6worsenings/year


    In preschool children at high risk for asthma, 2 years of ICS did not change the development of asthma symptoms or lung function during a third, treatment-free year.1

    CAMP at 4.8 year posttrial f/u no difference in lung function or asthma control seen in ICS vs placebo but still significant decreased mean height (1.1 cm)2

    1.Guilbert N Engl J Med 2006; 354 2. Strunk J Pediatr. 2009;154(5):682-7.


    66% of patients who requested an allergy medication change due to dissatisfaction did so because of lack of efficacy

    The majority of patients reported that the effects of their medication wore off over time

    Nearly a third of patients stopped taking their nasal allergy medication because it did not provide 24-hour relief

    Allergies in America Web site. Accessed September 3, 2007.

    According to Allergies in America, a Survey of

    2500 Nasal Allergy Sufferers

  • 3.3












    0 1 2 3 4 5 6

    Risk of Anaphylaxis

    Side Effects

    Limited Efficacy

    Cost of Therapy

    "Needle Phobia"

    Patient Concern/Lack ofCommitment on the Need for

    Frequent Office Visits

    Allergists (n=46)

    PCPs (n=46)

  • Allergen Immunotherapy and Asthma: the controversy

    Allergen specific immunotherapy has long been a controversial treatment for asthma. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. 1

    It is difficult to compare results from the various studies of IT because of the large number of variations in the clinical trial protocols. Given the heterogeneity of IT clinical trials as a group, it is not surprising that variable results occur. The use of multiple studies in a meta-analysis with its underlying assumption of homogeneity is problematic.2

    1. Abramson ,Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003

    2. Portnoy Ann Allergy Asthma Immunol 2001;87

  • Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials

    A meta-analysis of all 20 published prospective, randomized, PC trials of immunotherapy for asthma between 1954-1990

    These were statistically significant improvement in symptoms, medication use, and BHR.

    Mean improvement in FEV1 of 0.71 (CI 0.43-1.00) corresponding to an average FEV1 increase of 7.1%.

    Symptomatic improvement

    Medication reduction

    Decrease in Bronchial Hyperresponsiveness

    Odds ratio 3.2 Odds ratio 4.2 Odds ratio 6.8 Confidence interval (2.2-4.9)

    Confidence interval (2.2-7.9)

    Confidence interval (3.8-12)

    Abramson et al. Am J Respir Crit Care Med; 1995 151(4):969-74

  • The Many AIT Meta-analyses: Symptoms

    Burks, et al. Update on allergy immunotherapyAAAAI/EAACI /PRACTALL consensus report. J Allergy Clin Immunol. 2013 Mar 13

    SMD=Standardized Mean Difference is the difference of the means of both treatment arms divided by the pooled standard deviation.

  • Allergen Immunotherapy For Asthma Cochrane Database Systemic Review: 2010

    88 trials between 1954-2005 with a total of 3,459 with asthma, 13 new trials)

    42 trials of immunotherapy for house mite allergy

    27 pollen allergy trials

    10 animal dander allergy trials*

    2 Cladosporium mould allergy*

    1 latex*

    6 trials of multiple allergens*

    Concealment of allocation was assessed as clearly adequate in only 16 of these trials.

    Significant heterogeneity was present in a number of comparisons.*

    Abramson et al.,. Allergen immunotherapy for asthma Cochrane Database Syst Rev. 2010;8:CD001186.

    *no change from 20003 update

  • Allergen Immunotherapy For Asthma Cochrane Database Systemic Review: 2010

    Significant improvement in asthma symptom scores (SMD


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