Allergic Rhinitis Diagnosis. Allergic Rhinitis Economic Burden. Allergic Rhinitis Epidemiology. Allergic Rhinitis Quality of Life

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1 Allergic Rhinitis Epidemiology 6th Leading cause of chronic illness > 50m Americans suffer from allergies 10-30% Children and adults affected in U.S. 2.5% Of all clinician visits 1. US Department of Health and Human Services. Agency for Healthcare Research and Quality. Management of allergic and nonallergic rhinitis. May AHQR publication 02:E023, Boston, MA. Summary, Evidence Report/Technology Assessment: No Singh K, Axelrod S, Bielory L. J Allergy Clin Immunol 2010; 126: Allergic Rhinitis Economic Burden 2 mil Lost school days per year 6 mil Lost work days 2x Avg # of annual prescriptions vs patients without AR > $2-5b Direct annual cost > $2-4b Indirect annual cost AR causes greater loss of productivity than any other illness and accounts for ~1/4 of all lost productivity 1. D'Alonzo GE Jr. J Am Osteopath Assoc 2002; 102:S2. 2. Woods L, Craig TJ. Curr Opin Pulm Med 2006; 12: Schatz M, Zeiger RS, Chen W, et al. Ann Allergy Asthma Immunol 2008; 101: Bhattacharyya N. Laryngoscope 2011; 121: Lamb CE. Curr Med Res Opin Jun;22(6): Allergic Rhinitis Quality of Life What is Allergic Rhinitis (AR)? Sleep disturbed breathing Caused by congestion Hundreds of brief and subtle microarousals each night Cognitive and psychiatric issues in children and adolescents Attention-deficit hyperactivity disorder Lower exam scores during peak pollen seasons Poor concentration Impaired athletic performance Low self-esteem Cognitive and psychiatric issues in adults Anxiety & depression Reduced academic performance and work productivity Impaired sexual performance Inflammatory, IgE-mediated disease characterized by nasal congestion, rhinorrhea (nasal drainage), sneezing, and/or nasal itching Inflammation of the inside lining of the nose that occurs when a person is sensitized Animal dander Pollen House dust mites 1. Koinis-Mitchell D, Craig T, Esteban CA, Klein RB. J Allergy Clin Immunol 2012; 130: Meltzer EO, Nathan R, Derebery J, et al. Allergy Asthma Proc 2009; 30: Postolache TT, Lapidus M, Sander ER, et al. ScientificWorldJournal 2007; 7:1968. Allergic Rhinitis Pathophysiology Early-phase Reaction (Max at Minutes) Late-phase Reaction (Max at Hours) Allergens Blood vessels Mediator release IgE antibodies Cellular infiltration Nerves Glands Mast cell Eosinophils Basophils Monocytes Lymphocytes Late-phase reaction Priming Hyperresponsiveness Resolution Complications Irreversible disease (?) Allergic Rhinitis Diagnosis Sneezing Rhinorrhea Congestion 1. American Academy of Otolaryngology, Adapted from: Naclerio RM. N Engl J Med 1991; 325(12):

2 Questions To Ask a Patient With AR Do you have nasal congestion, runniness and/or sneezing? Do you have itchy, red and/or watery eyes? Are your symptoms impacting your daily activities or sleep? Do your symptoms change over the year and are they seasonal? Have antihistamines and/or prescription nasal sprays been effective? Have they been used consistently and had an adequate trial? Allergic Rhinitis Risk Factors Family history of atopy Male sex Birth during the pollen season Firstborn status Early use of antibiotics Maternal smoking exposure in the first year of life Exposure to indoor allergens, such as dust mite allergen Serum IgE >100 int. units/ml before age six Presence of allergen-specific immunoglobulin E (IgE) Presence of each of these factors was associated with a 3-5 positive likelihood ratio for the diagnosis of allergic rhinitis 1. Matheson MC, Dharmage SC, Abramson MJ, et al. J Allergy Clin Immunol 2011; 128: Saulyte J, Regueira C, Montes-Martínez A, et al. PLoS Med 2014; 11:e Gendo K, Larson EB. Ann Intern Med 2004; 140:278. Allergic Rhinitis Differential Diagnosis Allergic Rhinitis Differential Diagnosis Non-allergic rhinitis syndromes Vasomotor rhinitis (idiopathic rhinitis) Gustatory rhinitis (following food or alcohol consumption) Non-allergic rhinitis with eosinophilia syndrome (NARES) - nasal polyps common, similar to allergic rhinitis but with normal immunoglobulin E (IgE) levels, treated with topical corticosteroids Atrophic rhinitis Drug-induced rhinitis (e.g. ACE inhibitors, PDE-5 inhibitors, α-antagonists, NSAIDs, oral contraceptives Rhinitis medicamentosa due to topical decongestants or cocaine Infectious rhinitis Hormonal rhinitis Pregnancy rhinitis - reported in 20%-30% of pregnancies Physical obstruction and irritation Other causes of disturbed nasal function Nasal polyps Nasal septal deviation Tumors Hypertrophy of the nasal turbinates Cleft palate Laryngopharyngeal reflux Foreign body obstruction Cystic fibrosis Primary ciliary dyskinesia or other ciliary dysfunction Sinus disease Vasculitis (such as granulomatosis with polyangiitis) Cerebrospinal fluid rhinorrhea 1. Wallace DV, Dykewicz MS, Bernstein DI, et al; Joint Task Force on Practice; American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. J Allergy Clin Immunol Aug;122(2 Suppl):S Wallace DV, Dykewicz MS, Bernstein DI, et al; Joint Task Force on Practice; American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. J Allergy Clin Immunol Aug;122(2 Suppl):S1-84 Allergic Rhinitis IgE-specific Tests Allergic Rhinitis Classification Test Type Recommendation Advantages Disadvantages Skin tests (Skin prick or intradermal) Recommend Allows for direct observation of the body s reaction to a specific antigen Considered more sensitive than blood testing Intradermal can be used when additional sensitivity is required or skin prick negative Less expensive than blood testing Possible systemic allergic reaction (anaphylaxis) May be affected by patient medications Seasonal AR Often diagnosed by history alone (reproducible from year to year) Tree & grass pollen in spring Ragweed pollen in fall Episodic AR Can be diagnosed by history alone if there is an obvious connection between exposure and the onset of symptoms (i.e. exposure to animals) Perennial AR May not be readily apparent from the clinical history Usually reflects allergy to indoor allergens like dust mites, cockroaches, or animal dander Blood Recommend No risk of anaphylaxis Not affected by patient s medications Can be used for patients with skin conditions such as dermatographism or severe eczema Can be used for patients on β-blockers or with comorbid medical conditions that preclude skin testing Requires reliable laboratory, potential for laboratory errors Episodic Mild Mildmoderate Moderate- Severe Severe IgG or total IgE Recommend against Does not yield information helpful for management of AR Intermittent <4 days per week or <4 weeks per year vs Persistent >4 days per week and >4 weeks per year 1. Seidman MD, et al. Guideline Otolaryngology Development Group. AAO-HNSF. Clinical practice guideline: Allergic rhinitis. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S Wallace DV, Dykewicz MS, Bernstein DI, et al; Joint Task Force on Practice; American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. J Allergy Clin Immunol Aug;122(2 Suppl):S1-84 2

3 Allergic Rhinitis Diagnostic Approach Characteristic symptoms Suggestive Clinical History Physical Exam Imaging Sensitization testing Paroxysms of sneezing, rhinorrhea, nasal obstruction, nasal itching, postnasal drip, cough, irritability, and fatigue i.e. Presence of risk factors Allergic shiners, Dennie-Morgan lines, Allergic salute, and Allergic facies NOT usually performed unless a concomitant condition (i.e. chronic rhinosinusitis) Indicated when symptoms prove difficult to manage or the trigger(s) for the symptoms are not apparent Allergic Rhinitis Treatment Allergic Rhinitis Treatment Treatment Allergen Avoidance Environmental control measures and allergen avoidance Pharmacological management Allergen immunotherapy Pollens & outdoor molds Indoor allergens Reduction of outdoor exposure during the season Limit outdoor exposure on dry, sunny, and windy days Keep windows and doors of the house/car closed as much as possible Shower after outdoor exposure Humidifier (<50% humidity) Removal of standing water Removal of pets Dust barriers for pillows and mattresses HVAC and free-standing air filters HEPA vacuum cleaners Seidman MD, Gurgel RK, Lin SY, et al. Clinical practice guideline: Allergic rhinitis. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S1-43. Allergic Rhinitis Treatment Treatment Pharmacotherapy Environmental control measures and allergen avoidance Pharmacologic management Immunotherapy Intermittent: Mild-Moderate Environmental Control Persistent: Mild Environmental Control Persistent: Moderate AND Severe Non-sedating 2 nd generation oral antihistamine (AH) PRN Environmental Control AND Environmental Control AND AH and/or INCS AND AH + INCS or INAH Consider INAH AH + INCS + INAH Specialist referral Consider PO steroid (5d) AHs = Loratadine, desloratadine, cetirizine, fexofenadine, and levocetirizine INCS = triamcinolone, mometasone furoate, fluticasone, and budesonide INAH = azelastine, olopatadine, azelastine/fluticasone Specialist referral 1. Di Lorenzo G., Pacor M.L., Pellitteri M.E., et al. Clin Exp Allergy 2004; 34: pp Papadopoulos N.G., Bernstein J.A., Demoly P., et al. Allergy 2015; 70: pp Bousquet J., Bachert C., Bernstein J., et al. Expert Opin Pharmacother 2015; 16: pp

4 Treatment Oral Antihistamines (AH) Treatment Intranasal Antihistamines 1 st generation AHs Diphenhydramine, chlorpheniramine, and hydroxyzine Use limited by SEs (sedation and mucosal dryness) 2 nd generation AHs Preferred in almost all situations Comparative effectiveness Very few studies Cetirizine and levocetirizine are most potent but carry a modest risk of sedation of see with others Advantages or oral AHs Rapid onset of action Once-daily dosing Maintenance of effectiveness with regular use Availability of some drugs w/o a prescription Some patients who fail to improve with one agent may respond to another in the class Maximum benefit seen with continuous use 2 nd Generation AH Cetirizine Levocetirizine Fexofenadine Loratadine Desloratadine FDA Indications (Seasonal, Perennial) Both Both Seasonal Both Both Medication Olopatadine (Patanase) (as HCl) 0.6% (665 μg per spray); aqueous nasal spray Azelastine (Astelin) 0.1% solution (137 μg per spray) Azelastine (Astepro) 0.15% solution (205.5 μg per spray) Azelastine plus fluticasone (Dymista) (137 μg of azelastine, 50 μg of fluticasone per spray) FDA Indications Seasonal AR vasomotor AR Approved Ages Dosing Age 6-11y: 1 spray twice a day Age 12y: 2 sprays twice a day Age 6-11y: 1 spray twice a day Age 12y: 1-2 sprays twice a day or 2 sprays daily Age 6-11y: 1 spray twice a day Age 12y: 1-2 sprays twice a day or 2 sprays daily Seasonal AR 12y 1 spray per nostril 2x a day Azelastine and olopatadine (2 nd generation H 1 blockers) have equal efficacy Targeted delivery and increased dosage to nasal tissues while limiting SEs Have shown equality or superiority to oral AHs (better for nasal congestion vs oral AHs) Rapid onset of action of min (vs 150min for oral AHs) 1. Seidman MD, et al. Guideline Otolaryngology Development Group. AAO-HNSF. Clinical practice guideline: Allergic rhinitis. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S1-43. Treatment Intranasal Corticosteroids (INCS) Approved Medication FDA Indications Dosing Ages Triamcinolone acetonide Age 2-5 y: 1 spray per nostril every day (Nasacort Allergy 24HR), 55 μg 2y Age 6-11 y: 2 sprays per nostril every day per spray Age 12 y: 2 sprays per nostril 1 or 2 times per day Budesonide AR and nonallergic 2 sprays per nostril twice a day or 4 sprays per nostril (Rhinocort AQ) 32 μg per spray rhinitis in the morning Flunisolide Age 6-14 y: 1 spray per nostril 3 times per day or 2 (Nasalide or Nasarel), 25 μg per sprays per nostril twice a day spray Age >14 y: 2 sprays per nostril 2 or 3 times per day Fluticasone propionate AR and non allergic Age 4 y to adult: 1 spray per nostril every day 4y (Flonase), 50 μg per spray rhinitis Adult: 2 sprays per nostril every day Treatment Additional pharmacotherapy approaches Addition of oral AHs or a leukotriene-modifying agent (e.g. motelukast) to INCS = Little benefit 1-2 Combination of fluticasone + azelastine HCl = greater efficacy in reducing nasal symptoms vs either drug alone 3 If refractory to INCS and INAH brief course of oral corticosteroids DO NOT use long-acting depot IM injections due to side effects Mometasone furoate (Nasonex), 50 μg per spray Ciclesonide (Omnaris), 50 μg per Spray, nasal polyps 2y Age 2-11 y: 1 spray per nostril every day Age 12 y: 2 sprays per nostril every day Age 18 y with polyps: 2 sprays per nostril twice a day 2 sprays per nostril every day Daily use of montelukast may be considered but less effective than INCS Fluticasone furoate (Veramyst), 27.5 μg per spray 2y Age 2-11 y: 1-2 sprays per nostril every day Age >11 y: 2 sprays per nostril every day Qnasl 80 μg per spray 12y 2 sprays per nostril every day Ciclesonide (Zetonna) 37 μg per spray 12y 1 spray per nostril every day 1. Seidman MD, et al. Guideline Otolaryngology Development Group. AAO-HNSF. Clinical practice guideline: Allergic rhinitis. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S Di Lorenzo G., Pacor M.L., Pellitteri M.E., et al. Clin Exp Allergy 2004; 34: pp Papadopoulos N.G., Bernstein J.A., Demoly P., et al. Allergy 2015; 70: pp Bousquet J., Bachert C., Bernstein J., et al. Expert Opin Pharmacother 2015; 16: pp Allergic Rhinitis Treatment Case 1 David Environmental control measures and allergen avoidance Pharmacological management 25-year-old male student Chief Complaint: Allergic symptoms despite treatment PMHx: Asthma Current Treatment: Environmental control, INAH, and INCS Allergen Testing: polysensitization to trees, grass, cats, and dogs (usually worse in the spring) Allergen immunotherapy Is further testing indicated? What are his treatment options at this time? When would you refer this patient? 4

5 Approach to Allergic Rhinitis Treatment Allergen Immunotherapy (AIT) History should suggest AR Look for associated issues such as atopic dermatitis, asthma, family history Consider trial of non-sedating antihistamines, intranasal corticosteroids Specific allergen-avoidance suggestions should be based on proper allergy-testing results Pharmacotherapy Immunotherapy Consider referral to Allergy/Immunology One-third of children and two-thirds of adults with AR experience insufficient relief with pharmacotherapy alone AIT involves controlled, repetitive dosing of allergen(s) in patients diagnosed with AR by history and allergen specific IgE allergy testing AIT is the only potential curative therapy for SAR and/or PAR AIT should be considered in patients uncontrolled by allergen avoidance, regular use of medications, and those wishing to increase immune tolerance to the allergen(s) Important considerations in initiating AIT include patient preference, acceptance, expected adherence, and costs Treatment Overview of Allergen Immunotherapy (AIT) SCIT SLIT-T Effectiveness for AR Supported by systematic reviews of RCTs Supported by systematic reviews of RCTs Safety Deaths: 1 per 2.5 million injections No reported deaths Rate of systemic reactions Dosing FDA status Socioeconomic *SLIT-aqueous Dosing not standardized FDA off-label use No CPT code exists NOT covered by most insurance plans 0.06%-0.9% 0.056% Administered in clinician s office FDA approved CPT code exists for SCIT vial preparation and injections Covered by most insurance plans Administered at home 1 st dose of SLIT tablet should be administered in clinician s office SLIT tablets FDA approved in 2014 Limited number of allergens available for Tx SLIT tablet insurance coverage to be determined by individual insurance carriers SCIT Efficacy Systematic Review (74 RCTs) Compared to control in patients with rhinitis & rhinoconjunctivitis, SCIT was associated with 1 High-strength evidence for improvement in Rhinitis/rhinoconjunctivitis symptoms (based on 26 trials with 1,764 patients) Conjunctivitis symptoms (based on 14 trials with 1,104 patients) Combined nasal plus ocular plus bronchial symptoms (based on 6 trials with 591 patients) Combined rhinitis/rhinoconjunctivitis plus asthma medication use (based on 11 trials plus 768 patients) Rhinoconjunctivitis disease-specific quality of life (based on 6 trials with 889 patients) Moderate-strength evidence for improvement in Rhinitis/rhinoconjunctivitis medication use (based on 10 trials with 564 patients) Low-strength evidence for improvement in Combined rhinitis/rhinoconjunctivitis (with or without asthma) symptom and medication scores (based on 6 trials with 400 patients) 1. Agency for Healthcare Research and Quality. (March 2013). Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma: Comparative Effectiveness Review. Retrieved June 2, 2016, from SCIT Dosing Regimen Case 1 David Up-dosing Phase Maintenance Phase Build-up regimen Tolerated well Individual titration Increasing doses are administered to: Safely build up to a maintenance dose Carefully assess the sensitivity of the patient Practice parameters recommended maximal dose given every 2-4 weeks for 3-5 years 25-year-old male student Maintenance therapy (months) Experienced more symptom-free days Subsequent visits Decrease in rescue medications Eventual removal of controller therapies All injections are given in the doctor's office due to a small risk of inducing allergic reactions Longitudinal follow-up Confirmed long-lasting relief 5

6 SLIT-T Overview of Trials Durham, years Adults (N = 634) 3 years on Tx 2 years off Sustained effect ages Maloney, 2014 ~24 weeks Adults (N=1218) & Children (N=283) Assessed 1 st grass pollen season efficacy in subjects aged 5-65 (N=1501) Blaiss 2011 Grass Pollen ~24 weeks Children (N=344) Assessed 1 st grass pollen season efficacy in subjects aged 5-17 Nolte, 2013 ~52 weeks Adults Assessed peak ragweed pollen season efficacy vs placebo in individuals aged Creticos, 2013 Ragweed ~52 weeks Adults Assessed peak ragweed pollen season efficacy vs placebo in individuals aged Case 2 William Chief Complaint: Allergic symptoms despite treatment 41-year-old male Current Treatment: Environmental control, INAH, and consultant who travels INCS for work Allergen Testing (blood): Sensitization to timothy grass pollen What are his treatment options at this time? SCIT vs SLIT-T? SLIT Approved Tablet Doses SLIT Schedules Oralair (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky BlueGrass) Dose Age (years) Day 1 Day 2 Day 3 and following IR 2x 100 IR 300 IR IR 300 IR 300 IR Grastek (Timothy grass) Age Dose 5-65 years 2800BAUs SL tablet Once daily Ragwitek (Short ragweed) Age Dose years 12 Amb a 1 unit SL tab Once daily Pre-seasonal Treatment Treatment initiated12-16 weeks prior to the allergen season Treatment maintained through the end of season Grass and ragweed tablet Year-round Treatment Initiate 12 weeks before allergen season and continue throughout the year Does not appear to be superior to preseasonal treatment after the first year 1-2 Grass tablet (1) Pajno GB, Caminiti L, Crisafulli G, et al. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: a randomized controlled study. Pediatr Allergy Immunol 2011; 22:803. (2) Nakonechna A, Hills J, Moor J, et al. Grazax sublingual immunotherapy in pre-co-seasonal and continuous treatment regimens: is there a difference in clinical efficacy? Ann Allergy Asthma Immunol 2015; 114:73. (3) Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA. 2013;309(12): (4) Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;121:S1-S55. SLIT Immunotherapy Tablets SLIT Efficacy Throughout Entire Season Timothy Grass Start of grass pollen season Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol. 2011;127(1):64. 6

7 SLIT Grass Pollen SLIT-T Improves Total Combined Symptoms % % SLIT Grass Pollen SLIT Improves Symptoms & QOL Moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T compared with placebo Significantly better rhinoconjunctivitis quality of life scores Increased number of well days Efficacy was increased in the subgroup of patients who completed the recommended pre-seasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21% medication use, 29%) No safety concerns were observed TCS: Entire Season TCS: Peak Season Placebo MK Maloney J, Bernstein DI, Nelson H, Creticos P, Hébert J, Noonan M, Skoner D, Zhou Y, Kaur A, Nolte H. Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol Feb;112(2): e2. 1. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol Apr;117(4): Larsen JN, Broge L, Jacobi H. Allergy immunotherapy: the future of allergy treatment. Drug Discov Today Jan;21(1): SLIT Post-Treatment Disease Modification SLIT Immunotherapy Tablets Long-term Confirmatory Trial (5-grass SLIT-T) 3 years of pre- and co-seasonal treatment 2-year follow-up period Ragweed Statistically significant difference between active and placebo at all points were observed Disease modification is not in the label of this product 1. Hong, J. and Bielory, L. (2011) Oralair1: sublingual immunotherapy for the treatment of grass pollen allergic rhinoconjunctivitis. Expert Rev. Clin. Immunol. 7, Didier, A. et al. (2013) Post-treatment efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet in adults with grass pollen-induced allergic rhinoconjunctivitis. Clin. Exp. Allergy 43, Didier, A. et al. (2015) Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2 years after treatment cessation, as measured by a recommended daily combined score. Clin. Transl. Allergy SLIT Ragweed SLIT-T is Effective and Well-tolerated in Adults SLIT Ragweed SLIT-T is Effective and Well-tolerated in Adults % % % % 5.18 TCS: Peak Season TCS: Entire Season TCS: Peak Season Placebo TCS: Entire Season Regwitek Placebo Ragwitek 1. Nolte H, et al. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults. Ann Allergy Asthma Immunol Jun;110(6): e4. 1. Creticos PS, et, al. Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults. J Allergy Clin Immunol May;131(5): e6. 7

8 Case 2 William SLIT-T Dose Administration 41-year-old male consultant who travels for work Incomplete relief from medications Work scheduling conflicts Shared decision making SLIT-T alternative immunotherapy option Tablet should be placed under the tongue, where it dissolves Instruct the patient not to swallow for 1 minute Instruct the patient to avoid eating and drinking for 10 minutes Should be administered daily at approximately the same time each day The first dose will be administered in the office with a 30-minute observation period Observation period should be extended if significant AEs occur If further attention is required for the treatment of an AE and such treatment cannot be provided at the office/clinic, the patient should be transferred to an appropriate facility AIT Adverse Events SLIT Immunotherapy Tablets SCIT SLIT-T Local (0.6-58%) Redness & induration at injection site Systemic ( %) Urticaria, GI upset, wheezing, and anaphylaxis Deaths at 1 per 2.5 million injections (3.4 deaths per year) Contraindications Uncontrolled asthma Local (0.2-97%) Oral itching and discomfort Systemic (0.056%) Urticaria, GI upset, wheezing, and anaphylaxis No reported deaths Contraindications Severe, unstable, or uncontrolled asthma House Dust Mites (HDM) 1. Agency for Healthcare Research and Quality. (March 2013). Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma: Comparative Effectiveness Review. Retrieved June 2, 2016, from Allergic Rhinitis HDM High variation in prevalence between countries, regions, and individual test centers World Prevalence 1-2% of the world s population might be affected = million people European Community Respiratory Health Survey I Mean prevalence of sensitization to HDM = 21.7% 21% overall prevalence for asthma with HDM sensitization with significant interpopulation heterogeneity Latino women in the US 34-37% mean prevalence of sensitization to HDM Pediatric population in Taiwan > 80% prevalence SLIT HDM Tablets Reduce Symptoms & Improve QOL in Adults and Children 18-20% reduction in average adjusted symptom scores after 1 year of treatment (vs placebo) 1 Ocular itching, nasal congestion and pruritus, rhinorrhea, and sneezing Efficacy was maintained during AIT-free year 28% reduction in total combined rhinitis score in patients with HDM allergic asthma and rhinitis symptoms (vs placebo) 2 A significant difference was found for the total score of the Rhinitis Quality of Life Questionnaire with Standardized Activities RQLQ(S) No safety concerns were observed HDM SLIT-T is effective and safe in children Significantly smaller wheals to D. pteronyssinus after 1 year of treatment with 50:50% mixture of D. pteronyssinus and D. farinae 3 Significant differences in symptom and medication scores after 2-year of treatment 4 *HDM SLIT-T is not approved by the FDA 1. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D. Allergy 2007;62: Colloff MJ. Dust mites. (Dordrecht, The Netherlands): Springer, CSIRO Publishing; Available at: Accessed May 24, Chew GL, Reardon AM, Correa JC, Young M, Acosta L, Mellins R, et al. Indoor Air 2009;19: Sunyer J, Jarvis D, Pekkanen J, Chinn S, Janson C, Leynaert B, et al. J Allergy Clin Immunol 2004;114: (1) Bergmann KC, Demoly P, Worm M, et al. J Allergy Clin Immunol. 2014;133: (2) Mosbech H, Canonica GW, Backer V, et al. Ann Allergy Asthma Immunol. 2015;114: (3) Aydogan M, et al. Respir Med Sep;107(9): (4) Yukselen A, et al. Asian Pac J Allergy Immunol Sep;31(3):

9 Allergic Rhinitis Key Points AR is a significant medical burden Allergen identification is important Allergen skin tests are the best diagnostic test to confirm AR Intranasal corticosteroids are the mainstay of treatment for most patients that present with AR AIT is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for AR is not effective or is not tolerated SCIT is effective in the treatment of AR SLIT-T is a new, effective treatment option in AR Demonstrated safety Suitable for pediatric use Administered at home 9