Allergic Rhinitis Eric J Schenkel, MD

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1 Allergic Rhinitis Eric J Schenkel, MD This activitiy is supported by an educational grant from Teva Respiratory, LLC. Disclosures: Dr. Schenkel reports relationships as a consultant and/or speaker's bureau, or as having received research grants for the following companies: Merck, Teva, Glaxo and Sunovian Upon peer review of material, there are no conflicts of interest. The speaker has attested that he understands that the audience must be made aware of products that are not yet approved or are under review or investigation, if said products are addressed during his presentation. Speaker Biographical Information: Dr. Schenkel earned his medical degree from the Albert Einstein College of Medicine in New York and completed his residency at Temple University Hospital in Philadelphia. He completed his Fellowship in Adult and Pediatric Allergy at the Hospital of the University of Pennsylvania, Philadelphia. He is Board-Certified in Adult & Pediatric Allergy & Asthma Specialist. Dr. Schenkel is Past President of the Pennsylvania Allergy & Asthma Society. He is currently the Director of the Department of Allergy at the Easton Hospital.

2 Specialist Society Speaker Series Co-sponsored by: Supported by an educational grant from: Eric J. Schenkel, MD Medical Director Valley Clinical Research Center Bethlehem, Pennsylvania Director Department of Allergy/Immunology Easton Hospital Easton, Pennsylvania Clinical Assistant Professor of Medicine Drexel University College of Medicine Philadelphia, Pennsylvania 2 Faculty Disclosures Consultant/Advisory Board: Merck, Teva Investigator: Forest, Genentech, GlaxoSmithKline, Merck, Teva Speaker: Merck, Teva 3 1

3 Learning Objectives Recognize and differentiate allergic rhinitis (AR) symptoms from other common upper respiratory conditions Formulate management plans for patients with AR according to available evidence based clinical guidelines Describe the characteristics of available therapeutic options for patients with AR Implement strategies to improve treatment adherence while considering patient preferences for therapy 4 Key Issues to Consider What are the nature of and risk factors for nasal allergies? Is the prevalence of AR changing? What are the symptoms of AR and how do we differentiate these from other upper respiratory conditions? What is the impact of AR on patients? What causes patients to become dissatisfied with their therapies for AR? Are there any recent changes in therapeutic options to address patient dissatisfaction? What barriers exist to providing effective patient care? 5 Nature of Allergic Rhinitis 6 2

4 Allergic Patients Allergic patients generally have: Early onset of symptoms (80% <age 20) Family history of allergy Symptoms: Seasonally With animal exposure Worse outdoors and/or near fresh cut grass Improve in air conditioned environments Tobacco and chemicals are not primary allergic triggers 7 Types of Non allergic Rhinitis Vasomotor rhinitis Infectious rhinitis NARES Occupational rhinitis Hormonal rhinitis Drug induced rhinitis Atrophic rhinitis Rhinitis of inflammatory/immunologic disorders Gustatory rhinitis (after eating, particularly hot/spicy foods) 8 AR Risk Factors Family history of atopy Higher socioeconomic class Unknown influence of the following on AR: Infections Animals Secondary tobacco smoke Serum IgE >100 IU/mL before age 6 years Presence of a positive allergy skin prick test IgE, immunoglobulin E. 9 3

5 Seasonal AR (SAR) SAR is caused by an IgE mediated reaction to seasonal aeroallergens (eg, grass pollen) The length of seasonal exposure to these allergens is dependent on geographic location and climatic conditions 10 Perennial AR (PAR) PAR is caused by an IgE mediated reaction to perennial environmental aeroallergens These may include dust mites, molds, animal allergens, or certain occupational allergens, as well as pollen in areas where pollen is prevalent perennially 11 General Considerations Although the terms seasonal and perennial are clinically useful, therapeutic decisions should be guided by symptom: Frequency Duration Severity Responsiveness to past and current medications 12 4

6 Burden of AR Symptoms 13 AR is the Most Common Atopic Disease in the US AR symptoms are: Self reported in ~90 million people Physician diagnosed in ~70 million people 80% of patients with AR have symptoms <age 20 AR increases steadily from age 4 (3.4%) to age 18 (27.3%) and is more common in boys AR prevalence in children is estimated to be as high as 40% Practice burden: PCPs estimated that 27% of their patients 4 to 17 years of age had AR while ENTs estimated 44% Skoner DP. J Allergy Clin Immunol. 2001;108(suppl):S2-S8. Allergies in America: A Landmark Survey of Nasal Allergy Sufferers. Executive Summary. Florham Park, NJ: Altana Pharma; Nathan RA, et al. Allergy Asthma Proc. 2008;29(6): (Burden of Rhinitis in America Survey). Meltzer EO, et al. J Allergy Clin Immunol. 2009;124:S43-S70 (Pediatric Allergies in America Survey). Kurukulaaratchy RJ, et al. Clin Exp Allergy. 2011;41: Impact on Activities: Allergy vs Non allergy Sufferers Adults with nasal allergies who reported being frequently or sometimes limited in the following due to their health vs adults without nasal allergies who reported being frequently or sometimes limited in the following due to their health (%) Not doing well at work Limited in social activities 22% 14% 21% 41% Allergic adults (N=116) Non-allergic adults (N=406) Limited in having or playing with pets 8% 24% Outdoor activities limited 21% 44% Indoor activities limited 11% 20% 0% 10% 20% 30% 40% 50% Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. 15 5

7 Impact on Sleep: Allergy vs Non allergy Sufferers Adults with nasal allergies who reported being extremely or moderately troubled in the past week due to nasal allergies vs adults without nasal allergies who reported being extremely or moderately troubled due to their health (%) Lack of a good night's sleep 11% 26% Allergic adults (N=116) Non-allergic adults (N=406) Waking up during the night 13% 31% Difficulty getting to sleep 8% 24% 0% 10% 20% 30% 40% Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. 16 Impact on Daily Life: 2006 vs % 40% 30% 20% 10% 0% 25% 21% 15% 12% A Lot Patients Impacted by Nasal Allergies (%) Moderate Amount 26% 23% 22% 19% 21% 14% Some Little Does Not Impact 2010 (N=400) 2006 (N=2,500) 1% 1% Don't Know Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. Allergies in America: A Landmark Survey of Nasal Allergy Sufferers. Executive Summary. Florham Park, NJ: Altana Pharma US, Inc; Discussion Questions How does this information aid my practice? What of this information may help you manage a patient with AR? 18 6

8 Factors that Affect Care of Patients with AR in the Real World Proper assessment of nasal symptoms and differential diagnosis Adherence to clinical practice guidelines Selection of appropriate therapy Patient adherence to prescribed medications Overcoming barriers such as: Patient refusal to adapt environment (ie, pet control) Control of allergens Providing patient education 19 Assessing & Diagnosing AR: Using the Guidelines 20 Initial Evaluation for AR: History Effective evaluation determines: Pattern, chronicity, and seasonality Response to medications Presence of comorbid conditions, occupational exposures Detailed environmental history and identification of precipitating factors Include QOL assessment for nasal and non nasal AR severity Wallace DV. J Allergy Clin Immunol. 2008;122:S

9 Physical Examination EYES Possible conjunctivitis, clear watery discharge, allergic shiners EARS (pneumatic otoscopy) Possible otitis media NOSE External appearance: possible nasal crease NASAL PASSAGES (with anterior rhinoscopy) Possible pale blue, boggy, enlarged nasal turbinates, mucus production SINUSES Possible tenderness to palpation MOUTH & THROAT Possible posterior pharyngeal cobblestoning, clear posterior nasal discharge, lymphadenopathy 22 Additional Symptom Assessments Non nasal symptom severity Eye symptoms Throat symptoms Chronic Cough Ear symptoms Headache Mental function Global QOL assessment 23 Further Testing and Evaluation Consider specialist referral for: Skin prick testing Specific IgE in vitro Fiber optic endoscopy (nasal, laryngeal, nasolaryngeal) Rhinomanometry and acoustic rhinometry Nasal provocation testing Evaluation of obstructive sleep apnea or other comorbidities Pulmonary function tests for asthma Consider in patients with rhinitis to assess the possibility that asthma is present 24 8

10 Considerations for a Differential Diagnosis of AR Nasal polyps Structural/mechanical factors Deviated septum/septal wall anomalies Adenoidal hypertrophy Trauma Foreign bodies Nasal tumors Choanal atresia Cleft palate Pharyngonasal reflux Acromegaly (excess growth hormone) Cerebrospinal fluid rhinorrhea Ciliary dyskinesia syndrome 25 Case Study #1: 19 year old Female

11 History Case Study #1, 19 year old Female: Background No current diagnosis of AR Nasal symptoms over past several years History of otitis media Previous course of antibiotics for suspected sinusitis Allergy to penicillin Never been allergen tested Current medications Over the counter (OTC) antihistamine Cold medications Nasal sprays (saline and oxymetazoline) Limited success with OTC medicines 28 Case Study #1, 19 year old Female: Current Symptoms Persistent nasal symptoms that become more severe in spring and fall Nasal congestion severe enough to cause her to breathe through her mouth Pressure in sinuses and behind ears Nasal irritation, discharge, pruritus, and congestion 29 Case Study #1, 19 year old Female: Physical Exam Results Height: 5 3 ; weight: 115 lb; blood pressure: 119/79; heart rate: 65 bpm HEENT Head: normal Eyes: red, watery Ears: normal, canals clear Nose: nares normal, septum midline, swollen, red nasal turbinates, pale mucosa with mucus production, sinus tenderness with noted drainage, no polyps, no obstructions Throat: oropharynx clear Skin exam: color, texture, turgor normal. No rashes or lesions Tests Nasal symptom severity score: 5 Positive skin prick tests for cat dander, dust mite, timothy grass, and ragweed 30 10

12 Discussion Questions Were there any other features of the patients physical exam or history that may be important in this patient s management? Was there enough clinical evidence to have started a course of antibiotic therapy for this patient? Patient describes moderate to severe nasal congestion; would you have considered other therapies before an intranasal corticosteroid (INS)? 31 Case Study #1, 19 year old Female: Assessment and Treatment Diagnosis Moderately severe PAR with seasonal increase in symptoms Possible sinusitis Pharmacotherapy INS Additional considerations for treatment Would you recommend electrostatic filter for bedroom? Would you advise patient to place mattress in polybag? Is it valuable for patient to keep windows and doors closed during pollen season? How would you advise patient to manage cat in home? Follow up visit scheduled for 2 weeks to evaluate resolution of nasal symptoms and persistence of sinusitis 32 Evidence to Promote Early Recognition and Treatment of AR 33 11

13 What is the Unified Airway Model? The respiratory tract is considered an integrated system by which local inflammatory processes and systemic mediators promote reactions throughout the airspace (ie, nasal mucosa, sinuses, lungs, middle ear, and nasopharynx). Marple BF. Am J Rhinol Allergy. 2010;24: Mechanisms Associated with the Link Between the Upper and Lower Airways CNS, central nervous system. Bergeron C, Hamid Q. Allergy Asthma Clin Immunol. 2005;1(2): Evidence Supporting The Unified Airway Model AR and asthma can occur at any time in a person s life, but AR usually precedes asthma (49% 64%) ~20% of patients with AR report asthma as a comorbidity ~80% of patients with asthma have AR Presence of AR increases the risk for asthma 3 to 4 fold during 20+ year follow up ~40% of nonasthmatic patients with AR have increased bronchial inflammation Ramsdale EH, et al. J Allergy Clin Immunol. 1985;75: ; Derebery J, et al. Otolaryngol Head Neck Surg. 2008;139(2): ; Corren J. J Allergy Clin Immunol. 1997;99:S781-S786; Bousquet J, et al. Allergy. 2008;63(suppl 86):S8-S160; Linneberg A, et al. Allergy. 2002;57: ; Thomas M. BMC Pulm Med. 2006;6(suppl 1):S4; Shaaban R, et al. Lancet. 2008;372: ; Settipane RJ, et al. Allergy Proc. 1994;15:

14 Asthma in Adults and Children With AR Diagnosed with asthma Asthma symptoms in past 12 months Respondents (%) % 20% 39% 28% 10 0 Adults With AR (N=2,500) Children With AR (N=500) Allergies in America: A Landmark Survey of Nasal Allergy Sufferers. Executive Summary. Florham Park, NJ: Altana Pharma US, Inc; Meltzer EO, et al. J Allergy Clin Immunol. 2009;124(3):S43-S70 (Pediatric Allergies in America Survey). 37 Questions to Consider At what point do you evaluate your patients with AR for asthma? How many of your current patients with AR have comorbid asthma? Do you consider AR in your patients with asthma? 38 Environmental Control and Patient Education 39 13

15 Overcoming Barriers: Environmental Control Identify triggers when possible Implement avoidance measures when practical Keep windows and doors shut Outdoor activities are best after rain Control environment (ie, dampness, mold, cockroach) Irritant avoidance (eg, smoke) Judge success by clinical parameters Reduction in patient symptoms Medication scores How do you advise your patients to control pollen, dust, and animals? 40 Pet Control Limit exposure, confine to uncarpeted room, and keep out of bedroom Wash pet regularly Replace carpet with hard surface flooring Cover bedding Remove fabric upholstered furniture Remove pet from home Wash linens in hot water Change of clothing after exposure Use vacuums with HEPA filter HEPA, high-efficiency particulate air. Wallace DV. Allergy Asthma Proc. 2009;30: Bousquet J, et al. Allergy. 2008;63(Suppl 86): Optimizing AR Pharmacotherapy 42 14

16 Nasal Congestion is the Most Bothersome Symptom of AR Itching 4% Ear pain 4% Watering eyes 5% Facial pain 7% Repeated sneezing 9% Runny nose 10% Red, itching eyes 10% Post-nasal drip 14% Headache 14% Stuffed-up nose 22% 0% 5% 10% 15% 20% 25% Allergies in America: A Landmark Survey of Nasal Allergy Sufferers. Executive Summary. Florham Park, NJ: Altana Pharma US, Inc; Patient rated Troublesomeness of Nasal Allergy Symptoms in the Last Week How troubled have you been by these symptoms during the last week? Were you not at all troubled, hardly troubled, somewhat troubled, moderately troubled, or extremely troubled? Extremely Moderately Somewhat Sneezing 5% 15% 30% Stuffy nose 6% 15% 28% Postnasal drip 12% 15% 19% Headaches 7% 12% 18% 1% Nasal bleeding 5% 2% 0% 10% 20% 30% 40% 50% 60% Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. 44 AR Pharmacotherapy Intranasal Steroids Intranasal Antihistamines Oral Antihistamines Oral Leukotriene Antagonists Decongestants (oral and topical) Allergic Rhinitis Oral Corticosteroids Intranasal Anticholinergics Intranasal Cromolyn Nasal Saline 45 15

17 Oral Antihistamines A mainstay of AR pharmacotherapy Reduce rhinorrhea, pruritus, and sneezing Generally considered ineffective for nasal congestion Rapid onset of action: 30 minutes to 3 hours Second generation antihistamines have less anticholinergic/antiserotonergic side effects than firstgeneration American Academy of Allergy Asthma & Immunology. Available at: Accessed February 2, Greiner AN, Meltzer EO. J Allergy Clin Immunol. 2006;118: Intranasal Antihistamines (INAs) Recommended as first line treatment of AR Associated with clinically significant effect on nasal congestion Reduce rhinorrhea, pruritus, and sneezing Clinically significant rapid onset of action: as early as 15 minutes Equal or superior to second generation oral antihistamines May provide added benefit when used in combination with intranasal corticosteroids Bitter taste and sedation may occur 47 SAR Symptom Reduction Over 2 Weeks With Olopatadine Nasal Spray 0 TNSS Nasal Congestion Rhinorrhea "Itchy Nose" % Change From Baseline * * * -35 *P<.05 compared with vehicle. TNSS, total nasal symptom score. Ratner PH, et al. Ann Allergy Asthma Immunol. 2005;95: * Olo 0.6% Vehicle 48 16

18 SAR Symptom Reduction Over 2 Weeks With Azelastine Nasal Spray Mean Change From Baseline Placebo (sucralose/sorbitol based) P=.04 vs placebo P<.001 vs placebo Azelastine, 0.10% (saline based) P=.013 vs placebo P<.001 vs placebo P=.004 vs placebo Azelastine, 0.15% (sucralose/sorbitol based) P<.001 vs placebo P<.001 vs placebo P=.046 vs placebo Nasal Congestion Runny Nose Sneezing Itchy Nose Results based on 2 sprays per nostril twice daily (BID) Two-week, randomized, double-blind, parallel-group study to compare the 0.10% and 0.15% azelastine sprays vs placebo in patients with SAR (N=835). Efficacy was assessed by the change from baseline in the 12-hour reflective TNSS over the entire 2 weeks of treatment. Bernstein JA, et al. Am J Rhinol Allergy. 2009;23: Leukotriene Antagonists Less effective than INSs, and not more effective than antihistamines Targets LTC4, LTD4, and LTE4 to improve nasal congestion 10 mg improves symptoms (including nasal congestion) in 86.5% of patients with AR Marked improvement in QOL in 85.2% of patients Sleepiness similar to placebo in AR Montelukast approved for asthma, SAR, and PAR Useful in patients when these disorders are comorbid LTC, leukotriene C; LTD, leukotriene D; LTE, leukotriene E. Available at: Accessed March 10, Greiner AN, Meltzer EO. J Allergy Clin Immunol. 2006;118: Virchow JC, Bachert C. Respir Med. 2006;100: Intranasal Corticosteroids (INSs) INSs are the most effective class of drugs for the treatment of AR Efficacious for rhinorrhea, itching and sneezing, and nasal congestion Reduce nasal polyps, chronic rhinosinusitis, and allergic rhinoconjunctivitis INSs are superior to antihistamines in reducing inflammation and nasal congestion, which can result in decreased: Sleep disturbance Loss of productivity INSs have been shown to be more effective than the combined use of an antihistamine and a LTRA for the treatment of SAR LTRA, leukotriene receptor antagonist

19 INSs vs Oral Antihistamines: Meta analysis Study Géhanno Bronsky Munch Schoenwetter Van Bavel Bernstein Beswick Vervloet Wood Total Nasal Symptom Score Favors INS Favors PO Antihistamine Standardized Mean Difference (SMD) Weight (%) (95% Cl) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) ( to ) χ 2 =26.82; df=8; P<.001 PO, orally; CI, confidence interval. Weiner JM, et al. Br Med J. 1998;317: Overall Score 52 INSs vs INAs: Meta analysis Study Di Lorenzo Svensson Pelucchi Stern Newson-Smith Wang Total Nasal Symptom Score SMD (95% Cl Fixed) Weight (%) SMD (95% Cl Fixed) [-2.29, -0.11] [-1.50, -0.04] [-1.30, 0.37] [-0.73, 0.07] [-0.60, 0.01] 0.55 [-0.53, 1.62] Total (95% Cl) [-0.64, -0.29] Favors INS Favors INA χ 2 =6.45, df=5, NS NS, not significant. Yáñez A, Rodrgio GJ. Ann Allergy Asthma Immunol. 2002;89: Aqueous INS Sprays Generic Drug Fluticasone propionate Flunisolide Triamcinolone Mometasone Budesonide Fluticasone furoate Ciclesonide Type Pump 120 Pump 200 Pump 120 Pump 120 Pump 120 Pump 120 Pump 120 mcg/ Spray Adult Dose 2 sp/nos qd 2 sp/nos bid to tid 1-2 sp/nos qd 2 sp/nos qd 1-4 sp/nos qd 2 sp/nos qd 2 sp/nos qd Child Dose 1-2 sp/nos qd 2 sp/nos bid 1-2 sp/nos qd 1 sp/nos qd 1-2 sp/nos qd 1 sp/nos qd 2 sp/nos qd Age Limit (SAR) Pregnancy Nursing Risk Cat. C C C C B C C Qd, every day; sp, spray; nos, nostril. The Diagnosis and Management of Rhinitis: An Updated Practice Parameter. J Allergy Clin Immunol. 2008;122:S

20 Aerosolized INS Sprays Generic Drug Beclomethasone dipropionate HFA mcg/ Spray 12 Dose <12 Dose Pregnancy Approved Formulation 80 2 sp/nostril QD Not indicated C Ciclesonide HFA 37 1 sp/nostril QD Not indicated TBD QNASL Prescribing Information. Available at: Mohar D, et al. AAAAI poster presentation. 2011:P344. Case Study #2 16 year old Male 56 Current diagnosis Case Study #2, 16 year old Male: History PAR with moderate symptoms Intermittent asthma Never been allergen tested Current medications Intranasal antihistamine 1 spray per nostril bid Short acting beta 2 agonist as needed (PRN) and before gym class 57 19

21 Case Study #2, 16 year old Male: Physical Exam Results Height: 68 Weight: 140 lb Blood pressure: 121/81 Heart rate: 74 bpm HEENT exam: Swollen, red turbinates, postnasal drip, nasal discharge, and watery/itchy eyes present (allergic shiners) Skin exam Nothing notable Respiratory exam Wheeze noted on expiration Pulmonary function tests FEV 1 : 72% predicted Asthma Control Test (ACT) score: 14 FEV 1, forced expiratory volume in 1 second. 58 Case Study #2, 16 year old Male: Current Symptoms Daily nasal and ocular symptoms that worsen during allergy seasons In the last 3 months: Needs albuterol rescue every other day, which provides only temporary relief Is fatigued during the day Has 1 to 2 nighttime awakenings per week Experiences bronchospasm with exercise Productivity is lower at school Not tolerating current nasal antihistamine spray 59 AR Pharmacotherapy Intranasal Steroids Intranasal Antihistamines Oral Antihistamines Oral Leukotriene Antagonists Decongestants (oral and topical) Allergic Rhinitis Oral Corticosteroids Intranasal Anticholinergics Intranasal Cromolyn Nasal Saline 60 20

22 Diagnosis Case Study #2, 16 year old Male: Diagnosis and Treatment PAR with moderate to severe symptoms and seasonal exacerbations Moderate persistent asthma Treatment INS and a medium dose inhaled corticosteroid Continue to use SABA and intranasal antihistamine prn Provide patient education on allergic symptoms and asthma Refer to specialist for evaluation of allergic triggers by skin prick test Schedule follow up visit in 4 weeks to review allergic triggers and evaluate effectiveness of treatment plan SABA, short-acting beta 2 -agonist. 61 Medication Tolerability & Patient Preference 62 Overview of INS Safety & Tolerability Concerns Minimal to no systemic absorption Low risk of epistaxis (5% 20%) Local side effects are typically minimal with INSs (burning, stinging, dryness) Extremely rare: Nasal perforation Hypothalamic pituitary adrenal (HPA) axis suppression Greiner AN, Meltzer EO. J Allergy Clin Immunol. 2006;118: Vining EM. Ann Otol Rhinol Laryngol Suppl. 2006;196: Greiner AN. Med Clin North Am. 2006;90: Wallace DV. J Allergy Clin Immunol. 2008;122:S1-S

23 Reasons Patients Asked Their Healthcare Provider to Change Their Medication Was not effective Had bothersome side effects Effectiveness began wearing off after time Didn't provide 24 hour relief Taste It was hard to administer Other Not sure 6% 3% 2% 1% 5% 2% 28% 57% 0% 20% 40% 60% Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. 64 Negative Attributes Reported in Patients Who Use Nasal Sprays Sensory side effects (86%) 1 Aftertaste Odor Nasal irritation Throat irritation (84%) 1 Spray runoff down the nose and/or throat (71%) 1 In the NASL survey, 1 of 3 patients (33%) who have used a nasal steroid spray in the last year named dripping down the throat as a moderately or extremely bothersome side effect 2 1. Kaliner MA. Allergy Asthma Proc. 2001;22(suppl 1):S11-S Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory. 65 Dripping Feeling and Discomfort Associated With Dissatisfaction With Intranasal Sprays Patients Very or Somewhat Satisfied (%) 100% 80% 60% 40% 20% 0% Always, most of the time, or sometimes 94% 82% 81% Taste the Medicine 96% Feel Medication Drip Back Down Throat Rarely or never 66% 92% Feel Any Discomfort From Spray Nasal Allergy Survey Assessing Limitations. Executive Summary; Available at: Sponsored by Teva Respiratory

24 Discussion Questions What factors do we consider prior to initiating an oral or intranasal therapy for AR symptoms? How often do you find that patients want to switch or discontinue their therapy due to bothersome side effects? Do you consider bothersome side effects or other patient complaints when selecting an intranasal therapy? How can we help patients remain compliant with their prescribed medication? 67 Aerosolized Formulations of INSs 68 Is There a Role for Aerosolized INSs in AR Management? Evidence suggests that patients choose whether or not to take their medications based on sensory characteristics Why patients may prefer an aerosolized INS: The device and ease of use Lack of odor or bad taste No anterior and posterior runoff leading to throat irritation and pharyngitis Less of a drippy sensation after using Why patients may prefer an aqueous (AQ) INS: Familiarity with the device May find it soothing ( moistening ) Established safety and efficacy Wide variety of available options Luskin AT, et al. Allergy Asthma Proc. 2011;32:

25 Potential Benefits of Aerosolized INSs Patient Type Polyps Olfactory disorder (mild hyposmia of AR) Presurgery Postsurgery Children and adolescents Wet AR (profuse rhinorrhea) Previously failed AQ product Bothered by side effects or cannot tolerate AQ product Potential Benefit Distribution pattern of spray Distribution pattern of spray Drying effect and distribution of spray Distribution into paranasal sinuses, may slow return of disease/inflammation Spray volume and feel Drying effect and sensation Distribution and preference may contribute to success Preference may enhance compliance Adapted from: Luskin AT, et al. Allergy Asthma Proc. 2011;32: Ciclesonide (CIC) Hydroflouroalkane (HFA) for the Treatment of SAR Randomized, double blind, placebo controlled trial of 707 patients 12 years old with SAR CIC HFA given as 80 or 160 μg once in the AM for 2 weeks Improvement in reflective total nasal symptom score (rtnss) and instantaneous TNSS (itnss) significantly greater than placebo for both doses All 4 individual nasal symptom scores were also significantly improved Ratner PH, et al. Ann Allergy Asthma Immunol. 2010;105(Poster 331):A CIC HFA for the Treatment of PAR: Changes in TNSS Weekly Change in rtnss Time, Weeks LS Mean Change From Baseline * CIC-HFA 74 µg CIC-HFA 148 µg Placebo Error bars represent standard error of the least squares (LS) means. P<.001, P<.01, *P<.05 versus placebo. Mohar D, et al. AAAAI poster presentation. 2011:P

26 CIC HFA for the Treatment of PAR: Treatment Emergent Adverse Events (AEs) CIC HFA 74 µg (N=298) CIC HFA 148 µg (N=505) Placebo (N=307) Overall Treatment emergent AEs, n (%) 106 (32.0) 123 (24.4) 57 (18.0) Oropharyngeal pain 6 (2.0) 8 (1.6) 5 (1.6) Sinus headache 3 (1.0) 3 (0.6) 6 (2.0) Headache 18 (6.0) 11 (2.2) 5 (1.6) Nasopharyngitis 3 (1.0) 10 (2.0) 10 (3.3) Upper respiratory tract infection 14 (4.7) 20 (4.0) 5 (1.6) Blood tinged mucus 14 (4.7) 23 (4.6) 10 (3.3) Instillation site discomfort 7 (2.3) 8 (1.6) 0 Nasal discomfort 7 (2.3) 13 (2.6) 1 (0.3) Sinusitis 2 (0.7) 6 (1.2) 6 (2.0) Nausea 6 (2.0) 3 (0.6) 0 Reported by 2% of patients in any treatment group. 73 Mohar D, et al. AAAAI poster presentation. 2011:P344. Beclomethasone Dipropionate(BDP) HFA for the Treatment of SAR Randomized, double blind, placebo controlled trial of 340 patients 12 years old with SAR BDP HFA (320 μg [160 μg/nostril]) given once daily for 2 weeks Improvement in total: Nasal symptom score was significantly greater than placebo Ocular symptom score that was significantly greater than placebo Individual nasal and ocular symptom scores also significantly improved Improvement was evident as early as day 2 van Bavel J, et al. Ann Allergy Asthma Immunol. 2010;105(Poster 344):A121. van Bavel J, et al. Ann Allergy Asthma Immunol. 2011;107(Poster 357):A BDP HFA for the Treatment of PAR: Improvements in Individual Nasal Symptom Scores Reflective Instantaneous 0.0 Nasal Congestion Nasal Itching Rhinorrhea Sneezing Nasal Congestion Nasal Itching Rhinorrhea Sneezing Change From Baseline * -0.21* -0.20* * P<.003 for all 1.0 *LS mean treatment difference from placebo. Meltzer EO, et al. Allergy Asthma Proc Epub ahead of print * * BDP-HFA 320 µg/day (n = 232) * -0.21* Placebo (n = 234) 75 25

27 BDP HFA for the Treatment of PAR: Treatment Emergent AEs Treatment emergent AEs of 1% in Either Treatment Group. Adverse Event, n (%) Nasal discomfort Epistaxis Headache Upper respiratory tract infection Sinus headache Oropharyngeal pain Worsening AR BDP HFA 320 µg/day (n = 236) 14 (5.9) 4 (1.7) 3 (1.3) 3 (1.3) 3 (1.3) 2 (0.8) 0 Placebo (n = 238) 12 (5.0) 4 (1.7) 5 (2.1) 4(1.7) 0 4 (1.7) 5 (2.1) Meltzer EO, et al. Allergy Asthma Proc Epub ahead of print. 76 Satisfaction with Ease of Use of Aerosol Nasal Device vs Other Nasal Sprays Subjects (%) 70% 60% 50% 40% 30% 65.4% Somewhat satisfied or very satisfied Neither satisfied or unsatisfied Not satisfied at all or not very satisfied No response/not applicable 29.3% 20% 10% 0% The majority of subjects (65.4%) reported satisfaction with the ease of use with the nasal aerosol device compared with other nasal sprays used in the past. (N=466) Gross G, et al. AAAAI poster presentation. 2011:P % 2.1% Ease of Use 77 Current Guidelines Recommend INS As First line Treatment for AR Joint Task Force s Updated Practice Parameter states that INS are: The most effective class for continuous symptoms of AR Effective for the treatment of nasal congestion, rhinorrhea, itching, and sneezing Recommended for continuous use (defined as use over time on a regular basis) More effective than antihistamines in reducing inflammation and nasal congestion More effective than the combined use of an antihistamine and a leukotriene receptor antagonist 78 26

28 Patient Education 79 Guideline Recommendations: Patient Education Education of patient and caregivers is key to promoting adherence and optimizing AR treatment outcomes Basic element in patient follow up plan Education may include: Avoidance of environmental triggers Chronicity of rhinitis Institution of environmental control measures Medication benefits/side effects and importance of adherence Realistic expectations of treatment Availability of allergen immunotherapy 80 Guideline Recommendations: Encourage Compliance Written rhinitis action plan Medications and steps to take Treatment plan should be developed jointly with patient and family Take into account school or work schedule Patient preference (liquid, pill, spray) Realistic goals for environment modification What to do in the event of increased symptoms Long term management of nasal symptoms 81 27

29 Summary: Strategies for Improved Care Patients with AR should be evaluated for asthma and vice versa Goal of therapy is to reduce symptoms of AR by controlling underlying inflammation in the upper and lower airways Therapy chosen should be weighed by symptoms, treatment effectiveness, safety, and patient preference/experience INS are the most effective class of drugs for the treatment of AR Patient education and planning is a critical part of management 82 Questions & Answers 83 Thank you! 84 28

30 Nonallergic Patients Nonallergic patients generally have: Later onset of symptoms (70% >age of 20) No family history of allergy Tobacco smoke and chemicals primary excitants Weather changes provoke symptoms No seasonal aspect to symptoms No symptoms with exposure to dust No symptoms with exposure to animals 85 Episodic and Mixed Rhinitis Episodic rhinitis is a newer rhinitis category Allergic nasal symptoms elicited by sporadic exposures to inhalant aeroallergens Recommended treatment: INS as needed Mixed rhinitis is a combination of AR and nonallergic rhinitis Noted in approximately 44% 87% of patients with AR Mixed rhinitis is more common than either pure AR or nonallergic rhinitis AR severity ranges from mild and intermittent to seriously debilitating 86 Nasal Symptom Severity Assessment 87 29

31 Asthma Is Often Uncontrolled in Patients with AR Non-sufferers Mild AR Moderate/Severe AR Patients (%) % 28.6% 49.9% 20 0 Uncontrolled Asthma* *Indicated by Asthma Control Test (ACT) score <20. Derebery J, et al. Otolaryngol Head Neck Surg. 2008;139(2): (Burden of Rhinitis in America Survey). 88 Patients with AR Have Asymptomatic Lung Involvement 80 Lung Involvement in Patients with PAR (N=100) 72% Patients (%) % FEV 1 <80% PAR=perennial allergic rhinitis FEV 1 =forced expiratory volume in 1 second; FEF 25%-75% =forced expiratory flow mid expiratory phase. Ciprandi G, et al. Int Arch Allergy Immunol. 2004;133: % Reduced FEF 25%-75% Increased Bronchial Hyperreactivity 89 Increased Bronchial Impairment Correlates with Increased Nasal Inflammation FEV 1, % Predicted P<.001 r=-0.94 P<.001 r=-0.91 Nasal Airflow FEV 1, % Predicted P<.001 r= Nasal Eosinophils Nasal Airflow Relationship between nasal Relationship between nasal Relationship between nasal eosinophils and FEV 1 eosinophils and nasal airflow airflow and FEV 1 Ciprandi G, et al. Ann Allergy Asthma Immunol. 2004;93:

32 FEF in Patients with AR by Degree of Bronchial Hyperreactivity Larger Proportion of AR Patients with Severe Bronchial Hyperreactivity Have FEF 25%-75% 65% N=4781 Ciprandi G, et al. Allergy Asthma Proc. 2011:32:e4 e8. 91 Improved Control of Respiratory Symptoms with INS 20 subjects with AR and mild asthma were randomized to a 14 days of intranasal budesonide 100 μg, 1 puff per nostril twice a day, or placebo Percent eosinophils fell significantly (P=0.002) Changes were associated with improved ACT score (P=0.04) The improved control of respiratory symptoms obtained with intranasal budesonide may be mediated by functional changes in the peripheral airways Scichilone N, et al. J Asthma. 2011;48(1): INS Improves AR, Asthma, and Bronchial Reactivity Baseline Beclomethasone Dipropionate (Aqueous) Placebo * *P<0.05 BDP vs placebo after 4 weeks of treatment * 1 0 Rhinitis Scores Asthma Scores Geometric Mean PC 20 Methacholine Watson WT. J Allergy Clin Immunol 1993;91:

33 Guideline Recommendations by Symptom Severity STEP 1 Episodic: Decongestant (nasal, oral) Antihistamine (oral, nasal) Eye drops Intranasal corticosteroid Cromolyn Ipratropium STEP 2 Mild (1 medication): Intranasal corticosteroid Antihistamine (oral [D], nasal) Montelukast Ipratropium First line therapies: Intranasal corticosteroids Intranasal antihistamines STEP 3 Mild-moderate (2 medications or change medication): Intranasal corticosteroid Antihistamine (oral [D], nasal) Montelukast Ipratropium STEP 4 Moderate to severe (2 3 medications and/or change medications): Intranasal corticosteroid Antihistamine (oral [D], nasal) Montelukast Ipratropium STEP 5 Severe Oral corticosteroid 94 Consensus Panel Recommendations for the Treatment of AR Katial RK, et al. Ann Allergy Asthma Immunol. 2011;106(2 Suppl):S CIC HFA for the Treatment of PAR: Effect on HPA Axis Change from Baseline in Serum Cortisol Values at 6 Weeks (PP Population) Serum Cortisol AUC (0-24h), µg.h/dl Treatment Difference vs Placebo CIC-HFA 282 µg CIC-HFA 148 µg Error bars represent 95% conficence interals. CIC-HFA=Cicleosnide hydrofluoalkane nasal aerosol; AUC=Area under the curve. Hampel F, et al. AAAAI poster presentation. 2011;P

34 A Baseline Geometric Mean Concentration (µg/dl) BDP HFA for the Treatment of PAR: Effect on HPA Axis Geometric mean serum cortisol concentration-time profile by treatment at (A) baseline and (B) week 6 (PP population). B 24 Serum Cortisol Concentration-Time Profile at Baseline 24 Serum Cortisol Concentration-Time Profile at Week Week 6 Geometric Mean Concentration (µg/dl) Time (hours) Time (hours) Placebo BDP HFA 320 µg/d Placebo/Prednisone 10 mg/d Ratner PH, et al. AAAAI poster presentation. 2011;P