Allergic Rhinitis: 過敏性鼻炎 楊士維主任 基隆長庚耳鼻喉科 長庚大學助理教授
Contents Treatment of Allergic Rhinitis Nasonex clinical data in allergic rhinitis Nasonex clinical data in nasal polyposis Nasonex clinical data in nasal pediatrics Nasonex safety data Patient survey- Arthritis foundation 2
Definition and Prevalence of Allergic Rhinitis (AR) AR = IgE-mediated inflammation of the nasal mucosa AR is one of the most common chronic conditions, particularly in subjects under 18-500 million sufferers worldwide, 250 million in China - Up to 40% of children IgE = immunoglobulin E. Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):s147; Bauchau and Durham. Eur Respir J. 2004;24:758; Linneberg. BMJ. 2005:331.352; Wjst et al. PLoS Med. 2005;2:e294; Jarvis et al. J Allergy Clin Immunol. 2005;116:675. 3
Allergic Rhinitis: Common Comorbid Conditions Conjunctivitis - Prevalence ~50% Otitis media with effusion (OME) - In patients undergoing surgery, prevalence of AR is ~50% Rhinosinusitis - Prevalence of chronic rhinosinusitis >75% Pharyngitis Dental malocclusion - 4 times more common in mouth-breathers Asthma - 25%-35% of patients with AR also have asthma - >85% of patients with asthma have AR Eczema 4
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Classification of Allergic Rhinitis Intermittent symptoms <4 days per week Or < 4 weeks Persistent symptoms >4 days per week and >4 weeks Mild normal sleep normal daily activities normal work an school no troublesome symptoms Moderate-severe One or more items Abnormal sleep Impairment of daily activities, sport, leisure Problems caused at school or work Troublesome symptoms 6
Management of Allergic Rhinitis Allergen avoidance indicated when possible Pharmacotherapy safety effectiveness easily administered Immunotherapy effectiveness specialist prescription may alter the natural course of the disease Patient education always indicated Bousquet et al. Allergy. 2002;57:841. 7
ARIA Guidelines: Recommendations for Management of Allergic Rhinitis Moderate severe intermittent Mild persistent Moderate severe persistent Mild intermittent Intra-nasal steroid Local chromone Leukotriene receptor antagonists Second-generation nonsedating H1 antihistamine Intranasal decongestant (<10 days) or oral decongestant Allergen and irritant avoidance Immunotherapy ARIA = Allergic Rhinitis and its Impact on Asthma. Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):s147. 8
Congestion Is the #1 Symptom Sufferers Want to Prevent* 85% of allergy sufferers report nasal congestion Nasal Congestion Runny Nose Itchy Eyes Itchy Palate Sneezing Watery Eyes Itchy Ears Itchy Nose 12% 7% 11% 8% 8% 2% 8% 5% 4% 4% Data on file, Schering Corporation, Kenilworth, NJ. % who would most want to prevent this one symptom 17% 19% 17% 16% *Among those who experience symptom. Statistically significant difference. Caution: small base (n=69). Caution: small base (n=68). 50% Adults Children Based on a nationwide survey of 2355 self-reported people with allergic rhinitis, 2002 of whom were adult allergic rhinitis sufferers with nasal congestion or parents of a child with allergic rhinitis with nasal congestion. Data on file, Schering Corporation. 63% 10
Allergic rhinitis: ARIA treatment guidelines Congestion Rhinorrhoea Itching/ sneezing Duration Intranasal steroids +++ +++ ++/+++ 12-48h Oral antihistamines + ++ +++/++ 12-24h Oral decongestants + - -/- 3-6h Intranasal cromones + + +/+ 2-6h Anticholinergics - ++ -/- 4-12h Antileukotrienes ++ + -/- Not reported If PAR is diagnosed correctly then NIS will be prescribed instead of decongestants. Bousquet et al 2002; van Cauwenberge et al 2000 11
Congestion and Inflammation: Adverse Impact in Upper Respiratory Disease Allergic rhinitis Nasal polyps Asthma with AR Congestion Inflammation Sleep disturbance, including sleepdisordered breathing Common cold Rhinosinusitis (acute and chronic) 12
Improved Potency and Selectivity with mometasone furoate CH 2 Cl HO CH 3 C=O O O C O CH 3 CH3 Furoate 增加抗發炎效果 Cl Chlorinated 不會產生鼻黏膜萎縮 O 13
Efficacy 15
Comparison of Glucocorticoid- Receptor Binding Affinity 1400 1200 1235 Relative Binding Affinity 1000 800 600 813 400 200 258 164 100 0 MF FP BUD TAA DEX Compound Tested Smith CL, Kreutner W. Arzneimittelforschung/Drug Research. 1998;48:956 16
Mean change from baseline in total symptom score NASONEX Rapid Onset of Action: Significant Total Symptom Relief Within 5 Hours of a Single Dose in Patients with SAR 0 Change in Total Symptoms NASONEX 200 μg (n=119) -2 Placebo (n=116) -4-6 * * * * * * * * -8 * P<0.05 vs placebo. SAR =seasonal allergic rhinitis. 0 1 2 3 4 5 6 7 8 9 10 11 12 Berkowitz et al. Allergy Asthma Proc. 1999;20:167. Hours after dosing 17
Nasal Steroid Onset of Action Nasal Steroid Products NASONEX (mometasone furoate) Flixonase (fluticasone) Beconase, others (beclomethasone dipropionate) Pulmicort (budesonide) Nasacort (triamcinolone acetonide) Onset of Action Claims Within 5 hours and onward Some improvement after 12 hours, maximum relief after several days 3 days Some improvement after 24 hours, may take 3-7 days Some improvement after 12 hours, maximum improvement after 3-4 days 18
Treatment of PAR: MFNS vs. FP 550 PAR Patients Randomized Double-Blind Active-Controlled Parallel-Group Multicenter Mometasone Furoate Nasal Spray 200 mcg qd Fluticasone propionate 200 mcg qd 12 Weeks of Treatment Symptoms evaluated after 1, 2, 4, 8, and 12 weeks of treatment Mandl M, et al. Ann Allergy Asthma Immunol. 1997;79:370 19
MFNS vs. FP in PAR: Results 1.4 1.2 1 0.8 MFNS 200 mcg qd FP 200 mcg qd Placebo * * * * * * * * * * *P<0.05 vs placebo P<0.05 vs FP * * 0.6 0.4 0.2 0 Day 8 Day 15 Day 29 Week 8 Week 12 Endpoint Follow-up Mandl M, et al. Ann Allergy Asthma Immunol. 1997;79:370 20
Efficacy and Safety of Once-Daily NASONEX in Nasal Polyposis: Design of a Nordic Study A randomised, double-blind, placebo-controlled trial was conducted at 12 centres in Denmark, Finland, Norway, and Sweden 298 patients enrolled in the study had the following characteristics - At least 18 years of age - Diagnosis of bilateral nasal polyps - Clinically significant nasal congestion After a 2- to 4-week run-in period, patients were randomized to NASONEX 200 µg qd or matching placebo, administered once-daily in the morning Stjarne et al. Acta Otolaryngol. In press. 2005. Data on file, Schering Corporation, Kenilworth, NJ. 21
Patients with 1-point improvement in polyp size at end point (%) Nordic Study Results: Improvement in Polyp Size With NASONEX in Nasal Polyposis Improvement in Physician-Rated Polyp Size* at 4 Months 100 90 80 70 60 50 40 30 20 10 0 *Secondary endpoint. Stjarne et al. Acta Otolaryngol. In press. 2005. 41.4 NASONEX 200 µg qd (n=152) P=0.003 26.6 Placebo (n=139) 22
Anti-Inflammatory Activity of NASONEX in Nasal Mucosa of Patients with PAR Nasal Biopsies Before NASONEX Treatment After 12 Months of NASONEX 200 µg/day Treatment Disruption of epithelium Eosinophil infiltration Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648. Epithelium intact No eosinophil infiltration, No nasal atrophy 使用 Nasonex 一年之後, 上皮細胞的厚度並沒有變薄, 所以並不會造成 Nasal Atrophy ( 鼻腔黏膜萎縮 ) 的現象 23
Nasonex in Ped 24
Mean reduction in physicianrated total nasal symptom scores from baseline NASONEX in Pediatric Patients With PAR: Reduction in Total Nasal Symptom Scores Reduction in Physician-Rated Total Nasal Symptoms vs Baseline 0 Day 8 Day 15* Day 29 End point -1-2 -3-4 P<0.01 P=0.02 NASONEX 100 µg qd (n=190) Placebo (n=191) P=0.01 P<0.01 *Primary efficacy variable. End point = last visit during double-blind period with non-missing data. PAR = perennial allergic rhinitis. Data on file, Schering Corporation, Kenilworth, NJ. Protocol No. I96-090. 25
Mean change in height from baseline (cm) NASONEX Does Not Impair Long-Term Growth in Children 3-9 Years 8 NASONEX 100 μg od (n=49) 7 6 Placebo (n=49) 5 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 11 12 Months Schenkel et al. Pediatrics. 2000;105:E22. 26
Safety 27
Intranasal Steroids: Systemic Bioavailability Mometasone Furoate 0.1%* Fluticasone Propionate <2% (US labeling) Budesonide Flunisolide 11 % 20% to 50% Dexamethasone >80% 0 20 40 60 80 100 Bioavailability (percent) *1% intranasal bioavailability plus 43% systemic bioavailability from swallowed portion of intranasal administration. 1. Brannan et al. J Allergy Clin Immunol. 1996;97(pt 3):198; 2. Beconase PI. At: http://www.rxlist.com; 3. Rhinocort PI. At: http://www.az-air.com/phy_prod/rhinocort_prescribing_information.asp; 4. Flonase PI. At: http://www.flonase.com; 5. NASONEX PI. At: http://www.nasonex.com. 28
Plasma cortisol (μg/dl) NASONEX : No Effect on Plasma Levels of Cortisol in Adults at 20 Times the Recommended Dose Plasma Cortisol Profile Following Intranasal Administration of MFNS (NASONEX ) 20 MFNS 15 4000 μg 2000 μg 10 1000 μg Placebo 5 0 Pre-Tx 5 AM 6 AM 7 AM 8 AM 9 AM 11 AM 3 PM 6 PM 11 PM N=24 men. MFNS = mometasone furoate nasal spray. Brannan et al. J Allergy Clin Immunol. 1996;97:198. Abstract 62. 29
NASONEX : Incidence of Adverse Events* in Controlled Clinical Trials in Adult and Pediatric allergic rhinitis patients Adults and Adolescent Patients 12 years and older (%) Pediatric patients Ages 3 to 11 years (%) NASONEX 200 µg (n=2103) Placebo (n=1671) NASONEX 100 µg (n=374) Placebo (n=376) Headache 26 22 17 18 Viral infection 14 11 8 9 Pharyngitis 12 10 10 10 Epistaxis 11 6 8 9 Coughing 7 6 13 15 URI 6 2 5 4 Dysmenorrhea 5 3 1 0 Musculoskeletal 5 3 1 1 Pain Sinusitis 5 3 4 4 Vomiting 1 1 5 4 *Treatment-related adverse events occurring in 5% of subjects in any group. Epistaxis was defined as a wide range of bleeding episodes, from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. URI = upper respiratory infection. NASONEX prescribing Information, Schering Corp. 30
NASONEX offers Powerful Relief of Nasal Congestion in Upper Respiratory Diseases Enhanced Safety Profile: - Well tolerated in adult and pediatric patients - Virtually undetectable systemic bioavailability ( 0.1%) - No observed effect on HPA axis - No observed effect on growth in children - No observed nasal atrophy Targeted Control of Nasal Inflammation - Potent anti-inflammatory effects Powerful relief of congestion - Rapid onset, relief in SAR, PAR, nasal polyposis 31
NASONEX is Easy to Use 為一個健康組織擁有 4600 萬個關節炎的會員, 是全世界最大的傷殘組織. 成立於 1948 年, 總部在美國亞特蘭大, 有 45 個分會及 150 個服務據點. 也是世界上最大的私人且非營利的機構, 自 1948 年起已提供了三億八千萬美元做為研究調查的經費. 這個基金會藉由提供大眾健康教育及進行公共政策和法規的制定來改善關節炎患者的生活品質. 32
Start: 這項調查是從 2006 年 11 月開始 Patients type: 使用 Nasonex 的患者包含 1126 位成人 506 位小朋友 355 位老年人 562 關節炎患者 33
Patients Report NASONEX Easy to Use The NASONEX Nasal Spray is easy to use ( 方便使用 ) The NASONEX Nasal Spray applicator fits comfortably in the nostril 98% 97% ( 置入鼻孔內相當舒服 ) The NASONEX Nasal Spray is easy to pump/press ( 操作起來相當合適 ) The NASONEX Nasal Spray is comfortable to hold while administering a dose (or mist in the nose) ( 藥劑噴霧在鼻孔內感覺相當舒服 ) 96% 94% 50% 100% 34 Synovate Market Research, December 2006; n=1,500 Nasonex users
Conclusion 所以根據這個基金會所做的調查,Nasonex 有其他更多優點 - 如 : 氣味接受度高, 塑膠瓶設計不易摔破, 噴霧較細緻易附著在鼻黏膜上等 這個調查對患者而言 - 容易使用的 (easy to use),compliance 好, efficacy 就好 35
Nasonex 中文名內舒拿水溶性鼻用噴液劑 適應症成人 青少年及 2 歲以上兒童之季節性或常年性過敏性鼻炎亦用於治療 18 歲及以上成年人輕度到中度鼻息肉之相關症狀 用法用量 - 過敏性鼻炎 Allergic Rhinitis: 12yrs: 200 mcg/day (2 sprays/each nostril QD 2-11 yrs: 100 mcg/day (1 spray /each nostril QD) - 鼻息肉 Nasal Polyps: 18yrs: 400 mcg/day (2 sprays/each nostril, BID) 36
使用說明 拔開防塵蓋 ( 圖 A) 37
使用說明 使用前應充分振搖容器 第一次使用時, 以大拇指支撐瓶底, 食指和中指壓住瓶身白色的頸部往下壓, 以將幫浦引流 ( 圖 B) 壓 放幫浦約 6~7 次, 直到均勻的噴霧產生 此時噴霧幫浦已可使用 如果已有 14 天或更久未曾使用, 下次使用前應重新引流 38
使用說明 輕輕自鼻中吹氣以清潔鼻孔 壓住一邊鼻孔 頭部向前微傾, 持瓶身向上, 小心將噴頭伸進鼻孔 ( 圖 C) 以大拇指支撐瓶底, 食指和中指壓住瓶身白色的頸部充分一次壓到底是一個噴劑量, 噴完後自此鼻孔輕輕吸氣 39
使用說明 另一邊鼻孔重覆上述動作 將防塵蓋蓋回 另一邊鼻孔重覆上述動作 40
清洗方法 清潔噴頭時, 拔下防塵蓋, 輕輕自白色頸部將噴頭拔起, 與防塵蓋一起用冷水沖洗 待乾後將其裝回原位 41
Clinical Considerations: NASONEX Versus Other Intranasal Steroids NASONEX Flixonase Pulmicort Nasocort AQ Indicated to help treat congestion and other seasonal nasal allergy symptoms Indicated for the treatment of patients 2 years and older - - - Indicated for the treatment of nasal polyps - - Data on file, Schering Corporation, Kenilworth, NJ. Flonase [package insert]. Research Triangle Park, NC. GlaxoSmithKline; 2004. Rhinocort Aqua [package insert]. Wilmington, DE: AstraZeneca LP; 2004. Nasacort AQ [package insert]. Bridgewater, NJ: Aventis Pharmaceuticals Inc.; 2004. 42
Summary: Key point of choosing a nasal spray Affinity for glucocorticoid receptor Secetivity for glucocorticoid receptor Bioavailability Onset time Drug safety (pregnancy category) Age for use Nasal polyposis 43
Q&A 44