ANNALS OF
`Allergy,Asthma
`& Immunology
`
`
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`Ot'ricial Pablic'ation of the American College of
`A.“rgy, Asthma & Immunology
`' Contents of Annals of Allergy, Asithmma &
`In iunology Copyright © 2004 by the American.
`College of Allergy, Asthma & [mniun'ology
`ELITOR: Edward] 0Connell, MD
`Annals of Allergy, Asthma & Immunology
`" '1948Westfield Court SW
`Rochester MN 55902
`
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`oconnell.edward@rnayo.edu
`
`
`
`GUEST EDITORIAL
`
`What can we know about asthma by using administrative databases? ........................................ 1
`Edward Ted Naareckas, MD
`
`
`CME REVIEW ARTICLE
`
`Efficacy and safety of sublingual immunotherapy ........................................................................ 3
`Giovanni Passaiaeqiia, MD; Laura Guerra, MD; Mercedes Pasqaaii, MD;
`Carlo Lombardi, MD and Giorgio Waiter Canonica, MD
`
`
`REVIEW ARTICLE
`Biological control of fire ants: an update on new techniques .................................................... 15
`David F. Williams, PM) and Richard D. deShazo, MD
`
`
`CLINICAL ALLERGY-n-IMMUNOLOGY ROUNDS
`
`Unusually persistent rhinorrhea in a patient with allergic rhinitis .............................................. 23
`Min J. Kn, MD; Yaiamanchili A. K. Rae, MD; Bernard A. Siiverman, MD and
`Arlene T. Schneider, MD
`
`
`ORIGINAL ARTICLES
`
`Rates and characteristics of intensive care unit admissions and intubations among asthma-
`related hospitalizations .................................................................................................................. 29
`Trudy B. Pendergmaft MSPH; Richard H. Stanford PharmD MS, Richard Beasley, DM;
`David A Steinpei, MD; Craig Roberts PharmD, MPA and Trent McLaughlin, PhD
`
`Development and validation of school-based asthma and allergy screening questionnaires in a
`4—city study .................................................................................................................................... 36
`Susan Rediine, MD, MPH; Rebecca 5. Grachaila, MD, PhD; Raoul L. Wolf MD;
`Barbara P. Yawn, MD, MSe; Lydia Carrar, MA; Vanihaya Gan, MD; Patricia Nelson, RN
`and Peter Wollan, PhD
`
`Efficacy and safety of mometasone furoate dry powder inhaler vs fluticasone propionate
`metered-dose inhaler in asthma subjects previously using fluticasone propionate ....................49
`Andy Wardlaw, MD; Pierre Larivee, MD; Jorg Eller, MD; Donald W. Cockr‘rofr, MD;
`Lisa Gnarly, PharmD and Alan G. Harris, MD
`
`.....
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`i
`1
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`Exhibit 1 161
`(Continued on page A-8)
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`IPR2017-00807
`IPR2017-00807
`ARGENTUM
`_ ARGENTUM __
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`

`This material may be protected by Copyright law (Title 17 0.5. Code)
`
`
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` _
`
`Efficacy of azelastine nasal spray in seasonal
`allergic rhinitis patients who remain
`symptomatic after treatment with fexofenadine
`Craig F. LaForce, MD*; Jonathan Corren, MDT; William J. Wheeler, Ptht;
`William E. Berger, MD, MBA§; and the Rhinitis Study Group
`
`
`Background: Currently available oral second~generation antihistamines do not provide adequate symptom relief for many
`allergy patients.
`Objective: To determine the ability of azelastine nasal spray to improve rhinitis symptoms in patients with seasonal allergic
`rhinitis who remained symptomatic after treatment with fexofenadine.
`Methods: This was a multicenter, randomized, double—blind, placeboecontrolled, 2-week study in patients with moderates}-
`severe seasonal allergic rhinitis. The study began with a 1—week, open-label lead-in period, during which patients received
`fexofenadine, 60 mg twice daily. Patients who improved less than 25% to 33% with fexofenadine were randomized to treatmt at
`with (I) azelastine nasal spray, 2 sprays per nostril twice daily; (2) azelastine nasal spray, 2 sprays per nostril twice daily, plus
`fexofenadine, 60 mg twice daily; or (3) placebo (saline) nasal spray and placebo capsules twice daily. The primary efficacy
`variable was the change from baseline to day 14 in the total nasal symptom score (TNSS), consisting of runny nose, sneezir g,
`itchy nose, and nasal congestion symptom scores.
`Results: A total of 334 patients who remained symptomatic after treatment with fexofenadine were included in the efficacy
`analysis. After 2 weeks of treatment, azelastine nasal spray (P : .007) and azelastine nasal spray plus fexofenadine ( = .003)
`significantly improved the TNSS compared with placebo. Azelastine nasal spray monotherapy was as effective as me
`combination of azelastine nasal spray plus fexofenadine as measured by the TNSS and individual symptoms of the TNSS.
`Conclusions: Azelastine nasal spray is effective monotherapy for patients who remain symptomatic after treatment wrth
`fexofenadine and should be considered in the initial management of patients with seasonal allergic rhinitis.
`Ann Allergy Asthma Immnnot’. 2004;93:154—l59.
`
`INTRODUCTION
`
`Oral and intranasal second-generation antihistamines are
`recommended as first-line therapy for allergic rhinitis‘; how«
`ever, patients who remain symptomatic after treatment with
`oral second-generation antihistamines frequently are pre-
`scribed other antihistamines, either alone or in combination
`
`regimens. In a study of drug utilization patterns in patients
`beginning treatment for seasonal allergic rhinitis, it was re-
`ported that nearly one third of the patients either switched
`drugs or added drugs during the study period, resulting in a
`2—fold to 3-fold increase in the number of prescriptions com-
`pared with patients treated with monotherapy.2 In addition,
`results of a survey of more than 1,400 secondary school
`students with allergic rhinitis indicated that 73% of the stus
`dents used 2 or more rhinitis medications to treat their aller-
`gies, whereas only 27% used monotherapys‘
`
`* Carolina Allergy and Asthma Consultants, Raleigh, North Carolina.
`'i Allergy Research Foundation Inc. Los Angeles, California.
`3 MedPointe Pharmaceuticals. Somerset, New Jersey.
`§ Southern California Research Center, Mission Viejo, California.
`Tins mudy unm supponed by a grant firnn hfledPohnc Phannaceuficak.
`Somerset, NJ.
`Received fin pubhcadon January 27,2004.
`Accepted for publication in revised form February 25. 2004.
`
`A survey sponsored by the American College of Aller, y,
`Asthma and Immunology cited inadequate symptom relief
`with secondegeneration antihistamines as the primary reason
`for switching medications or for using combination therapy
`by 86% of allergists and 78% of primary care physicians.
`Additionally, it was reported that 52% of allergists and 95%
`of primary care physicians prescribed more than 1 oral anti—
`histamine for their rhinitis patients.4 These findings suggest
`that the currently available oral second-generation antihis’. a~
`mines do not provide adequate symptom relief for many
`' patients.
`Azelastine nasal spray is a topically administered second-
`generation antihistamine with demonstrated efficacy in treat-
`ing symptoms of seasonal allergic rhinitis and nonallergic
`vasomotor rhinitis?6 In a large, prospective, open-label eval-
`uation of azelastine nasal spray in patients with seasonal
`allergic rhinitis and nonallergic vasomotor rhinitis, 45% Of
`3,107 patients reported having had an unsatisfactory response
`to prior treatment with oral antihistamines, and 54% of ILJSB
`patients reported using 2 or more antihistamines during the 12
`months before enrollment in the study.7 In this study, azelas—
`tine monotherapy improved nasal symptoms of rhiniti
`in
`more than 80% of patients who reported dissatisfaction with
`oral antihistamine therapy.
`
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`W
`
`In a doublerblind, placebo—controlled trial in patients with
`seasonal allergic rhinitis who remained symptomatic after 1
`wrek of treatment with loratadine, azelastine nasal spray
`monotherapy significantly improved the total nasal symptom
`ct nplex of rhinorrhea, sneezing, nasal
`itching, and nasal
`congestion when compared with placebo.8 Azelastine nasal
`spray monotherapy was shown to be as effective as the
`combination of azelastine nasal spray plus loratadine for the
`total nasal symptom complex and for each of the individual
`3:, .nptoms. Forty-three percent of the patients who completed
`the study had used 2 or more oral antihistamines during the
`1,. months before enrollment. The results of this trial demon-
`strated that azelastine nasal spray is an effective treatment for
`patients with an inadequate response to loratadine and is an
`a’ ernative to switching to another oral second—generation
`antihistamine or to using multiple antihistamines. Based on
`tl.ese findings, the current study was conducted to determine
`the ability of azelastine nasal spray to improve rhinitis symp-
`toms in patients with seasonal allergic rhinitis who remained
`s). mptomatic after 1 week of treatment with fexofenadine.
`
`METHODS
`
`This was a 2-week, multicenter, randomized, double-blind,
`placebo-controlled, parallel-group trial conducted at 21 in—
`vr stigational sites during the 2003 spring allergy season.
`Male and female patients 12 years and older with a minimum
`2Ayear history of seasonal allergic rhinitis and a documented
`positive allergy skin test result during the previous year were
`candidates for participation. Patients were excluded from
`p: rticipation for the following reasons: use of concomitant
`medications that could affect the evaluation of efficacy; any
`medical or surgical condition that could affect the metabolism
`of the study medications; clinically significant nasal disease
`other than seasonal allergic rhinitis or significant nasal struc-
`tt:"al abnormalities; respiratory infection or other infection
`that requires antibiotic therapy within 2 weeks of beginning
`th: baseline screening period; significant pulmonary disease
`and/or active asthma that requires daily medication; and
`either a history of or current alcohol or other drug abuse.
`Women of child—bearing potential were excluded from the
`study if they were not using an accepted method of contra—
`Ct ption. Women who were pregnant or breastfeeding also
`were excluded from participation. The use of all concomitant
`medications was discontinued before beginning the open—
`la'iel lead—in period; oral antihistamine use was discontinued
`for a minimum of 3 days and intranasal steroid use for a
`minimum of I4 days. All patients or their guardians (if the
`patient was younger than 18 years) signed an institutional
`review boardiapproved informed consent agreement before
`participation.
`The study began with a liweek, open—label lead—in period
`(t' .ty *7 to day 1) during which all patients were treated with
`fexofenadine, 60-mg tablets twice daily, and recorded their
`symptom severity scores and daily use of study medication in
`diary cards. Patients qualified for randomization into the
`double-blind treatment period if their total nasal symptom
`
`score (TNSS; defined as the severity score for individual
`symptoms of runny nose, sneezing,
`itchy nose, and nasal
`congestion) on day *7 was 8 or higher and improved by less
`than 25% to 33% on 3 days during the l—week fexofenadine
`leadsin period. Each symptom was scored on a 4-point rating
`scale: 0 indicates no symptoms; 1, mild symptoms; 2, mod;
`erate symptoms; and 3, severe symptoms. One of the 3 TNSS
`qualification scores (either AM or PM) during the lead-in
`period had to be recorded within 3 days of beginning the
`double-blind treatment period on day 1.
`Patients who did not meet the symptom qualification cri-
`teria or other study entry criteria on day l or who did not
`complete the diary as required were discontinued from the
`study. Patients who met
`the study entrance criteria were
`randomized to blinded treatment with ('l) azelastine (Astelin;
`MedPointe Pharmaceuticals. Somerset, NJ) nasal spray, 2
`sprays per nostril twice daily, plus placebo capsules twice
`daily; (2) azelastine nasal spray, 2 sprays per nostril twice
`daily, plus fexofenadine (Allegra; Aventis Pharmaceuticals,
`Bridgewater, NJ), 60 mg in capsules twice daily; or (3)
`placebo (saline) nasal spray, 2 sprays per nostril twice daily,
`plus placebo capsules twice daily. Patients were instructed to
`take 1 blinded capsule each morning and evening and 2
`sprays per nostril from the blinded nasal spray bottles each
`morning and 2 sprays per nostril each evening approximately
`12 hours after the morning dose.
`The primary efficacy variable was the change from base-
`line to day 14 in the TNSS, as measured by symptom scores,
`which were recorded twice daily (AM and PM)
`in the diary
`cards. The baseline score was defined as the average of the
`combined morning and evening TNSS during the lead-in
`period. The TNSS for each patient consisted of the combined
`score for all 4 symptoms (runny nose, sneezing, itchy nose,
`and nasal congestion). Baseline scores were subtracted from
`the daily TNSS to calculate the change from baseline. Change
`from baseline for each active treatment group during the
`2—week study period was compared with placebo using a
`repeated—measure analysis of variance (ANOVA) according
`to the restricted maximum likelihood estimation for mixed-
`
`effect models. The change from baseline in individual symptom
`severity scores was evaluated using a similar repeatedmeasure
`ANOVA model. The primary analysis was an intent—to-treat
`analysis that included all patients who were randomized. Miss—
`ing TNSS values in the intent-to-treat population were imputed
`using the last observation carried forward method. The safety
`analysis included all randomized patients who received at least
`1 dose of study medication and had at least 1 safety evaluation
`following drug administration. The incidence of adverse expe-
`riences was summarized for each treatment group.
`Based on the change from baseline in TNSS in previous
`studies with azelastine nasal spray, and assuming a .05 level
`of significance, 80% power, and an average difference reduc—
`tion of 1.0 unit in TNSS with a standard deviation of 2.5, a
`
`sample size of approximately 100 patients per treatment
`group was required. All inferential statistics were calculated
`at. the .05 level of significance.
`
`VOLUNH391 AUGUST,flM4
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`
`RESULTS
`
`Patient Disposition
`A total of 443 patients were screened for participation in the
`trial. Three hundred thirty-four patients were randomized to
`double-blind treatment and had sufficient postbaseline diary
`data to be included in the efficacy analyses (1 patient in the
`placebo group was excluded because of no postbaseline diary
`data). Of the 108 patients who did not qualify for random—
`ization, 54 failed to meet the inclusion and exclusion criteria
`at day *7, and 54 did not meet the minimum symptom score
`criteria at day l. A total of 324 patients completed the
`2-week, double—blind treatment period. Three patients in the
`azelastine monotherapy group (1 consent withdrawal, 1 treat-
`ment failure, and 1 protocol violation), 3 in the azelastine plus
`fexofenadine group (2 treatment failures and 1 protocol vio-
`lation), and 5 in the placebo group (4 adverse events and 1
`treatment failure) discontinued the study before completing 2
`weeks of treatment.
`
`Demographic and Pretreatment Characteristics
`
`The 3 treatment groups were comparable with regard to
`demographic characteristics and baseline TNSS. The patients
`ranged in age from 12 to 80 years, with a mean age of
`approximately 35 years. Sixty-two percent of the patients
`were female, 81% were white, 1 1% were black, and 8% were
`
`Asian or other racial background (Table 1).
`
`Efiicacy
`
`After 2 weeks of treatment, the mean percentage change from
`baseline in the overall TNSS was 18.5% with azelastine nasal
`
`spray (P = .007 vs placebo), 18.3% with azelastine nasal
`spray plus fexofenadine (P = .003 vs placebo), and 10.5%
`with placebo (saline) nasal spray (Table 2 and Figure 1). The
`mean absolute improvements from baseline and the relative
`contributions of the individual symptoms to the TNSS are
`shown in Figure 2.
`Patients treated with azelastine nasal spray monotherapy
`had statistically significant
`improvements vs placebo for
`rhinorrhea (18.6% vs 9.0%; P : .004), sneezing (21.4% vs
`9.6%; P = .006), and itchy nose (19.4% vs 11.4%; P : .04).
`Improvements in individual rhinitis symptoms in patients
`treated with azelastine nasal spray plus fexofenadine were
`
`to those seen with azelastine nasal spr:-y
`nearly identical
`monotherapy, with statistically significant differences vs pla—
`cebo for TNSS (P = .003), rhinorrhea (P = .002), sneezii g
`(P = .007), and itchy nose (P = .004). Although nasal
`congestion was improved with azelastine nasal spray,
`tlle
`differences from placebo were not statistically significant. In
`the patient global evaluation, symptom improvement was
`rated significantly better with azelastine nasal spray (P = .03)
`and azelastine nasal spray plus fexofenadine (P : .03) than
`with placebo.
`
`Safely
`There was a low incidence of adverse events in this study (Table
`3). Bitter taste was reported by 10.7% of the patients treated with
`azelastine nasal spray monotherapy and by 9.8% of the patier ts
`treated with azelastine nasal spray plus fexofenadine. Nasal
`passage irritation was reported by 4.5% of the patients treat 3d
`with azelastine nasal spray monotherapy and by 3.6% of the
`patients treated with azelastine nasal spray plus fexofenadine.
`Somnolence was reported by 1 patient (0.9%) in each of the
`azelastine treatment groups. All of the discontinuations due to
`adverse experiences were in the placebo (saline) group.
`
`DISCUSSION
`
`In view of the role of inflammatory mediators in allerg‘c
`rhinitis, histamine antagonists, such as azelastine, that have
`additional antiallergic or anti—inflammatory properties ha? 3
`advantages in the treatment of allergic rhinitis.9 In addition to
`histamine antagonism, azelastine has demonstrated inhibitOry
`effects on other chemical mediators of the inflammatorv
`
`including leukotrienes,10“3 kinins and substance
`response,
`PJ‘HE inflammatory cytokines,”-'8 and intercellular adhesio
`molecule 1.19 Further, the higher local concentrations of anti-
`histamine in the nasopharynx that can be achieved with
`topical administration may enhance any antiallergic or anti-
`inflammatory activity, resulting in a rapid onset of action and
`a lower incidence of systemic adverse effects than with or? f.
`administration.20
`
`The clinical versatility of azelastine nasal spray has been
`demonstrated in several well-controlled clinical trials. In dov—
`
`ble-blind, placebo-controlled trials in patients with seasonal
`allergic rhinitis, azelastine nasal spray significantly improve '1.
`
`Table 1. Demographic Characteristics
`
`
`
`Azelastine nasal spray plus
`Azelastine nasal spray
`
`(n = 112)
`fexofenadine (n = 112)
`Characteristic
`Placebo (n = 111)
`
`Sex, no. (94:)
`Male
`Female
`Race, no. (%)
`89 (80.2)
`90 (80.4)
`91 (81.8)
`White
`16(144)
`11 (9.8)
`11 (9.8)
`Black
`2 (1.8)
`6 (5.4)
`5 (4.5)
`Asian
`4 (3.6)
`5 (4.5)
`5 (4.5)
`Other
`
`Age, mean (range), y
`34.5 (12—80)
`35.1 (12—75)
`35.2 (12—68)
`
`40 (35.7)
`72 (64.3)
`
`42 (37.8)
`69 (62.2)
`
`46 (41.1)
`66 (58.9)
`
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`Table 2. Change From Baseline in Mean AM and PM Total Nasal Symptom Scores UNSS) and Individual Symptom Scores
`Azelastine nasal spray plus fexofenadine
`Placebo (n = 110)‘
`Azelastine nasal spray in = 112)
`
`{n = 112)
`Mean
`Mean
`%
`P
`Mean
`Mean
`%
`P
`Mean
`Mean
`“/0
`baseline improvement improvement value baseline improvement improvement value baseline improvement improvement
`
`.NSS
`Mean
`AM
`PM
`Hhinorrhea
`Mean
`AM
`PM
`Sneezing
`Mean
`AM
`PM
`itchy nose
`Mean
`AM
`PM
`’Zongestion
`11.6
`0.59
`5.08
`.372
`13.6
`0.72
`5.29
`.214
`15.3
`0.76
`4.98
`Mean
`11.2
`0.29
`2.60
`.344
`13.3
`0.36
`2.71
`.153
`15.4
`0.39
`2.53
`AM
`
`
`
`
`
`
`
`
`
`
`
`2.45 0.37 15.1 .439 2.57 0.35 13.6 .554 2.49 0.31PM 12.5
`One patient in the placebo group had no postbaseline diary data and was not included in the efficacy analysis.
`
`18.3
`18.4
`18.1
`
`18.9
`19.1
`18.6
`
`20.8
`21.3
`20.4
`
`20.9
`21.4
`20.4
`
`.003
`.002
`.017
`
`.002
`.003
`.007
`
`.007
`.010
`.024
`
`.004
`.001
`.028
`
`17.95
`9.02
`8.97
`
`4.42
`2.22
`2.21
`
`4.07
`2.02
`2.06
`
`4.40
`2.19
`2.21
`
`1.89
`0.90
`1.02
`
`0.40
`0.19
`0.22
`
`0.39
`0.19
`0.21
`
`0.50
`0.22
`0.29
`
`10.5
`10.0
`11.4
`
`9.0
`8.6
`10.0
`
`9.6
`9.4
`10.2
`
`11.4
`10.0
`13.1
`
`17.86
`8.91
`8.94
`
`4.62
`2.29
`2.32
`
`3.92
`1.92
`1.99
`
`4.34
`2.17
`2.19
`
`3.31
`1.61
`1.70
`
`0.86
`0.38
`0.49
`
`0.84
`0.41
`0.43
`
`0.84
`0.43
`0.42
`
`18.5
`18.1
`19.0
`
`18.6
`16.6
`21.1
`
`21.4
`21.3
`21.6
`
`19.4
`19.8
`19.2
`
`.007
`.008
`.014
`
`.004
`.028
`.002
`
`.006
`.013
`.013
`
`.041
`.018
`.111
`
`18.69
`9.38
`9.30
`
`4.72
`2.36
`2.37
`
`3.99
`1.97
`2.01
`
`4.69
`2.34
`2.35
`
`3.42
`1.73
`1.88
`
`0.89
`0.45
`0.44
`
`0.83
`0.42
`0.41
`
`0.98
`0.50
`0.48
`
`300A) 7,
`
`I Azelastina Masai Spray + Placebo Capsule {n E 112)
`El Azelasiine Nasal Spray +Fexufanadine {n = 11 2)
`Fl Piacebo Capsule + Placebo Saline Nasal Spray (n = 110)
`:
`.
`’"‘ P<.01 V5.13Eaceb0
`l
`“
`P“: 05 vs, placebo
`i
`. __
`**
`w
`21.4 ms
`
`_
`
`n
`203
`.
`g. .7-
`19.4 -
`
`it
`,.
`18.6 133
`"
`
`15.3
`
`1”
`
`
`
`9.0
`
`l
`
`i
`
`s 6
`-
`
`Rhinorrhea
`
`|
`
`Sneezing
`
`I
`
`11.4
`
`E
`
`‘
`1
`l
`Itchy Nose
`
`l
`l
`
`_.__.
`
`r
`
`.
`Congestion
`
`‘
`
`
`
`;
`
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`"l
`
`.
`_
`‘
`_
`Figure I. Mean pelcent Improvement trom base-
`.
`.
`,
`.
`.
`line in total nasal symptom score (TNSS) and Ind]-
`_
`_
`Viduttl symptom Stem.
`
`..
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`18.5 183
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`..
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`TNSS
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`
`
`t asal and nonnasal symptoms in short-term modelszm and
`over 27 and 41-week study periods-”334 In the placebo-con-
`t.'olled trial of seasonal rhinitis patients who remained symp—
`tomatic after 1 week of treatment with loratadine, azelastine
`
`nasal spray monotherapy was statistically superior to placebo
`i 1 treating the total nasal symptom complex and was similar
`to combination therapy with azelastinc nasal spray plus lora-
`t..dine.8 In addition, 2 placebo-controlled, double—blind trials
`in patients with nonallergic vasomotor rhinitis demonstrated
`tnat azelastine nasal spray significantly improved all symp—
`1
`'ms of the vasomotor rhinitis symptom complex, including
`nasal congestion during 3 weeks of treatment.“
`
`In the current study. 86% of the patients treated with fexofe-
`nadine for 1 week during the lead—in period remained at least
`moderately symptomatic based on the specified study entrance
`criteria. Statistically significant (P < .01) improvement in the
`TNSS and statistically significant (P < .05) improvements in 3
`of the 4 individual symptoms making up the TNSS were ob
`served when these patients were switched to treatment with
`azelastine nasal spray for 2 weeks. Further, no additional clinical
`benefit was achieved by combining fcxofenadine with azciastine
`nasal spray when compared with azelastine nasal spray as mono—
`therapy. As anticipated, bitter taste was the most common ad-
`verse event, reported by approximately 10% of the patients
`
`W
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`
`
`I Azeiastine Nasal $pray + Piacebo Capsule (n ”-“ 112)
`
`E Azeiastine Nasai Spray + fexofenodine tn =112)
`
`Cl Piacebo Capsule + Placebo Saline Nasal Spray (n = 119)
`
`
`
`
`‘ “ P<.01 vs. placebo
`* P<.05 vs. placebo
`
`
`
`
`Figure 2. Mean absolute improvement from base-
`line in total nasal symptom score (TNSS) and indi-
`vidual symptom scores.
`
`
`
`n
`
`u
`
`n *1
`0.34 0.33
`use "“39
`.:
`r".
`::-
`
`'
`0.40
`0.39
`
`
`
`MeanAbsoluteimprovementfromBaseline
`
`
`
`
`
`TESS
`
`Rhlnoniiea
`
`Sneezing
`
`ltchy Nose
`
`Congestion
`
`Table 3. Percentage of Most Commonly Reported Adverse Events
`Azelastine
`
`plus
`Azelastine,
`fexofenadine,
`Placebo,
`
`Adverse event
`(n = 112)
`[n = 112)
`(n = 111)
`Bitter taste
`10.7
`9.8
`0.0
`
`Nasal passage
`irritation
`
`Sneezing
`Headache
`
`4.5
`
`1.8
`0.0
`
`3.6
`
`1.8
`1.8
`
`0.9
`
`0.9
`1.8
`
`0.0
`1.8
`0.9
`Epistaxis
`
`
`
`0.9 0.9Somnolence 0.0
`
`treated with azelastine nasal spray; however, the incidence of
`somnolence with azelastine was less than 1%, comparable to the
`incidence in the placebo group.
`Although nasal congestion was not significantly improved
`in this study, statistically significant improvements in nasal
`congestion have been demonstrated with azelastine nasal
`spray in placebo-controlled studies in patients with seasonal
`allergic rhinitis5 and nonallcrgic vasomotor rhinitis.6 In Lere
`rick’s open-label study,7 of a subset of 1,402 patients who
`reported an unsatisfactory response to previous antihistamine
`therapy, 53% identified nasal congestion as their most both-
`ersome symptom and 80% reported that nasal congestion was
`improved after 2 weeks of treatment with azelastine nasal
`spray when compared with their prior therapy. Statistically
`significant
`improvements in nasal airway resistance during
`treatment with azelastine nasal spray have been demonstrated
`objectively using anterior rhinomanometry in patients with
`seasonal allergic rhinitis.35 in an openslabel pilot
`trial
`in
`patients with seasonal allergic rhinitis, azelastine nasal spray
`significantly improved nasal peak inspiralory [low rates
`within 30 minutes of initial administration and at the 7eday
`end point when compared with baseline.26 Objective mea-
`
`suremcnt techniques, such as rhinomanometry and nasal peak
`inspiratory flow rate, may be more sensitive indicators of the
`effect of second—generation antihistamines on nasal conges-
`tion than subjective symptom scores.
`
`CONCLUSION
`
`The economic impact of allergic rhinitis is substantial, and
`there is increased concern about the costs of treating rhinitis
`in health plans, where allergy is one of the most expensive
`categories.27 Medication costs for rhinitis therapy alone ac—
`count for as much as $2.4 billion annually, and total direct
`and indirect costs approach $6 billion annually.28 With aller-
`gic, nonallergic, and mixed rhinitis affecting up to 60 million
`persons in the United States annually/$29 and considering the
`high costs of treatment,
`the use of combination treatment
`regimens may unnecessarily increase costs to patients and
`previdcrs if it is shown that monotherapy is equally effective.
`This study demonstrated that azelastine nasal spray is
`effective as monotherapy for patients with seasonal allergic
`rhinitis who remained symptomatic after treatment with fexo—
`fenadine. The outcome of this trial, along with reSUlts of a
`trial in patients with an unsatisfactory response to loratadine,
`suggests that patients who remain symptomatic after treat—
`ment with a nonsedating, oral second—generation antihista—
`mine may benefit by switching to azelastine nasal spray
`monotherapy. Azelastine nasal spray is well tolerated, pro—
`vides effective symptom control, and should be considered in
`the initial management of patients with seasonal allergic
`rhinitis.
`
`ACKNOWLEDGMENTS
`
`Members of the Rhinitis Study Group are Dean Atkinson,
`MD, Oklahoma City, OK; James W. Baker, MD, Lake Os-
`wcgo, OR; Charles Ban0v, MD, Charleston, SC; David Bern-
`stein, MD, Cincinnati, OH; Leonard Caputo, MD, Mobile,
`AL; David Cook. MD, Danville, CA; Albeit Finn, MD,
`
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`fl
`
`Charleston. SC; Alan Goldsobel, MD, San Jose, CA; Fred
`
`(hogan, MD, Cordova, TN ; Frank Hampel, MD, New Brann-
`fels, TX: Dennis Ledford, MD, Tampa. FL; Jonathan Matz,
`MD. Baltimore, MD: Brian Miller, MD, Killeen, TX; John
`1t- ()l'l'lS, MD, Louisville, KY; Bruce Prenner, MD, San Diego,
`CA; Paul Ratner, MD, San Antonio, TX; Julius Van Bavel,
`lViD, Atlstin, TX; and Michael Welch, MD, San Diego, CA.
`
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