ANNALS OF.AlleeAsthma_
`&Immunology—
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`Ofticial Publication of the American College of ~
`Allergy, Asthma & Immunology
`| Contents ‘ofAnnalsof Allergy, Asthma & |
`In nunology Copyright © 2004by the American00.
`College of Allergy, Asthma & Inumunyology.
`—Cover pliolalfahsan grass.
`EDITOR:Edward-J--"Connell;MD ~
`— Sorghum halépente
`fj
`Annals of Allergy, Asthma & Immunology
`Filowering1is“Tengihy,Fron THY rough
`Rochester, MN 55902
`1948Westfield Court SW>-
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`(507)261=8251-8-00am=5:00pm-MaBo eptember
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`i ;oconnell.edward@mayo.edu |_(referttopageA-4-6)
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`
`GUEST EDITORIAL
`What can we know about asthma by using administrative databases? ............::ceceeseeseeeeteeeeeee 1
`Edward Ted Naureckas, MD
`
`CME REVIEW ARTICLE
`Efficacy and safety of sublingual immunotherapy ..............ccccsccsseesseeteeeeeeeeeseesssnenseasensssanseeasenas 3
`Giovanni Passalacqua, MD; Laura Guerra, MD; Mercedes Pasquali, MD;
`Carlo Lombardi, MD and Giorgio Walter Canonica, MD
`
`REVIEW ARTICLE
`Biological control of fire ants: an update on new teChMiqUes
`David F. Williams, PhD and Richard D, deShazo, MD
`
`-......... cece esetetseteeteeseteeseteeneens iS)
`
`CLINICAL ALLERGY-IMMUNOLOGY ROUNDS
`Unusually persistent rhinorrhea in a patient with allergic rhimitis .........cesceeeseetetseteeeneeteeaens2S
`Min J. Ku, MD; Yalamanchili A. K. Rao, MD; Bernard A. Silverman, MD and
`Arlene T. Schneider, MD
`
`ORIGINAL ARTICLES
`Rates and characteristics of intensive care unit admissions and intubations among asthma-
`related hospitalizations .2...........eeeseseegeseesecesceeseesesseseesesensessassseaasecnseseaneesseneesecessensetanseeseeeesenesnens 29
`Trudy B. Pendergraft, MSPH; Richard H. Stanford, PharmD, MS; Richard Beasley, DM;
`David A. Stempel, MD; Craig Roberts, PharmD, MPA and Trent McLaughlin, PhD
`Development and validation of school-based asthma and allergy screening questionnaires in a
`TETT senemneatsnemnannss sinemamanexensconns ranean aXesRNND KEUROOOTTE Oommen seesmmmerr tye <wnmmninnns seretmninnnn cS 36
`Susan Redline, MD, MPH; Rebecca S. Gruchalla, MD, PhD; Raoul L. Wolf, MD;
`Barbara P. Yawn, MD, MSc; Lydia Cartar, MA; Vanthaya Gan, MD; Patricia Nelson, RN
`and Peter Wollan, PhD
`Efficacy and safety of mometasone furoate dry powderinhaler vs fluticasone propionate
`metered-dose inhaler in asthma subjects previously using fluticasone propionate .............049
`Andy Wardlaw, MD; Pierre Larivee, MD; Jorg Eller, MD; Donald W. Cockcroft, MD;
`Lisa Ghaly, PharmD and Alan G, Harris, MD
`
`Exhibit 1161
`Exhibit 1161
`(Continued on page A-8)
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` This material may be protected by Copyrightlaw (Title 17 U.S. 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, MD+; William J. Wheeler, PhD::;
`William E. Berger, MD, MBAS; 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 improverhinitis symptoms in patients with seasonal allergic
`rhinitis who remained symptomatic after treatment with fexofenadine.
`Methods: This was a multicenter, randomized, double-blind, placebo-controlled, 2-week study in patients with moderate-to-
`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 randomizedto treatmeat
`with (1) 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, sneezing,
`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 weeksof treatment, azelastine nasal spray (P = .007) and azelastine nasal spray plus fexofenadine (P = .003)
`significantly improved the TNSS compared with placebo. Azelastine nasal spray monotherapy was as effective as tie
`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 with
`fexofenadine and should be considered in the initial managementof patients with seasonal allergic rhinitis.
`Ann Allergy Asthma Immunol. 2004;93:154-159.
`
`INTRODUCTION
`Oral and intranasal second-generation antihistamines are
`recommendedasfirst-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 numberof prescriptions com-
`pared with patients treated with monotherapy.’ In addition,
`results of a survey of more than 1,400 secondary school
`students with allergic rhinitis indicated that 73% of the stu-
`dents used 2 or more rhinitis medications to treat their aller-
`gies, whereas only 27% used monotherapy.*
`
`* Carolina Allergy and Asthma Consultants, Raleigh, North Carolina,
`7 Allergy Research Foundation Inc, Los Angeles, California.
`+ MedPointe Pharmaceuticals, Somerset, NewJersey.
`§ Southern California Research Center, Mission Viejo, California.
`This study was supported by a grant from MedPointe Pharmaceuticals,
`Somerset, NJ.
`Received for publication January 27, 2004.
`Accepted for publication in revised form February 25, 2004.
`
`A survey sponsored by the American College of Allerzy,
`Asthma and Immunology cited inadequate symptom relief
`with second-generation antihistamines as the primary reason
`for switching medications or for using combination theravy
`by 86% of allergists and 78% of primary care physicians.
`Additionally, it was reported that 52% ofallergists and 3%
`of primary care physicians prescribed more than | oral anti-
`histamine for their rhinitis patients.* These findings suggest
`that the currently available oral second-generation antihisa-
`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 nonallerzic
`vasomotorrhinitis.°° 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 these
`patients reported using 2 or more antihistamines during the !2
`months before enrollment in the study.’ In this study, azelas-
`tine monotherapy improved nasal symptoms of rhinitis
`in
`more than 80%of patients who reported dissatisfaction with
`oral antihistamine therapy.
`
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`In a double-blind, placebo-controlled trial in patients with
`seasonal allergic rhinitis who remained symptomatic after |
`week of treatment with loratadine, azelastine nasal spray
`monotherapysignificantly improved the total nasal symptom
`complex of rhinorrhea, sneezing, nasal
`itching, and nasal
`congestion when compared with placebo.* 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
`symptoms. Forty-three percentof the patients who completed
`the study had used 2 or moreoral antihistamines during the
`12 months before enrollment. The results of this trial demon-
`strated that azelastine nasal spray is an effective treatmentfor
`patients with an inadequate responseto loratadine and is an
`alernative to switching to another oral second-generation
`antihistamine or to using multiple antihistamines. Based on
`these findings, the current study was conducted to determine
`the ability of azelastine nasal spray to improve rhinitis symp-
`toms in patients with seasonalallergic rhinitis who remained
`symptomatic 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-
`vestigational sites during the 2003 spring allergy season.
`Male and female patients 12 years and older with a minimum
`2-year 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
`perticipation 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 seasonalallergic rhinitis or significant nasal struc-
`tural abnormalities; respiratory infection or other infection
`that requires antibiotic therapy within 2 weeks of beginning
`the 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.
`Womenof child-bearing potential were excluded from the
`study if they were not using an accepted method of contra-
`ception. Women who were pregnant or breast-feeding also
`were excludedfrom participation. The use of all concomitant
`medications was discontinued before beginning the open-
`label lead-in period; oral antihistamine use was discontinued
`for a minimum of 3 days and intranasal steroid use for a
`minimum of 14 days. All patients or their guardians (if the
`patient was younger than 18 years) signed an institutional
`review board—approved informed consent agreement before
`perticipation.
`The study began with a 1-week, open-label lead-in period
`(day —7 to day 1) during whichall patients were treated with
`fexofenadine, 60-mg tablets twice daily, and recorded their
`symptomseverity scores and daily use of study medicationin
`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 1-week fexofenadine
`lead-in period. Each symptom was scored on a 4-pointrating
`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 | 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 (1) 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 eachpatient 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 repeated-measure
`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 atleast
`1 dose of study medication andhad atleast | 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.
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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 1. A total of 324 patients completed the
`2-week, double-blind treatment period. Three patients in the
`azelastine monotherapy group (1 consent withdrawal, | treat-
`mentfailure, and | protocolviolation), 3 in the azelastine plus
`fexofenadine group (2 treatment failures and | protocol vio-
`lation), and 5 in the placebo group (4 adverse events and 1
`treatmentfailure) 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, 11% were black, and 8% were
`Asian or other racial background (Table 1).
`
`Efficacy
`After 2 weeksof 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 spray
`nearly identical
`monotherapy, with statistically significant differences vs pla-
`cebo for TNSS (P = .003), rhinorrhea (P = .002), sneezir.g
`(P = .007), and itchy nose (P = .004). Although nasal
`congestion was improved with azelastine nasal spray,
`the
`differences from placebo were notstatistically significant. Tn
`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.
`
`Safety
`There wasa low incidence of adverse events in this study (Table
`3). Bitter taste was reported by 10.7% ofthe patients treated with
`azelastine nasal spray monotherapy and by 9.8% ofthe patierts
`treated with azelastine nasal spray plus fexofenadine. Nasal
`passage irritation was reported by 4.5% of the patients treated
`with azelastine nasal spray monotherapy and by 3.6% of the
`patients treated with azelastine nasal spray plus fexofenadine.
`Somnolence was reported by | 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 allergic
`rhinitis, histamine antagonists, such as azelastine, that have
`additional antiallergic or anti-inflammatory properties hay2
`advantages in the treatmentofallergic rhinitis.’ In addition to
`histamine antagonism, azelastine has demonstrated inhibitory
`effects on other chemical mediators of the inflammatory
`response,
`including leukotrienes,!°-' kinins and substance
`P,!*-!° inflammatory cytokines,'”'® and intercellular adhesio
`molecule 1.'? 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 ora!
`administration.”
`The clinical versatility of azelastine nasal spray has bee.
`demonstrated in several well-controlled clinical trials. In dou-
`ble-blind, placebo-controlled trials in patients with seasonal
`allergic rhinitis, azelastine nasal spray significantly improve!
`
`Table 1. Demographic Characteristics
`
`
`
`Azelastine nasal spray plus
`Azelastine nasal spray
`
`(n = 112)
`fexofenadine (n = 112)
`Characteristic
`Placebo(n = 111)
`
`Sex, no, (%)
`Male
`Female
`Race, no. (%)
`89 (80.2)
`90 (80.4)
`91 (81.3)
`White
`16 (14.4)
`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 35.2 (12-68) 34.5 (12-80) 35.1 (12-75)
`
`
`
`46 (41.1)
`66 (58.9
`
`40 (35.7)
`72 (64.3)
`
`42 (37.8)
`69 (62.2)
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`<AaaaaaaengNNENGIFTLIIL,HIRTPETANNINTHINNATIONSaLTTEARTO)ETONASPENOCEREAL
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`Azelastine nasal spray (n = 112)
`
`Table 2. Change From Baseline in Mean am and pm Total Nasal Symptom Scores (TNSS) and Individual Symptom Scores
`
`Azelastine nasal spray plus fexofenadine
`(n = 112)
`Placebo (n = 110)
`Mean
`P
`Mean
`Mean
`%
`
`Mean
`P
`%
`Mean
`Mean
`baseline improvement improvement value baseline improvement improvement value baseline improvement improvement
`
`%
`
`iNSS
`Mean
`AM
`PM
`Rhinorrhea
`Mean
`AM
`PM
`
`Sneezing
`Mean
`AM
`PM
`
`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
`0.44
`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
`11
`
`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
`1.68
`
`0.89
`0.45
`0.44
`
`0.83
`0.42
`0.41
`
`0.98
`0.50
`0.48
`
`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
`
`ltchy nose
`Mean
`AM
`PM
`
`Congestion
`Mean
`AM
`PM
`
`4.98
`2.53
`2.45
`
`0.76
`0.39
`0.37
`
`15.3
`15.4
`15.1
`
`214
`.153
`439
`
`5.29
`2.71
`2.57
`
`0.72
`0.36
`0.35
`
`13.6
`13.3
`13.6
`
`372
`344
`554
`
`5.08
`2.60
`2.49
`
`0.59
`0.29
`0.31
`
`11.6
`11.2
`12.5
`
`* One patient in the placebo group had no postbaseline diary data and was notincluded in the efficacy analysis.
`
`
`
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`
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`°
`
`@ Azelastine Nasal Spray + Placebo Capsule (n = 112)
`@ Azelastine Nasal Spray +Fexofenadine (n = 112)
`(1 Placebo Capsule + Placebo Saline Nasal Spray (nm = 110)
`.
`““P<.01 vs. placebo
`|
`* P<.05 vs. placebo
`aan
`aoa
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`214 og
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`wt
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`19.4
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`9.0
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`1
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`9.6
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`18-3
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`13.6
`
`114
`
`4.6
`
`
`
`Congestion
`
`Lf
`
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`.
`.
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`Figure 1. Mean percent improvement from base-
`3
`;
`i
`53
`line in total nasal symptom score (TNSS) and indi-
`fa
`al
`oy
`on
`vidual symptom scores.
`
`
`,
`;
`Rhinorrhea
`Sneezing
`ltchy Nose
`
`|
`
`|
`
`Lt
`
`TNSS
`
`_
`
`nasal and nonnasal symptomsin short-term models*!~” and
`over 2- and 4-week study periods.°>** In the placebo-con-
`trolled trial of seasonal rhinitis patients who remained symp-
`tomatic after 1 week of treatment with loratadine, azelastine
`nasal spray monotherapy wasstatistically superior to placebo
`in treating the total nasal symptom complex and was similar
`to combination therapy with azelastine nasal spray plus lora-
`tadine.® In addition, 2 placebo-controlled, double-blindtrials
`in patients with nonallergic vasomotorrhinitis demonstrated
`that azelastine nasal spray significantly improved all symp-
`toms 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 andstatistically 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 additionalclinical
`benefit was achieved by combining fexofenadine with azelastine
`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
`
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`
`
`MeanAbsoluteImprovementfromBaseline
`
`
`
`
`
`
`
`@ Azelastine Nasal Spray + Placebo Capsule (n = 112)
`
`© Azelastine Nasal Spray + fexofenodine (n = 112)
`
`© Placebo Capsule + Placebo Saline Nasal Spray (n = 110)
`
`
`
`| * 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.
`
`
`
`to
`
`+
`
`
`
`
`
`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
`
`Epistaxis
`Somnolence
`
`4.5
`
`1.8
`0.0
`
`0.9
`0.9
`
`3.6
`
`1.8
`1.8
`
`1.8
`0.9
`
`0.9
`
`0.9
`1.8
`
`0.0
`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 rhinitis’ and nonallergic vasomotor rhinitis.® In Ler-
`rick’s open-label study,’ 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.2° In an open-label pilot
`trial
`in
`patients with seasonal allergic rhinitis, azelastine nasal spray
`significantly improved nasal peak inspiratory flow rates
`within 30 minutes of initial administration and at the 7-day
`end point when compared with baseline.*° Objective mea-
`
`surement 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.*’ 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.** With aller-
`gic, nonallergic, and mixedrhinitis affecting up to 60 million
`persons in the United States annually,'’’ and considering the
`high costs of treatment,
`the use of combination treatment
`regimens may unnecessarily increase costs to patients and
`providers 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 outcomeofthis 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-
`wego, OR; Charles Banov, MD, Charleston, SC; David Bern-
`stein, MD, Cincinnati, OH; Leonard Caputo, MD, Mobile,
`AL; David Cook, MD, Danville, CA; Albert Finn, MD,
`
`a 0
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`_
`
`[EARSwastartondovetnarnelaAcEanateRormmeiAPVARASIRTNPRAALAOParatea
`
`Charleston, SC; Alan Goldsobel, MD, San Jose, CA; Fred
`Grogan, MD, Cordova, TN: Frank Hampel, MD, New Braun-
`fels, TX; Dennis Ledford, MD, Tampa, FL; Jonathan Matz,
`MD, Baltimore, MD; Brian Miller, MD, Killeen, TX; John
`Morris, MD, Louisville, KY; Bruce Prenner, MD, San Diego,
`CA; Paul Ratner, MD, San Antonio, TX: Julius Van Bavel,
`MD, Austin, TX; and Michael Welch, MD, San Diego, CA.
`
`he
`
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