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`2 The Journal of Family Practice,~Vol. 4 7, No; t(July); 19§8
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`L
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`

`

`ORIGINAL RESEARCH
`
`A Comparison of the Efficacy of Fluticasone
`Propionate Aqueous Nasa~ Spray and Loratadine,
`Alone and in Combination, for the Treatment of
`Seasonal Allergic Rhinitis
`Paul H. Ratner, MD; Julius H. van Bavel, MD; Bruce G. Martin, DO; Frank C. Hampel.,_ Jr., MD;
`William C. Howland, III, MD; PaulaR. Rogenes, PhD,' RonaldE. Westlund;Brian W. Bowers, PharmD;
`and Cindy K .. Cook
`San Antonio, Austin, and New Braunfels, Texas; and Research Triangle Pa_.r,k, North Carolina
`
`BACKGROUND. Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasoR(cid:173)
`al allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely
`been evaluated. This study was designed to compare the efficacy, safety, and impact on quality of life of fluticas(cid:173)
`one propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous
`nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in
`south central Texas.
`
`_METHODS. Bix hundred pafamts with seasonaJ~llergic rhinitis were tregjEld_ for 2 weeks with either FP ANS
`200 µg once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a
`multicenter, randomized, double-blind, double-dummy, parallel-group study.
`
`RESULTS. Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy
`and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups
`compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in
`clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus lorata(cid:173)
`dine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated
`symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life
`Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001 ) in quality of life in the
`FP ANS group than in the group of patients receiving loratadine only or placebo, and no significant benefit was
`demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual
`drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adv.erse events
`profile or frequency.
`
`CONCLUSIONS. In the treatment of seasonal allergic rhinitis, FP ANS is superior to loratadine and placebo, and
`adding loratadine to FP ANS does not confer meaningful additional benefit.
`
`KEY WORDS. Rhinitis, allergic, seasonal; loratadine; antihistamine; fluticasone propionate aqueous nasal spray
`[non-MeSH]. (J Fam Pract 1998; 47:118-125)
`
`I ntranasall.y administ. ered corticosteroids and
`
`nonsedating, second-generation oral antihista(cid:173)
`mines currently form the core of pharma(cid:173)
`cotherapy for seasonal allergic rhinitis. 1
`2 Both
`treatments have been shown to alleviate or sig(cid:173)
`nificantly reduce the rhinorrhea, sneezing, and nasal
`itching characteristics of allergic rhinitis.2 While
`intranasal corticosteroids reduce nasal blockage
`more effectively than oral antihistamines, 1 antihista-
`
`•
`
`Submitted, revised, May 7, 1998. From Sylvana Research, San
`Antonio, Texas (P.H.R.); Allffrgy Associates of Austin
`Diagnostic Clinic (J.H. V.) and HealthQuest Research (WC.B),
`Austin, Texas; Southwest Allergy and Asthma Research
`Center, San Antonio, Texas (B.G.M); and Central Texas
`Health Research, New Braunfels (EC.H.); Gla.xo Wellcome Inc,
`Research Triangle Park, North Carolina (R.E. W., B. W.B.,
`'·
`P.R.R., C.KC.). Requests for reprints should be addressed to
`Paul H Ratner, MD, Sylvana Research, 7711 Louis Pasteur
`-Drive-; Suite 406, · San Antonio, TX 78229.
`
`mines tend to have a more pronounced effect on eye
`symptoms.1-3 The cho.ice of ohe mode of pharrna·
`cotherapy over the other is generally based on patient
`preference, with the goal of achieving the most effec(cid:173)
`tive control of rhinitis symptoms with the fewest side
`effects.
`One currently available intranasal corticosteroid
`preparation, fluticasone propionate aqueous nasal
`spray (FP ANS) (Flonase Nasal Spray, 0.05% w/w,
`Glaxo Wellcome Inc, NC); was developed to provide a
`high ratio of local anti-inflamrt].atory to systemic activ(cid:173)
`ity. <-7 In clinical trials of 2 to 4 weeks' duration com·
`paring FP ANS with ,oral antihistamines, FP ANS
`demonstrated significantly greater effectiveness than
`loratadine s.u terfenadine 12·14 astemizole 15 and ceti·
`'
`'
`'
`.
`rizine 16 in relieving nasal symptoms of rhinitis.
`Drouin and colleagues17 have suggested that the
`concomitant administration of an intranasal corticos·
`teroid regimen. with an oral aritiliistamine regimen
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`118 The Journal of FmnilyPractice, Vol. 47, No. 2 (Aug), 1998
`
`I
`
`© 1998 Appleton & Lange/ISSN 0094-3509 t .. A
`
`

`

`FLUTICASONE VS LORATADINE IN RHINITIS
`
`medication received both a placebo nasal spray and
`active ~oral medication, and patients randomized to
`active nasal spray received both the active nasal spray
`and placebo oral medication. At the screening visit,
`clinicians evaluated potential study candidates by rat(cid:173)
`ing their nasal symptoms (sneezing, nasal blockage,
`rhinorrhea, and nasal itching) according to a visual
`analog.scale, ranging from 0 (absent) to 100 (severe), 21
`and by completing the following: a medical history,
`skin testirig for allergy to mountain cedar allergen (if
`not done within previous 12 months), a physical exam(cid:173)
`ination, clinical laboratory tests, pregnancy test, and
`an examination of the nose and oropharynx for evi(cid:173)
`dence of Candida. Patients who had symptoms began
`the 7~ to 30-day run-in period immediately after screen(cid:173)
`ing, and patients ·who were free of symptoms were
`instructed to record their allergy symptoms associated
`with mountain cedar as soon as they began, so that the
`run-in period could be initiated.
`During the run-in period and throughout the study,
`patients used the visual analog scale described above
`to rate their nasal symptoms daily on diary cards.
`-Symptoms were rated in the evening to represent
`symptoms for the entire day. To quall.fy for enrollment,
`the total nasal symptom score (derived by adding indi(cid:173)
`vidual symptom scores for nasal blockage, rhinorrhea,
`sneezing, and nasal itching for the day) was required to
`be at least 200 of a possible 400 on 4 of the 7 days
`immediately preceding enrollment.
`Patients who met this criterion were randomly
`assigned on day 0 (baseline) to receive one of four reg(cid:173)
`imens for 14 days: FP ANS 200 µg (two 50-µg sprays
`per nostril) plus one placebo capsule {to match the
`loratadine dosing form) once daily at 8 AM; placebo
`nasalspray (two sprays per nostril) plus one encapsu(cid:173)
`lated loratadine 10-mg tablet once daily at 8 AM; FP
`ANS 200 µg (two 50-µg sprays per nostril) plus one
`encapsulated loratadine 10-mg tablet once daily at 8
`AM; placebo spray (two sprays per nostril) plus one
`placebo capsule once daily at 8 AM. The formulation of
`loratadine used for encapsulation was Claritin tablets
`(Schering Corporation, Kenilworth, NJ). Dissolution
`testing confirmed that active capsules were compara(cid:173)
`ble with unencapsulated tablets.
`
`EFEICACY ANALYSIS
`Patients recorded their nasal symptoms and use of
`study medication daily on diary cards thr6ughoutthe
`treatment phase. Nasal symptorris were assessed by
`the clinician on day 0 (before the first dose of drug was
`administered), day 7, and day 14. During the treatment
`period, patients were not permitted to use any other
`medication that might affect rhinitis symptoms. At
`every clinic visit, clinicians recorded the occurrence of
`adverse events ( defined as any untoward medical
`occurrence, drug-related or not), recorded concomi(cid:173)
`tant medications used, checked compliance by diary
`
`The Journal of Family Practice, Vol. 47, No. 2 (Aug), 1998 119
`
`r
`I
`
`theoretically should result in greater relief of both
`nasal and ocular rhinitis symptoms than is achievable
`with either regimen alone. Although several clinical tri(cid:173)
`als have evaluated
`the efficacy of intranasal
`beclomethasone dipropionate in combin.ation with an
`oral antihistamine, 11
`19 and one study has investigated
`•
`I an FP ANS-cetirizine combination, 20 there have been
`I no studies to date evaluating a combination of FP ANS
`· and-loratadine. The purpose of the present study was
`f
`. to compare the efficacy, safety, and impact on quality
`j of Jife of FP ANS, loratadine, FP ANS combined with
`ioratadine, and placebo over·~ 2-week period in the
`treatment of nasal symptoms of seasonal allergic rhini(cid:173)
`tis due to mountain cedar pollen.
`
`1UiwU•111:-1.
`
`PATIENTS
`Male and nonpregnant female outpatients, aged 12
`years or older, were eligible for the study if they had
`moderate to severe seasonal allergic rhinitis diagnosed
`according to four criteria: ( 1) positive ( a 2+ reaction,
`scored on a sc;:tle of 0 to 4, defined as a wheal diame(cid:173)
`ter at least 3 mm greater than diluent control) skin test
`reaction to mountain cedar (Juniperus ashei) allergen
`
`L
`
`a run:-in. Patients were ineligible for the study if they
`
`i within 12 months; (2) appearance of the nasal mucosa
`I consistent with a diagnosis of seasonal allergic rhini(cid:173)
`tis; (3) a history of seasonal onset and offset of symp-
`1 toms for at least two previous mountain cedar pollen
`i seasons; and ( 4) moderate to severe symptoms of
`It rhinitis evidenced by patient diary card ratings during
`I had received, before the screening visit, treatment
`,, with loratadine within 1 week, astemizole within 6
`t weeks, cromolyn sodium within 2 weeks, over-the(cid:173)
`! counter or prescription medications that •Could affect
`1 rhinitis symptomatology (eg, nasal decongestants)
`
`within 72 hours, or inhaled, intranasal, or systemic cor~
`ticosteroids within 1 month. Patients could not have
`( either a septal deviation (>50% blockage) or a nasal
`
`11
`
`I polyp that could obstruct penetration of an intranasal
`
`spray. Patients were not included if they had a history
`of nasal septal surgery or nasal septal perforation.
`Patients were excluded if they had clinically signifi(cid:173)
`cant physical examination findings at screening, had
`evidence of candidal infection, .or were pregnant or
`lactating: Patients were also excluded if they had any
`condition or impairment that might affeet their ability
`to complete the study or provide informed consent.
`I
`.
`I STUDY DESIGN
`The protocol for this double-blind, placeboacontrolled,
`Parallel-group comparative trial was approved by an
`institutional review board for each of the five study
`sites. All patients or · their guardians gave written
`
`design in which patients randomized to active oral
`
`I informed consent. This study was a double-dummy
`l
`
`

`

`FLUTICASONE VS LORATADINE IN RHINITIS
`
`.card and .capsule counts, and exam(cid:173)
`ined patients for evidence of nasal
`and oropharyngeal Candida. On day
`14, clinicians and patients indepen(cid:173)
`dently recQrded their overall evalua~
`tion of treatment, and patients under(cid:173)
`went a final physical examination.
`
`TABLE 1
`
`Demographic Characteristics and Disposition of Pat_ients
`
`Placebo _ Loratadine*
`
`FPANS
`F~ANS* + Loratadine*
`
`Number of patients
`
`150
`
`150
`
`150
`
`150
`
`Mean age, yr
`Range
`
`Sex, no.(%)
`Male
`Female
`
`Ethnic origin, no. (%)
`White
`Hispanic
`.Other
`
`Compliancet (%)
`With capsule
`With spray
`
`Patients withdrawn, no. (%)
`Adverse event
`Failed to return
`Lack of efficacy
`Other
`
`42.0
`16-74
`
`-1:D.i
`15-70
`
`40.7
`13-80
`
`61 (41)
`89 (59)
`
`. 69 (46)
`81 (54)
`
`68 (45)
`82 (55)
`
`115 (77)
`30 (20)
`5 ( 3)
`
`110 (73)
`28 (19)
`12 ( 8)
`
`117 (78)
`22 (15)
`11 ( 7)
`
`97.5
`97.9
`
`10 (7)
`3 ( 2)
`2 ( 1)
`4 ( 3)
`1 ( 1)
`
`97.0
`96.8
`
`8 ( 5)
`2 ( 1)
`0 (0)
`3 ( 2)
`3 ( 2)
`
`97.8
`97.9
`
`8 (5)
`3 (2)
`0(0)
`4 (3)
`i (<"1)
`
`42.2
`15-78
`
`74 (49)
`76(51)
`
`120 (80)
`26 (17)
`4 (3)
`
`98.0
`98.2
`
`5 ( 3)
`0 ( 0)
`1 (<1)
`2 ( 1)
`2 ( 1)
`
`QUALITY-OF-LIFE ANALYSIS
`At baseline and on day 14, patients
`completed the Rhinoconjunctivitis
`Quality
`of Life Questionnaire
`(RQLQ). 22 This 28-item, self-adminis(cid:173)
`tered, disease-specific questionnaire
`measures quality of life globally. and
`across
`seven different domains
`known to be affected by rhinocon- _
`junctivitis: nasal symptoms; eye
`symptoms; activities; practicl)..l prob(cid:173)
`lems; sleep; emotional issues; and
`symptoms other than those involving
`the nose or eye, such as fatigue, irri(cid:173)
`tability, and tiredness. Patients were
`asked to rate each item on a 7-point
`scale (where O = not troubled or none
`of the time and 6 = extremely troubled
`or l;!.lL"of the time), capturing the
`• FP ANS = fiuticasone propionate aqueous nasal spray 200 µg daily; loratadine dosage is 1 0 mg once_
`impact of rhinoconjunctivitis for each
`~~
`item over the previous 7 days. Each
`t Percent of patients who took at least 80% of study medication.
`domain provides a scale i:;core, and
`' - - - - - - - - -~ -
`the mean of all the items provides an
`with respect to sex, ethnic origin, childbearing poten· [
`overall global score. An improvement in rhinoconjunc(cid:173)
`tial, pregnancy status, type of birth control used, and
`tivitis quality of life was indicated by a decrease in
`clinician- -and patient-rated overall ev::iluations. The
`domain and global srores at day 14.
`analysis of variance F test was used to compare differ·
`ences with respect to age, sex, ethnic origin, and indi·
`vidual and total clinician- and patient-rated symptom
`scores. In the RQLQ, descriptive statistics were used .
`to evaluate differences among treatment _ groups ror
`baseline scores, and descriptive and inferential statis·
`tics were used to compare the mean change from base(cid:173)
`line RQLQ scores among and between the four treat(cid:173)
`ment groups.
`Safety measures included the incidence · of poten·
`tially drug-related adverse events. Fisher's exactTest
`was performed on pairs of treatments to detect differ(cid:173)
`ences in the number of patients with potentially ctrug·
`related adverse event~ overall and by body system.
`
`I
`
`'
`
`, -I
`
`PATIENT CHARACTERISTICS
`Six hundred pati_ents were enrolled in the study, and
`569 (95%) completed it. Eight patients discontinued
`the study because of adverse events, 13 withdrew
`·because of lack of efficacy, and seven withdrew for
`other reasons. Demographic charactertstics and corn-
`
`STATISTICAL ANALYSIS
`All patients randomly assigned to treat;ment received
`at least one dose of the study dtug, and reported base(cid:173)
`line scores were included. in the analysis.· Patients
`remained in the analysis (daily and weekly timepoints)
`until their efficacy scores were missing because of
`withd_rawal or loss to follow-up. All tests performed
`tested two-sided hypotheses, and a difference was con(cid:173)
`sidered statistically significant when the two-tailed P
`value was s.05. Efficacy measures were changes in
`mean clinician- and patient-rated nasal symptoms
`(both total and individual nasal symptom scores), and
`frequency of patient- <!lld clinician-scored ratings of
`overall response to treatment. It was estimated that
`150 patients per treatment arm would provide approx(cid:173)
`imately 80% power to detect a difference between
`active treatments of at least 30 in mean change from
`baseline in clinician-rated and patient-rated totalnasal
`symptom scores at a significance level of .05.
`Demographic and baseline disease characteristics of
`patients were summarized by treatment group. The
`chi~squate test was performed to compare differences
`
`1_20 The Journal of Family Practice, Ver 47; No. 2 (Aug), 1998
`
`

`

`-
`
`--
`
`-
`
`FLUTICASONE VS LORATADINE IN RHINITIS
`
`pliance rates were similar among the
`·treatment
`groups
`(Table
`1).
`Approximately 90% of the patients
`enrolled were recruited from the
`offices of primary care physicians or
`were under no medical care for their
`rhinitis symptoms. Less than 10% of
`the patients enrolled in the study
`were recruited from the practices of
`allergists who particip;;tted in the
`study.
`
`EFFICACY DATA
`Nasa( Symptoms. Scores. A,t base(cid:173)
`line, mean clinician-rated total nasal
`symptom scores were not signifi(cid:173)
`cantly different between treatment
`groups. At clinic visits after 1 week
`of therapy (day 7), clinician-rated
`total nasal sympto:m scores were sig(cid:173)
`nificantly lower (P < .001) in the FP
`ANS and FP ANS plus loratadine
`groups than in the loratadine only or
`placebo groups (Figure 1). At these
`timepoints, loratadine did not differ
`significantly from placebo aqueous
`nasal spray, ~and the FP ANS plus
`loratadine combination did not dif(cid:173)
`fer from FP ANS monotherapy
`(Table 2). After 2 weeks of therapy
`(day 14), total nasal symptoms were
`even further reduced hi all treatment
`groups, with significantly lower
`scores in the FP ANS and FP ANS
`plus loratadine groups than in the
`loratadine or placebo groups. Again,
`loratadine did not differ significantly
`from placebo and there was no dif(cid:173)
`ference between the FP ANS plus
`loratadine combination and FP ANS
`monotherapy.
`The data for clinician-rated indi(cid:173)
`vidual nasal symptoms were similar
`to the total nasal symptom data
`(Table 2). At both the day 7 and day
`14 assessments, scores in the FP
`ANS and FP ANS plus loratadine
`groups were significantly lower (P ~
`.05) than loratadine alone and place(cid:173)
`bo group scores for blockage, dis(cid:173)
`sneezing.
`itching, and
`charge,
`Clinician-rated scores for all individ(cid:173)
`ual nasal symptoms did not differ
`significantly between the FP. ANS
`monotherapy and FP ANS plus
`loratadine combination treatment
`groups. Mean total and individual
`
`FIGURE 1 ,__ - - - - - - - - - - - -~ - - - - - -
`
`Clinician-rated and patient-rated total nasal symptom scores after 1 and 2 weeks
`of therapy for seasonal allergic rhinitis.
`
`· Clinician-Rated
`
`400
`
`400
`
`Patient-Rated
`
`'""'FPANS
`
`-
`
`Loratadine
`
`•••• •• FP ANS+ Loratadine
`
`---200
`
`1,· I I I
`I
`l
`
`100-
`
`'t
`
`0+ - - - - - - - - - - -
`1
`14
`
`0 - 1 - - -~ - - - - - - - -~
`-6-0
`1-7
`8-14
`
`Treatment Day
`Treatment Day
`FP ANS denotes fluticasone propionate aqueous nasal spray 200 µg daily; loratadine dosage, 1 0 mg
`once daili
`•p < .001 versus placebo.
`W < . 001 versus loratadine.
`+P < .05 versus FP ANS for mean change from baseline.
`
`I
`
`; I r TABLE 2
`Fl~ Baseline and Mean Change from Baseline at Day 7 and Day 14 for Clinician-Rated
`
`Nasal Symptom Scores
`Placebo
`Score (SE)
`
`I
`.
`
`,n-
`nd
`'he
`er-
`.di-,
`,ed I
`)ID I
`tis- I
`se-1·
`iat-
`en-1
`:est
`fer(cid:173)
`ug-
`
`for
`
`Total symptom
`score
`Baseline
`Day7
`Day 14
`
`Blockage
`Baseline
`Day 7
`Day 14
`Discharge
`Baseline
`--Gay 7
`Day 14
`Itching
`Baseline
`Day7
`Day:14
`Sneezing
`Baseline
`Day 7
`Day 14
`
`loratadine
`Score (SE)
`
`FP ANS
`Score (SE)
`
`FP ANS + Lor
`Score (SE)
`
`302.4 (4.2)
`-71.0 (7.9)
`-102.0 (8.8)
`
`313.3 (4.0)
`-86.1 (8.6)
`-102.0 (9.9)
`
`304.9 (4.6)
`_ -149.0 (8.2) t+
`-187.0 (8.5) t+
`
`304.9 (4.7)
`-158.0 (9.0) t+
`-186.0 (9.4) t+
`
`77.0 (1.4)
`-14.2 (2.2)
`-20.0 (2.4)
`
`80.2 (1 .2)
`-16.8 (2.3)
`-20.0 (2.6)
`
`78.0 (1.4)
`-32.8 (2.2) t+
`-42.5 (2.3) t+
`
`80.5 (1.4)
`-35.8 (2.5) t:J:
`-42.6 (2.7)t+
`
`81.3 (1.2)
`-18.1 (2.1)
`-27.1 (2.5)
`
`85.0 (1.1)
`-20.1 (2.4)
`-26.9 (2.7)
`
`82.8 (1.2)
`-38.5 (2.5) t+
`-46.3 (2.6) t+
`
`83.0 (1.3)
`-40.7 (2.5) t+
`-49.6 (2.7) t:J:
`
`76.0 (1.7)/
`-19.9 (2.4)
`-28.4 (2.6)
`
`76,3 (1.6)
`-26.4 (2.5)
`-29.3 (2.8)
`
`74.4 (1.8)
`-38.6 (2.6) t:J:
`-50.0 (2.5) t:J:
`
`73.6 (1.9)
`-41 .0 (3.0)t:J:
`-48.2 (2.7) t:I:
`
`68.1 (1.9)
`-18.9 (2.5)
`·26.6 (2.7)
`
`71.7 (1.7)
`-22.7 (2.7)
`-26.3 (2.9)
`
`69.7 (1.8)
`-38.8 (2.6) t+
`-48.4 (2.6) t+
`
`67.8 (2.0)
`-40.1 (2.7)t+
`-45.7 (2.9)t:I:
`
`Total symptom score is the sum of blockage, discharge, itching, and sneezing (maximum total possible
`~ 400).
`FP ANS denotes fluticasone propionate aqueous nasal spray; Lor, loratadine; SE, standard error.
`t P < .. 05 versus placebo.
`+ P < .05 versus loratadine.
`
`The Journal of Family Practice, Vol. 47, No. 2 (Aug), 1998 121
`
`

`

`FLUTICASONE VS LORATADINE IN RHINITIS
`
`FIGURE 2 1 - - - - - - - - - - - - - - - - - - - ,
`
`FIGURE 3
`
`Clinician-rated overall response to therapy after 2 weeks of
`therapy for seasonal allergic rhinitis.
`
`Patient-rated overall response to therapy after 2 weeks of
`therapy for seasonal allergic rhinitis.
`
`■ Significant improvement
`D Moderate improvement
`\lli Mild improvement
`Ii! No change
`Ill Mildly worse
`D Moderately worse
`s Significantly worse
`
`50
`
`45
`
`40
`
`35
`
`15
`
`. 10
`
`Placebo
`
`Loraladine
`
`FP ANS + Lor't
`
`FP ANS denotes fluticasone propionate aqueous nasal spray 200 µg
`daily; loratadine dosage, 10 mg once daily.
`*P < .001 versus placebo.
`tP < .001 ver\>u.s loratadine.
`
`nasal symptom scores for the loratadine and placebo
`treatment groups did not differ significantly at either
`the day 7 or day 14 evaluations,
`The pattern of improvement observed in patie1it(cid:173)
`rated total nasal symptom scores was similar to that
`reported in the clinician ratings, except that scores in
`the FP ANS plus loratadi.ne combination group were sig(cid:173)
`nificantly lower than those in the FP ANS monotherapy
`group at the evaluations on. days 1 through q and days 8
`through 14 (P values .006 and .017, respectiv~ly) (Figure
`1). Indivi_dual nasal symptom score data generally con(cid:173)
`fonned to a pattern similar to t):lat seen for total nasal
`symptom scores; at days 1 through 7 and days 8 through
`14, symptom scores in the FP ANS and FP ANS plus
`loratadine · treatment groups were significantly lower
`than those in the loratadine only group (P <.05) and
`placebo group (P < .001). Individual nasal scores in the
`FP ANS plus loratadine group were significantly lower
`than those reported by patients in the FP ANS monother(cid:173)
`apy group for .nasal blockage, nasal discharge, and
`sneezing at days 1 through 7 and 8 through 14, and for
`nasal itching at days 1 through 7.
`
`Clinicians' Overall Evaluation. In the clinician's
`overall evaluation at day 14, FP ANS and FP ANS plus
`loratadine were equivalent in efficacy and significantly
`more effective than placebo or loratadine only
`(P < .00l)(Figure 2). No significant difference was
`observed between the loratadine and placebo treat(cid:173)
`ment groups.
`
`122 ·The Journal of Family Practice, Vol.-217, No: 2 {Aug), 1998
`
`60
`
`50
`
`40
`
`Ill Significant improvement
`D Moderate improvement
`Mild improvement
`Ill! No change
`Ill Mildly worse
`D Moderately worse
`s Significantly worse
`
`~ ..
`i e: 30
`C .. e ..
`
`0
`
`"- 20
`
`10
`
`FP ANS denotes fluticasone propionate aqueous nasal spray 200 µg
`daily; loratadine dosage, 1 O mg once daily.
`•p < .001 versus placebo.
`tP < .001 versus loratadine.
`
`Patients' Overall Evaluation. Overall patient eval(cid:173)
`uations were in close agreement with overall clinical
`evaluations. FP ANS and FP ANS plus loratadine were
`significantly more effective than placebo or loratadine
`only (P < .00l)(Figure 3), but were not significantly dif·
`ferent from each other. No significant difference was
`observed between the loratadine and placebo treat·
`ment groups.
`
`Ii,:.•_
`
`ll
`
`PATIENT-RATED QUALITY-OF-LIFE
`CHANGES
`At baseline, the mean global RQLQ scores and scores
`on each of the seven domains did not differ between or
`among
`the
`four
`treatment groups
`(Table 3),
`Significantly greater improvements in mean global
`RQLQ scores from baseline to day 14 were observed in
`the FP ANS treatment group than in the placebo and
`loratadine only treatment groups (P <. 001). There
`were no significant differences in the mean change
`from baseline RQLQ scores between the loratadine
`only and placebo groups. Significantly greater
`improvements were seen in the FP ANS plus loratadine
`group than in either the loratadine only or placebo
`treatment groups (P<.001); however, the RQLQ scores
`did not differ significantly between the FP ANS plus
`loratadine and FP ANS monother:apy groups.
`
`SAFETY DATA.
`The incidence and pattern of drug-related adverse
`events 'did not differ among the treatment. grouP5·
`
`

`

`l
`
`TABLE 3
`
`FLUTICASONE VS LORATADINE IN RHINITIS
`
`Mean Global and Individual Domain Scores on the Rhinoconjurictivitis Quality- of life
`Questionnaire
`
`Placebo.
`Score (SE)
`
`Loratadine
`Score (SE)
`
`4.0 (0.1)
`-1.3 (0.1)
`
`4.5 (0.1)
`-1 .4 (0.1)
`
`3.8 (0.1)
`-1 .2 (0.1)
`
`4.4 (0.1)
`-1 .5 (0.1)
`
`4.2 (0.1)
`-1.3(0.1)
`
`3.5 (0.1)
`-1.2 (0.1)
`
`3.5 (0.1)
`-1.3 (0.1)
`
`3.6 (0.1)
`-1.3(0.1)
`
`4.1 (0.1)
`-1.3 (0.1)
`
`4.6 (0.1)
`-1.4(0.1)
`
`3.8 (0.1)
`-1.3 (0.1)
`
`4.6 (0.1)
`-1.5 (0.1)
`
`4.5 (0.1)
`-1.3 (0.1)
`
`3.8 (0.1)
`-1.2 (0.2)
`
`3.5 (0.1)
`-1.1 (0.1)
`
`3.5 (0.1)
`-1.1 (0.1)
`
`FPANS
`Score (SE)
`
`FPANS +
`Loratadine
`Score (SE)
`
`4.1 (0.1)
`- -2.2 (0.1)t:J:
`
`4.0 (0.1)
`-2.3 (0.1)t+
`
`4.6 (0.1)
`-2.5 (0.1)t+
`
`4.5 (0.1)
`-2.7 (0.1)t:j:
`
`3.8 (O.i)
`-1.9 (O.i)t:j:
`
`3.8 (0.1)
`-2.0 (0.1)t+
`
`4.4 (O.i)
`-2;3 (O:i)t:J:
`
`4A (0.1)
`-2.5 (O. i )t+-
`
`4.4(0.1)
`-2.5 (0:1)t+
`
`4.3 (0.1)
`-2.7 (0.1)t:j:
`
`3.7 (0.1)
`-2.1 (0. i )t+
`
`3.7 (O,i)
`-2.2 (0.1)t+
`
`3.5 (O.i)
`-1.9(0.i)t:J:
`
`3.4 (0.1)
`-2, 1 (0, 1 )t+
`
`3.7 (O.i)
`-1.9 (O.i)t:J:
`
`3.5 (0.1)
`-1.9 (0.1)t:j:
`
`icantly more effective than
`loratadine 10 mg once daily
`or placebo. Adding loratadine
`to FP ANS offered no signifi(cid:173)
`cant improvement over FP
`ANS alone with respect to
`clinician ratings, overall clini(cid:173)
`cal evaluation, overall patient
`evaluation, and patient-rated
`quality of life. The combina(cid:173)
`tion was considered more
`effective according to some
`patient ratings. A lack of any
`significant
`differences
`·. between FP ANS and FP ANS
`in combination with lorata(cid:173)
`dine also has been demon(cid:173)
`strated in the analysis of
`pharmacoeconomic
`out(cid:173)
`comes in this same patient
`population (reported else(cid:173)
`where), 23 with FP ANS plus
`loratadine
`providing
`no
`advantages over FP ANS
`monotherapy with respect to
`patient-rated overall satisfac(cid:173)
`tion with treatment, patient(cid:173)
`perceived effectiveness with
`symptom relief, impact of
`treatment
`on
`patient
`work/school
`attendance,
`patient effectiveness with
`work/school activities, and
`interference of rhinitis symp(cid:173)
`toms with patient perfor(cid:173)
`mans;e in leisure_,irecreation
`activities.
`The superiority of FP ANS .
`over loratadine' for treating
`nasal symptoms was not
`unexpected. Four previous double-blind, double(cid:173)
`dummy comparative trials have shown that_ FP ANS
`200 µg once daily, administered to patients with sea(cid:173)
`sonal allergic rhinitis for 4 weeks, significantly
`reduced nasal symptoms to a greater degree than
`loratadine. 8
`11 With the exception of one study, 11 these
`•
`clinical trials relied solely on subjective variables to
`assess efficacy. Jordana et al, 11 using portable peak
`inspiratory flowmeter measurements as an objective
`variable, found that FP ANS produced significantly
`greater nasal air flow than loratadin