Budesonide and terfenadine, separatelyand in
`combination, in the treatment of hay fever
`
`Richard J. Simpson, MB, ChB
`
`Background: While hay fever is a very common experience, its treatment
`in primary care setting has been little reported in controlled studies.
`Objective: This study sought to evaluate the patient’s assessment of efficacy
`of an intranasal steroid spray (budesonide) alone or in combination with an
`antihistamine (terfenadine) against terfenadine alone or placebo alone.
`Methods: A double-blind parallel group, placebo-controlled trial design
`was used,»comparing the four groups. Each group used an active or placebo
`spray and active or placebo tablets. Symptom scores were recorded daily in
`diaries over a 21-day period.
`Results: Overall assessment of efficacy by the lO6 patients was significantly
`greater (P < .05) for budesonide versus terfenadinc or placebo alone. There
`was a 40% placebo response. Budesonide was more effective than terfenadine
`for all individual symptom scores, particularly nasal blockage, against which
`terfenadine was ineffective. Adverse effects were mild and transient for all
`groups.
`Conclusions: Budesonide alone is a highly effective treatment for hay fever
`with few side effects.
`
`- INTRODUCTION
`It has been estimated that 10% to
`17% of North Americans experi-
`ence allergic rhinitis‘ and that hay
`fever, an allergy to pollen resulting
`in rhinitis and conjunctival symp-
`toms,
`is one of the most common
`forms of the disease. Following ex-
`posure to the allergen, lgE-mediated
`stimulation of mast cells results in
`
`.
`
`the release of allergy mediators such
`as histamine, which cause increased
`vascular permeability, mucous se-
`cretion, and stimulation of neural
`reflexes (resulting in pruritus and
`sneezing). Late-phase inflammatory
`reactions2 include the attraction and
`infiltration of inflammatory cells,
`such as mast cells, eosinophils, ba-
`sophils, neutrophils and lympho-
`
`From the Forth Valley GP Research
`Group, Department of Clinical Psychology,
`University of Stirling, Stirling, UK.
`This study was supported by a grant from
`Astra Draco AB, Lund, Sweden.
`Received for publication February 22,
`1994.
`Accepted for publication in revised form
`iuly 6, 1994.
`
`cytes into the mucosa?‘ The in-
`creased irritability of the nose ob-
`served during the allergy season is
`largely due to this inflammatory re-
`action. The result of these processes
`is the characteristic nasal symptoms
`of hay fever including pruiitus, na-
`sal congestion,
`runny nose, and
`sneezing.
`Treatment of hay fever includes
`antihistamines, decongestants,
`so-
`dium cromoglycatef topical (intra-
`nasal),“ or systemic6 steroids and
`immunotherapyzf Antihistamines
`are well-established in the treatment
`
`of hay fever, reflecting the role of
`histamine release in its pathogen-
`esis, but their usefulness has until
`recently been limited because of
`their anticholinergic, central nerv-
`ous system and sedative side ef-
`fects,8 which are potentiated by sed-
`atives, hypnotics, antidepressants,
`and alcohol. More recent H1-recep-
`tor antagonists produce a much
`lower incidence of sedationg; how-
`ever, terfenadine, the most widely
`prescribed antihistamine, and a sec-
`ond compound in this group, as-
`
`temizole, have both been shown to
`cause ventricular arrhythmias in
`overdose“) or when used in com-
`
`bination with erythromycin or other
`macrolide antibiotics and the anti-
`
`fungal preparation lcetoconazolefl
`Although clinical trials have shown
`antihistamines to relieve symptoms
`such as sneezing,
`itchy nose and
`runny nose, in general they are not
`thought to be effective in relieving
`nasal blockage, and thus may be
`formulated in combination with a
`decongestant. ‘2
`Systemic treatment with corti-
`costeroids can be used in hay fever,
`but is usually reserved for the most
`severe and persistent cases because
`of the risk of adverse effects associ-
`
`ated with the long-term use of this
`type of therapy.” lntranasal corti-
`costeroids, on the other hand, pro-
`vide one of the most potent thera-
`pies for hayfeverld“ and their local
`mode of application avoids the ad-
`verse effects associated with sys-
`temic corticosteroids while at least
`
`equalling their efficacy.” They also
`lack the sedative effects of antihis-
`tamines. The limitations of intra-
`
`nasally applied steroids are that. due
`to their localized action, they may
`not be effective in controlling eye
`symptoms and that some patients
`experience nasal irritation or mild
`epistaxis as a result of using them.”
`In the current study, the efficacy
`of intranasal budesonide, a corti-
`costeroid preparation, was com-
`pared with that of terfenadine and a
`combination of the two in the treat-
`ment of hay fever, in a double-blind,
`parallel-group,
`placebo-controlled
`study.
`
`MATERIALS AND METHODS
`
`Patients
`
`Men and women aged 15 years or
`
`
`
`VOLUME 73, DECEMBER, 1994
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`over at entry were recruited from a
`primary care setting into the trial.
`All patients had experienced symp-
`toms of hay fever between May 1
`and August 31 for at least 2 years
`preceding the study, and at the time
`of recruitment were suffering from
`two or more of the following symp-
`toms: blocked nose,
`runny nose.
`itching nose, or sneezing. Any pa-
`tients who were taking oral corti-
`costeroids, were suffering from res-
`piratory tract infections (bacterial.
`viral, or fungal) at the time of re-
`cruitment, had taken desensitiza-
`tion therapy during the previous 17’,
`months or who suffered hay fever
`symptoms outside
`the
`specified
`period were excluded from the
`study, as were pregnant women.
`The nature and purpose of the
`study were explained to the patients
`in both oral and written form, and
`their written consent to participa-
`tion in the study was obtained. The
`study was approved by the local eth-
`ics committee and was performed
`in accordance with the Declaration
`of Helsinki.
`
`Study Procedures
`Patients visited their general practi-
`tioner on entry to the study, at
`which time demographic details and
`the patient’s assessment of hay fever
`symptoms during the previous 24
`hours were recorded. The symp-
`toms assessed were blocked nose,
`runny nose,
`itchy nose, sneezing
`bouts, runny eyes, and sore eyes.
`Symptoms were scored using a 4-
`point system where 0 = no symp-
`toms,
`1 = mild symptoms (present
`but not troublesome), 2 = moderate
`symptoms (some discomfort expe-
`rienced), and 3 = severe symptoms
`(discomfort
`experienced
`during
`most of the waking hours). A mini-
`mum score of 2 was required for
`entry into the study.
`On entry to the study, patients
`were randomized to one of four
`
`parallel groups receiving (1) intra-
`nasal budesonide (Rhinocort, Astra
`Draco AB, Lund, Sweden), 200 pg
`bid, plus
`terfenadine
`(Triludan,
`Marion Merrell Dow, Uxbridge,
`
`
`
`Middlesex, UK), 60 mg bid; (2) ter-
`fenadine,\6O mg bid, plus a placebo
`nasal spray (identical to the bude-
`sonide nasal spray but delivering
`propellant and lubricant only): (3)
`intranasal budesonide. 200 ug bid,
`plus placebo tablets identical in ap-
`pearance to the terfenadine tablets:
`and (4) placebo nasal spray plus pla-
`cebo tablets. Patients were
`in-
`structed to deliver two puffs from
`the nasal spray into each nostril
`morning and evening, and to take
`one tablet in the morning and one
`in the evening, for 21 days. The use
`of other medications for hay fever,
`particularly oral corticosteroids and
`antihistamines, was forbidden but
`in the event of troublesome eye
`symptoms patients were permitted
`to use xylometazoline or metazoline
`eye drops.
`Patients were supplied with diary
`booklets and asked to record, at the
`end of each day, symptom scores
`experienced during the day for
`blocked nose, runny nose, sneezing,
`itchy nose, runny eyes and sore eyes,
`using the same scoring system as on
`entry to the study. The number of
`eye drops used during each 24 hours
`was also recorded, as were any com-
`ments about the symptoms or treat-
`ment.
`
`Patients visited their general prac-
`titioner after seven days’ treatment,
`and were reminded of their option
`to withdraw from the study if the
`previous week’s treatment had been
`ineffective. The diary booklets were
`checked for accuracy and complete-
`ness, and any comments made by
`the patients were recorded. At the
`final visit, after 21 days of treat-
`ment, comments by either the pa-
`tient or the physician were recorded,
`any inconsistencies in the diary
`booklets clarified, and patients were
`asked to make a global assessment
`of the efficacy of treatment accord-
`ing to a 4-point scale where 0 »==
`ineffective,
`1 = slightly effective, 2
`= noticeably effective, and 3 == very
`effective.
`
`Statistical Analysis
`Mean weekly symptom scores for
`
`000002
`
`
`
`ff‘:
`
`each patient who completed the
`study were determined from the di-
`ary booklets and overall means for
`each treatment group calculated
`from these. One—way analysis of var-
`iance (using pooled variance) was
`carried out on the 3-week ‘t1‘eatrn<—:nt
`mean.
`the last week of '[l‘E‘:3.1L1T1»?I]’[
`
`and 3 sepa1‘ately.
`and weeks l.
`Where statistically significant treat-
`ment differences were irrdicatcd by
`the F-ratio.
`l.ll1€3.,t’
`contrasts were
`used to deterrnine the s‘ta“”:tical zig-
`nificance of lI1Cll\’iCl1.l,8.l
`‘iI1‘FL8.iL[I.Ifl’l'l
`differences.
`
`_’r1SSESS1'.t1€TI’}'l' and eye Cir up
`Global
`subjected to l<Crusl<:1l-
`use were
`Wallis one-way analysis of variance
`follotved Thy
`t.b.e
`".3*.’,ilco7:orir
`1?? rl<
`sum-W test where appropriate.
`
`RESULTS
`
`Eflicacy
`One hundred forty-three patients re-
`porting to their general practitioner
`with symptoms of hay fever were
`recruited into the study. Records
`from six patients were unusable be-
`cause of confused numbering (five
`patients) and lost data (one patient).
`Twenty patients withdrew because
`of lack of treatment efficacy,
`the
`majority of these (12) being in the
`placebo group A further three pa-
`tients withdrew as a result of adverse
`events and five patients failed to
`return for assessment on one or
`more occasions. Three patients se-
`verely violated the protocol during
`the trial, and were withdrawn. Table
`1 shows demographic characteristics
`and symptom severity at baseline
`for the 106 patients who were eval-
`uated for efficacy. On entry to the
`study,
`the four treatment groups
`were well matched with respect to
`symptom severity and demographic
`characteristics, with the exception of
`the placebo group which had a
`higher proportion of men than the
`other groups.
`Figure 1 shows the results of the
`patients” overall assessment of the
`efficacy of treatment, whereas Fig-
`ure 2 shows the analysis of individ-
`ual symptom scores derived from
`
`1‘
`
`Tab
`/i\ss
`
`“
`
`,
`
`i-Ktlfl
`
`06%
`«dir
`= racy
`-‘zffei
`
`V Judi
`with
`, SOD
`
`‘ ical
`-f:i1CE
`‘ 161'}
`
`iillCl<
`b udc
`
`fngn;
`lie/[xx
`
`ANNALS OF ALLERGY
`
`i
`
`VOL
`
`
`
`000002
`
`

`

`
`
` ..j
`
`npleted the
`from the di-
`1 means for
`calculated
`alysis of var-
`riance) was
`ak treatment
`f treatment
`
`1 separately.
`ficant treat-
`
`ndicated by
`itrasts were
`
`zatistical sig-
`1
`treatment
`
`1d eye drop
`0 Kruskal-
`of variance
`:0x0n rank
`Jpriate.
`
`: patients re-
`practitioner
`fever were
`ly. Records
`rnusable be-
`
`bering (five
`)ne patient).
`'ew because
`
`the
`afficacy,
`)eing in the
`:r three pa-
`lt of adverse
`ts failed to
`on one or
`
`patients se-
`ocol during
`rawn. Table
`aracteristics
`at baseline
`3 were eval-
`:ntry to the
`.ent groups
`1 respect to
`emographic
`zxception of
`rich had a
`an than the
`
`suits of the
`nent of the
`rhereas Fig-
`of individ-
`:rived from
`
`—
`
`F ALLERGY
`;.
`
`
`
`VOLUME 73, DECEMBER, 1994
`
`000003
`
`
`
`the difference
`symptoms,
`nasal
`being statistically significant in the
`case of nasal blockage. The combi-
`nation of budesonide and terfena-
`dine produced symptom scores sim-
`ilar to budesonide alone for blocked
`
`itchy nose and runny nose,
`nose,
`and reduced the mean sneezing
`score by more than either terfena-
`dine or budesonide alone, the differ-
`ences being statistically significant
`(P < .05). Figure 3 shows changes
`in mean total nasal symptom scores
`during the first week of treatment.
`Terfenadine used alone achieved its
`
`maximum efficacy within one to
`two days. After two to three days,
`the symptom scores with budeson-
`ide were lower than with terfena-
`
`dine, and symptoms continued to
`improve over days 3 to 7. Budeson-
`ide and terfenadine combination
`
`treatment produced a similar effect
`to treatment with budesonide alone.
`
`Analysis of diary records of eye
`symptoms and eye drop use re-
`vealed that there were no statisti-
`
`cally significant differences in eye
`symptom scores between treatment
`groups, although the scores tended
`to be lower in the active treatment
`groups than in the placebo—treated
`patients. Eye drop use
`in
`all
`groups remained relatively constant
`throughout the study; although use
`in the budesonide group was higher
`than that in the terfenadine group.
`this did not reach statistical signifi-
`cance.
`
`Safety
`The six patients whose records were
`lost or confused were excluded from
`
`the safety assessment. Nineteen of
`the 137 patients evaluated for safety
`experienced adverse events. These
`events were generally mild and tran-
`sient, the most common being local
`effects related to use of the nasal
`
`spray, such as sneezing and nasal
`irritation after its use. One patient
`treated with combined budesonide
`
`and terfenadine experienced palpi-
`tations one hour after taking the
`tablets, as she had previously when
`taking chlorpheniramine maleate
`(Piriton)
`tablets. Three patients
`
`Table 1. Demographic Characteristics and Baseline Mean Symptom Scores (: SD) of Patients
`Assessed for Efficacy
`
`l
`
`Placebo
`
`Treatment Group
`Budesonide +
`Terfenadine
`
`Budesonide Terfenadine
`
`Demographic characteristics
`Number of patients
`Men/women (°/s)
`Age, yr (mean : SD)
`Mean symptom scores
`Blocked nose
`Sneezing bouts
`Nasal itching
`Runny nose
`Soreeyes
`Runnyeyes
`
`23
`30
`21
`53/47
`43/57
`71/29
`27.7 (: 12.2) 26.8 (: 12.4) 29.7 (: 11.7)
`
`32
`41/59
`25.7 (i: 7.8)
`
`1.6 :1.1
`2.3 : 0.6
`1.1:1.1
`2.0 : 0.9
`1.8:1.2
`1.5:-1.3
`
`1.9 : 0.9
`2.1 : 0.8
`1.2:1.0
`1.9 11.1
`1.8:1.1
`1.5:1.2
`
`1.6 i 1.2
`1.9 i1.1
`1.4:1.1
`1.7 :12
`1.7:1.1
`1.34.-1.2
`
`1.8 : 1.0
`1.9 : 0.7
`1.2:1.1
`1.6 1- 0.8
`1.3:1.3
`1.3:1.1
`
`100
`
`C 80
`§
`Q.
`5
`
`40
`
`20
`
`0
`
`9 5
`
`EQ.
`
`Noticeably effective
`60 - Very effective
`
`
`
`Placebo
`n:21
`
`.
`.
`.
`.
`Terfenadine Budesonide Combination
`n=23
`n=30
`n=32
`
`Figure 1. Patients‘ overall assessment of the efficacy of treatment. Percentage of patients in
`each treatment group who reported the global efficacy of their treatment at week 3 as noticeably
`effective or very effective, with statistical comparison between groups (Wilcoxon rank sum-W
`test). NS = not significant.
`
`G:
`
`patient booklets. Forty percent of
`patients in the placebo group and
`46% of patients treated with terfen-
`adine alone rated the overall effi-
`
`cacy of their treatment as noticeably
`effective or very effective, in com-
`parison to 85% of patients receiving
`budesonide alone or in combination
`
`with terfenadine (Fig l). A compar-
`ison between groups showed statis-
`tically significant (P < .05) differ-
`ences in the patients’ overall assess-
`ment of treatment efficacy between
`budesonide versus terfenadine and
`budesonide versus placebo, but no
`significant difference was observed
`between terfenadine versus placebo
`
`or between budesonide alone versus
`budesonide in combination with
`terfenadine.
`treatment
`Figure 2 shows that
`with terfenadine alone resulted in
`
`statistically significant (P < .05) re-
`ductions in symptom scores
`for
`runny nose and itchy nose as com-
`pared with placebo. Terfenadine,
`however, had no effect on nasal
`blockage. Treatment with budeson-
`ide alone reduced all mean nasal
`
`symptom scores as compared with
`placebo, the differences being statis-
`tically significant (P < .05). Bude-
`sonide also reduced mean symptom
`scores more than terfenadine for all
`
`000003
`
`

`

`
`
`3_ - Placebo n = 21
`- Tertenadine n : 28
`
`Budesonide n = 30
`Combination n : 32
`
`2 —
`
`E
`O0<0
`UG.)
`E
`
`C(
`
`9O0U)
`6CD
`2
`
`C(
`
`1 —
`
`O
`
`(a) Blocked nose
`
`(b) Runny nose
`
`3 ‘ - Placebo n = 2'!
`Z Terfenadine n 2 23
`
`"_ Budesonide n .-:.- 30
`Combiriation n = 8’)
`
`
`
` *T1
`
`than placebo in the treatment of hav
`fever symptoms. This confirms pre-
`vious studies with budesonide” and
`terfenadine.” Budesonide,
`how-
`ever, was found to control all nasal
`symptoms of hay fever whereas ter-
`fenadine did not significaritly affmyt
`nasal blockage. The lack. of efficacy
`of terfenadine against nasal blO<:l<:
`age has been observed in O'I'jl‘;=‘)l‘
`studies‘9*2° and is likely to be clJni~
`cally significant, as 59% of patients
`in the present study complairieri of
`nasal blockage. Scores for eye syn rp-
`toms were similar on ti:'eatmen't wl lh
`budesonide or
`terfenadine,
`seoa—
`rately or in combination, and lower‘
`than scores in the placebo group.
`although the difference was not sta-
`tistically significant. More xylorne-
`tazolirie or metazoline eye drops
`were used by patients in the bude-
`sonide group, which may indicate
`better control of eye symptoms with
`terfenadine.
`Budesonide was found to be con-
`
`siderably more effective than terfen-
`adine, according to the overall
`sessment of treatment effect by the
`patients. In the budesonide group,
`85% of patients rated their treat-
`ment as noticeably effective or very
`effective compared with 4-6% in the
`terfenadine group and 40% in the
`placebo group, a level of placebo
`response that emphasizes the im-
`portance of adequate control groups
`in hay fever studies. indeed, placebo
`nasal spray can produce a st1bstan--
`tial reduction in symptoms.“ Al-
`though the scores for individuajl na»
`sal symptoms tended to be lower
`with combined budesonide and
`fenadine treatment than with either
`
`drug used alone, the global assess-
`ments of combination therapy and
`budesonide alone were very similar,
`indicating that the lower scores for
`individual symptoms were not per~
`ceived by patients as improvements
`in their overall condition. Terfena—
`dine, budesonide, and combination
`therapy all had a good safety profile;
`adverse effects were minor and in-
`
`treatments, and
`frequent with all
`patients on active treatments expe-
`J
`
`ANNALS OF ALLERGY
`
`<
`
`‘
`
`-
`
`4
`
`ii
`
`‘I'ab|«
`
`llfl
`
`as 2
`
`tihi
`of
`exc
`
`int]
`sho
`bec
`tree
`
`the
`
`rur
`cot
`or
`
`or i
`was
`
`ide
`reg
`CO1
`per
`nif
`
`ing
`alo
`
`AC
`
`edg
`titi
`
`ley
`
`(c) Itchy nose
`
`(d) Sneezing
`
`Figure 2. Assessment of nasal symptom scores at week 3 as derived from patients’ diary
`booklets. * Statistically significant difference versus placebo (P < .05). 1“ Statistically significant
`difference versus terfenadine (P < .05). 1; Statistically significant difference versus budesonide (P
`< .05).
`
`I
`
`-J>-
`
`Meanscore
`
` Tertenadine
`
`--- .. Budesonide
`‘N - =9 ' *”’ Combination
`u l
`
`L
`
`a
`
`>
`
`Days
`
`Figure 3. Changes in mean total nasal symptom scores in each treatment group during the
`first week of treatment.
`
`withdrew from the study as a result
`of adverse events; these were one
`placebo-treated patient who suf-
`fered from nausea after taking the
`tablets, one budesonide-treated pa-
`tient who suffered from fatigue, and
`one patient on combination therapy
`who experienced intolerable sneez-
`
`ing and headache after using the
`nasal spray. A summary of adverse
`events is shown in Table 2.
`
`DISCUSSION
`
`The current study demonstrates that
`both intranasal budesonide and oral
`terfenadine were more
`effective
`
`
`
`000004
`
`
`
`000004
`
`

`

`
`
`Table 2. Number of Patients Reporting Adverse Events
`
`E‘’‘’'“
`Nasal adverse events
`
`Sneezing after use of
`Nasal spray
`Nasal irritation*
`CNS adverse events
`Headache
`
`Fatigue
`Other adverse events
`Nausea
`
`Dry mouth
`Palpitations
`
`Placebo
`(n = as)
`
`Terfenadine
`(n = 29)
`
`.
`Budesonide
`(n = 35)
`
`Budeson‘de +
`'
`Te(:e=n::')ne
`
`1
`
`O
`
`0
`
`1
`
`0
`0
`
`2
`O
`
`O
`
`0
`
`O
`
`O
`O
`
`2
`1
`
`O
`
`2
`
`1
`
`0
`0
`
`2
`1
`
`2
`
`0
`
`0
`
`1
`
`"' Described as stinging, itching, or irritation.
`
`rienced no more adverse effects than
`
`those taking placebo.
`The lack of efficacy of terfenadine
`and other antihistamines in the
`
`treatment of nasal congestion in hay
`fever may be an indication of the
`inflammatory nature of the late-
`phase response in allergic rhinitis;
`anti-inflammatory agents such as
`corticosteroids could be considered
`as a more rational solution than an-
`tihistamines for the nasal symptoms
`of hay fever, especially given the
`excellent safety profile when applied
`intranasally. Budesonide has been
`shown to be more effective than
`
`beclomethasone dipropionate in the
`treatment of hay fever”*23 and thus
`represents an excellent choice for
`the treatment of this condition.
`
`of
`symptoms
`conclusion.
`In
`runny or itchy nose and sneezing
`could be improved by terfenadine
`or budesonide administered alone
`or in combination, but blocked nose
`was only improved when budeson-
`ide was included in the treatment
`
`in
`regime. Budesonide, alone or
`combination with terfenadine, was
`perceived by patients as being sig-
`nificantly more effective in alleviat-
`ing symptoms
`than terfenadine
`alone.
`
`ACKNOWLEDGMENTS
`The author would like to acknowl-
`
`edge the work of the General Prac-
`titioner members of the Forth Val-
`
`ley GP Research Group, and the
`
`assistance of Mrs V. Swanson, Re-
`search Administrator.
`
`REFERENCES
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`fenadine,
`sepa-
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`More xylome-
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`h may indicate
`symptoms with
`
`)und to be con-
`tive than terfen-
`the overall as-
`
`nt effect by the
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`ted their treat-
`
`:ffective or very
`vith 46% in the
`nd 40% in the
`:ve1 of placebo
`iasizes the i1n-
`
`: control groups
`Indeed, placebo
`iuce a substan-
`
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`:d to be lower
`:sonide and ter-
`han with either
`
`3 global assess-
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`:re very similar,
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`s were not per-
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`lition. Terfena-
`.d combination
`
`d safety profile;
`minor and in-
`'eatments, and
`eatments expe-
`
`_j..j.:.__
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`S OF ALLERGY
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`
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`
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`
`A
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`H41:
`Wt
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`has
`abst
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`5
`
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`part
`N1’?
`Wm
`Dag
`she.
`stra<
`ma‘
`ms‘
`and
`inst
`blin
`9“?
`first
`den
`for:
`514”
`
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`add
`300
`5
`
`me,
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`Nu‘
`Eff
`pear
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`r
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`that
`
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`
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`
`21. Spector SL, Toshener D, Gay 1, et
`
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`
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`
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`
`Requeszfor reprintsshouldbe addressedto;
`
`Ric/Idrdf SIWIPSOIL MB. C113
`F0”/I Va//By GP Research Gmup
`
`Dept. PS1/Ch0/Ogy
`
`UIliV67‘Sl'ly Of511'!‘/ling
`Slit/int’ FK9 4L4 UK
`
`LONG—TERM TREATMENT or CHILDREN wrrrr jlNHALlEl_)~
`BUDESONIDE IMPROVES CONTROL OF ASTHMA WITH NO
`ADVERSE EFFECT UPON ‘GROWTH
`
`To evaluate effects of inhaled budesonide the authors studied 278
`children with mild or moderate asthma at initial ages of 3 to 11 years.
`After having been followed for 1-3 years during which they received no
`corticosteroid for more than 2 weeks per year, 216 children received inhaled
`budesonide, 800 pg/day via Nebuhaler for 6 to 8 weeks. After establishment
`of optimal control the dosage was gradually by reduced 25% at monthly
`intervals as tolerated. These children continued to receive inhaled bude—
`sonide for 2 to 6 years (mean 3.7 years). Sixty—two children whose parents
`did not want them to receive an inhaled corticosteroid because of fear of
`adverse effects served as controls and were followed for 3 to 7 years (mean
`5.2 years).
`During treatment with budesonide the mean daily dose decreased from
`710 to 430 pg with no evidence of tachyphylaxis. The number of annual
`hospital admissions for acute severe asthma decreased from 0.03 to 0.004
`per child (P <.00l) and FEV1 improved significantly as compared with
`both the run-in period and the control group. There was a significant
`relationship between the duration of asthma at initiation of treatment with
`budesonide and the annual increase in FEV1 during treatment with bude—
`sonide. Children who started treatment more than 5 years after the onset
`of asthma had significantly lower FEV1 (96% predicted) after 3 years of
`treatment with budesonide than those who received budesonide within the
`first 2 years after onset of asthma (10l% predicted, P <1 .05). There were
`no significant changes in growth velocity or weight gain during treatment
`with budesonide as compared with the run=in period or controls.
`These data indicate inhaled budesonide at doses of 400 ug per day does
`not inhibit linear growth in most children with mild or moderate asthma.
`Early treatment with inhaled corticosteriod may be more effective than
`treatment more than 5 years after the onset of asthma.
`
`——RMS
`Ageitoft L, Pedersen S. Effects of long-terrn treatment with an inhaled
`corticosteriod on growth and pulmonary function in asthmatic children.
`Respir Med l994;88:373—8l.
`
`502
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`ANNALS OF ALLERGY
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