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`F
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`REVIEW ARTICLE
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`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Drugs2001; 61 (11): 1563-1579
`0012-6667 /01/0011-1563/$27.50/0
`
`© Adis International Limited. All rights reseNed.
`
`Intranasal Corticosteroids for
`Allergic Rhinitis
`Superior Relief?
`
`Lars Peter Nielsen},2 Niels Mygind2 and Ronald Dahl2
`l Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark
`2 Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark
`
`Contents
`.......... ':
`Abstract ·
`l. Antihistamines
`. . . . . .
`l. l -- General Considerations-_-,_
`1.2 Oral Antihistamines . . . . .
`1.3 Topical Antihistamines ...
`. l .4 Comparative Effect of Antihistamines
`1.4. l Single Dose Studies . . . .
`l .4.2 Perennial Allergic Rhinitis .
`l .4.3 Seasonal Allergic Rhinitis .
`l .4.4 Studies in Children . . . . .
`1.4.5 Topical vs Oral Antihistam.ines
`l.4.6 Safety . . . . . . .
`2. Corticosteroids· . . . . . . . . .
`2.1 General Considerations .
`2.2
`Intranasal Corticosteroids
`___ 2.3 Comparative Effect of_lntrana§al Corticoster~o-'-"id=s---'--'---'--
`2.3. l Perennial Allergic Rhinitis
`2.3.2 Seasonal Allergic Rhinitis . . . . . . . . . . .
`2.~.3 Safety . . . . ._ . . . . . . . . . . . . . . . . .
`3. Comparing Antihistamines and Intranasal Corticosteroids
`3.1 Perennial Allergic Rhinitis . . . . . . . . . . . . . . . . .
`3.2 Seasonal Allergic Rhinitis . . . . . . . . . . . . . . . . .
`3.3 Combination of Antihistamines and Intranasal Corticosteroids
`3.4 Safety · ...... .
`3.5 Cost Effectiveness
`4. Conclusion
`
`1563
`1564
`7564
`1564'
`1565
`1565
`1565
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`1566
`1566
`1566
`1566
`1567
`1567
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`1568
`1568
`1569
`7569
`1569
`1569
`1572
`1572
`1573
`7573
`
`Abstract
`
`Whether first-line pharmacological treatment of allergic rhinitis should be
`antihistamines or intranasal corticosteroids has been discussed for several years.
`First-generation antihistamines are rarely used in. the treatment of allergic
`rhinitis, mainly because of sedative and anticholinergic adverse effects. On the
`basis of clinical evidence of efficacy, no second-generation antihistamine seems
`preferable to another. Similarly, comparisons of topical and oral antihistamines
`
`

`

`1564
`
`r
`
`Nielsen et al.
`
`'
`have been unable to demonstrate superior efficacy for one method of administra-
`tion over the other.
`,,
`/
`Current data documents no striking differences in efficacy and safety param(cid:173)
`eters-13etween-intr-anasal -corticosteroids-.---------,,---~------
`When the efficacy of antihistamines and intranasal corticosteroids are com(cid:173)
`pared in patients with allergic rhinitis, present data favours intranasal co:rpcoste(cid:173)
`roids. Interestingly, data do not show antihistamines as superior for the tr&atme:iit
`of conjunctivitis. Safety data from comparative studies in patients with allergic
`rhinitis do not indicate differences between antihistamines and intranasal corti(cid:173)
`costeroids. Combining antihistamines and intranasal corticosteroids in the treat(cid:173)
`ment of allergic rhinitis does not provide any additional effect to intranasal
`corticosteroids alone. On the basis of current data, intranasal corticosteroids seem
`to offer superior relief in allergic rhinitis than antihistamines.
`
`A.11ergic rhinitis is a common cond11:Ion ehc1tecf
`by an immunoglobulin (Ig)E-mediated allergic in~
`flammation of the nasal mucosa and characterised
`by nasal obstruction, rhinorrhoea, sneezing and na(cid:173)
`sal itch, and often accompanied by conjuhctivitis.
`It is present in 10 to 20% of the population in in(cid:173)
`dustrialised count.ries.E1l Moreover, this prevalence
`seems to be increasing.[2,3l Although allergic rhini(cid:173)
`tis is not a life-threatening disease, it can severely
`impact on quality of life[4-6l and be associated with
`comorbidity from other diseases, for example,
`asthma and conjunctivitisPl
`Treatment of allergic rhinitis consists of aller(cid:173)
`gen avoidance, allergen-specific imrnunotherapy and
`pharmacological intervention, of which the former
`two lie beyond the scope of the present review. Two
`mainstream options have evolved for pharmaco(cid:173)
`logical treatment, antihistamines and topical corti(cid:173)
`costeroids. The choice between these options has
`been extensively discussed since the introduction
`of intranasal corticosteroid treatment. l8l
`This review considers first-line pharmacologi(cid:173)
`cal treatment of allergic rhinitis and will deal only
`with antihistamines and intranasal corticosteroids
`(INCS), as we consider cromones, anticholiner(cid:173)
`gics, leukotriene modifiers, decongestants and sys(cid:173)
`temic corticosteroids as secondary treatment op-
`·
`tions in allergic rhinitis.
`Only data obtained in patients with allergic rhi(cid:173)
`nitis have been considered for the comparative ev(cid:173)
`idence presented in this review.
`
`© Adis International Limited. All rights reseived.
`
`1: Anfihlsf amines
`
`J . l General Considerations
`
`Histamine is the major pathophysiological me(cid:173)
`diator of allergic rhinitis. Its role is almost exclu(cid:173)
`sively mediated through the histamine H1-receptor,
`whereas the role of other histamine receptors in.
`allergic rhinitis remains to be clarified. Thu&, in the
`context of allergic rhinitis, antihistamines are H 1-
`receptor antagonistsJ9,io1 In addition to Hi-recep(cid:173)
`tor blockade, an anti-inflammatory effect of anti(cid:173)
`histamines has be~n proposed, as some of the newer
`compounds have been shown to influence cytokirie
`prodi;iction, mediatorrelease and inflammatory cell
`:fluxJ11 -19l However, other studies have been unable
`to confirm these findingsJ20-231 Whether antihista(cid:173)
`mines offer a cli_nically beneficial anti-inflammatory
`effect in addition to inhibition of histamine remains
`a question to be answered.
`
`1.2 Oral Antihistamlnes
`
`Numerous Hi-receptor antagonists have been
`developed. For oral use, these can be divided into
`older first-generation [e.g. chlorphenamine (chlor(cid:173)
`pheniramine), diphenhydramine,' promethazine
`and triprolidine] and newer second-generation an(cid:173)
`tihistamines (acrivastine, astemizole, cetirizine,
`ebastine, fexofenadine, loratadine, mizolastine and
`terfenadine). This review deals with the newer an-•
`tihistamines as the use of the older drugs in allergic
`
`Drugs2001;61 (ill
`
`___,,,,,...
`
`

`

`Corticosteroids in Allergic Rhinitis
`
`1565
`
`· 1.3 TopicarAntihistamines
`
`izole remains unknown as there is a lack of data on
`the other second-generation antihistamines for this
`measure.
`Whereas CNS-related adverse effects were a
`major characteristic of the first-gerieration antihis(cid:173)
`tamines, the piperazine/piperidine-derived struc(cid:173)
`tures of the newer generation agents reduce CNS
`penetration, although sedative effects have been
`described for some of the compounds, for example,
`acrivastinel441 and cetirizine.l45l The binding affin(cid:173)
`ity to muscarinic receptors is also decreased with
`the second-generation agents. With the exception
`of the cardiac adverse effects, this provides a more
`acceptable therapeutic index for the second-gener(cid:173)
`ation antihistamines.
`
`b"nitis is limited by their adverse effects, mainly
`r 11
`.
`•
`• •
`,, dation and antichohnerg1c act1v1ty .
`.,e All of the newer antihistamines are effective in
`the treatment of allergic rhinitis by decreasing na(cid:173)
`sal itching, sneezing and rhinorrhoea, but they are
`less effective for nasal congestion)2
`311 They are
`4-
`also effective for conjunctivitis and recent results
`seero to indicate some influence on lower airway
`symptoms_ [32,331
`Moreover, the pharmacokinetic profile of second(cid:173)
`o-eneration antihistamines are advantageous when
`~oropared with the first-generation agents.l341 They
`have an onset of action of I to 2 hours which lasts
`for 12 to 24 hours, except for acrivastine, which
`has to be administered at 8-hourly intervals. With
`the exception of cetirizine and fexofenadine,
`which are excreted almost unchanged, the remain-
`Two newer H 1-receptor antagonists are avail-
`ing drugs in this group are metabolised via the he-
`patic cytochrome P45O (CYP) system by CYP3A.
`able for topical use, azelastine and levocabastine.
`When applied intranasally, they have both proven
`As a number of other compounds, that is, anti-
`effective in the treatment of allergic rhinitis,
`mycotic azoles, macrolide antibiotics and grape-
`mainly relieving nasal itching and sneezing.l46A71
`fruit juice, are also substrates for this enzyme, this
`obviously provides a risk for interactions. l35J This
`They have a faster onset of action than oral antihis-
`taminesand act within 15 to 30 minutes. They only
`is probably a contributive factor to the occurrence
`need to be applied twice daily.
`of severe cardiac arrhythmias, for example, 'tor-
`No sedative effects have been seen with either
`sade de pointes', and fatalities, which have been
`drug,l46•481 whereas the occurrence of a short last-
`described following treatment with terfenadine
`ing perversion of taste has been_ described for
`__ and astemiz.Qle..~t~These effects seem to be en-
`abled through a quinidine-like action, causing ;---azelastineJ491
`· ·-· - · ·
`· ···
`----'- ·
`prolongation of the QT interval. [39,4o1 At present,
`1.4 Comparative Effect of Antihistamines
`no clinical evidence has demonstrated cardiac ad-
`verse effects with other second-generation antihis-
`1_4_ 1 Single Dose studies
`Many studies have been performed to compare
`tamines when they are used at therapeutically ap~
`propriate levels. However, it is recommended to
`the effects of oral second-generation antihisfa-
`mines in the treatment of allergic rhinitis. Single
`avoid antihistamines which are CYP45O metabo-
`lised or which possess quinidine-like actions in
`dose studies in patients with allergic rhinitis have
`demonstrated that cetirizine and terfenadine have
`risk groups, that is, patients with impaired hepatic
`a faster onset of action than loratadine and astern"'
`function or cardiac-arrhythmia.l411
`Astemizote~carr.Jls6~"Ct-a-s-an-appetite-stimulant-~ -izole._.!50,5.ll-A:H-4 ·drugs were equally-effective--
`and result in increased bodyweight. [ 42•431 The cause
`against nasal symptoms and histamine-induced in-
`for this action remains obscure, although a central
`creases in nasal airway resistance. This contrasts
`nervous system (CNS)-mediated mechanism, for ex-
`somewhat with the results of 2 studies in which
`ample, serotonin (5-hydroxytryptamine)-antago(cid:173)
`cetirizine was superior to loratadine after adminis(cid:173)
`tration of a single dose in both symptom reliefl521
`nism, is a theoretical possibility. However,whether
`and response to histamine challenge. [531 One study
`this adverse effect is seen exclusively with astern-
`
`© Adis International Limited. All rights reserved.
`
`Drugs 2001; 61 (71)
`
`

`

`r
`
`-
`
`1
`
`•
`
`1566
`
`Nielsen et al.
`
`was able to demonstrate a significantly faster onset
`of action for fexofenadine compared with terfenad(cid:173)
`ine in relief of rhinorrhoea and sneezing immedi-
`----ately after nasaf allergen challenge. [54J This may be --
`explained on the basis of fexofenadine being the
`active metabolite of terfenadine.
`·
`
`shows cetirizine to have a faster onset of action
`than terfenadine,[731 while another 9Jaiin.s ebastine
`to achieve maximum effect faster than cetiriz(cid:173)
`ine. [721-The:use-of-otherobjective-endpoims-snch
`as nasal peak flow[JOland inflammatory mediators
`in nasal lavage fluidl74l has not shown c;lifferences
`between agents.
`,,,_
`
`1.4.2 Perennial Allergic Rhinitis
`_ Relatively few studies investigating continuous
`i..4 . .4 Studies in Children
`·
`·th a11•
`D t
`ff"
`-'
`·
`h"ldr
`th
`administration of antihistamines are in patients
`e e 1cacy m c 1
`en w1
`a a on
`·
`erg1c
`rhinitis are sparse. One single-blind study in chil-
`with perennial allergic rhinitis (PAR). Six studies
`dren with SAR for 2 weeks showed equal effect of
`ranging from 1 to 8 weeks, included comparisons of
`astemiiolel55,56l cetirizine [56-581 ebastine [571 lorata-
`loratadine and astemizoleP5f In another 4-week
`'
`'
`dine (55,59,601 mizolastine[59i and terf enadine. [58,601
`.
`.
`.
`. . .
`·
`.
`study m children with PAR, cetmzme was supenor
`'.
`t er -- ----cr~fi- -- - t -i- - - -- - - [tFl6J
`No difforenees between agent.s-wer~-.seen--except- - t
`i
`O ora a me accor mg O paren a asses.smen · -- --
`that astemizole was more effective than loratadine
`for rhinorrhoea in 1 short.term study, [551 and cetiriz(cid:173)
`1.4.5 Topical vs Oral Antihistamines
`ine was better than ebastine according to the inves(cid:173)
`In comparisons between oral_ and topical anti(cid:173)
`tigators opinion in another study.C57l Interestingly,
`histamines, most topical regimens have included
`in 1 of the studies, nonresponders were crossed to
`intranasal as well as ocular medications or reports
`the opposite drug at the end of a 2 week treatment
`have only addressed nasal symptoms. In 1 study,
`period, resulting in an effect in 11 of the 16 pa(cid:173)
`intranasal azelastine was more effective than cetir(cid:173)
`tients_l60l
`izine at relieving nasal congestion,(771 wher~as other
`studies have demonstrated azelastine to be equally
`effective as cetirizine,[781 ebastine,[79l loratadinel80l
`and_ terfenachne.l81l In 2 studies, intranasal Jevo(cid:173)
`cabastine has been marginally more effective than
`terfenadine in relieving single symptoms, ie.
`· sne~zingl82l and nasal itching,[83l whereas a third
`study did not show any difference.[841 In 1 study,[831
`levocabastine given as eye drops were also judged
`superior to terf enadine for relieving ocular symp(cid:173)
`toms. A comparison of levocabastine and loratad(cid:173)
`ine showed identical efficacyJ85l
`
`1.4.3 Seasona/Allergic Rhinitis
`The lack of difference in effectiveness between
`second-generation drugs is also found in patients
`with seasonal allergic rhinitis (SA&j. One placebo(cid:173)
`controlled study in 202 patients with SAR seems
`to designate cetirizine as superior to loratadine,[6iJ
`as seen in the single-dose study,[511 when all symp(cid:173)
`toms following allergen challenge were consid(cid:173)
`ered. However, this effectiveness in symptom re(cid:173)
`lief after a quite s_hort treatment period of 2 days
`could not be confirmed in another placebo-control(cid:173)
`led, cross-over study of identical treatments given .
`for 1 week. [621
`Several seasonal studies involving acrivastine,[631
`astemizole[42-64l cetirizine,(64-691 ebastine,[671 fexo(cid:173)
`fenadine,(681 loratadine,[42,70l rnizolastine[69J and
`terfenadine[65,66,70l have been unable to demonstr(cid:173)
`ate any difference in efficacy for symptom relief.
`Some studies demonstrate small differences, that
`is, 'subjective rating' of cetirizine over astemiz(cid:173)
`olel71l or investigator preference of ebastine over
`cetirizine[72l without any support for this in other
`endpoints, for example, symptom relief. One study
`
`1.4.6 Safety
`When considering adverse effects, only 2 of the
`previously mentioned studies indicate differences.
`A large, placebo~controlled, 2-week ·study· in 821
`patients with SAR showed a significantly higher
`degree of sedation after cetirizine than fexofenad(cid:173)
`ine. [68l
`In another smaller 8-week study in 27 patients
`with SAR, terfenadine revealed more adverse ef(cid:173)
`fects, that is, headache and dizziness, than a com(cid:173)
`bination of intranasal and ocular levocabastine. [Sll
`
`© Adis International Limited. All rights reserved.
`
`Drugs 2001; 61 (lD
`
`

`

`r
`
`Corticosteroids in Allergic Rhinitis
`
`1567
`
`2. corticosteroids
`
`2. 1 General Considerations
`
`intranasal application, all characterised by a high .
`receptor affinity and an extensive first-pass meta-
`bolism in the liver. Effectiveness in relieving the
`symptoms of allergic rhinitis, including nasal con(cid:173)
`Allergic rhinitis is an inflammatory disease of
`gestion, have been demonstrated for beclometh(cid:173)
`the nasal mucosa and corticosteroids are, at pres-
`asone, [I04J budesonide,[1D5J flunisolide,[106J fluticasone
`ent, the most potent anti-inflammatory medica-
`propionate,[IO?J mometasone[IOSJ and triamcino(cid:173)
`tions commercially available for the treatment of
`lone_[I09J In addition., s.ome reports have indicated
`allergic rhinitis.[86J Corticosteroids exert their ef-
`that INCS may have a beneficial effect towards
`feet by combining with a glucocorticoid receptor
`bronchial hyperresponsiveness and asthma symp-
`localised in target cell cytoplasm. The resulting ac-
`tomsJll0-115]
`tivated glucocorticoid receptor complex is able to
`interact with cellular DNA, thereby enabling reg-
`It has been generally .considered that INCS
`ulation of cellular functionsJ87,8SJ
`have a slow onset of action. However, they usu-
`ally act within 12 to 24 hours_l116-118l Recent re-
`Corticosteroids act upon ~any of the cell 1types
`sults have even indicated that budesonide acts after
`and inflammatory mediators participating in aller-
`3 hours.[1191 However, maximum treatment effi-
`gicinflammation.Antigen-preserttingLangerhans'
`cacy occurs after days or a few weeks:l-1201 Once--
`cells are reduced ihnumbet15yINCS.f89,90J More~
`daily application has proven sufficient to treat
`over, such treatment seems to impair their process-
`most patients with allergic rhinitis,l121-125l al-
`ing of antigen.l91l Similarly, the migration ofbaso-
`though those with severe symptoms may benefit
`phils ·and mast cells to the nasal epithelium is
`from twice daily administration.[1261
`inhibited by INCS.[91-941 Evidence suggesting an
`The different potencies of INCS are important
`impact on the release of mast cell mediators, that
`is, histamine, has also been presented_l95l. Cortico-
`when considering comparative data. It is well es-
`tablished that fluticasone propionate is twice as po-
`steroid therapy interferes with several pivotal as-
`tent as beclornethasone.l107l There is controversy
`pects of eosinophil function. Cell survival is de-
`regarding relative potencies between other INCS.
`creased and the ability to release preformed
`However, it appears that the newer drugs2 that is,
`cytotoxic proteins, that is, eosinophil cationic pro-
`.
`: :_ i.:i. · d_[96 97J
`·
`d . - ,-
`·d
`1-._:1
`-
`-
`---=---'tern an _eosmopilll per:oxi ase, 1s_j_Jjj_uu1te - - :_____ -tl.uti.cawn€--pr0p-1-0nate and-mometasone-,-aice-m0re
`potent than the others. l117l ·
`Moreover, formation of a number of cytokines and
`chemokines vital to eosinophil lifespan are inhib-
`Currently available INCS are generally well tol-
`ited, for example, interleukin (IL)-5 (forma-
`erated. Sneezing caused by nasal hyperactivity can
`tion),l98l IL-4 (adhesion)l99J and RANTES [Regu-
`occur at the start of therapy but this usually disap-
`lated on Activation, Normal T cell Expressed and
`pears with tirne_[I27J
`.
`Secreted] (chemotaxis)_[IOOJ Results demonstrating
`Occasionally, mild and transient dryness, crusting
`an inhibitory effect of intranasal corticosteroid on
`ap_d blood-stained secretions occur, and these are often
`activated T cells in nasal epithelium have been pre.:.
`responsive to a reduction of INCS dose_l120,12s,1291
`sented.(IOlJ In 2 studies, the allergen-induced in-
`Septal perforation has been described as a rare
`crease of specific IgEin-patients with-PAR during
`complication.lB0,131J Atrophy of the mucosa;cor-
`--···-.seas0n.-was-a00l1slled:[ 1 °2-1 o3J In-all,-tli.i-s-i-nElieat-es
`respondmg to dermal atrophy, after prolonged use
`profound effecis of corticosteroids on the inflam-
`of INCS has not been observed_[I32,I33J
`matory process seen in allergic rhinitis.
`Because a proportion of intranasally applied
`corticosteroids end up in the gastrointestinal tract
`and is systemically absorbed, the risk of systemic
`adverse effects has been a concern for this class of
`drugs. However, these compounds, especially the
`
`2.2 Intranasal Corticosteroids
`
`Since the introduction of beclornethasone,l8l
`several corticosteroids have been developed for
`
`© Adis International Limited. All rights reserved.
`
`Drugs 2001: 61 (11)
`
`

`

`1568
`
`Nielsen-et al.
`
`newer fluticasone propionate and mometasone,
`have low systemic bioavailability, mainly because
`of their massive first-pass metabolism in the
`~ver.~1-171-wli:en used exclusively mtranasany-at
`therapeutic dosages, the drugs in this class do not
`seem to exhibit any influence on the hypothala(cid:173)
`mus-pituitary-adrenal (HPA)-axisP34-137l How(cid:173)
`ever, a lack of HPA-axis suppression does not guar(cid:173)
`antee against other systemic adverse effects. Data
`demonstrating an inhibitory effect on the short
`term growth rate of children have been presented
`for beclomethasone and budesonide l138,139l al-
`.. -
`,
`.
`though the result for budesonidewas only achieved
`by giving an adult dose of 200µg twice daily. More(cid:173)
`over, this could not be reconfirmed in a recent study
`in which the impact on child growth, as measured
`by lower leg knemometry, of budesonide 400µ,g
`daily was comparable to placebo.l1401 Other sys(cid:173)
`temic adverse effects, which have been linked to
`inhaled therapy, for example, cataract, glaucoma
`and dermal thinning, do not seem to occur in pa(cid:173)
`tients receiving treatment exclusively by the intra(cid:173)
`nasal route.C141l
`
`2.3 Comparative Effect of
`· Intranasal Corticosteroids
`
`2.3. 1 Perennial Allergic Rhinitis
`As corticosteroids need continuous application
`to achieve maximum effect, single dose studies are,
`obviously, not very useful for comparing efficacy.
`Considering the many comparisons performed, not
`many have used a randomised, double-blind and
`eventually placebo-controlled design. Unless oth(cid:173)
`erwise stated, the comparative studies discussed in
`this section (2.3) have used the drugs in standard
`recommended doses for allergic rhinitis.
`Four placebo-controlled studies in patients with
`PAR have been published. Two studies[142,143l com(cid:173)
`pared 1 dose of beclomethasone with 2 dose levels
`of fluticasone propionate in 183 patients for 12
`weeks and in 466 patients for 26 weeks, respec(cid:173)
`tively. The 2 remaining studies, each lasting 12
`weeks, both considered mometasone. One was a
`comparison with beclomethasone at twice the
`standard daily dose in 387 patientsl123l and the
`
`© Adis International Limited. All rights reserved.
`
`other regarded an equi-nominal dose of fl.uticasone
`propionate in 459 patients.l144l ,N6;;:e of these
`studies revealed any difference' in the relief of
`symptoms ofallergic rninitisor in theph:ysicians
`assessment of treatment efficacy. Moreover, nasal·
`cytology specimens were -uiia.oltdo demonstrate
`differences between treatments in 2 6f the stud(cid:173)
`ies. [142,143]
`One randomised, double-blind, I-year study in
`251 patients reported a significantly better effect
`with fluticasone propionate compared with an
`equi-nominal dose of beclomethasone on nasal
`congestion and secretion as well as relief of ocular
`symptoms.l145l These findings can partly be ex(cid:173)
`plainectl,y tneliigher potencf of fluticas_pne propi(cid:173)
`onate. Of note, the difference was not reccmfirmed
`by the 2 studies discussed in the previous para(cid:173)
`graph.l142,143l A smaller randomised, double-blind,
`cross-over :;;tudy comparing beclomethasone and
`flunisolide in 23 patients with perennial rhinitis, 15
`of whom were allergic, did not show differences in
`efficacy for symptom relief or on more objective
`parameters of nasal blockage, that is, nasal peak
`flow and posterior rhinomanometry_l146l
`In contrast, 2 studies comparing beclorneth(cid:173)
`asone and budesonidewith-single~blin&147l or non(cid:173)
`blind[148l design seem. to favour the latter. Two
`single-blind studies have compared fluticasone
`propionate and budesonide. One studyl149l demon(cid:173)
`strated budesonide to be superior, especially for re(cid:173)
`lief of nasal congestion. The other study, l128l which
`compared budesonide 200 and 400µg daily given
`by turbuhaler to fluticasone propionate 200µg
`daily, did not reconfirm this. One single-blindl 150l
`and 1 non-blind study[151l have shown beclometh(cid:173)
`asone and flunisolide to be equally effective.
`
`2.3.2 Seasonal Allergic Rhinitis
`Comparisons of efficacy betweeri INCS iri pa(cid:173)
`tients with SAR do not differ significantly from
`those in patients with PAR. Two randomised, dou(cid:173)
`ble-blind, placebo-controlled comparisons of
`beclomethasone and mometasone, which both in(cid:173)
`cluded >300 patients, over a period of 4 and 8
`weeks, respectively,l152,153l did not demonstrate
`differences between the 2 agents. Similarly, no dif-
`
`. Drugs 2001; 61 (lll
`
`___,,j
`
`

`

`Corticosteroids in Allergic Rhinitis
`
`1569
`
`a single-blind, cross-over, placebo-controlled de(cid:173)
`sign with treatment periods. of five days in 20 pa(cid:173)
`tients with allergic rhinitis. No differences between •
`treatments were seen for any of the parameters.
`
`3. Comparing Antihistamines and
`Intranasal Corticosteroids
`
`3.1 Perennial Allergic Rhinitis
`
`ference in treatment effect was seen in another
`study of similar design, which compared beclo(cid:173)
`methasone and fluticasone propionate in 313 pa(cid:173)
`tients for 2 weeksP54l Only 1 randomised, double(cid:173)
`blind study has shown a difference between 2
`INCS, that is, beclomethasone and budesonide.[1551
`However, this 7-week study, which included 56 pa(cid:173)
`tients, had variable dose administration, ranging
`from o to 800µg daily, and the difference was seen
`as less consumption of doses in the budesonide
`group.
`No differences in treatment effect were seen in
`1 non-blind[156l and 2 single-blindl157,158l compar(cid:173)
`isons of beclomethasone and flunisolide, ;even
`though 1 study used a rather low dose of beclo(cid:173)
`methasone.l158l Similarly, in sing!e-blind compar(cid:173)
`isons, flunisolide was equivalent toJ)l1desopid~l159l
`and triamcinolone was equivalent to fluticasone
`propionate. [1601. Budesonide was superior to beclo(cid:173)
`methasone in relief of sneezing in 1 single-blind
`comparisonD61l and for relief of sneezing, nasal
`secretion and itching in another.£1621 In a single(cid:173)
`blind study, 2 dose levels of budesonide were com(cid:173)
`pared with 1 dose level -of fluticasone propio(cid:173)
`nare.l1631 This showed a marginally better effect of
`the higher dose of budesonide on sneezing but oth(cid:173)
`erwise no differences between the 2 drugs.
`
`~
`
`A number of studies have compared antihista(cid:173)
`mines and INCS in patients with allergic rhinitis
`(table I and II).
`Few studies have been performed in patients
`with PAR. Two 4-week studies compared terfenad(cid:173)
`ine to beclomethasonel164l and astemizole with
`budesonide,D95l respectively. Both demonstrated
`that the INCS was superior for the relief of nasal
`symptoms. One small (n = 8) 12-week study of
`astemizole and beclomethasone was unable to
`show differences between the 2 drugs)166J
`Topical antihistamines a:nd INCS have also
`been compared, with no demonstrable differences
`shown between azelastine and beclomethasone for
`relief of.symptoms, physicians assessment of effi(cid:173)
`cacy or nasal blockage, as measured by rhino(cid:173)
`manometryJ1671 Howey_er, when azelastine was
`compared with budesonide, the INCS was signifi(cid:173)
`--=----=-'-'=~~anfu'_superior for_~n nasal sy~IJ!Omsl~6_8l A
`2~3:3-sarer