Pharmacologic and anti-IgE treatment of allergic rhinitis ARIAupdate (in collaboration with GA2LEN)
The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evi-
dence-based and step-wise approach based on the classification of the symptoms.
The ARIA workshop, held in December 1999, published a report in 2001 and
new information has subsequently been published. The initial ARIA document
lacked some important information on several issues. This document updates the
ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis.
Literature published between January 2000 and December 2004 has been in-
cluded. Only a few studies assessing nasal and non-nasal symptoms are presented
as these will be discussed in a separate document.
W. Fokkens15,*, P. Howarth16,*,J. Kemp17, M. L. Kowalski18,*,V. Kvedariene13, B. Lipworth19,R. Lockey20, V. Lund21,S. Mavale-Manuel22, E. O. Meltzer23,J. Mullol24,*, R. Naclerio25,K. Nekam26, K. Ohta27,N. Papadopoulos28,*,G. Passalacqua29, R. Pawankar30,T. Popov31, P. Potter32, D. Price33,G. Scadding34, F. E. R. Simons35,V. Spicak36, E. Valovirta37,D.-Y. Wang38, B. Yawn39, O. Yusuf401University Hospital and INSERM U454, Montpellier,France; 2Ghent University, Ghent, Belgium; 3TheUnion, Paris, France; 4University Hospital Ghent,Belgium; 5University of Cordoba, Argentina; 6StJosephÕs Hospital, La Malbaie, Quebec, Canada;7Department of Otolaryngology, Mahidol University,Bangkok, Thailand; 8University of Genoa, Italy;9Voksentoppen BKL, University of Oslo, Norway;10Capital Institute of Pediatrics, Beijing, China;11Federal University of Bahia School of Medicine,Brazil; 12University of Manchester, Manchester, UK;13University of Vilnius, Lithuania; 14Royal BromptonHospital and Imperial College, London, UK;15University of Amsterdam, the Netherlands;16University of Southampon, UK; 17San Diego, CA,USA; 18Lodz University, Poland; 19Asthma andAllergy Research Group, University of Dundee, UK;20Division of Allergy and Immunology, University ofSouth Florida, Tampa, FL, USA; 21Institute ofLaryngology and Otology, Ear Institute, UniversityCollege London, London, UK; 22University ofMaputo, Mozambique; 23Allergy and AsthmaMedical Group and Research Center, San Diego, CA,USA; 24Hospital Clínic de Barcelona, Catalonia,Spain; 25Otolaryngology University of Chicago, USA;26Hospital of the Hospitaller Brothers, Budapest,Hungary; 27Department of Medicine, TeikyoUniversity School of Medicine, Tokyo, Japan;28University of Athens, Greece; 29University ofGenova, Italy; 30Department. of Otolaryngology,Nippon Medical School, Tokyo, Japan;
31Clinical Centre of Allergology, Medical UniversitySofia, Bulgaria; 32Allergy Diagnostic and ClinicalResearch Unit, University of Cape Town LungInstitute, Cape Town, South Africa; 33University ofAberdeen, Aberdeen, UK; 34Royal National TNEHospital, London, UK; 35Department of Pediatricsand Child Health, University of Manitoba, Canada;36Czech Initiative for Asthma, Sokolska,Prague,Czech Republic; 37Turku Allergy Center,Turku, Finland; 38National University of Singapore,Singapore; 39University of Minnesota, USA; 40TheAllergy and Asthma Clinics, Islamabad, Pakistan
Key words: ARIA; asthma; GA2LEN; IgE; pharmaco-therapy; rhinitis.
Prof. J. BousquetClinique des Maladies RespiratoiresHôpital Arnaud de VilleneuveCentre Hospitalier Universitaire34295 Montpellier Cedex 5France
tis. Literature published between January 2000 and
December 2004 has been included. Complementary and
The management of allergic rhinitis includes patient educa-
alternative medicine is not evaluated in this document as
tion, allergen and pollutant (e.g. tobacco) avoidance, phar-
it is discussed in a separate section (G. Passalacqua,
macotherapy and allergen-specific immunotherapy (1–3).
unpublished data). Moreover, only a few studies assessing
Pharmacologic treatment encompasses efficacy, safety
nasal and non-nasal symptoms are presented as these
and cost-effectiveness of medications, patient preference
will also be discussed in a separate document (A.A. Cruz
and the objective of treatment (4), likely adherence to
recommendations (5), severity of the disease as well as thepresence of co-morbidities. Medications used for rhinitisare usually administered intranasally or orally. The
efficacy of medications may differ among patients.
The pharmacologic treatment of allergic rhinitis pro-
posed by ARIA is an evidence-based and step-wise
• Studies were sought from MEDLINE (1 January 2000 to 31
approach based on the classification of the symptoms.
December 2004) and EMBASE. Moreover, we used the expert
The ARIA workshop, held in December 1999, published a
group database to assess whether certain papers may not have
report in 2001 (2) and new information has subsequently
been retrieved by the electronic search.
been published. The initial ARIA document lacked some
• The following key words were used for the search strategy:
important information on issues such as complementary
• Antihistamine, H1-blocker, (intra)nasal corticosteroid, intra-
and alternative medicine (CAM) and occupational rhinitis.
nasal steroid, anti-cholinergic, decongestant, immunotherapy,leukotriene receptor antagonist, Azelastine, Beclomethasone,Budesonide,
Cromoglycate, Desloratadine, Diphenhydramine, Ebastine,Emedastine, Fexofenadine, Fluticasone, Ipratropium, Ketoti-
fen, Levocetirizine, Loratadine, Mizolastine, Mometasone,
This document updates the ARIA sections on the
Montelukast, Olopatadine, Omalizumab, Oxatomide, Pran-
pharmacologic and anti-IgE treatments of allergic rhini-
lukast, Pseudoephedrine, Rupatadine, Triamcinolone and Za-firlukast.
Abbreviations: ARIA, Allergic Rhinitis and its Impact on Asthma;
BID, twice a day; CAM, complementary and alternative medicine;
HPA, hypothalamic-pituitary-adrenal; OD, once a day; PAF,
• Moreover, we searched for rhinitis [OR] conjunctivitis [AND]
platelet activating factor; PRN, as needed; QOL, quality-of-life;
RQLQ, rhinoconjunctivitis quality of life questionnaire (Juniper).
Table 1. Optimal properties of oral H1-antihistamines
• Only randomized, double-blind, placebo-controlled clinical
trials published as full papers were selected including some key
Potent and selective H1 receptor blockage
• Key case reports and observational studies were used for drug
No clinically relevant pharmacokinetic interference by foods, medications
• Full manuscripts published in peer-reviewed journals. Ab-
No known interaction with cytochrome P4503A (CYP3A)
No known interaction with other diseases to avoid toxic reactions
Effective in the treatment of intermittent and persistent rhinitis as defined in the
Effective for all nasal symptoms including nasal obstruction
• Studies using methods which make it very difficult to assess
• Challenge studies including chamber and park models (6–13).
Improvement of asthma symptoms (short-term studies)
Reduction of asthma exacerbations (long-term studies)
• Methodological papers using single-blind trials (14–19).
An improvement of the pulmonary function tests, even though in pollen-induced
• Reviews in which the methodology was not clearly stated
bronchial symptoms, FEV1 and peak flow rates are usually not altered
If a claim for a preventive effect is proposed, appropriate trials should be
• Studies on non-allergic rhinitis, rhino-sinusitis or nasal polyp-
osis (21–28) or sleep disordered breathing (29, 30).
Studies should be carried out in young children and old age patients
All studies meeting the search strategy were examined by two of the
experts, reviewed by the chair of the group and discussed during
plenary sessions of the ARIA Scientific Committee.
No sedation, cognitive or psychomotor impairmentNo anti-cholinergic effectsNo weight gain
Pharmacologic treatment of allergic rhinitis
No cardiac side effects (prolongation of the QT interval)Possible use in pregnancy and breast feeding
Oral H1 antihistamines. H1-blockers or H1-antihistamines block
Studies should be carried out in young children and old age patients
histamine at the H1 receptor level (neutral antagonists or inverse
agonists) (31). Some also possess additional anti-allergic proper-
ties. During the last 20 years, pharmacologic research has
Rapid onset of action, so that clinical benefits are noted quickly and so drugs
produced compounds with minimal sedative effect and impair-
Long duration of action, at least persistence of clinical effects over 24 h,
opposed to the first-generation H1-antihistamines (32). The term
so the drug can be administered once a day
ÔthirdÕ generation should be reserved for an H1-antihistamine with
No likelihood of development of tolerance (tachyphylaxis).
Comparison with other drugs used to treat rhinitis (conjunctivitis)
Oral H1-antihistamines improve the quality-of-life of patients by
their effectiveness against symptoms mediated by histamine, inclu-ding rhinorrhea, sneezing, nasal itching and eye symptoms. They
Long-term (6 months) treatment with Cetirizine reduces allergic
are, however, less effective on nasal congestion.
symptoms and the need for rescue medication in children with mite
Long-term treatment (years) with an oral H1-antihistamine is
allergy as compared with placebo (39).
safe, including little or no sedation or impairment. Some, but not
In infants 6–11 months of age, a double-blind, placebo-controlled
all, oral H1-antihistamines undergo hepatic metabolism via the
study has demonstrated the safety of Cetirizine (40). Another study
cytochrome P450 system and are prone to drug interactions.
produced no adverse effects on behavior, and learning processes
Although cardiotoxicity is not a class effect (33), major concerns
were associated with the prolonged use of Cetirizine in young
existed about the arrhythmogenic action of terfenadine, astemizole
children with atopic dermatitis (41).
and high doses of diphenhydramine, which have rarely been asso-
Although, in children, Chlorpheniramine and Cetirizine increased
P300 latency (an event-related potential used as an objective test of
H1-antihistamines have been approved for young children (34).
sedation) when compared with baseline (42), the significant increase
Table 1 summarizes the desirable characteristics of an anti-his-
in P300 latency was not accompanied by a change in subjective
tamine medication for use in allergic rhinitis (35).
somnolence as measured on a visual analog scale.
Recently, Loratadine, a major second-generation anti-histamine
Cetirizine, compared with placebo, delays or, in some cases,
medication in the USA, has taken on a non-prescription or over the
prevents the development of asthma in a subgroup of infants with
counter (OTC) status (36). This has resulted in increased out of
atopic dermatitis sensitized to grass pollen and, to a lesser extent,
pocket expenses for patients as OTC medications are not part of an
house dust mite (43). Further studies are required focusing specif-
insurance or drug benefit program. Insurers are continuing to adjust
ically on sensitized groups to substantiate this finding.
drug benefits for other anti-histamines in view of the 44% drop inanti-histamine use by patients who have lost drug benefits for anti-
Desloratadine. Desloratadine in 5 mg dosage provided significant
24 h relief of seasonal allergic rhinitis signs and symptoms. There wereno statistically significant differences among the four largest doses
Cetirizine. Cetirizine provides a positive impact on work/school-
suggesting that Desloratadine 5 mg OD offers the best therapeutic
related productivity and activity impairment in patients with pollen-
profile (44). Recommended OD doses of Fexofenadine and Deslor-
atadine were equally effective in improving nasal peak flow and nasal
symptoms in seasonal allergic rhinitis (45). Desloratadine reduces
significantly affected by Loratadine or Diphenhydramine (76). This
nasal congestion (46), rapidly and safely reduces the symptoms of
report differs from previous studies (38, 77).
perennial allergic rhinitis, and its efficacy did not diminish during4 weeks of treatment (47). In two studies, Desloratadine also reduced
Mizolastine. Over a 4-week period, Mizolastine 10 mg OD was as
bronchial symptoms during the pollen season in patients with
effective as Loratadine 10 mg OD in relieving symptoms of
seasonal asthma and seasonal rhinitis (48, 49).
perennial allergic rhinitis in adult patients, and the tolerability
At the recommended dose of 5 mg, Desloratadine appears to be
free of adverse effects on psychomotor performance, daytime sleeplatencies, and subjective sleepiness and could prove suitable for
Rupatadine. Rupatadine is a new second-generation H1-antihista-
those involved in skilled activity and transportation (50). Deslor-
mine with OD dosing that may have the potential to provide better
atadine at a therapeutic dose does not impair driving performance
control of symptoms than the currently used oral H1-antihista-
(51). Desloratadine has no clinically relevant electrocardiographic
mines. This is due to its dual pharmacologic profile (anti-PAF and
or pharmacodynamic interactions with Ketoconazole (52), Eryth-
anti-H1) which does, however, require testing in controlled com-
parative studies. Rupatadine 10 mg per day was superior to placeboand non-significantly superior to Ebastine 10 mg in alleviating the
Ebastine. In pollen-induced rhinitis, Ebastine 20 mg OD was
symptoms of seasonal allergic rhinitis over a 2-week period (79).
significantly superior to Loratadine 10 mg OD. It improved the
Somnolence was reported in 2.4% of patients treated with placebo,
total rhinitis symptom score throughout the day and in the morning
10.8% with Ebastine and 17.7% with Rupatadine.
when awakening at the end of the 24 h dosing interval over a 4-weekperiod (55–57).
Topical H1-antihistamines. Intranasal H1-antihistamines are effect-
At its recommended therapeutic dose, it did not alter objective
ive in reducing itching, sneezing, runny nose and nasal congestion.
measures of psychomotor and cognitive function (58, 59). At five
Given ocularly, they are effective in reducing allergic eye symptoms.
times the recommended therapeutic dose, it did not cause clinically
They can be effective within 20 min of administration. Topical H1-
relevant changes in the QTc interval (60). There is no effect of food
antihistamines require twice a day dosing. In general, topical H1-
intake in the efficacy of Ebastine (61).
antihistamines are well tolerated. However, both oral and topicalantihistamines are significantly less effective than intranasal gluco-
Fexofenadine. In one study, Fexofenadine (120 mg OD) was signi-
corticosteroids for the treatment of allergic rhinitis, particularly for
ficantly more effective than Loratadine in relieving eye symptoms and
nasal congestion and was significantly better than Loratadine inimproving the rhinitis-quality-of-life questionnaire (RQLQ) (62).
Nasal administration. Azelastine nasal spray was found to be an
In 259 patients, no differences were found between the Fexofen-
effective treatment for patients with seasonal allergic rhinitis who do
adine and placebo groups on reaction times, decision-making or
not respond to loratadine and is an alternative to switching to
another oral antihistamine or to using multiple antihistamines (80).
Fexofenadine was efficacious and safe in 6- to 11-year-old chil-
Azelastine nasal spray is effective in treating severe seasonal allergic
dren with seasonal allergic rhinitis (64, 65).
rhinitis patients who remain symptomatic after treatment withFexofenadine (81).
Emedastine. Emedastine was studied in a double-blind, random-ized, parallel-group trial without a placebo group (66).
Ocular administration. A 10-week, randomized, double-blind, par-allel group compared olopatadine 0.1% ophthalmic solution BID vs
Levocetirizine. In the treatment of seasonal allergic rhinitis, by
placebo in 131 patients with pollen-induced rhinitis and conjunc-
comparison with other dosages, Levocetirizine 5 mg OD has an
tivitis. Olopatadine controlled ocular and nasal symptoms and was
optimal benefit/risk ratio (67). Levocetirizine is effective for the
relief of nasal congestion in adolescents and adults (perennial
Epinastine has been tested in a randomized, double-blind, par-
allergic rhinitis) sensitized to house dust mites (68). In this study,
allel-group study without a placebo arm in patients with allergic
somnolence was reported in 2.8% of the placebo group and in 6.0%
An important trial examined the effect of Levocetirizine given for
Intranasal glucocorticosteroids. Glucocorticosteroids are the most
over 6 months to 551 patients with moderate to severe persistent
efficacious medications available for the treatment of allergic and
allergic rhinitis (XPERTÒ study). It was found that, compared with
non-allergic rhinitis. The rationale for using intranasal glucocorti-
placebo, Levocetirizine improves nasal symptoms including nasal
costeroids in the treatment of allergic rhinitis is that high drug
obstruction and quality of life (RQLQ and SF-36) and reduces
concentrations can be achieved at receptor sites in the nasal mucosa,
medical costs involved in the long-term management of these pa-
with minimal risk of systemic adverse effects. Because of their
tients (69). Levocetirizine is currently the only antihistamine with
mechanism of action, efficacy appears after 7–8 h of dosing, but
the indication of persistent allergic rhinitis in Europe.
maximum efficacy may require up to 2 weeks. These medications
Single and repeated doses of Levocetirizine have no effect on
are effective at improving all symptoms of allergic rhinitis. For nasal
cognitive and psychomotor functions in healthy volunteers (70–72)
congestion or frequent symptoms, an intranasal glucocorticosteroid
is the most appropriate first-line treatment. Intranasal glucocorti-costeroids are well tolerated and adverse effects are uncommon, of
Loratadine. Loratadine syrup 5 or 10 mg OD was effective in
mild severity and have approximately the same incidence as
improving the symptom scores of children aged 3–12 years with
placebo. Evidence shows that the long-term use of intranasal
allergic rhinitis without side effects (74). Loratadine was well
glucocorticosteroids is free of the concerns associated with the long-
tolerated by a selected group of children aged 2–5 years at a dose
term use of oral glucocorticosteroids.
similar to the adult dose (i.e. 10 mg per day) (75). Learning and
Ideal properties which should be met by intranasal Glucocorti-
response time in children attending a laboratory school were not
costeroids are listed in Table 2 (35).
Table 2. Optimal properties of intranasal glucocorticosteroids
Fluticasone propionate. Fluticasone propionate aqueous nasal spray[when used as needed (PRN) (84, 85)] improves nasal symptoms of
seasonal allergic rhinitis. PRN has a lower incidence of adverse
events than typically associated with regular one per day use (85).
The PRN use of Fluticasone propionate has been approved in some
countries. Future studies are still needed to show the optimal use of
intranasal glucocorticosteroids in the controlling of nasal symp-
toms, especially in persistent allergic rhinitis. It has been confirmed
Effective in the treatment of intermittent and persistent rhinitis as defined
by one of the studies that a significant difference of total symptom
scores between the treatment of fluticasone propionate aqueous and
placebo was found only after 5 days of treatment (84). Whether
there is a need for a minimum duration of treatment by intranasal
glucocorticosteroids in PRN remains to be investigated.
Improvement of asthma symptoms (short-term studies)
A randomized placebo-controlled trial compared Fluticasone
Reduction of asthma exacerbations (long-term studies)
propionate aqueous nasal spray in mono-therapy, Fluticasone
An improvement in pulmonary function tests, even though in pollen-induced
propionate plus Cetirizine, Fluticasone propionate plus Montelukast
bronchial symptoms, FEV1 and peak flow rates are usually not altered
and Cetirizine plus Montelukast for seasonal allergic rhinitis (98). The
If a claim for nasal polyposis or sinusitis is proposed, adequate appropriate trials
results of this comparative study showed that Fluticasone propionate
is highly effective for treating patients with allergic rhinitis, with an
If a claim for a preventive effect is proposed, appropriate trials should be
efficacy exceeding that of Cetirizine plus Montelukast in combined
therapy. This study also suggested that there was little advantage in
adding Cetirizine or Montelukast to Fluticasone propionate.
Intranasal Fluticasone propionate is also effective for treating
perennial non-allergic rhinitis with or without eosinophilia (99) and
significantly improves ocular symptoms in patients with seasonal
And in association with the inhaled (intrabronchial) form
No long-term effect on growth in children
The effect of drugs on sleep in allergic rhinitis has already been
reported. A recent study reported an improvement in subjective
sleep disturbances in perennial allergic rhinitis treated with intra-
nasal Fluticasone propionate for 8 weeks. However, polysomnog-
raphy, the current gold standard for sleep studies, was unchanged
Long duration of action, at least 24 h, ability to be administered once a day
If a claim for a prn use is proposed, appropriate trials should be conducted
Rhinitis during pregnancy, a common condition with long-
Comparison with other drugs used to treat rhinitis
standing nasal congestion, is troublesome for the mother. A studyof 53 pregnant women showed no effect of Fluticasone propionate
Clinical and pharmacologic effects. The onset of action of intranasal
on fetal growth or pregnancy outcome (102). Although safe in
corticosteroids may be shorter than previously thought (84, 85).
pregnant women, it was not very effective for this condition.
Budesonide is effective after 12 h of administration (86).
Intranasal Fluticasone propionate was tested for its effect on the
bioavailability and pharmacokinetics of single-dose intranasal
important but may depend on local costs. Few studies are available.
Hydromorphone hydrochloride in patients with allergic rhinitis(103). Hydromorphone was rapidly absorbed after nasal adminis-
Side effects of intranasal glucocorticosteroids. In children, the rate of
tration, with maximum concentrations occurring for most subjects
growth was slightly reduced in those regularly treated twice a day
within 30 min suggesting that Fluticasone propionate does not
with intranasal Beclomethasone over 1 year (87). However, no
growth slowing has been observed in 1 year follow-up studies ofchildren treated with Fluticasone propionate (88) or Mometasone
Mometasone furoate. Mometasone furoate nasal spray relieves
furoate (89–91). Moreover, a pharmacokinetic/pharmacodynamic
cough and nasal symptoms associated with seasonal allergic rhinitis
model of the relationship between systemic corticosteroid exposure
and growth velocity has been proposed and may be useful for thedevelopment of future locally acting corticosteroids (90, 91).
Triamcinolone acetonide. Intranasal Triamcinolone acetonide gi-
Budesonide aqueous nasal spray does not affect the HPA-axis in
ven for 4 weeks improves symptom scores and RQLQ in patients
children with allergic rhinitis (92). Concurrent use of intranasal and
with perennial allergic rhinitis. The ability of Triamcinolone to
orally inhaled Fluticasone propionate does not affect hypothalamic-
relieve nasal congestion symptoms was correlated with improve-
pituitary-adrenal-axis function (93).
ments in RQLQ (105). The Food and Drug Administration
In a study of 360 patients with allergic rhinitis, Fluticasone
(FDA) recently approved the HFA formulation of Triamcinolone
propionate, Mometasone furoate and Beclomethasone dipropionate
caused variations in the intraocular pressure measured by Gold-man’s tonometry at 3 weeks, 6 weeks, 3 months, 6 months and
Decongestants. The decongestant effect of an H1-antihistamine
1 year, but the variations were within normal limits (94).
Pseudoephedrine fixed-dose combination was demonstrated by
In the elderly, intranasal corticosteroids, at the recommended dose,
using the novel method of endoscopic inferior turbinate photogra-
have not been associated with an increased risk of fractures (95).
phy, in addition to acoustic rhinometry and visual analogue scalescores (106). Pseudoephedrine has been banned for Olympic
Budesonide. Allergic contact dermatitis has occasionally been
athletes. This has important implications for the correct and
reported after the intranasal or inhaled administration of Budeso-
prominent labeling of pharmacologic treatments for rhinitis,
particularly for over-the-counter remedies.
Antileukotrienes. Several pivotal studies of seasonal allergic rhinitis
compared Montelukast and placebo, and in some studies thecombination Montelukast-Loratadine (107–111). Montelukast, in
trials involving a large number of patients, was consistently more
effective than placebo for all nasal and ocular symptoms and there
was no significant difference between Montelukast and Loratadine,
even for nasal obstruction. Moreover, contrary to the first study
(112), the combination Montelukast-Loratadine did not provide
any statistically significant additive beneficial effect to the two drugs
given alone. In all these studies, Montelukast improved all nasal
symptoms of rhinitis, symptoms of conjunctivitis and RQLQ, and
was well tolerated. Montelukast is equally effective in patients
exposed to low and high pollen counts (111). In a study carried outin patients with seasonal allergic rhinitis and asthma, Montelukast
B*: by extension of studies in persistent allergic rhinitis of 4 weeks and longer, but
was found to improve nasal and bronchial symptoms (113).
studies using the new classification have to be performed to confirm efficacy in this
As-needed beta-agonist use (puffs/day) was also reduced with
Montelukast. Combined Montelukast and Cetirizine treatment,
B**: by extension of studies in seasonal allergic rhinitis of 4 weeks.
when started 6 weeks before the pollen season, is effective in
A***: most studies included small numbers of patients.
preventing AR symptoms and reduces allergic inflammation in the
nasal mucosa during natural allergen exposure (114).
Leukotriene receptor antagonists are less effective in allergic rhi-
nitis than intranasal corticosteroids and have an efficacy similar tooral H
al SIT decreases ocular and nasal symptom scores and
Montelukast does not modify skin prick test results (117, 118) and
rescue medication use in grass pollen allergic children
therefore does not need to be discontinued before skin testing.
(132). This combination might prove useful for thetreatment of allergic rhinitis, particularly for polysensi-
Humanized monoclonal antibodies against IgE
The recombinant humanized monoclonal anti-IgE anti-
body (Omalizumab) forms complexes with free IgE,blocking its interaction with mast cells and basophils
Perennial rhinitis in children under 4 years of age is a
and lowering free IgE levels in the circulation. In a large
difficult problem to treat safely and effectively. A rand-
pivotal trial, Omalizumab decreased serum free IgE levels
omized, multicentre, double-blind, double dummy, pla-
and provided clinical benefit in a dose-dependent fashion
cebo-controlled study compared intranasal Fluticasone
in patients with seasonal allergic rhinitis (119). Oma-
propionate and ketotifen (133). Generally, except for
lizumlab was found to decrease all nasal symptoms and
nasal itching/rubbing over weeks 1–3, the patients taking
improve RQLQ in patients with rhinitis induced by birch
Fluticasone propionate had lower recorded symptom
and ragweed pollens as well as in patients with sensiti-
scores for all individual symptoms measured. Nasal
zation to outdoor allergens (adults and adolescents) (120,
blockage, in particular, was significantly reduced over
121). Moreover, the treatment was safe and well tolerated
the 4–6-week periods. There were no reports of serious
(122, 123). In patients with asthma and rhinitis, Oma-
adverse events, the incidence of drug-related adverse
lizumab improved nasal and bronchial symptoms and
events was low and there was no statistical difference in
reduced unscheduled visits to physicians for asthma
regard to safety between the groups.
(124). The clinical benefit of treatment with Omalizumabis associated with an anti-inflammatory effect on cellularmarkers in blood and nasal tissue (125, 126) as well as a
reduction in mast cell FceRI expression and function(127). Omalizumab inhibits allergen challenge-induced
New studies have been performed since the ARIA
nasal response (128). Omalizumab rapidly decreases nasal
workshop report and they are listed in this report. A
allergic response and FceRI on basophils (129) and
revised level of evidence can be proposed (Table 3). It is
dendritic cells (130). The relative efficiency of this
clear that studies using the new ARIA classification
treatment compared to H1-antihistamines and intranasal
(intermittent and persistent rhinitis) should be carried out
glucocorticosteroids needs to be established.
for all treatments in order to fully appreciate the efficacy
Specific immunotherapy (SIT) and treatment with
of treatments used in allergic rhinitis.
monoclonal anti-IgE antibodies have complementarymodes of action. Omalizumab conferred a protectiveeffect independent of the type of allergen. Additional
clinical benefit was demonstrated in both pollen seasons,whether there was coverage by SIT or not (131). The
The authors would like to thank Drs R Dubakiene and V Lund for
co-seasonal application of Omalizumab after pre-season-
subjects with seasonal allergic rhinitis.
Allergy Asthma Proc 2004;25:59–68.
12. Perry TT, Corren J, Philip G, Kim EH,
macy. Allergic rhinitis and its impact on
lergy Clin Immunol 2003;111:770–776.
Curr Med Res Opin 2004;20:891–902.
trolled trial. Allergy 2003;58:733–741.
Coutie WJ, Paterson MC, Lipworth BJ.
flow. Clin Exp Allergy 2000;30:833–838.
23. Penttila M, Poulsen P, Hollingworth K,
allergic rhinitis in an allergen-exposure
and tolerability of fluticasone propion-
twice daily in the treatment of bilateral
function in seasonal allergic rhinitis.
symptoms of seasonal allergic rhinitis.
antagonists in seasonal allergic rhinitis.
nasal spray. Rhinology 2001;39:75–79.
Williams JW Jr, Califf RM, Simel DL.
Trial: a randomized controlled trial.
tration of topical budesonide to allergic
patients with chronic rhinosinusitis fol-
with perennial allergic rhinitis. Clin Exp
27. Bucher HC, Tschudi P, Young J, Periat
fect of amoxicillin-clavulanate in clinic-
omized trial in general practice. ArchIntern Med 2003;163:1793–1798.
patients. Rhinology 2004;42:57–62.
29. Kiely JL, Nolan P, McNicholas WT.
et al. Safety of cetirizine in infants 6 to
treatment with intranasal budesonide.
31. Leurs R, Church MK, Taglialatela M.
tirizine on the behavioral, cognitive, and
young children with atopic dermatitis.
effects. Clin Exp Allergy 2002;32:489–
52. Banfield C, Herron J, Keung A, Padhi
system side effects of first- and second-
children with perennial allergic rhinitis:
Bousquet J. Structure and classification
tween desloratadine and erythromycin.
Marino M, Clement R, Affrime M et al.
44. Salmun LM, Lorber R. 24-hour efficacy
patients with seasonal allergic rhinitis.
tis and its Impact on Asthma (ARIA).
impact of payer policies after the Rx-to-
Pace JE, Solomon MD, Laouri M et al.
47. Simons FE, Prenner BM, Finn A Jr.
seasonal allergic rhinitis. J Investig Al-
lergol Clin Immunol 2004;14:56–63.
48. Berger WE, Schenkel EJ, Mansfield LE.
allergic rhinitis and nasal congestion.
seasonal allergic rhinitis: a randomized,
double-blind, placebo-controlled study.
58. Hindmarch I, Shamsi Z. The effects of
68. Potter PC. Levocetirizine is effective for
tine provides effective symptom relief in
patients suffering from perennial aller-
dine and placebo in healthy volunteers.
Curr Med Res Opin 2001;17:273–281.
Durham SR, Klimek L, Mullol J et al.
et al. Differential cognitive effects of
agement of persistent allergic rhinitis. J
70. Gandon JM, Allain H. Lack of effect of
unsatisfactory response to loratadine.
sub-chronic effects of levocetirizine, ce-
cebo-controlled study of the efficacy and
motor performance, and weal and flare.
ment of seasonal allergic rhinitis. J Clin
Curr Med Res Opin 2001;17:241–255.
junctivitis. Clin Ther 2003;25:931–947.
EJ et al. Driving ability after acute and
with seasonal allergic conjunctivitis.
safe in children (aged 6–11 years) with
seasonal allergic rhinitis. J Allergy Clin
treatment of allergic rhinitis in children
allergic rhinitis – a pooled analysis of
syrup in children aged 2 to 5 years. Clin
H. Children’s school performance is not
perennial allergic rhinitis, with an onset
67. Leynadier F, Mees K, Arendt C, Pinelli
ME. Efficacy and safety of levocetirizine
histamine effects on children’s learning.
rhinolaryngol Belg 2001;55:305–312.
Chervinsky P, Morris R, Seltzer J et al.
corticosteroids in patients using inhaled
or intranasal corticosteroids for allergic
fluticasone plus cetirizine, fluticasone
lergy Asthma Proc 2002;23:407–413.
tis. Clin Exp Allergy 2004;34:259–267.
109. Van Adelsberg J, Philip G, Pedinoff AJ,
Meltzer EO, Ratner PH, Menten J et al.
children with perennial allergic rhinitis
et al. Intranasal fluticasone propionate
treatment period. Allergy 2003;58:1268–
rhinitis with or without eosinophilia.
110. Van Adelsberg J, Philip G, Laforce CF,
Baidoo CA, Cook CK, Philpot EE et al.
uating the clinical benefit of monteluk-
ast for treating spring seasonal allergic
Bardelas J, Nayak A, Marchal JL et al.
rhinitis: effect of pollen exposure in 3
V. The effect of topical nasal fluticasone
somnolence in perennial allergic rhinitis.
Allergy Asthma Proc 2003;24:53–58.
function in children with allergic rhini-
allergic rhinitis: a randomized, placebo-
controlled clinical trial. J Allergy Clin
Leynadier F, Vrijens F, Dass SB et al.
of fluticasone propionate nasal spray on
Astorga Del Toro R, Bravo-Escobar G.
rhinitis: influence on clinical symptoms
Effects of three nasal topical steroids in
and nasal allergic inflammation. Allergy
the intraocular pressure compartment.
115. Pullerits T, Praks L, Ristioja V, Lotvall
of life in patients with persistent allergic
96. Isaksson M, Bruze M. Allergic contact
reactivated by inhalation of the allergen.
J Am Acad Dermatol 2002;46:880–885.
symptoms in seasonal allergic rhinitis: a
antagonists for allergic rhinitis: a sys-
double-blind, placebo-controlled study.
129. Lin H, Boesel KM, Griffith DT, Prussin
response and FcepsilonRI on basophils.
lergy Asthma Immunol 2001;86:44–50.
118. Hill SL III, Krouse JH. The effects of
130. Prussin C, Griffith DT, Boesel KM, Lin
Boulet LP, Hedgecock S, Blogg M et al.
120. Adelroth E, Rak S, Haahtela T, Aasand
et al. The effect of omalizumab on nasal
G, Rosenhall L, Zetterstrom O et al.
adolescents with seasonal allergic rhini-
126. Bez C, Schubert R, Kopp M, Ersfeld Y,
seasonal allergic rhinitis. J Allergy Clin
cation use in grass pollen allergic chil-
128. Hanf G, Noga O, O’Connor A, Kunkel
problem to treat safely and effectively?
A et al. Tolerability of retreatment with
tients with seasonal allergic rhinitis.
Allergy Asthma Proc 2003;24:323–329.
Riassunto delle caratteristiche del prodotto eventi avversi di fratture ossee riportati da studi clinici randomizzati, controllati, in doppio ciecoin oltre 8.100 pazienti trattati con pioglitazone e 7.400 trattati con farmaco di confronto per unperiodo superiore ai 3,5 anni, è stata osservata un’aumentata incidenza di fratture ossee nelledonne. Sono state osservate fratture nel 2,6% delle
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