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.
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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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