The role of allergoids in allergen immunotherapy: from injective to sublingual route.

Summary: Summary Allergen immunotherapy (AIT) is aimed at inducing tolerance to allergens, such as pollens, dust mites or moulds, by administering increasing amounts of the causative allergen through subcutaneous or sublingual route. The evidence of efficacy of AIT is high, but the issue of safety, especially for the subcutaneous route, must be taken into account. The search for safer AIT products aimed at reducing the allergenicity, and thus adverse reactions, while maintaining the immunogenicity, that is essential for effectiveness, gave rise to the introduction of allergoids, which were conceived to fulfill these requirements. In the first allergoids glutaraldehyde or formaldehyde were used as cross-linking agent to polymerize allergens, this resulting in high molecular weight molecules (200,000 to 20,000,000 daltons) which were significantly less allergenic due to a decreased capacity to bridge IgE on its specific receptor, while maintaining the immunogenicity and thus the therapeutic efficacy. In recent years further agents, acting as adjuvants, such as L-tyrosine, monophosphoryl lipid A, aluminium hydroxide, were added to polymerized extracts. Moreover, a carbamylated monomeric allergoid was developed and, once adsorbed on calcium phosphate matrix, used by subcutaneous route. At the same time, in virtue of its peculiarities, such allergoid revealed particularly suitable for sublingual administration. A lot of clinical evidences show that it is well tolerated, largely safer and effective. Importantly, the higher safety of allergoids allows faster treatment schedules that favor patient compliance and, according to pharmaco-economic studies, they might be more cost-effective than other AIT options.

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

BACKGROUND: In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. METHODS: In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. RESULTS: The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P < 0.1). The percentage of patients with an improved CPT threshold was higher in the active treatment groups (300 UA/day: 73.9%; 1000 UA/day: 76.0%; 2000 UA/day: 88.5%; 3000 UA/day: 76.0%) than in the placebo group (64.3%). The difference between placebo and 2000 UA/day was statistically significant (P = 0.04). In 13 (10%) exposed patients, a total of 20 treatment-related adverse events of mild severity were observed. CONCLUSIONS: The 12-week daily treatment using 2000 UA/day monomeric allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients.

The contribution of sublingual immunotherapy to the achievement of control in birch-related mild persistent asthma: a real-life randomised trial.

BACKGROUND: Asthma control represents the main goal of asthma management and different strategies aim to avoid the long term downsides of inhaled corticosteroids. We investigated in real-life conditions the contribution of sublingual immunotherapy in achieving the control of birch-related mild persistent asthma compared to two usual step-up therapeutic options. METHODS: A three-year open randomised study included 84 asthmatics, uncontrolled during the previous birch pollen season, despite a treatment with budesonide 400µg/day. Patients randomly received budesonide 800µg/day, budesonide 1600µg/day, budesonide 400µg/day plus montelukast 10µg/day and budesonide 400µg/day plus carbamylated allergoid of betulaceae pre-coseasonally. Asthma Control test, combined allergy symptoms and medications score, albuterol consumption, lung function, nasal eosinophils and nasal steroids usage were assessed as changes from the first to last pollen season. RESULT: Seventy-six patients concluded the study. All options, except budesonide 800µg/day, produced an improvement of mean monthly Asthma Control test (p<0.05). Patients undergoing low-dose budesonide plus immunotherapy achieved, after three years, an appreciable control (ACT mean score 24). A significant improvement was seen in all groups for allergy symptoms plus medications and bronchial reactivity. Albuterol consumption and lung function improved in all but the first group. Only budesonide plus immunotherapy reduced nasal eosinophils and nasal steroids usage. Two mild self-resolving adverse events were reported. CONCLUSIONS: For patients with respiratory allergy due to birch pollen and mild persistent asthma, sublingual immunotherapy added to low-dose inhaled corticosteroids appears effective in maintaining long-term seasonal asthma control, representing a safe opportunity to reduce the cumulative amount of delivered corticosteroids.

Effect of two doses of carbamylated allergoid extract of dust mite on nasal reactivity.

Background and Objective. Single SLIT studies with native allergen extracts support a dose-response effect for clinical and immunological outcomes. Conversely for carbamylated allergoids this dose-response effects is less evident, likely because the threshold for efficacy is more easily reached through the enhanced bioavailability of the extract consequent to the selective chemical modification. Thus this pilot study investigates the dose-response effect on nasal specific reactivity and safety of two unusual doses of carbamylated allergoid in patients mono-sensitized to house dust mites. Methods. A prospective open randomized study involved 6-65 year-old Italian patients with clinically relevant sensitization to house dust mites and positive response to nasal provocation challenge. Monomeric carbamylated allergoid was delivered once daily at the dose of 1000 AU or 2000 AU from June to September 2009, during the lowest level of mites exposure. Primary outcomes were the change of the threshold of allergen concentration for a positive nasal provocation test (NPT) before and after the treatment and the product safety. Secondary outcome was the change  in the mean percentage fall of peak nasal inspiratory flow (PNIF) following nasal challenge. Results. Thirty-four patients were enrolled. Fifteen in group 1 and 14 in group 2 concluded the study. After 12 weeks all patients treated in group 1 and all but one in group 2 showed an increase in the threshold dose provoking a positive NPT. Those with no symptoms onset with the highest dose delivered were 80% in group 1 and 78.6% in group 2 (p=0.92). From first to second challenge, the mean percentage fall of PNIF  was reduced with no statistical difference between groups (p=0.95), and with no difference between the final mean percentage falls (p=0.65). No serious adverse reactions occurred and the frequency of events, all mild, was similar in the two groups. Conclusions. Twelve weeks of carbamylated sublingual allergoid delivered at 1000AU or 2000AU once daily appear equally safe and show comparable effect in increasing  the threshold of allergen concentration for a positive nasal provocation test, confirming the apparent absence of a dose response effect for the used doses.

Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis.

Cow's milk is a common cause of food allergy in children. Children usually outgrow cow's milk allergy by the age of 3-5 years, but some will have persistent symptoms beyond childhood. We performed a systematic review of randomized controlled trials (RCTs) and observational studies to assess the evidence supporting the use of oral immunotherapy in IgE-mediated cow's milk allergy to inform the World Allergy Organization guidelines. Of 1034 screened articles published until May 2011, five RCTs and five observational studies fulfilled a priori specified inclusion criteria. RCTs including 218 patients showed that oral immunotherapy, compared to elimination diet alone, increased the likelihood of achieving full tolerance of cow's milk [relative risk: 10.0 (95% CI: 4.1-24.2)]. Adverse effects of immunotherapy include frequent local symptoms (16% of doses), mild laryngospasm [relative risk: 12.9 (1.7-98.6)], mild asthma [rate ratio: 3.8 (2.9-5.0)], reactions requiring oral glucocorticosteroids [relative risk: 11.3 (2.7-46.5)] or intramuscular epinephrine injection [rate ratio 5.8 (1.6-21.9)]. Results of observational studies were consistent with those of RCTs. Despite the availability of RCTs, the overall low quality of evidence leaves important uncertainty about anticipated effects of immunotherapy due to very serious imprecision of the estimates of effects and the likelihood of publication bias for some of the critical outcomes. A potentially large benefit of oral immunotherapy in patients with cow's milk allergy may be counterbalanced by frequent and sometimes serious adverse effects. Additional, larger RCTs measuring all patient-important outcomes are still needed.

Systematic review on the efficacy of fexofenadine in seasonal allergic rhinitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

RATIONALE: Evidence-based medicine represents the effort to highlight the best intervention for patients, clinicians, and policy makers, each from their respective viewpoint, to solve a particular health condition. According to a recently diffused grading system of evidence and recommendations for medical interventions, efficacy and safety represent 2 of the most important features to consider, and data from meta-analyses of randomized controlled clinical trials (RCTs) is the strongest supporting demonstration. Fexofenadine has been used for its efficacy and safety in the treatment of allergic rhinitis (AR) for many years although no meta-analyses supporting its use currently exist. The aim of this study is to assess for the first time the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analytic analysis of existing RCTs. Since specific evidence should be provided to address recommendations in a pediatric population, the quality of the estimates of this subgroup analysis is assessed. METHODS: All double-blind, placebo-controlled randomized trials assessing the efficacy of fexofenadine in AR were searched for in OVID, Medline, and Embase databases up to December 2007. Outcomes were extracted from original articles; when this information was not available, the authors of each trial were contacted. Some graphics were digitalized. The RevMan 5 program was used to perform the analysis. GradePro 3.2.2 was used to assess the quality of the evidence for a pediatric population. RESULTS: Of 2,152 identified articles, 20 were potentially relevant trials. Eight studies satisfied the inclusion criteria and were included in the meta-analysis. The main reasons for exclusion were: unnatural exposure, strong study limitations, an atypical outcome measurement, a design for other outcomes, and not being a placebo-controlled, single-blind study. Seven trials investigated a mixed population of adults and children, 1 trial investigated only children, and 1 trial only adults. In 1,833 patients receiving fexofenadine (1,699 placebo), a significant reduction of the daily reflective total symptom scores (TSS) (SMD ­0.42; 95% CI ­0.49 to ­0.35, p < 0.00001) was found. Positive results were also found for morning instantaneous TSS and individual nasal symptom scores (sneezing, rhinorrhea, itching, and congestion). The safety analysis did not show a significant difference in reported adverse events (AE) between the active and placebo treatment groups (OR = 1.03; 95% CI 0.87­1.22, p = 0.75). A very low heterogeneity between the studies was detected, so a fixed-effects model was used. The mean quality level of the included trials was medium. Specific information for a pediatric population may be assumed with a moderate quality of evidence from only 1 study and with a low quality of evidence, mainly due to indirectness, from the others. CONCLUSIONS: This study has 5 major strengths: it represents the first attempt to evaluate the efficacy and safety of fexofenadine in the treatment of AR by means of a meta-analysis of RCTs; there was consistency between positive results in terms of efficacy in TSS and in individual symptoms; a large population was studied; there was an irrelevant interstudy heterogeneity, and the AE frequency was similar in both groups. All of these values encourage the recommendation of fexofenadine for AR. Further research focused on the benefits and disadvantages for a pediatric population is needed.

Risk assessment of immediate systemic reactions from skin tests with ß-lactam antibiotics.

BACKGROUND: Some clinical studies have demonstrated that skin tests for ß-lactam antibiotics may cause more adverse reactions than skin tests for common allergens. OBJECTIVE: To assess the risk of systemic reactions from penicillin skin testing, based on a pre-test categorization of patients, in order to establish an appropriate strategy for preempting and dealing with cases. METHODS: A case series of 175 patients with a suspected allergy to penicillin was reviewed, and patients were classified as having a low or high probability of allergic sensitization to penicillin, according to their clinical history. For every group, the rate and the increase in the relative risk (RRI) of systemic reactions by skin testing were calculated. The results were compared to those reported in the available literature. RESULTS: In our case series of 175 patients, 52 were classified as having a high probability of being allergic to penicillin, according to their clinical history. Five systemic reactions to skin testing were observed, and these were exclusively in this group (9.61%, RRI = 479). In agreement with the literature, patients with a high likelihood of penicillin allergy showed an increase of up to 10% in the occurrence of systemic reactions at skin testing; in patients who had had severe allergic reactions, this figure was up to 20%. CONCLUSIONS: The RRI of systemic reactions by skin testing is proportional to the pre-test probability of a true immediate hypersensitivity reaction to ß-lactam antibiotics. In the present case series, only patients with high pre-test probability were at risk, and this group should therefore be skin tested and monitored in a hospitalization regimen, where resuscitation staff and access to an emergency room are immediately available.

Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA(2) LEN taskforce position paper.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations and suggestions for assessing patient-reported outcomes (PROs) including health-related quality of life in patients with urticaria. We recommend that PROs should be used both in clinical trials and routine practice for the evaluation of urticaria patients. We suggest that PROs should be considered as the primary outcome of future clinical trials. Two validated and disease-specific instruments for assessing PROs are available, the urticaria activity score (for symptoms) and the chronic urticaria questionnaire on quality of life CU-Q(2)oL. This latter tool, CU-Q(2)oL, is available in many languages and should be preferred, where available, over more generic instruments for assessing urticaria-specific effects on quality of life. CU-Q(2)oL is only suited for the investigation of patients with chronic spontaneous urticaria. Similar instruments for other forms of urticaria have yet to be developed and validated. Also, tools for assessing other chronic spontaneous urticaria PROs besides quality of life and symptoms are needed.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Effects of mometasone furoate on the quality of life: a randomized placebo-controlled trial in persistent allergic rhinitis and intermittent asthma using the Rhinasthma questionnaire.

BACKGROUND: Allergic rhinitis, especially when persistent (PER) and associated with asthma heavily impairs patients' quality of life (QoL). OBJECTIVE: This study assessed the effect of mometasone furoate nasal spray (MFNS) on the QoL of patients with PER and asthma, using the Rhinasthma questionnaire (EUDRACT n. 2007-004683-45). METHODS: Patients with moderate/severe PER and intermittent asthma were randomized to MFNS (alcohol-free) 200 µg/day or placebo for 28 days. Rhinasthma was completed at baseline and at weeks 2 and 4. The total five symptom score (T5SS) for rhinitis, the asthma symptom score and the sum of the two [global symptoms score (GSS)] were recorded daily. The primary outcome was the change in the Rhinasthma global summary (GS) at the end of treatment. Secondary end-points were (a) the change from baseline to end of treatment of each Rhinasthma factor: upper airways (UAs), lower airways (LAs) and respiratory allergy impact; (b) the change from baseline to end of treatment of the T5SS and of the GSS and (c) the use of rescue medication. RESULTS: Fifty-two adults were randomized. Compared with placebo, MFNS produced a significant change in the Rhinasthma GS (-10.4 vs. 0.4; P<0.01). MFNS also achieved a significant improvement of the UA (-16.6 vs. 0.1; P<0.001), LA (-10.8 vs. 1.1; P<0.001) and GSS (-6.7 vs. -3.1; P=0.019). The change of the T5SS was greater in the MFNS group but did not reach statistical significance. CONCLUSION: In patients with PER rhinitis and intermittent asthma, MFNS improves the QoL and the burden of respiratory symptoms. Treating rhinitis may affect the asthma-related QoL.

Efficacy and safety of sublingual immunotherapy with grass monomeric allergoid: comparison between two different treatment regimens.

BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric carbamylated allergoid proved to be well tolerated, safe and effective in patients with respiratory allergy. Standard administration regimens are expected to require a long time before clinical benefit can be appreciated. We investigated whether pre-seasonal and perennial regimens differently affect the clinical efficacy of grass pollen SLIT. METHODS: Adult patients with allergic rhino-conjunctivitis with/without mild intermittent asthma due to grass pollen were included into this open prospective study and randomised to receive SLIT with a continuous regimen (Group 1: 1,000 AU/week for the entire study period) or a pre-seasonal regimen (Group 2: 5,000 AU/week for 10 weeks/year for 2 years), or on demand drug therapy alone (Group 3) for two years. At entry (November 2005), at the end of the first and second pollen season, a Visual Analogue Scale (VAS) was used to assess patients' well-being. Symptom score and drug consumption were evaluated during the seasons. Methacholine challenge was performed at study entry and conclusion. Adverse events were recorded along the whole study duration. RESULTS: Thirty-two patients were divided into Group 1 (n = 10), Group 2 (n = 11) and Group 3 (n = 11). A significant VAS improvement was observed in both SLIT groups, after the first and second pollen season, compared to baseline and to Group 3 (p < 0.05). Less symptoms and need for medications resulted during the second season (p < 0.05). No relevant variations in bronchial hyper-reactivity have been observed between the three groups. Only 2 patients experienced local or mild reactions in SLIT groups. CONCLUSION: Both pre-seasonal and continuous regimen of SLIT with monomeric allergoid turned out effective and safe, suggesting that a pre-seasonal course with 5,000 AU/week for 10 weeks may represent a convenient option in patients with grass pollen allergic rhinitis with/without mild intermittent asthma. Further research is urgently needed to consolidate these preliminary evidences.

GAPP Italy: "A survey on asthma on Italian physicians and patients".

Guidelines recognize the importance of achieving and maintaining asthma control: the treatment strategies nw available allow the control of the great majority of patients with asthma but despite many efforts only 5% of patients achieve guideline-defined asthma control. The GAPP (The Global Asthma Physician and Patient survey) is a global quantitative survey with the aiim of identifying barriers to optimal management of asthma. Physicians and adult patients with persistent asthma have been interviewed with closed-ended questions questionnaire. This study has been conducted in 16 countries. In Italy the survey has revealed that physicians prescribe a combination of ICS and LABA more often in the other countries. They consider ICS the first-line treatment for mild persistent asthma. They are not completely satified with ICS because of local and systemic side effects. At the same time, the reason why patients change asthma medication is the potential for side effects. The two group responses were found to differ about the time spent discussing how to improve the management of asthma. A better communication between physician and patient and a new treatment option with lower side effect profile could be the key point to achieve asthma control in a larger number of patients.

Specific recommendations for PROs and HRQoL assessment in allergic rhinitis and/or asthma: a GA(2)LEN taskforce position paper.

The GA(2)LEN taskforce on Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) published in 2009 a position paper concerning PROS and HRQoL assessment in clinical trials on allergy. Because of the specificity of this topic in asthma and rhinitis, specific recommendations are needed. The aim of this position paper is to define PROs and their meaning in asthma and rhinitis research, explore the available tools to provide criteria for a proper choice, identify patient-related factor which could influence PROs assessment, define specific recommendations for assessment, analysis and results spreading, underline the unexplored areas and unmet needs. PROs assessment is gaining increasing importance, and it must be performed with a rigorous methodological procedure and using validated tools. This approach enables to better understand patient-related factors influencing clinical trials and real-life management outcomes, identify patients subgroups that can benefit from specific treatment and management plan and tailor treatment to address PROs (not only physician-defined targets) to improve asthma and rhinitis management.

Recommendations for assessing patient-reported outcomes and health-related quality of life in clinical trials on allergy: a GA(2)LEN taskforce position paper.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre-post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data.

The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis.

Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD -0.95; CI 95%-1.77 to -0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD -0.95; CI 95%-1.74 to -0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD -1.88; CI 95%-3.65 to -0.12 P = 0.04) in 89 patients, and AA (SMD -1.48; CI 95%-2.70 to -0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.

The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper.

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.

Minimal persistent inflammation in allergic rhinitis: implications for current treatment strategies.

Patients with allergic rhinitis have traditionally been placed into 'seasonal' and 'perennial' categories, which do not account for the subclinical inflammatory state that exists in many patients. In subjects with seasonal and perennial allergic rhinitis, even subthreshold doses of allergen have been found to cause inflammatory cell infiltration in the nasal mucosa, including increases in expression of cellular adhesion molecules, nasal and conjunctival eosinophilia, and other markers of inflammation, which do not result in overt allergy symptoms. This state - which has been termed 'minimal persistent inflammation'- may contribute to hyperreactivity and increased susceptibility to development of clinical symptoms as well as common co-morbidities of allergic rhinitis, such as asthma. Treating overt allergy symptoms as well as this underlying inflammatory state requires agents that have well-established clinical efficacy, convenient administration, potent anti-inflammatory effects and proven long-term safety, so that long-term continuous administration is feasible. Of the three major classes of commonly used allergic rhinitis medications - intranasal corticosteroids, anti-histamines, and anti-leukotrienes - intranasal corticosteroids appear to represent the most reasonable therapeutic option in patients who would benefit from continuous inhibition of persistent inflammation.

Inmunoterapia específica para enfermedades alérgicas respiratorias: estado de la cuestión de acuerdo a los metanálisis actuales / Specific inmunotherapy for respiratory allergy: state of the art according to current meta-analyses

Objetivos: evaluar la eficacia de la inmunoterapia alergeno especifica (IT)en el tratamiento del asma y la rinitis alérgica de niños y adultos, mediante el examen de diferentes metanálisis (MTA) realizados hasta la actualidad.

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials.

RATIONALE: Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta-analysis to determine the overall treatment effect. METHODS: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double-blind, placebo-controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non-nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta-analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. DATA SYNTHESIS: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD -0.49, 95% CI: -0.60 to -0.38; P < 0.00001; I(2) = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (-0.41; 95% CI: -0.56 to -0.27), rhinorrhoea (-0.44; 95% CI: -0.66 to -0.21), sneezing (-0.40; 95% CI: -0.57 to -0.23) and nasal itching (-0.39; 95% CI: -0.53 to -0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (-0.30; 95% CI: -0.43 to -0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81-1.20; P = 0.91). CONCLUSIONS: This meta-analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.