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

SummaryAllergen 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

Complementary and alternative medicine for the treatment and diagnosis of asthma and allergic diseases

The use of Complementary/Alternative Medicines (CAM) is largely diffused and constantly increasing, especially in the field of allergic diseases and asthma. Homeopathy, acupuncture and phytotherapy are the most frequently utilised treatments, whereas complementary diagnostic techniques are mainly used in the field of food allergy- intolerance. Looking at the literature, the majority of clinical trials with CAMS are of low methodological quality, thus difficult to interpret. There are very few studies performed in a rigorously controlled fashion, and those studies provided inconclusive results. In asthma, none of the CAM have thus far been proved more effective than placebo or equally effective as standard treatments. Some herbal products, containing active principles, have displayed some clinical effect, but the herbal remedies are usually not standardised and not quantified, thus carry the risk of toxic effects or interactions. None of the alternative diagnostic techniques (electrodermal testing, kinesiology, leukocytotoxic test, iridology, hair analysis) have been proved able to distinguish between healthy and allergic subjects or to diagnose sensitizations. Therefore these tests must not be used, since they can lead to delayed or incorrect diagnosis and therapy

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 0.87–1.22, 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

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

100 Years of Immunotherapy: The Monaco Charter

Aims of the Monaco Charter: (1) to present the current evidence on the efficacy and safety of allergen-specific immunotherapy (SIT) and to address the reasons for its underuse in clinical practice; (2) to develop strategies to increase the awareness about the benefits and the hazards of SIT in allergic patients, lay public and healthcare professionals not trained in allergy, and (3) to make SIT accessible and affordable to eligible patient

Specific immunotherapy by the sublingual route for respiratory allergy

Specific immunotherapy is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy. Sublingual immunotherapy (SLIT) was introduced as an option to subcutaneous immunotherapy (SCIT), the clinical effectiveness of which is partly counterbalanced by the issue of adverse systemic reactions, which occur at a frequency of about 0.2% of injections and 2-5% of the patients and may also be life-threatening. A large number of trials, globally evaluated by several meta-analyses, demonstrated that SLIT is an effective and safe treatment for allergic rhinitis and allergic asthma, severe reactions being extremely rare. The application of SLIT is favored by a good compliance, higher than that reported for SCIT, in which the injections are a major factor for noncompliance because of inconvenience, and by its cost-effectiveness. In fact, a number of studies showed that SLIT may be very beneficial to the healthcare system, especially when its effectiveness persists after treatment withdrawal because of the induced immunologic changes

Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews

Background: there is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma.Objectives: to undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma.Methods: we searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized.Results: we identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions.Conclusions: AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT