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Moises A Calderon - One of the best experts on this subject based on the ideXlab platform.

  • Guideline recommendations on the use of Allergen Immunotherapy in house dust mite allergy: Time for a change?
    Journal of Allergy and Clinical Immunology, 2017
    Co-Authors: Moises A Calderon, Jean Bousquet, G. Walter Canonica, Lars-olaf Cardell, Dolores Hernandez Rojas, Jörg Kleine-tebbe, Pascal Demoly
    Abstract:

    Guidelines on the treatment of asthma, allergic rhinitis (AR), and Allergen Immunotherapy (AIT) lack recommendations for house dust mite (HDM) allergy. An expert panel reviewed current guidelines in the light of new data to assess whether guidelines could be improved. Most guidelines and key position papers did not provide specific recommendations on treatment of allergic asthma (AA) caused by HDM allergy, although some included AIT as a treatment option for AA in general. Around half of the guidelines stated that AIT with HDM extract was an effective treatment for AR, with several indicating sublingual Immunotherapy as an option. This heterogeneity is caused by quality issues affecting studies of AIT with perennial Allergens in patients with AA and AR, including use of different diagnosis and severity criteria, lack of consistent scoring or grading systems for primary and safety outcomes, and lack of consensus on treatment parameters. There is a need for well-designed clinical trials to serve as a basis for guideline recommendations. Although results from recent studies strengthen the evidence base for the efficacy and safety of sublingual Immunotherapy in patients with HDM-induced AA and AR, their effect on subsequent guideline updates will depend on the methodology and evidence model used by each guideline.

  • defining pollen exposure times for clinical trials of Allergen Immunotherapy for pollen induced rhinoconjunctivitis an eaaci position paper
    Allergy, 2017
    Co-Authors: Oliver Pfaar, Moises A Calderon, P Demoly, Katharina Bastl, Uwe Berger, Jeroen T M Buters, Bernard Clot, U Darsow, Stephen R Durham
    Abstract:

    Background Clinical efficacy of pollen Allergen Immunotherapy has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods pre-defined on the basis of the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen-exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert-consensus. Methods A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen-exposure in the context of defining relevant time intervals for evaluation of efficacy in Allergen Immunotherapy trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered in order to achieve a consensus. Results The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for ‘pollen season’, ‘high pollen season’ (or ‘Peak pollen period’) and ‘high pollen days’. Conclusion This EAACI position paper provides definitions of pollen exposures for different pollen types for use in Allergen Immunotherapy trials. Their validity as standards remains to be tested in future studies. This article is protected by copyright. All rights reserved.

  • Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles
    Current Allergy and Asthma Reports, 2017
    Co-Authors: Harold S. Nelson, Moises A Calderon, Stephen R Durham, David I. Bernstein, Thomas B. Casale, Jens S. Andersen, Robert Esch, Linda S. Cox, Hendrik Nolte
    Abstract:

    Progress has been made in the harmonization of efficacy and safety outcome measures for Allergen Immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

  • Allergen Immunotherapy for insect venom allergy a systematic review and meta analysis
    Allergy, 2017
    Co-Authors: Sangeeta Dhami, Evamaria Varga, Gunter J Sturm, Danijela Bokanovic, Hadar Zaman, M. Beatrice Bilò, Dario Antolinamerigo, Antonella Muraro, Cezmi A Akdis, Moises A Calderon
    Abstract:

    Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom Immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03–0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04–1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

  • the effect of a new communication template on anticipated willingness to initiate or resume Allergen Immunotherapy an internet based patient survey
    Allergy Asthma & Clinical Immunology, 2015
    Co-Authors: Moises A Calderon, Oliver Pfaar, Thomas B. Casale, P Demoly, Hansjorgen Malling, Joaquin Sastre, Linda Cox, Ralph Mosges, Musa Khaitov
    Abstract:

    Background: A patient’s knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness. Methods: To assess patients’ understanding of allergy and acceptance of Allergen Immunotherapy on the basis of (i) information given by their physician at the time of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent “early abandoners” (having discontinued Allergen Immunotherapy before the end of the prescribed course) or “non-starters” (having decided not to initiate a course of Allergen Immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study’s main objectives were to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume Allergen Immunotherapy. Results: We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 “early abandoners” and 134 “non-starters”. The mean time since symptom onset and selection for the study was 14.5 years. Subcutaneous Allergen Immunotherapy had been prescribed in 60 % of cases. Twenty-eight percent of the participants did not know for which allergy they were being treated. Early abandoners reported a perception of low effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt better informed afterwards, and 67 % stated that viewing the communication template would have made them more likely to continue or initiate Allergen Immunotherapy (overall willingness score: 5.65 out of 10 before viewing and 7.1 out of 10 afterwards). Conclusions: After viewing a new communication template on allergy and Allergen Immunotherapy, patients participating in the survey felt better informed and more likely to initiate or complete this therapy. It now remains to investigate the communication template’s effect on actual acceptance of and adherence to Allergen Immunotherapy.

Oliver Pfaar - One of the best experts on this subject based on the ideXlab platform.

  • development of subcutaneous Allergen Immunotherapy part 2 preventive aspects and innovations
    Allergo journal international, 2019
    Co-Authors: Ludger Klimek, Regina Treudler, Randolf Brehler, Eckard Hamelmann, Matthias Kopp, Johannes Ring, Thilo Jakob, Margitta Worm, Oliver Pfaar
    Abstract:

    Allergen Immunotherapy with subcutaneous injection (SCIT) of the relevant Allergen is the classic causal treatment method for IgE-mediated allergic respiratory disease and has already been successfully used for over 100 years. This publication is based on a selective literature search in PubMed and MEDLINE. Recent publications in German-language journals that are not available in literature databases were also analyzed. This literature search included original and review articles both in German and in English. Primary, secondary and tertiary prevention characteristics have been demonstrated for SCIT; however, these require further evaluation. In combination with biologic agents, the safety, and in some cases the efficacy, of SCIT can be increased. Adjuvants seem to offer enormous development potential for SCIT. Aluminum salts, microcrystalline tyrosine (MCT), and monophosphoryl lipid A (MPL) are already used in commercial SCIT preparations. At the same time, other adjuvants are being researched, e.g., liposomes, microspheres, CpG motifs (C: nucleotide cytosine, p: phosphate, G: nucleotide guanine), or virus-like particles (VLPs). The therapeutic extracts themselves are also undergoing further development, for instance as recombinant Allergens, hypoAllergenic variants such as site-directed mutants (SDM), conformational variants, Allergen fragmentation, Allergen oligomers, deletion mutants, and hybrid Allergens/mosaic antigens. SCIT preparations are among the most innovative treatment options in the Immunotherapy of allergic diseases. Due to the numerous immunological approaches, they will make treatment safer and more effective in the future with reduced effort.

  • sublingual Allergen Immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma
    The Journal of Allergy and Clinical Immunology, 2019
    Co-Authors: Oliver Pfaar, Ludger Klimek, Claus Bachert, Piotr Kuna, Petr Panzner, Maria Džupinova, Maroesja J Van Nimwegen, Johan D Boot, Dirk Jan E Opstelten
    Abstract:

    Background Sublingual Allergen Immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, Allergen Immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results Primary efficacy results demonstrated a significant (P  Conclusion This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).

  • Allergen manufacturing and quality aspects for Allergen Immunotherapy in europe and the united states an analysis from the eaaci ait guidelines project
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Timon, Ronald L Rabin, J Bridgewater, Carlo Pini, M Hoefnagel, J E Slater, Oliver Pfaar
    Abstract:

    Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for Allergen Immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. Since the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As Allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific Allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines. This article is protected by copyright. All rights reserved

  • Allergen manufacturing and quality aspects for Allergen Immunotherapy in europe and the united states an analysis from the eaaci ait guidelines project
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Timon, Jay E Slater, Ronald L Rabin, J Bridgewater, Carlo Pini, M Hoefnagel, Oliver Pfaar
    Abstract:

    Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for Allergen Immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As Allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific Allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

  • challenges in the implementation of eaaci guidelines on Allergen Immunotherapy a global perspective on the regulation of Allergen products
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Hoefnagel, M Timon, Jay E Slater, Ronald L Rabin, J Bridgewater, Carlo Pini, Oliver Pfaar
    Abstract:

    textabstractRegulatory approaches for Allergen Immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While Allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of Allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of Allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Graham Roberts - One of the best experts on this subject based on the ideXlab platform.

  • Allergen manufacturing and quality aspects for Allergen Immunotherapy in europe and the united states an analysis from the eaaci ait guidelines project
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Timon, Ronald L Rabin, J Bridgewater, Carlo Pini, M Hoefnagel, J E Slater, Oliver Pfaar
    Abstract:

    Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for Allergen Immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. Since the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As Allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific Allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines. This article is protected by copyright. All rights reserved

  • Allergen manufacturing and quality aspects for Allergen Immunotherapy in europe and the united states an analysis from the eaaci ait guidelines project
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Timon, Jay E Slater, Ronald L Rabin, J Bridgewater, Carlo Pini, M Hoefnagel, Oliver Pfaar
    Abstract:

    Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for Allergen Immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As Allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific Allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

  • challenges in the implementation of eaaci guidelines on Allergen Immunotherapy a global perspective on the regulation of Allergen products
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Hoefnagel, M Timon, Jay E Slater, Ronald L Rabin, J Bridgewater, Carlo Pini, Oliver Pfaar
    Abstract:

    textabstractRegulatory approaches for Allergen Immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While Allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of Allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of Allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

  • challenges in the implementation of eaaci guidelines on Allergen Immunotherapy a global perspective on the regulation of Allergen products
    Allergy, 2018
    Co-Authors: A Bonertz, Graham Roberts, M Hoefnagel, M Timon, Jay E Slater, Ronald L Rabin, J Bridgewater, Carlo Pini, Oliver Pfaar
    Abstract:

    Regulatory approaches for Allergen Immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While Allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of Allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of Allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

  • Allergen Immunotherapy for allergic asthma a systematic review and meta analysis
    Allergy, 2017
    Co-Authors: Sangeeta Dhami, Antonella Muraro, Artemisia Kakourou, Felix Asamoah, Ioana Agache, S Lau, Marek Jutel, Graham Roberts
    Abstract:

    Background To inform the development of the European Academy of Allergy and Clinical Immunonology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. Methods We performed a systematic review, which involved searching nine databases. Studies were screened against pre-defined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses. Results 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95%CI -1.66, -0.56). This was robust to a pre-specified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95%CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95%CI -0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes subcutaneous Immunotherapy (SCIT) improved quality of life and decreased Allergen specific airways hyperreactivity (AHR) but this was not the case for sub-lingual Immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and non-specific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual Immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. Conclusions AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness. This article is protected by copyright. All rights reserved.

P Demoly - One of the best experts on this subject based on the ideXlab platform.

  • defining pollen exposure times for clinical trials of Allergen Immunotherapy for pollen induced rhinoconjunctivitis an eaaci position paper
    Allergy, 2017
    Co-Authors: Oliver Pfaar, Moises A Calderon, P Demoly, Katharina Bastl, Uwe Berger, Jeroen T M Buters, Bernard Clot, U Darsow, Stephen R Durham
    Abstract:

    Background Clinical efficacy of pollen Allergen Immunotherapy has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods pre-defined on the basis of the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen-exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert-consensus. Methods A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen-exposure in the context of defining relevant time intervals for evaluation of efficacy in Allergen Immunotherapy trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered in order to achieve a consensus. Results The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for ‘pollen season’, ‘high pollen season’ (or ‘Peak pollen period’) and ‘high pollen days’. Conclusion This EAACI position paper provides definitions of pollen exposures for different pollen types for use in Allergen Immunotherapy trials. Their validity as standards remains to be tested in future studies. This article is protected by copyright. All rights reserved.

  • the effect of a new communication template on anticipated willingness to initiate or resume Allergen Immunotherapy an internet based patient survey
    Allergy Asthma & Clinical Immunology, 2015
    Co-Authors: Moises A Calderon, Oliver Pfaar, Thomas B. Casale, P Demoly, Hansjorgen Malling, Joaquin Sastre, Linda Cox, Ralph Mosges, Musa Khaitov
    Abstract:

    Background: A patient’s knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness. Methods: To assess patients’ understanding of allergy and acceptance of Allergen Immunotherapy on the basis of (i) information given by their physician at the time of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent “early abandoners” (having discontinued Allergen Immunotherapy before the end of the prescribed course) or “non-starters” (having decided not to initiate a course of Allergen Immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study’s main objectives were to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume Allergen Immunotherapy. Results: We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 “early abandoners” and 134 “non-starters”. The mean time since symptom onset and selection for the study was 14.5 years. Subcutaneous Allergen Immunotherapy had been prescribed in 60 % of cases. Twenty-eight percent of the participants did not know for which allergy they were being treated. Early abandoners reported a perception of low effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt better informed afterwards, and 67 % stated that viewing the communication template would have made them more likely to continue or initiate Allergen Immunotherapy (overall willingness score: 5.65 out of 10 before viewing and 7.1 out of 10 afterwards). Conclusions: After viewing a new communication template on allergy and Allergen Immunotherapy, patients participating in the survey felt better informed and more likely to initiate or complete this therapy. It now remains to investigate the communication template’s effect on actual acceptance of and adherence to Allergen Immunotherapy.

  • an eaaci european survey on adverse systemic reactions in Allergen Immunotherapy eassi the methodology
    Clinical and Translational Allergy, 2014
    Co-Authors: Moises A Calderon, Oliver Pfaar, C Vidal, J Just, Allan Linneberg, P Demoly
    Abstract:

    At present, there is no European report on clinically relevant systemic reactions due to the regular use of Allergen Immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a “harmonised terminology” according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated “national coordinator” was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed.

  • recommendations for the standardization of clinical outcomes used in Allergen Immunotherapy trials for allergic rhinoconjunctivitis an eaaci position paper
    Allergy, 2014
    Co-Authors: Oliver Pfaar, Stephen R Durham, P Demoly, Hansjorgen Malling, Jean Bousquet, Giorgio Walter Canonica, Gerth R. Van Wijk, S Bonini, Lars Jacobsen, R Mosges
    Abstract:

    Background Allergen Immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual Immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.

  • a meta analysis of sublingual Allergen Immunotherapy and pharmacotherapy in pollen induced seasonal allergic rhinoconjunctivitis
    BMC Medicine, 2014
    Co-Authors: Philippe Devillier, P Demoly, Jeanfrancois Dreyfus, Moises A Calderon
    Abstract:

    Background: The capacity of sublingual Allergen Immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. Methods: We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo -s coreActive)/scorePlacebo. Results: Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. Conclusions: In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.

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  • defining pollen exposure times for clinical trials of Allergen Immunotherapy for pollen induced rhinoconjunctivitis an eaaci position paper
    Allergy, 2017
    Co-Authors: Oliver Pfaar, Moises A Calderon, P Demoly, Katharina Bastl, Uwe Berger, Jeroen T M Buters, Bernard Clot, U Darsow, Stephen R Durham
    Abstract:

    Background Clinical efficacy of pollen Allergen Immunotherapy has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods pre-defined on the basis of the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen-exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert-consensus. Methods A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen-exposure in the context of defining relevant time intervals for evaluation of efficacy in Allergen Immunotherapy trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered in order to achieve a consensus. Results The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for ‘pollen season’, ‘high pollen season’ (or ‘Peak pollen period’) and ‘high pollen days’. Conclusion This EAACI position paper provides definitions of pollen exposures for different pollen types for use in Allergen Immunotherapy trials. Their validity as standards remains to be tested in future studies. This article is protected by copyright. All rights reserved.

  • Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles
    Current Allergy and Asthma Reports, 2017
    Co-Authors: Harold S. Nelson, Moises A Calderon, Stephen R Durham, David I. Bernstein, Thomas B. Casale, Jens S. Andersen, Robert Esch, Linda S. Cox, Hendrik Nolte
    Abstract:

    Progress has been made in the harmonization of efficacy and safety outcome measures for Allergen Immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

  • recommendations for the standardization of clinical outcomes used in Allergen Immunotherapy trials for allergic rhinoconjunctivitis an eaaci position paper
    Allergy, 2014
    Co-Authors: Oliver Pfaar, Stephen R Durham, P Demoly, Hansjorgen Malling, Jean Bousquet, Giorgio Walter Canonica, Gerth R. Van Wijk, S Bonini, Lars Jacobsen, R Mosges
    Abstract:

    Background Allergen Immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual Immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.

  • dropouts in sublingual Allergen Immunotherapy trials a systematic review
    Allergy, 2014
    Co-Authors: Melina Makatsori, Erminia Ridolo, Guy W Scadding, C Lombardo, G Bisoffi, Stephen R Durham, Gianenrico Senna
    Abstract:

    Participant dropouts can reduce the power of Allergen Immunotherapy clinical trials. Evaluation of the dropout rate and reasons for dropout are important not only in the planning of clinical studies but are also relevant for adherence to Immunotherapy in daily clinical practice. A systematic review was carried out in order to establish the overall dropout rate among published double-blind, placebo-controlled randomized clinical trials of sublingual Immunotherapy for respiratory allergic diseases. Dropouts were analysed in regards to Allergen, formulation, treatment schedule, participant age, study size, number of centres and type of allergic disease. Relative dropout rates in placebo and active groups as well as reasons for dropout were also assessed. A total of 81 studies, comprising 9998 patients, were included. Dropout rates in sublingual Immunotherapy controlled studies do not appear to be a major problem with a composite dropout percentage of 14% (95% CI:11.9–16). Furthermore, they are not different for active compared to placebo-treated participants. This lends support to the positive clinical outcomes seen in meta-analyses of these trials.

  • Allergen Immunotherapy for house dust mite clinical efficacy and immunological mechanisms in allergic rhinitis and asthma
    Expert Opinion on Biological Therapy, 2013
    Co-Authors: Aarif O Eifan, Moises A Calderon, Stephen R Durham
    Abstract:

    Introduction: There is an increasing prevalence of atopic diseases such as allergic rhinitis and asthma with house dust mite (HDM) being the common Allergen that is highly associated with allergic rhinitis and asthma. Allergen avoidance and pharmacotherapy are part of treatment but it has proved difficult to change the course of HDM-related allergic diseases. Allergen Immunotherapy (AIT) has been in use for the past century and has been shown to be effective in the treatment of allergic respiratory disease. Areas covered: This review exclusively focuses on HDM-AIT and discusses the differences in clinical efficacy and safety, long-term effect after discontinuation and immunological changes observed in both HDM-subcutaneous Immunotherapy (SCIT) and HDM-sublingual Immunotherapy (SLIT) in the treatment of allergic rhinitis and asthma in both pediatric and adult populations. Expert opinion: The majority of studies involved small numbers of patients, variable doses of major Allergens and are of variable qualit...