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Journal ArticleDOI

International consensus on allergy immunotherapy

TL;DR: The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice.
Abstract: Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT.
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Journal ArticleDOI
TL;DR: Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.
Abstract: Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.

437 citations

Journal ArticleDOI
01 Apr 2018-Allergy
TL;DR: In general, broad evidence for the clinical efficacy of AIT for AR exists but a product‐specific evaluation of evidence is recommended, and SCIT and SLIT are recommended for both seasonal and perennial AR for its short‐term benefit.
Abstract: Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

436 citations

Journal ArticleDOI
TL;DR: To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).
Abstract: BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

401 citations

Journal ArticleDOI
TL;DR: To determine that oral immunotherapy (OIT) to egg is safe and effective to desensitize patients and induce sustained unresponsiveness, a double-blind, randomized placebo-controlled study of 55 children, sensitive to egg, is conducted.
Abstract: AW Burks, SM Jones, RA Wood; Consortium of Food Allergy Research (CoFAR) N Engl J Med 2012;367(3):233–243 To determine that oral immunotherapy (OIT) to egg is safe and effective to desensitize patients and induce sustained unresponsiveness A double-blind, randomized placebo-controlled study of 55 children, 5 to 11 years of age, sensitive to egg, with 40 receiving OIT and 15 placebo Initial dose escalation and buildup, maintenance phases up to 2 g of egg protein (one-third egg) This was followed by an oral …

288 citations

Journal ArticleDOI
01 Aug 2017-Allergy
TL;DR: Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers that are predictive of the clinical response to AIT.
Abstract: Background Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. Method The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). Results All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. Conclusions It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.

262 citations


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References
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Journal ArticleDOI
Jean Bousquet, N. Khaltaev, Alvaro A. Cruz1, Judah A. Denburg2, W. J. Fokkens3, Alkis Togias4, T. Zuberbier5, Carlos E. Baena-Cagnani6, Giorgio Walter Canonica7, C. van Weel8, Ioana Agache9, Nadia Aït-Khaled, Claus Bachert10, Michael S. Blaiss11, Sergio Bonini12, L.-P. Boulet13, Philippe-Jean Bousquet, Paulo Augusto Moreira Camargos14, K-H. Carlsen15, Y. Z. Chen, Adnan Custovic16, Ronald Dahl17, Pascal Demoly, H. Douagui, Stephen R. Durham18, R. Gerth van Wijk19, O. Kalayci19, Michael A. Kaliner20, You Young Kim21, Marek L. Kowalski, Piotr Kuna22, L. T. T. Le23, Catherine Lemière24, Jing Li25, Richard F. Lockey26, S. Mavale-Manuel26, Eli O. Meltzer27, Y. Mohammad28, J Mullol, Robert M. Naclerio29, Robyn E O'Hehir30, K. Ohta31, S. Ouedraogo31, S. Palkonen, Nikolaos G. Papadopoulos32, Gianni Passalacqua7, Ruby Pawankar33, Todor A. Popov34, Klaus F. Rabe35, J Rosado-Pinto36, G. K. Scadding37, F. E. R. Simons38, Elina Toskala39, E. Valovirta40, P. Van Cauwenberge10, De Yun Wang41, Magnus Wickman42, Barbara P. Yawn43, Arzu Yorgancioglu44, Osman M. Yusuf, H. J. Zar45, Isabella Annesi-Maesano46, E.D. Bateman45, A. Ben Kheder47, Daniel A. Boakye48, J. Bouchard, Peter Burney18, William W. Busse49, Moira Chan-Yeung50, Niels H. Chavannes35, A.G. Chuchalin, William K. Dolen51, R. Emuzyte52, Lawrence Grouse53, Marc Humbert, C. M. Jackson54, Sebastian L. Johnston18, Paul K. Keith2, James P. Kemp27, J. M. Klossek55, Désirée Larenas-Linnemann55, Brian J. Lipworth54, Jean-Luc Malo24, Gailen D. Marshall56, Charles K. Naspitz57, K. Nekam, Bodo Niggemann58, Ewa Nizankowska-Mogilnicka59, Yoshitaka Okamoto60, M. P. Orru61, Paul Potter45, David Price62, Stuart W. Stoloff63, Olivier Vandenplas, Giovanni Viegi, Dennis M. Williams64 
Federal University of Bahia1, McMaster University2, University of Amsterdam3, National Institutes of Health4, Charité5, Catholic University of Cordoba6, University of Genoa7, Radboud University Nijmegen8, Transilvania University of Brașov9, Ghent University10, University of Tennessee Health Science Center11, University of Naples Federico II12, Laval University13, Universidade Federal de Minas Gerais14, University of Oslo15, University of Manchester16, Aarhus University17, Imperial College London18, Erasmus University Rotterdam19, George Washington University20, Seoul National University21, Medical University of Łódź22, Hai phong University Of Medicine and Pharmacy23, Université de Montréal24, Guangzhou Medical University25, University of South Florida26, University of California, San Diego27, University of California28, University of Chicago29, Monash University30, Teikyo University31, National and Kapodistrian University of Athens32, Nippon Medical School33, Sofia Medical University34, Leiden University35, Leiden University Medical Center36, University College London37, University of Manitoba38, University of Helsinki39, Finnish Institute of Occupational Health40, National University of Singapore41, Karolinska Institutet42, University of Minnesota43, Celal Bayar University44, University of Cape Town45, Pierre-and-Marie-Curie University46, Tunis University47, University of Ghana48, University of Wisconsin-Madison49, University of British Columbia50, Georgia Regents University51, Vilnius University52, University of Washington53, University of Dundee54, University of Poitiers55, University of Mississippi56, Federal University of São Paulo57, German Red Cross58, Jagiellonian University Medical College59, Chiba University60, American Pharmacists Association61, University of Aberdeen62, University of Nevada, Reno63, University of North Carolina at Chapel Hill64
01 Apr 2008-Allergy
TL;DR: The ARIA guidelines for the management of allergic rhinitis and asthma are similar in both the 1999 ARIA workshop report and the 2008 Update as discussed by the authors, but the GRADE approach is not yet available.
Abstract: Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

3,769 citations

Journal ArticleDOI
TL;DR: This systematic review and meta-analyses confirmed the findings of a previous study published in “Rhinitis and Asthma: Causes and Prevention, 2nd Ed.” (2015) as well as new findings of “Mechanisms of Respiratory Disease and Allergology,” which confirmed the role of EMTs in the development of these diseases.
Abstract: Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

3,368 citations

Journal ArticleDOI
TL;DR: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children and patients are encouraged to use these recommendations in their daily practice and to support their decisions.
Abstract: Background: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. Objective: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. Methods: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. Results: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. Conclusion: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.

1,398 citations

Journal ArticleDOI
TL;DR: Althoughthere was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression.
Abstract: Background Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. Methods We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not r...

1,242 citations

Related Papers (5)
01 Apr 2008-Allergy
Jean Bousquet, N. Khaltaev, Alvaro A. Cruz, Judah A. Denburg, W. J. Fokkens, Alkis Togias, T. Zuberbier, Carlos E. Baena-Cagnani, Giorgio Walter Canonica, C. van Weel, Ioana Agache, Nadia Aït-Khaled, Claus Bachert, Michael S. Blaiss, Sergio Bonini, L.-P. Boulet, Philippe-Jean Bousquet, Paulo Augusto Moreira Camargos, K-H. Carlsen, Y. Z. Chen, Adnan Custovic, Ronald Dahl, Pascal Demoly, H. Douagui, Stephen R. Durham, R. Gerth van Wijk, O. Kalayci, Michael A. Kaliner, You Young Kim, Marek L. Kowalski, Piotr Kuna, L. T. T. Le, Catherine Lemière, Jing Li, Richard F. Lockey, S. Mavale-Manuel, Eli O. Meltzer, Y. Mohammad, J Mullol, Robert M. Naclerio, Robyn E O'Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, Nikolaos G. Papadopoulos, Gianni Passalacqua, Ruby Pawankar, Todor A. Popov, Klaus F. Rabe, J Rosado-Pinto, G. K. Scadding, F. E. R. Simons, Elina Toskala, E. Valovirta, P. Van Cauwenberge, De Yun Wang, Magnus Wickman, Barbara P. Yawn, Arzu Yorgancioglu, Osman M. Yusuf, H. J. Zar, Isabella Annesi-Maesano, E.D. Bateman, A. Ben Kheder, Daniel A. Boakye, J. Bouchard, Peter Burney, William W. Busse, Moira Chan-Yeung, Niels H. Chavannes, A.G. Chuchalin, William K. Dolen, R. Emuzyte, Lawrence Grouse, Marc Humbert, C. M. Jackson, Sebastian L. Johnston, Paul K. Keith, James P. Kemp, J. M. Klossek, Désirée Larenas-Linnemann, Brian J. Lipworth, Jean-Luc Malo, Gailen D. Marshall, Charles K. Naspitz, K. Nekam, Bodo Niggemann, Ewa Nizankowska-Mogilnicka, Yoshitaka Okamoto, M. P. Orru, Paul Potter, David Price, Stuart W. Stoloff, Olivier Vandenplas, Giovanni Viegi, Dennis M. Williams