EAACI guidelines on allergen immunotherapy: Prevention of allergy

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease‐modifying treatment for IgE‐mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence‐based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer‐review of draft recommendations. Our key recommendation is that a 3‐year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate‐to‐severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post‐AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post‐AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease‐modifying treatment exists but there is an urgent need for more high‐quality clinical trials.

[1]  A. Sheikh,et al.  Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy , 2018, Allergy.

[2]  A. Sheikh,et al.  EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis , 2018, Allergy.

[3]  P. Devillier,et al.  Sublingual immunotherapy provides long‐term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real‐world database analysis , 2017, Allergy.

[4]  E. Valovirta,et al.  Results from the 5‐year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy , 2017, The Journal of allergy and clinical immunology.

[5]  Joaquim Mullol,et al.  Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines—2016 revision , 2017, The Journal of allergy and clinical immunology.

[6]  A. Sheikh,et al.  Allergen immunotherapy for allergic asthma: A systematic review and meta‐analysis , 2017, Allergy.

[7]  A. Sheikh,et al.  Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta‐analysis , 2017, Allergy.

[8]  P. Demoly,et al.  European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): a real‐life clinical assessment , 2017, Allergy.

[9]  A. Sheikh,et al.  Allergen immunotherapy for insect venom allergy: a systematic review and meta‐analysis , 2017, Allergy.

[10]  A. Sheikh,et al.  Allergen immunotherapy for the prevention of allergy: A systematic review and meta‐analysis , 2017, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[11]  P. Demoly,et al.  The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment , 2017, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[12]  S. Halken,et al.  The prevalence of atopic diseases and the patterns of sensitization in adolescence , 2016, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[13]  A. Bozek,et al.  The effect of allergen-specific immunotherapy on offspring. , 2016, Allergy and asthma proceedings.

[14]  A. Sheikh,et al.  Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review , 2016, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[15]  D. Larenas-Linnemann Direct comparison of efficacy of sublingual immunotherapy tablets for rhinoconjunctivitis. , 2016, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[16]  R. Van Ree,et al.  International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics. , 2016, The Journal of allergy and clinical immunology.

[17]  D. Larenas-Linnemann,et al.  Dosing of European sublingual immunotherapy maintenance solutions relative to monthly recommended dosing of subcutaneous immunotherapy. , 2016, Allergy and Asthma Proceedings.

[18]  G. Roberts,et al.  Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. , 2015, The Journal of allergy and clinical immunology.

[19]  J. Schmitt,et al.  Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study. , 2015, The Journal of allergy and clinical immunology.

[20]  C. Bachert,et al.  Allergen immunotherapy on the way to product-based evaluation—a WAO statement , 2015, The World Allergy Organization journal.

[21]  G. Roberts,et al.  Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood: findings from 2 Isle of Wight birth cohorts 12 years apart , 2015, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[22]  R. Van Ree,et al.  International consensus on allergy immunotherapy. , 2015, The Journal of allergy and clinical immunology.

[23]  S. Thomsen,et al.  Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. , 2015, The Journal of allergy and clinical immunology.

[24]  A. Plaia,et al.  Efficacy of Grass Pollen Allergen Sublingual Immunotherapy Tablets for Seasonal Allergic Rhinoconjunctivitis: A Systematic Review and Meta-analysis. , 2015, JAMA internal medicine.

[25]  K. Takeuchi,et al.  Immunological parameters in prophylactic sublingual immunotherapy in asymptomatic subjects sensitized to Japanese cedar pollen. , 2015, Allergology international : official journal of the Japanese Society of Allergology.

[26]  H. Sitter,et al.  Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases , 2014, Allergo Journal International.

[27]  R. Valenta,et al.  Preventive sublingual immunotherapy in preschool children: First evidence for safety and pro‐tolerogenic effects , 2014, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[28]  S. Simoens,et al.  Economic burden of inadequate management of allergic diseases in the European Union: a GA2LEN review , 2014, Allergy.

[29]  E. Valovirta,et al.  Allergy and asthma prevention 2014 , 2014, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[30]  A. Sheikh,et al.  EAACI Food Allergy and Anaphylaxis Guidelines. Food allergy health-related quality of life measures. , 2014, Allergy.

[31]  A. Sheikh,et al.  EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy , 2014, Allergy.

[32]  Xiaoping Lin,et al.  [Efficacy evaluation of standardized dust mite allergen specific immunotherapy to patients of allergic rhinitis]. , 2014, Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery.

[33]  A. Sheikh,et al.  The epidemiology of food allergy in Europe: a systematic review and meta‐analysis , 2014, Allergy.

[34]  P. Sly,et al.  Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. , 2013, The Journal of allergy and clinical immunology.

[35]  S. Halken,et al.  The natural course of sensitization and allergic diseases from childhood to adulthood , 2013, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[36]  J. Bousquet,et al.  Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language. , 2013, The Journal of allergy and clinical immunology.

[37]  C. Li,et al.  Long-term Efficacy of Specific Immunotherapy on House Dust Mite–Induced Allergic Rhinitis in China , 2013, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[38]  EAACI Food Allergy and Anaphylaxis Guidelines , 2013 .

[39]  R. Dominicus 3-years' long-term effect of subcutaneous immunotherapy (SCIT) with a high-dose hypoallergenic 6-grass pollen preparation in adults. , 2012, European annals of allergy and clinical immunology.

[40]  E. Valovirta,et al.  Design and recruitment for the GAP trial, investigating the preventive effect on asthma development of an SQ-standardized grass allergy immunotherapy tablet in children with grass pollen-induced allergic rhinoconjunctivitis. , 2011, Clinical therapeutics.

[41]  G. Giles,et al.  Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: a prospective cohort study over 4 decades. , 2011, The Journal of allergy and clinical immunology.

[42]  Michelle E. Kho,et al.  AGREE II: advancing guideline development, reporting and evaluation in health care , 2010, Canadian Medical Association Journal.

[43]  Gene Feder,et al.  AGREE II: advancing guideline development, reporting and evaluation in health care. , 2010, Journal of clinical epidemiology.

[44]  T. Keil,et al.  Allergic rhinitis as a predictor for wheezing onset in school-aged children. , 2010, The Journal of allergy and clinical immunology.

[45]  G. Canonica,et al.  Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. , 2010, The Journal of allergy and clinical immunology.

[46]  R. Lockey,et al.  Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. , 2010, The Journal of allergy and clinical immunology.

[47]  K. Harmancı,et al.  Evaluation of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. , 2010, Asian Pacific journal of allergy and immunology.

[48]  M. Fernández-Rivas,et al.  Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen. , 2010, Journal of investigational allergology & clinical immunology.

[49]  T. Brüning,et al.  Allergen content of grass pollen preparations for skin prick testing and sublingual immunotherapy , 2009, Allergy.

[50]  Y. Nakai,et al.  Immunotherapy for cure and prophylaxis of allergic rhinitis , 2009 .

[51]  L. Lynd,et al.  Economic burden of asthma: a systematic review , 2009, BMC pulmonary medicine.

[52]  G. Canonica,et al.  Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study. , 2008, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[53]  P. Lieberman,et al.  Epidemiology of Anaphylaxis , 2009 .

[54]  J. Maloney Long-term Immunologic Effects of Broad-Spectrum Aeroallergen Immunotherapy , 2007, Pediatrics.

[55]  D. Johns,et al.  Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. , 2007, The Journal of allergy and clinical immunology.

[56]  E. Valovirta,et al.  Specific immunotherapy has long‐term preventive effect of seasonal and perennial asthma: 10‐year follow‐up on the PAT study , 2007, Allergy.

[57]  D. Can,et al.  Development of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. , 2007, Asian Pacific journal of allergy and immunology.

[58]  C. M. Reha,et al.  Specific immunotherapy is effective in the prevention of new sensitivities. , 2007, Allergologia et immunopathologia.

[59]  A. Graham,et al.  Evidence-Based Medicine: Levels of Evidence and Grades of Recommendation , 2007 .

[60]  Y. Sertdemir,et al.  Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite. , 2007, Journal of investigational allergology & clinical immunology.

[61]  S Dreborg,et al.  Five‐year follow‐up on the PAT study: specific immunotherapy and long‐term prevention of asthma in children , 2006, Allergy.

[62]  K. C. Brown,et al.  Long-Term Immunologic Effects of Broad-Spectrum Aeroallergen Immunotherapy , 2006, International Archives of Allergy and Immunology.

[63]  P. Eng,et al.  Twelve‐year follow‐up after discontinuation of preseasonal grass pollen immunotherapy in childhood , 2006, Allergy.

[64]  G. Passalacqua,et al.  Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real‐life: clinical efficacy and more , 2004, Allergy.

[65]  S. Burastero,et al.  Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. , 2004, The Journal of allergy and clinical immunology.

[66]  C. Vancheri,et al.  A randomized, controlled study of specific immunotherapy in monosensitized subjects with seasonal rhinitis: effect on bronchial hyperresponsiveness, sputum inflammatory markers and development of asthma symptoms. , 2004, Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna.

[67]  R. Asero Injection Immunotherapy with Different Airborne Allergens Did Not Prevent de novo Sensitization to Ragweed and Birch Pollen North of Milan , 2004, International Archives of Allergy and Immunology.

[68]  G. Passalacqua,et al.  Long‐lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10‐year prospective study , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[69]  G. Feder,et al.  Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project , 2003, Quality & safety in health care.

[70]  F. Cluzeau,et al.  Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project , 2003 .

[71]  J. Bartra,et al.  Effects of specific immunotherapy on the development of new sensitisations in monosensitised patients. , 2003, Allergologia et immunopathologia.

[72]  A. Boner,et al.  Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three‐year prospective study , 2002, Allergy.

[73]  P. Eng,et al.  Long‐term efficacy of preseasonal grass pollen immunotherapy in children , 2002, Allergy.

[74]  S. Guerra,et al.  Rhinitis as an independent risk factor for adult-onset asthma. , 2002, The Journal of allergy and clinical immunology.

[75]  Erkka Valovirta,et al.  Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). , 2002, The Journal of allergy and clinical immunology.

[76]  N. York,et al.  Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six‐year follow‐up study. , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[77]  R. Merendino,et al.  Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not. A retrospective study , 2001, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[78]  R. Djukanović,et al.  Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness. , 2000, American journal of respiratory and critical care medicine.

[79]  J Bousquet,et al.  Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. , 1998, The Journal of allergy and clinical immunology.

[80]  H. Løwenstein,et al.  Immunotherapy with partially purified and standardized tree pollen extracts. IV. Results from long‐term (6‐year) follow‐up , 1997, Allergy.

[81]  J. Bousquet,et al.  Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. , 1997, The Journal of allergy and clinical immunology.

[82]  H. Ipsen,et al.  Immunotherapy with partially purified and standardized tree pollen extracts , 1988, Allergy.

[83]  B. Björkstén,et al.  Oral Immunotherapy of Children with Rhinoconjunctivitis due to Birch Pollen Allergy A Double Blind Study , 1986, Allergy.