Real-world safety and effectiveness evidence of a microcrystalline tyrosine-associated mite allergoid in children and adolescents with allergic rhinitis

Main Article Content

Dr. Sala
Dr Almeida
Dr. García
Dr. Laín
Dr. Martínez
Dr. Martos
Dr. Núñez
Dr. Ramírez
Dr. Boronat
Dr. Torán
Dr. Justicia


allerghic rhinitis, children and adolescents, microcrystalline tyrosine, mites, real-world evidence, subcutaneous allergen immunotherapy


Evidence regarding allergen immunotherapy (AIT) in pediatric population is scarce. We have assessed safety and effectiveness of subcutaneous AIT with a microcrystalline tyrosine (MCT)- associated mite allergoid, Acarovac Plus®, in children and adolescents with allergic rhinitis (AR), with and without asthma, in the real-world setting. This was a retrospective, multicenter study including children and adolescents aged 5 years to 17 years with AR, with and
without asthma, and sensitized to mites, receiving AIT with Acarovac Plus® during ≥6 months. Primary and secondary objectives were safety and effectiveness, respectively. Effectiveness variables were assessed during 12 months before and after AIT and included unscheduled visits to the healthcare center and emergency room admissions, rhinitis and asthma symptoms according to ARIA and GEMA classifications, respectively, medication use, and patients’ and physicians’ disease perception graded on a visual analog scale (VAS). All 79 patients included had a mean (SD) age of 12.7 (3.3) years. Two patients experienced systemic adverse reactions (none severe). Unscheduled visits to the healthcare center and emergency room admissions decreased (mean (SD) 3.02 [2.48] and 0.63 [1.35] vs. 1.08 [1.38] and 0.09 [0.38], before and after treatment, p < 0.001 and p = 0.001, respectively). After AIT, rhinitis and asthma classification changed (p < 0.0001 for all classifications), showing improvements in symptoms and a significant decrease in rhinitis and use of medication for asthma and VAS scores grading patients’ and physicians’ disease perception (p < 0.001). In conclusion, these results show that AIT with an MCT-associated mite allergoid appears safe and effective in children and adolescents with AR treated in the real-world setting.

Abstract 103 | pdf Downloads 65 XML Downloads 2 HTML Downloads 7


1. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma
(ARIA) 2008*. Allergy [Internet]. 2008 Apr 15 [cited 2020 Mar 6];63(11):8–160. Available from:
2. Meltzer EO. Allergic Rhinitis. Immunol Allergy Clin North Am [Internet]. 2016 May 1 [cited 2020 Mar 29];36(2):235–48.
Available from:
3. Calderón MA, Linneberg A, Kleine-Tebbe J, De Blay F, Hernandez Fernandez de Rojas D, Virchow JC, et al. Respiratory allergy caused by house dust mites: What do we really know? J Allergy Clin Immunol [Internet]. 2015 Jul [cited 2020 Mar 29];136(1):38-48. Available from: https://linkinghub.
4. Lodge CJ, Lowe AJ, Gurrin LC, Hill DJ, Hosking CS, Khalafzai RU, et al. House dust mite sensitization in toddlers predicts current wheeze at age 12 years. J Allergy Clin Immunol [Internet]. 2011 Oct [cited 2020 Sep 9];128(4):782–788.e9. Available from:
5. Illi S, von Mutius E, Lau S, Niggemann B, Grüber C, Wahn U. Perennial allergen sensitisation early in life and chronic asthma in children: A birth cohort study. Lancet [Internet]. 2006 Aug 26 [cited 2020 Mar 29];368(9537):763–70. Available
6. Halken S, Larenas-Linnemann D, Roberts G, Calderón MA, Angier E, Pfaar O, et al. EAACI guidelines on allergen immunotherapy: Prevention of allergy. Pediatr Allergy Immunol [Internet]. 2017 Dec [cited 2020 Mar 30];28(8):728–45.
Available from:
7. Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, et al. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy [Internet]. 2018 Apr 1 [cited 2020 Apr 17];73(4):765–98. Available from:
8. Rodríguez del Río P, Vidal C, Just J, Tabar AI, Sanchez- Machin I, Eberle P, et al. The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment. Pediatr Allergy Immunol [Internet]. 2017 Feb [cited 2020 Mar 31];28(1):60–70.
9. Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis. Allergy [Internet]. 2017 Nov [cited 2020 Sep 4];72(11):1597–631. http://doi.wiley.
10. Agache I, Lau S, Akdis CA, Smolinska S, Bonini M, Cavkaytar O, et al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma. Allergy [Internet]. 2019 May 16 [cited 2020 Sep 3];74(5):855–73.
11. Rudman Spergel AK, Minnicozzi M, Wheatley LM, Togias A. Is Allergen Immunotherapy in Children Disease Modifying? A
Review of the Evidence. Curr Allergy Asthma Rep [Internet]. 2018 Sep 11 [cited 2020 Sep 3];18(9):47.
12. Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Høst A, et al. Specific immunotherapy has longterm
preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy [Internet]. 2007 Aug [cited 2020 Sep 2];62(8):943–8.
13. Schmitt J, Schwarz K, Stadler E, Wüstenberg EG. Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study. J Allergy Clin Immunol [Internet]. 2015 Dec [cited 2020 Sep 2];136(6):1511–6.
14. Eng PA, Borer-Reinhold M, Heijnen IAFM, Gnehm HPE. Twelve-year follow-up after discontinuation of preseasonal
grass pollen immunotherapy in childhood. Allergy [Internet]. 2006 Feb [cited 2020 Sep 2];61(2):198–201.
15. Roger A, Malet A, Moreno V, Parra A, Gutiérrez D, Lleonart R, et al. Real-life effect of a microcrystalline tyrosine adjuvanted mite immunotherapy in patients with allergic rhinitis. Immunotherapy [Internet]. 2020 Jan [cited 2020 Mar 06];12(1):53–62.
16. Calderón MA, Bousquet J, Canonica GW, Cardell L-O, Fernandez de Rojas DH, Kleine-Tebbe J, et al. Guideline recommendations on the use of allergen immunotherapy in house dust mite allergy: Time for a change? J Allergy Clin Immunol [Internet]. 2017 Jul [cited 2020 Mar 29];140(1):41–52.
17. Devillier P, Demoly P, Molimard M. Allergen immunotherapy: What is the added value of real-world evidence from retrospective claims database studies? Expert Rev Respir Med [Internet]. 2020 Mar 4 [cited 2020 Mar 30];14(5):445–52.
18. Incorvaia C, Barberi S, Pastorello E, Ciprandi G. Allergic reactions after vaccination: Translating guidelines into clinical
practice. Eur Ann Allergy Clin Immunol [Internet]. 2019 Jan [cited 2020 Sep 4];51(03):115.
19. Sala-Cunill A, Pérez-Formoso JL, Torán-Barona C, Almeida-Sánchez ZM, Álvarez-Fernández JA, García-Núñez I, et al. Safety and effectiveness of a microcrystalline tyrosine-associated mite extract immunotherapy for allergic rhinitis. Immunotherapy [Internet]. 2020 Sep 19 [cited 2020 Sep 7];12(13):1007–19.
20. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization
Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol [Internet]. 2010 Mar [cited 2020 Apr 14];125(3):569-574.e7.
21. EMA (European Medicine Agency). ICH E6 (R2) Good clinical Practice [Internet] [cited 2020 Apr 4]. Available from:
22. GEMA 4.2 Guía española para el manejo del asma (Spanish guidelines for asthma management) [Internet]. 2016 [cited
2020 Jan 11]. Available from:
23. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines—2016 revision. J Allergy Clin Immunol [Internet]. 2017 Oct [cited 2020 Mar 10];140(4):950–8. Available from:
24. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention [Internet]. 2019 [cited 2020
Sep 18]. Available from:
25. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*. Allergy [Internet]. 2008 Apr [cited 2020 Mar 29];63:8–160. Available from:
26. Calderon MA, Gerth van Wijk R, Eichler I, Matricardi PM, Varga EM, Kopp M V, et al. Perspectives on allergen-specific
immunotherapy in childhood: An EAACI position statement. Pediatr Allergy Immunol [Internet]. 2012 Jun [cited 2020 Sep 4];23(4):300–6.
27. Pfaar O, Gerth van Wijk R, Klimek L, Bousquet J, Creticos PS. Clinical trials in allergen immunotherapy in the age group of
children and adolescents: Current concepts and future needs. Clin Transl Allergy [Internet]. 2020 Dec 24 [cited 2020 Jul 17];10(1):11.
28. EMA (European Medicine Agency). Human Medicines Development and Evaluation EMA/PDCO Standard Paediatric
Investigation Plan for Allergen Products for Specific Immunotherapy Revision 4. [Internet]. 2015 [cited 2020 Sep 8]. Available from:
29. Weimer K, Gulewitsch MD, Schlarb AA, Schwille-Kiuntke J, Klosterhalfen S, Enck P. Placebo effects in children: A
review. Pediatr Res [Internet]. 2013 Jul 18 [cited 2020 Sep 10];74(1):96–102. Available from:
30. Nolte H, Bernstein DI, Nelson HS, Kleine-Tebbe J, Sussman GL, Seitzberg D, et al. Efficacy of house dust mite sublingual
immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial. J Allergy Clin Immunol [Internet]. 2016 Dec [cited 2020 Sep 8];138(6):1631– 8. Available from:
31. Okubo K, Masuyama K, Imai T, Okamiya K, Stage BS, Seitzberg D, et al. Efficacy and safety of the SQ house dust mite sublingual immunotherapy tablet in Japanese adults and adolescents with house dust mite–induced allergic rhinitis. J Allergy Clin Immunol [Internet]. 2017 Jun [cited 2020 Sep 8];139(6):1840–1848.e10. Available from:
32. Masuyama K, Okamoto Y, Okamiya K, Azuma R, Fujinami T, Riis B, et al. Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet in Japanese children. Allergy [Internet]. 2018 Dec [cited 2020 Sep 7];73(12):2352–63.
33. Song Y, Long J, Wang T, Xie J, Wang M, Tan G. Long-term efficacy of standardised specific subcutaneous immunotherapy
in children with persistent allergic rhinitis due to multiple allergens including house dust mites. J Laryngol Otol [Internet]. 2018 Mar 28 [cited 2020 Sep 7];132(3):230–5. Available from:
34. Jutel M, Brüggenjürgen B, Richter H, Vogelberg C. Realworld evidence of subcutaneous allergoid immunotherapy in
house dust mite‐induced allergic rhinitis and asthma. Allergy [Internet]. 2020 Aug 12 [cited 2020 Apr 1];75(8):2046–54.
35. Yukselen A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB. Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: A randomized, placebo-controlled, double-blind, double-dummy study. Int Arch Allergy Immunol [Internet]. 2012 [cited 2021 Jan 2];157(3):288–98. Available from:
36. Calderon MA, Casale TB, Nelson HS, Demoly P. An evidence-based analysis of house dust mite allergen immunotherapy:
A call for more rigorous clinical studies. J Allergy Clin Immunol [Internet]. 2013 Dec [cited 2021 Jan 2];132(6):1322–36. Available from:
37. Jensen‐Jarolim E, Bachmann MF, Bonini S, Jacobsen L, Jutel M, Klimek L, et al. State‐of‐the‐art in marketed adjuvants
and formulations in Allergen Immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy [Internet]. 2020 Apr 21 [cited 2020 Mar 19];75(4):746–60. Available from: https://onlinelibrary.
38. Alvaro‐Lozano M, Akdis CA, Akdis M, Alviani C, Angier E, Arasi S, et al. Allergen immunotherapy in children user’s guide. Pediatr Allergy Immunol [Internet]. 2020 May 21 [cited 2020 Jul 21];31(S25):1–101. Available from:
39. Leuthard DS, Duda A, Freiberger SN, Weiss S, Dommann I, Fenini G, et al. Microcrystalline tyrosine and aluminum as
adjuvants in allergen-specific immunotherapy protect from IgE-mediated reactivity in mouse models and act independently
of inflammasome and TLR signaling. J Immunol [Internet]. 2018 May 1 [cited 2020 Oct 28];200(9):3151–9. Available from:
40. Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, et al. Recommendations for the standardization
of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: An EAACI Position Paper. Allergy
[Internet]. 2014 Jul [cited 2020 Apr 2];69(7):854–67.