Evaluation of the safety of dose escalation period of subcutaneous specific allergic immunotherapy in patients with rhino-conjunctivitis or allergic asthma previously vaccinated against SARS-CoV-2

Main Article Content

Jonnathan Andrés Acevedo Galvis Sara Bautista Villanueva María del Mar Cano Mollinedo Mario Ferrer Vázquez Mónica Fernández Rodríguez Emilio Domingo Funes Vera Genoveva Marimar García Álvarez-Leire Leticia Herrero Lifona María Teresa Lizaso Bacaicoa Alfonso Javier Miranda Paez Esther Moreno Rodilla Óliver Alexis Muñoz Daga Olinda Desiree Pérez Quintero Marta Reguero Capilla Isadora Suárez Lorenzo Begoña Soler- López Nataly Cancelliere


BACKGROUND: More than 90% of the Spanish population has been vaccinated against the SARS-CoV-2 virus in our setting. The administration of this vaccine is not contraindicated in allergic subjects; however, it is unknown whether any precaution should be taken when initiating subcutaneous allergen immunotherapy after this vaccination.

The objective of the study was to analyze the safety of subcutaneous allergen immunotherapy during the dose escalation phase in subjects sensitized to pollens or mites previously vaccinated against SARS-CoV-2.

METHODS: An observational study with retrospective data collection from protocolled patients' medical records was designed. Outpatients older than 12 years with diagnosis of pollen or house dust mite allergic rhinitis with or without bronchial allergic asthma were selected who had completed the subcutaneous immunotherapy dose escalation phase. A complete SARS-CoV-2 vaccination was required for the inclusion.

RESULTS: Three hundred and seventy-nine patients were included by 53 investigators. The mean age was 31 years old and 55,9% female. Time from last SARS-Cov-2 vaccination dose to subcutaneous immunotherapy initiation was 4.1 months (95%CI 3.8-4.4). subcutaneous immunotherapy with a pollen allergoid was administered to 135 patients (35.6%) with a total of 739 injections, while subcutaneous immunotherapy using a house dust mite allergoid was administered to 244 patients (64.4%) with a total of 1311 doses. During the dose escalation phase with the pollen allergoid, 45 patients (33.3%) suffered 93 local adverse reactions (12.6% of injections), while 17 patients (12.6%) experienced 17 systemic allergic reactions (2.3% of injections) of them 14 were World Allergy Organization Grade 1 and 3 of Grade 2. During the dose escalation phase with the house dust mite allergoid, 55 patients (22.5%) reported 133 local adverse reactions (10.1% of injections), and 7 patients (2.9%) showed 7 World Allergy Organization Grade 1 systemic reactions (0.5% of injections). No systemic reactions Grade 3 or higher were reported.

CONCLUSIONS: The well-known safety profile of the subcutaneous allergen immunotherapy using pollen or house dust mite allergoids has not been changed after the SARS-CoV-2 vaccine administration. No relevant differences in the incidence of local or systemic allergic reactions during the dose escalation phase were identified, so it is considered that the patient’s safety has not been compromised to initiate this treatment after the SARS-CoV-2 vaccine administration.

Keywords: Allergen immunotherapy, subcutaneous immunotherapy, dose escalation, pollen, house dust mites, safety, COVID-19, SARS-CoV-2 vaccine

Article Details

How to Cite
ACEVEDO GALVIS, Jonnathan Andrés et al. Evaluation of the safety of dose escalation period of subcutaneous specific allergic immunotherapy in patients with rhino-conjunctivitis or allergic asthma previously vaccinated against SARS-CoV-2. Medical Research Archives, [S.l.], v. 11, n. 4, apr. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3750>. Date accessed: 29 may 2023. doi: https://doi.org/10.18103/mra.v11i4.3750.
Research Articles


1. Agencia española de medicamentos y productos sanitarios. 19º Informe de farmacovigilancia sobre vacunas COVID-19, 19 de enero de 2023; Accessed February 5, 2023. https://www.aemps.gob.es/laAEMPS/docs/informe-farmacovigilancia-diciembre-2022.pdf
2. Sokolowska M, Eiwegger T, Ollert M, et al. EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines. Allergy. 2021;76:1629-1639. doi: https://doi.org/10.1111/all.14739.
3. Bousquet J, Lockey RF, Malling HJ. WHO position paper. Allergen immunotherapy: therapeutic vaccines for allergic diseases. Allergy. 1998; 53 (suppl 44): 1-42. doi: https://doi.org/10.1111/j.1398-9995.1998.tb04930.x
4. Abramson M, Puy R, Weiner J. Immunotherapy in asthma: an update systematic review. Allergy. 1999; 54: 1022-1041. doi: https://doi.org/10.1034/j.1398-9995.1999.00102.x.
5. Moreno C, Cuesta-Herranz J, Fernandez-Tavora L, Alvarez Cuesta E on behalf of the SEAIC: “Immunotherapy safety: a prospective multicentric monitoring study of biologically standardized therapeutic vaccines for allergic diseases”. Clin Exp Allergy 2004; 34: 527-531. doi: https://doi.org/10.1111/j.1365-2222.2004.1819.x.
6. Jutel M, Agache I, Bonini S, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556-568. doi: https://doi.org/10.1016/j.jaci.2015.04.047.
7. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G, Editors. Speaking the same language: The world allergy organization subcutaneous immunotherapy systemic reaction grading system. Allergy Clin Immunol. 2010; 125: 569-574. doi: https://doi.org/10.1016/j.jaci.2009.10.060.
8. Chaker AM, Al-Kadah B, Luther U, Neumann U, Wagenmann M. An accelerated dose escalation with grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial. Clin Transl Allergy. 2016;6:4. doi: https://doi.org/10.1186/s13601-016-0093-z
9. Zielen S, Plückhahn K, Akboga Y, Rieker-Schwienbacher J, Thieme U, Rosewich M. Fast up-dosing with a birch allergoid is safe and well tolerated in allergic rhinitis patients with or without asthma. Immunotherapy. 2019;11(3):177-187.d: https://doi.org/10.2217/imt-2018-0143
10. Koop VM, Bovermann X, Klimek L. Accelerated dose escalation with three injections of an aluminum hydroxide-adsorbed allergoid preparation of six grasses is safe for patients with moderate to severe allergic rhinitis. Int Arch Allergy Immunol. 2020;181:94-102. doi: https://doi.org/10.1159/000503684
11. Bovermann X, Ricklefs I, Vogelberg C, Klimek L, Koop MV. Accelerated dose escalation with 3 injections of an aluminum hydroxide-adsorbed allergoid preparation of 6 grasses is safe for children and adolescents with moderate to severe allergic rhinitis. Int Arch Allergy Immunol. 2021;182:524-534. doi: https://doi.org/10.1159/000512561
12. Klimek L, Fox GC, Thum-Oltmer S. SCIT with a high-dose house dust mite allergoid is well tolerated: safety data from pooled clinical trials and more than 10 years of daily practice analyzed in different subgroups. Allergo J Int. 2018;27:131-139. doi: https://doi.org/10.1007/s40629-018-0059-x
13. Liu J-L, Ning W-X, Li S-X, Xu Y-C, Wu L, Wang Y-S et al. The safety profile of subcutaneous allergen immunotherapy in children with asthma in Hangzhou, East China. Allergol Immunopathol (Madr). 2017; 45:541–8. doi: https://doi.org/10.1016/j.aller.2017.04.002
14. Roberts, G.; Pfaar, O.; Akdis, C. A.; Ansotegui, I. J.; Durham, S. R.; van Gerth Wijk, R. et al. EAACI guidelines on allergen immunotherapy. Allergic rhinoconjunctivitis. Allergy. 2018;73 765–798. doi: https://doi.org/10.1111/all.13317
15. Caruso C, Borgonovo L, Bramé B, et al. Safety of an accelerated build-up phase with pollen allergoids: a retrospective study. J Investig Allergol Clin Immunol. 2018; 28:283–4. doi: 10.18176/jiaci.0269
16. Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database of Syst Rev, 2007;(1): CD001936. doi: https://doi.org/10.1002/14651858.
17. Abramson M, Puy R, Weiner J. Injection allergen immunotherapy for asthma. Cochrane Database of Systc Rev. 2010(8): CD001186. doi: https://doi.org/10.1002/14651858.
18. Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA 2013;309:1278–1288. doi: https://doi.org/10.1001/jama.2013.2049.
19. Lin SY, Azar A, Suárez-Cuervo C, et al.The role of immunotherapy in the treatment of asthma. Comparative effectiveness review n°. 196 AHRQ publication n°. 17(18)-EHC029-EF. Rockville, MD: Agency for Healthcare Research and Quality. March 2018. doi: https://doi.org/10.23970/AHRQEPCCER196
20. Rice JL, Diette GB, Suárez-Cuervo C, et al. Allergen-specific immunotherapy in the treatment of pediatric asthma: a systematic review. Pediatrics. 2018;141(5):e20173833. doi: https://doi.org/10.1542/peds.2017-3833
21. Justicia JL, Barasona MJ, Serrano P, Moreno C, Guerra F. Predicting patients at high-risk of systemic reactions to cluster allergen immunotherapy: A pilot prospective observational study. J Investig Allergol Clin Immunol. 2007; 17: 386-392.
22. Bernstein DI, Wanner M, Borish L, Liss GM, Immunotherapy Committee, American academy of allergy, asthma and immunology. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-201. J Allergy Clin Immunol. 2004; 113: 1129-1136. doi: https://doi.org/10.1016/j.jaci.2004.02.006.
23. Rodríguez Del Río P, Vidal C, Just J, et al et al. The European survey on adverse systemic reactions in allergen immunotherapy (EASSI): a pediatric assessment. Pediatr Allergy Immnol. 2017; 28(1): 60-70. doi: https://doi.org/10.1111/pai.12660
24. Larenas-Linnemann D, Rodríguez-Pérez N, Ortega-Martell JA, Blandon-Vijil V, Luna-Pech JA. Coronavirus disease 2019 and allergen immunotherapy: Theoretical benefits invite to adjustments in practice recommendations. Ann Allergy Asthma Immunol. 2020;125(3):247-249. doi:https://doi.org/10.1016/j.anai.2020.06.009.
25. Klimek L, Jutel M, Akdis C, et al. Handling of allergen immunotherapy in the COVID-19 pandemic: An ARIA-EAACI statement. Allergy. 2020;75(7):1546-1554. doi: https://doi.org/10.1111/all.14336.
26. Pfaar O, Klimek L, Jutel M, et al. COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper. Allergy. 2021;76(3):648-676. doi: https://doi.org/10.1111/all.14453.
27. Klimek L, Pfaar O, Hamelmann E, et al. COVID-19 vaccination and allergen immunotherapy (AIT) - A position paper of the German Society for Applied Allergology (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI). Allergologie select. 2021;5:251-259. doi: https://doi.org/10.5414/ALX02245E.
28. Jutel M, Torres MJ, Palomares O, et al. COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations. Allergy. 2022;77(8):2313-2336. doi: https://doi.org/10.1111/all.15252.
29. Pfaar O, Hamelmann E, Klimek L, et al. Allergen immunotherapy during the COVID-19 pandemic-A survey of the German Society for Allergy and Clinical Immunology. Clin Transl Allergy. 2022;12(3):e12134. doi: https://doi.org/10.1002/clt2.12134.
30. Sánchez-López J, Heffler E, Canonica GW. Impact of COVID-19 in allergen immunotherapy: An Italian survey. Allergol Immunopathol (Madr). 2022;50(5):57-60. doi: https://doi.org/10.15586/aei.v50i5.595.\