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Accelerated Immunotherapy: Why Are We Going So Slow?

  • Specific Immunotherapy (L Cox, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of review

Accelerated schedules for administering subcutaneous aeroallergen immunotherapy have the potential to provide convenience, reduce the cost, and improve compliance over conventional (weekly) schedules. In this review, we describe studies of cluster and rush immunotherapy (RIT), the risk of systemic allergic reactions (SARs) for various schedules, and methods to reduce that risk.

Recent findings

Cluster schedules are associated with a slightly increased risk of a SAR that can be reduced by taking an H1 antihistamine on the day of injections. The risk of a SAR can also be reduced with depo extracts, fewer injections per cluster, and administration of fewer than 3 clusters per week. RIT is associated with a 27 to 38% risk of a SAR that can be reduced with administration of corticosteroids, an H1 and H2 antihistamine and possibly a leukotriene blocker for 3 days prior to the procedure and by stopping at a lower dose. Reactions tend to occur 1–2 h after the last injection on the day of RIT, and there is an increased risk of a reaction if subsequent weekly doses are missed.

Summary

Accelerated immunotherapy schedules can offer benefits over weekly schedules; however, the increased risk of a SAR needs to be considered when deciding to recommend such a schedule.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–55 A practice parameter that describes guidelines for administering aeroallergen immunotherapy.

    Article  PubMed  Google Scholar 

  2. Cox LS, Sanchez-Borges M, Lockey RF. World Allergy Organization Systemic Allergic Reaction Grading System: is a modification needed? J Allergy Clin Immunol Pract. 2017;5(1):58–62 e5.

    Article  PubMed  Google Scholar 

  3. Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999;341(7):468–75.

    Article  CAS  PubMed  Google Scholar 

  4. •• Cox L. Accelerated immunotherapy schedules: review of efficacy and safety. Ann Allergy Asthma Immunol. 2006;97(2):126–37 quiz 37–40, 202. A comprehensive review of accelerated immunotherapy schedules as of 2006.

    Article  CAS  Google Scholar 

  5. Tabar AI, Echechipia S, Garcia BE, Olaguibel JM, Lizaso MT, Gomez B, et al. Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus. J Allergy Clin Immunol. 2005;116(1):109–18.

    Article  PubMed  Google Scholar 

  6. Sharkey P, Portnoy J. Rush immunotherapy: experience with a one-day schedule. Ann Allergy Asthma Immunol. 1996;76(2):175–80.

    Article  CAS  PubMed  Google Scholar 

  7. Portnoy J, King K, Kanarek H, Horner S. Incidence of systemic reactions during rush immunotherapy. Ann Allergy. 1992;68(6):493–8.

    CAS  PubMed  Google Scholar 

  8. Cox L. Advantages and disadvantages of accelerated immunotherapy schedules. J Allergy Clin Immunol. 2008;122(2):432–4.

    Article  PubMed  Google Scholar 

  9. Xie W, Zhang H, Chen J, Wang Y. Clinical efficacy and safety of rush immunotherapy in patients with allergic rhinitis. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015;50(8):641–5.

    PubMed  Google Scholar 

  10. Cohn JR, Pizzi A. Determinants of patient compliance with allergen immunotherapy. J Allergy Clin Immunol. 1993;91(3):734–7.

    Article  CAS  PubMed  Google Scholar 

  11. •• Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Risk factors for fatal and nonfatal reactions to subcutaneous immunotherapy: National surveillance study on allergen immunotherapy (2008–2013). Ann Allergy Asthma Immunol. 2016;116(4):354–9 e2 A recent surveillance study of SRs in patients receiving subcutaneous immunotherapy to aeroallergens.

    Article  Google Scholar 

  12. Kohno Y, Minoguchi K, Oda N, Yokoe T, Yamashita N, Sakane T, et al. Effect of rush immunotherapy on airway inflammation and airway hyperresponsiveness after bronchoprovocation with allergen in asthma. J Allergy Clin Immunol. 1998;102(6 Pt 1):927–34.

    Article  CAS  PubMed  Google Scholar 

  13. Van Metre TE Jr, Adkinson NF Jr, Amodio FJ, Kagey-Sobotka A, Lichtenstein LM, Mardiney MR Jr, et al. A comparison of immunotherapy schedules for injection treatment of ragweed pollen hay fever. J Allergy Clin Immunol. 1982;69(2):181–93.

    Article  PubMed  Google Scholar 

  14. Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. AAAAI/ACAAI surveillance study of subcutaneous immunotherapy, years 2008–2012: an update on fatal and nonfatal systemic allergic reactions. J Allergy Clin Immunol Pract. 2014;2(2):161–7.

    Article  PubMed  Google Scholar 

  15. Nielsen L, Johnsen CR, Mosbech H, Poulsen LK, Malling HJ. Antihistamine premedication in specific cluster immunotherapy: a double-blind, placebo-controlled study. J Allergy Clin Immunol. 1996;97(6):1207–13.

    Article  CAS  PubMed  Google Scholar 

  16. Massanari M, Nelson H, Casale T, Busse W, Kianifard F, Geba GP, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol. 2010;125(2):383–9.

    Article  CAS  PubMed  Google Scholar 

  17. Parmiani S, Fernandez Tavora L, Moreno C, Guardia P, Rico P. Clustered schedules in allergen-specific immunotherapy. Allergol Immunopathol (Madr). 2002;30(5):283–91.

    Article  CAS  PubMed  Google Scholar 

  18. Winslow AW, Turbyville JC, Sublett JW, Sublett JL, Pollard SJ. Comparison of systemic reactions in rush, cluster, and standard-build aeroallergen immunotherapy. Ann Allergy Asthma Immunol. 2016;117(5):542–5.

    Article  PubMed  Google Scholar 

  19. Copenhaver CC, Parker A, Patch S. Systemic reactions with aeroallergen cluster immunotherapy in a clinical practice. Ann Allergy Asthma Immunol. 2011;107(5):441–7.

    Article  PubMed  Google Scholar 

  20. Cox LS. Shooting for a faster approach to the immunotherapy target: will cluster become conventional? Ann Allergy Asthma Immunol. 2009;102(3):177–8.

    Article  PubMed  Google Scholar 

  21. Bousquet J, Hejjaoui A, Skassa-Brociek W, Guerin B, Maasch HJ, Dhivert H, et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract. J Allergy Clin Immunol. 1987;80(4):591–8.

    Article  CAS  PubMed  Google Scholar 

  22. Bousquet J, Hejjaoui A, Dhivert H, Clauzel AM, Michel FB. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. Systemic reactions during the rush protocol in patients suffering from asthma. J Allergy Clin Immunol. 1989;83(4):797–802.

    Article  CAS  PubMed  Google Scholar 

  23. Hejjaoui A, Dhivert H, Michel FB, Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. IV. Systemic reactions according to the immunotherapy schedule. J Allergy Clin Immunol. 1990;85(2):473–9.

    Article  CAS  PubMed  Google Scholar 

  24. Harvey SM, Laurie S, Hilton K, Khan DA. Safety of rush immunotherapy to multiple aeroallergens in an adult population. Ann Allergy Asthma Immunol. 2004;92(4):414–9.

    Article  PubMed  Google Scholar 

  25. Smits WL, Giese JK, Letz KL, Inglefield JT, Schlie AR. Safety of rush immunotherapy using a modified schedule: a cumulative experience of 893 patients receiving multiple aeroallergens. Allergy Asthma Proc. 2007;28(3):305–12.

    Article  CAS  PubMed  Google Scholar 

  26. Temino VM, Wu P, Konig J, Fahrenholz JM. Safety of multiple aeroallergen rush immunotherapy using a modified schedule. Allergy Asthma Proc. 2013;34(3):255–60.

    Article  PubMed  Google Scholar 

  27. • Sastre J, Vallejo L, Hernandez E, Fernandez-Nieto M, Nieto PR. A novel mode for delivering immunotherapy using an infusion pump. Ann Allergy Asthma Immunol. 2011;107(5):459–60.A novel mode for delivering immunotherapy using an infusion pump.

  28. Uriarte Obando SA, Sastre Dominguez J. Safety of rush subcutaneous immunotherapy administered in real life using an infusion pump. Ann Allergy Asthma Immunol. 2015;115(6):527–9.

    Article  PubMed  Google Scholar 

  29. •• Fajt ML, Rosenberg SL, Yecies E, Traister RS, Petrov AA. A 10-year experience of a novel and safe modified environmental rush immunotherapy protocol. Allergy Asthma Proc. 2017;38(4):309–16 A recent and extensive review of experience with rush immunotherapy.

    Article  CAS  PubMed  Google Scholar 

  30. Fernandez Tavora L. Aqueous extracts and cluster schedule: a good approach for immunotherapy buildup phase. Allergy. 1995;50(26):0592.

    Google Scholar 

  31. Mellerup MT, Hahn GW, Poulsen LK, Malling H. Safety of allergen-specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side-effects during induction treatment. Clin Exp Allergy. 2000;30(10):1423–9.

    Article  CAS  PubMed  Google Scholar 

  32. Quiralte J, Justicia JL, Cardona V, Davila I, Moreno E, Ruiz B, et al. Is faster safer? Cluster versus short conventional subcutaneous allergen immunotherapy. Immunotherapy. 2013;5(12):1295–303.

    Article  CAS  PubMed  Google Scholar 

  33. Tabar AI, Muro MD, Garcia BE, Alvarez MJ, Acero S, Rico P, et al. Dermatophagoides pteronyssinus cluster immunotherapy. A controlled trial of safety and clinical efficacy. J Investig Allergol Clin Immunol. 1999;9(3):155–64.

    CAS  PubMed  Google Scholar 

  34. Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol. 2001;107(1):87–93.

    Article  CAS  PubMed  Google Scholar 

  35. Winther L, Malling HJ, Mosbech H. Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II. Side-effects. Allergy. 2000;55(9):827–35.

    Article  CAS  PubMed  Google Scholar 

  36. Cardona R, Lopez E, Beltran J, Sanchez J. Safety of immunotherapy in patients with rhinitis, asthma or atopic dermatitis using an ultra-rush buildup. A retrospective study. Allergol Immunopathol (Madr). 2014;42(2):90–5.

    Article  CAS  PubMed  Google Scholar 

  37. Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117(1):134–40.

    Article  CAS  PubMed  Google Scholar 

  38. Klunker S, Saggar LR, Seyfert-Margolis V, Asare AL, Casale TB, Durham SR, et al. Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding. J Allergy Clin Immunol. 2007;120(3):688–95.

    Article  CAS  PubMed  Google Scholar 

  39. • Morais-Almeida M, Arede C, Sampaio G, Borrego LM. Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in pediatric age. Asia Pac Allergy. 2016;6(1):35–42 Recent study of Ultrarush using a 1-day protocol with allergoids.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Pfaar O, van Twuijver E, Hecker H, Boot JD, van Ree R, Klimek L. Accelerated up-dosing of subcutaneous immunotherapy with a registered allergoid grass pollen preparation. Int Arch Allergy Immunol. 2013;160(4):420–4.

    Article  CAS  PubMed  Google Scholar 

  41. • Portnoy J, Bagstad K, Kanarek H, Pacheco F, Hall B, Barnes C. Premedication reduces the incidence of systemic reactions during inhalant rush immunotherapy with mixtures of allergenic extracts. Ann Allergy. 1994;73(5):409–18 Initial study showing that premedication reduces the risk of a SR in 1-day RIT.

  42. Stevens WJ, Verhelst JA, van den Bogaert W, Bridts CH. Clinical and biological evaluation of semi-rush and ordinary immunotherapy schemes in type I allergic respiratory diseases. Allergy. 1985;40(6):447–52.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Section of Allergy, Asthma & Immunology, Children’s Mercy Hospital, 2401 Gillham Road, Kansas, MO, 64108, USA

    Jessica Van Mason MD & Jay M. Portnoy MD

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  1. Jessica Van Mason MD
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  2. Jay M. Portnoy MD
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Correspondence to Jay M. Portnoy MD.

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Jessica Van Mason declares that she has no conflict of interest.

Jay M. Portnoy declares that he has no conflict of interest.

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Key points

• Cluster schedules are associated with a slightly increased risk of a SAR that can be reduced by taking an H1 antihistamine on the day of injections

• RIT is associated with a 27 to 38% risk of a SAR

• The risk of a SAR can be reduced with administration of corticosteroids, an H1 and H2 antihistamine and possibly a leukotriene blocker for 3 days prior to RIT

• Reactions during RIT tend to occur 1–2 h after the last injection so patients should be observed for that amount of time

This article is part of the Topical Collection on Specific Immunotherapy

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Van Mason, J., Portnoy, J.M. Accelerated Immunotherapy: Why Are We Going So Slow?. Curr Treat Options Allergy 6, 396–409 (2019). https://doi.org/10.1007/s40521-019-00212-3

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  • DOI: https://doi.org/10.1007/s40521-019-00212-3

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