Skip to main content

Advertisement

SpringerLink
Log in

Accelerated Immunotherapy Schedules

  • IMMUNOTHERAPY (L COX, SECTION EDITOR)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Rush and cluster immunotherapy schedules are accelerated immunotherapy build-up schedules. A cluster immunotherapy schedule involves the patient receiving several allergen injections (generally 2–4) sequentially in a single day of treatment on nonconsecutive days. The maintenance dose is generally reached in 4–8 weeks. In rush immunotherapy protocols, higher doses are administered at 15- to 60-min intervals over a 1- to 3-day period until the maintenance dose is achieved. This review will serve as an update for accelerated immunotherapy schedules. The review will include recent investigations demonstrating the safety of cluster schedules in atopic dermatitis, pediatric patients, and inhalant allergen mixtures and an accelerated protocol utilizing an infusion pump for allergen delivery. There has also been further elucidation on the immunological changes which occur during accelerated immunotherapy. Finally, new studies analyzing systemic reaction risk factors are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. • Kim M-E, Kim J-E, Sung J-M, et al. Safety of accelerated schedules of subcutaneous allergen immunotherapy with house dust mite extract in patients with atopic dermatitis. J Korean Med Sci. 2011;26:1159–64. Study examining cluster in atopic dermatitis patients.

    Article  PubMed  CAS  Google Scholar 

  2. Hernandez N, Ibero M, Ridao M, et al. Safety of specific immunotherapy using a depigmented and polymerized extract of Dermatophagoides pteronyssinus in children under five years of age. Allergol Immunopathol (Madr). 2011;39(5):267–70.

    Article  CAS  Google Scholar 

  3. Schubert R, Eickmeier O, Garn H, et al. Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy. Int Arch Allergy Immunol. 2009;148(3):251–60.

    Article  PubMed  CAS  Google Scholar 

  4. • Copenhaver C, Parker A, Patch S. Systemic reactions with aeroallergen cluster immunotherapy in a clinical practice. Ann Allergy Asthma Immunol. 2011;107:441–7. Recent American study using the cluster schedule recommended in the practice parameter and analyzing systemic reaction risk factors to cluster immunotherapy.

    Article  PubMed  Google Scholar 

  5. Pfaar O, Mosges R, Hormann K, Klimek L. Safety aspects of cluster immunotherapy with semi-depot allergen extracts in seasonal allergic rhinoconjunctivitis. Eur Arch Otorhinolaryngol. 2010;267:245–50.

    Article  PubMed  Google Scholar 

  6. • Davis LS, Bhutani S, Barnett SR, Khan D. Early gene expression changes with rush immunotherapy. Clin Mol Allergy. 2011;9:12. This study examined whole genome expression profiling to identify changes in mRNA expression of peripheral blood mononuclear cells from allergic patients undergoing RIT.

    Article  PubMed  CAS  Google Scholar 

  7. Lou W, Wang C, Wang Y, et al. Enhancement of the frequency and function of IL-10-secreting type 1 T regulatory cells after 1 year of cluster allergen-specific immunotherapy. Int Arch Allergy Immunol. 2012;159:391–8.

    Article  PubMed  CAS  Google Scholar 

  8. Lou W, Wang C, Wang Y, et al. Responses of CD4(+) CD25(+) Foxp3(+) and IL-10-secreting type 1 T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children. Pediatr Allergy Immunol. 2012;23:140–9.

    Article  PubMed  Google Scholar 

  9. • Sastre J, Vallejo L, Hernandez E, et al. Rush allergen subcutaneous immunotherapy administered with infusion pump. Ann Allergy Asthma Immunol. 2011;107:459–60. This study utilized a portable battery-operated infusion pump to deliver allergen subcutaneously to 81 allergic rhinitis subjects and analyzed systemic reaction rates.

    Article  PubMed  Google Scholar 

  10. Justicia JL, Barasona MJ, Serrano P, et al. Predicting patients at high-risk of systemic reactions to cluster allergen immunotherapy: a pilot prospective observational study. J Investig Allergol Clin Immunol. 2006;17(6):386–92.

    Google Scholar 

  11. • Vegh AB, George KC, Lotfi-Emran S, et al. Total tryptase levels indicated risk for systemic reactions to rush immunotherapy and mast cell activation. Ann Allergy Asthma Immunol. 2011;106:342–3. This recent study found higher baseline tryptase levels in systemic reaction patients compared to non-SR patients undergoing RIT to an inhalant mixture.

    Article  PubMed  Google Scholar 

  12. Nanda A, O’Connor M, Anand M, et al. Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. J Allergy Clin Immunol. 2004;114:1339–44.

    Article  PubMed  CAS  Google Scholar 

  13. Tabar AI, Echechipia S, Garcia BE, et al. Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus. J Allergy Clin Immunol. 2005;116:109–18.

    Article  PubMed  Google Scholar 

  14. Francis JN, James LK, Paraskevopoulos G, et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol. 2008;121:1120–5.

    Article  PubMed  CAS  Google Scholar 

  15. Serrano P, Justicia JL, Sanchez C, et al. Systemic tolerability of specific subcutaneous immunotherapy with index-of-reactivity-standardized allergen extracts administered using clustered regimens: a retrospective, observational, multicenter study. Ann Allergy Asthma Immunol. 2009;102:247–52.

    Article  PubMed  Google Scholar 

  16. Zhang L, Wang C, Han D, Wang X, Zhao Y, Liu J. Comparative study of cluster and conventional immunotherapy schedules with dermatophagoides pteronyssinus in the treatment of persistent allergic rhinitis. Int Arch Allergy Immunol. 2009;148:161–9.

    Article  PubMed  CAS  Google Scholar 

  17. Martinez-Canavate A, Eseverri JL, Rodenas R, et al. Evaluation of paediatric tolerance to an extract of Alternaria alternate under two treatment regimes. A multicentre study. Allergol Immunopathol. 2005;33(3):138–41.

    Article  CAS  Google Scholar 

  18. 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;97:1207–13.

    Article  PubMed  CAS  Google Scholar 

  19. Winther L, Malling HJ, Mosbech H. Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II: side-effects. Allergy. 2000;55:327–35.

    Google Scholar 

  20. 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;30:1423–9.

    Article  PubMed  CAS  Google Scholar 

  21. Subiza J, Feliu A, Subiza JL, et al. Cluster immunotherapy with a glutaraldehyde-modified mixture of grasses results in an improvement in specific nasal provocation tests in less than 2.5 months of treatment. Clin Exp Allergy. 2008;38(6):987–94.

    Article  PubMed  CAS  Google Scholar 

  22. Pfaar O, van Twuijver E, Hecker H, et al. Accelerated up-dosing of subcutaneous immunotherapy with a registered allergoid grass pollen preparation. Int Arch Allergy Immunol. 2012;160(4):420–4.

    Article  PubMed  Google Scholar 

  23. Colas C, Monzon S, Venturini M, Lezaun A. Double-blind, placebo-controlled study with a modified therapeutic vaccine of Salsola kali (Russian thistle) administered through use of a cluster schedule. J Allergy Clin Immunol. 2006;117:810–6.

    Article  PubMed  CAS  Google Scholar 

  24. Cox L. Accelerated immunotherapy schedules: review of efficacy and safety. Ann Allergy Asthma Immunol. 2006;97:126–38.

    Article  PubMed  CAS  Google Scholar 

  25. Stewart GE, Lockey RF. Systemic reactions from allergen immunotherapy. J Allergy Clin Immunol. 1992;90:567–78.

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. 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;107:87–93.

    Article  PubMed  CAS  Google Scholar 

  28. Mauro M, Russello M, Alesina R, et al. Safety and pharmacoeconomics of a cluster administration of mite immunotherapy compared to the traditional one. Eur Ann Allergy Clin Immunol. 2006;38(1):31–4.

    PubMed  Google Scholar 

  29. Harvey SM. Safety of rush immunotherapy to multiple aeroallergens in an adult population. Ann Allergy Asthma Immunol. 2004;92:414–9.

    Article  PubMed  Google Scholar 

  30. 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 Asthma Immunol. 1994;73:409–18.

    CAS  Google Scholar 

  31. Bernstein JA, Kagen SL, Bernstein DI, Bernstein IL. Rapid venom immunotherapy is safe for routine use in the treatment of patients with Hymenoptera anaphylaxis. Ann Allergy. 1994;73:423–8.

    PubMed  CAS  Google Scholar 

  32. Roll A, Hofbauer G, Ballmer-Weber BK, Schmid-Grendelmeier P. Safety of specific immunotherapy using a four-hour ultra-rush induction scheme in bee and wasp allergy. J Investig Allergol Clin Immunol. 2006;16:79–85.

    PubMed  CAS  Google Scholar 

  33. Goldberg A, Confino-Cohen R. Rush venom immunotherapy in patients experiencing recurrent systemic reactions to conventional venom immunotherapy. Ann Allergy Asthma Immunol. 2003;91:405–10.

    Article  PubMed  CAS  Google Scholar 

  34. Schiavino D, Nucera E, Pollastrini E, et al. Specific ultrarush desensitization in Hymenoptera venom-allergic patients. Ann Allergy Asthma Immunol. 2004;92:409–13.

    Article  PubMed  Google Scholar 

  35. Tankersley MS, Walker RL, Butler WK, Hagan LL, Napoli DC, Freeman TM. Safety and efficacy of an imported fire ant rush immunotherapy protocol with and without prophylactic treatment. J Allergy Clin Immunol. 2002;109:556–62.

    Article  PubMed  Google Scholar 

  36. Dietrich JJ, Moore LM, Nguyen S, Hagan LL, Tankersley MS. Imported fire ant hypersensitivity: a 1-day rush immunotherapy schedule without premedication. Ann Allergy Asthma Immunol. 2009;103:535–6.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. Heijaioui A, Ferrando R, Dhivert H, Michel FB, Bousquet J. Systemic reactions occurring during immunotherapy with standardized pollen extracts. J Allergy Clin Immunol. 1992;89:925–33.

    Article  Google Scholar 

  39. Armentia-Medina A, Blanco-Quiros A, Martin-Santos JM, et al. Rush immunotherapy with a standardized Bermuda grass pollen extract. Ann Allergy Asthma Immunol. 1989;63:127–35.

    CAS  Google Scholar 

  40. Bousquet J, Braquemond P, Feinberg J, Guerin B, Maasch H, Michel FB. Specific IgE response before and after rush immunotherapy with a standardized allergen or allergoid in grass pollen allergy. Ann Allergy Asthma Immunol. 1986;56:456–9.

    CAS  Google Scholar 

  41. Bousquet J, Hejjaoui A, Skassa-Brociek W, 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;80:591–8.

    Article  PubMed  CAS  Google Scholar 

  42. Moverare R, Vesterinen E, Metso T, Sorva R, Elfman L, Haahtela T. Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody concentrations. Ann Allergy Asthma Immunol. 2001;86:337–42.

    Article  PubMed  CAS  Google Scholar 

  43. Casale TB, Busse WW, Kline JN, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117:134–40.

    Article  PubMed  CAS  Google Scholar 

  44. Bousquet J, Becker WM, Hejjaoui A, et al. Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple-pollen species, II: efficacy of a double-blind, placebo-controlled, specific immunotherapy with standardized extracts. J Allergy Clin Immunol. 1991;88:43–53.

    Article  PubMed  CAS  Google Scholar 

  45. Bousquet J, Guerin B, Dotte A, et al. Comparison between rush immunotherapy with a standardized allergen and an alum adjuved pyridine extracted material in grass pollen allergy. Clin Allergy. 1985;15:179–93.

    Article  PubMed  CAS  Google Scholar 

  46. Bousquet J, Maasch HJ, Hejjaoui A, et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids, III: efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma. J Allergy Clin Immunol. 1989;84:546–56.

    Article  PubMed  CAS  Google Scholar 

  47. Dolz I, Martinez-Cocera C, Bartolome JM, Cimarra M. A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. Allergy. 1996;51:489–500.

    PubMed  CAS  Google Scholar 

  48. Pfaar O, Urry Z, Robinson DS, et al. A randomized placebo-controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy. Allergy. 2012;67(2):272–9.

    Article  PubMed  CAS  Google Scholar 

  49. Horst M, Hejjaoui A, Horst V, Michel FB, Bousquet J. Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract. J Allergy Clin Immunol. 1990;85:460–72.

    Article  PubMed  CAS  Google Scholar 

  50. Hedlin G, Graff-Lonnevig V, Heilborn H, et al. Immunotherapy with cat- and dog-dander extracts, V: effects of 3 years of treatment. J Allergy Clin Immunol. 1991;87:955–64.

    Article  PubMed  CAS  Google Scholar 

  51. Hedlin G, Braff-Lonnevig V, Heilborn H, et al. Immunotherapy with cat- and dog-dander extracts, II: in vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study. J Allergy Clin Immunol. 1986;77:488–96.

    Article  PubMed  CAS  Google Scholar 

  52. Hedlin G, Heilborn H, Lilja G, et al. Long-term follow-up of patients treated with a three-year course of cat or dog immunotherapy. J Allergy Clin Immunol. 1995;96:879–85.

    Article  PubMed  CAS  Google Scholar 

  53. Lilja G, Sundin B, Graff-Lonnevig V, et al. Immunotherapy with cat- and dog-dander extracts, IV: effects of 2 years of treatment. J Allergy Clin Immunol. 1989;83:37–44.

    Article  PubMed  CAS  Google Scholar 

  54. Portnoy J, King K, Kanarek H, Horner S. Incidence of systemic reactions during rush immunotherapy. Ann Allergy Asthma Immunol. 1992;68:493–8.

    CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Brehler R, Klimek L, Pfaar O, et al. Safety of a rush immunotherapy build-up schedule with depigmented polymerized allergen extracts. Allergy Asthma Proc. 2010;31(3):e31–8.

    Article  PubMed  CAS  Google Scholar 

  57. Sturm G, Kranke B, Rudolph C, Aberer W. Rush Hymenoptera venom immunotherapy: a safe and practical protocol for high-risk patients. J Allergy Clin Immunol. 2002;110:928–33.

    Google Scholar 

  58. Patella V, Florio G, Giuliano A et al. Hymenoptera Venom Immunotherapy: Tolerance and efficacy of an ultrarush protocol versus a rush and a slow conventional protocol. Journal of Allergy 2012; article ID 192192, 8 pages.

  59. Riccio AM, Saverino D, Pesce G, et al. Effects of different up-dosing regimens for Hymenoptera venom immunotherapy on serum CTLA-4 and IL-10. PLoS One. 2012;7(6):e37980.

    Article  PubMed  CAS  Google Scholar 

  60. Celesnik N, Vesel T, Rijavec M, et al. Short-term venom immunotherapy induces desensitization of FcεRI-mediated basophil response. Allergy. 2012;67(12):1594–600.

    PubMed  CAS  Google Scholar 

  61. Patella V, Incorvaia C, Ricciardi L, et al. The adhesion molecule ICAM-1 is overexpressed in patients with Hymenoptera venom allergy and decreases after ultrarush venom immunotherapy. J Biol Regul Homeost Agents. 2011;25(3):465–8.

    PubMed  CAS  Google Scholar 

  62. Cichocka-Jaroxz E, Dorynska A, Pietrzyk JJ, Spiewak R. Laboratory markers of mast cell and basophil activation in monitoring rush immunotherapy in bee venom-allergic children. Immunotherapy. 2011;3(8):1013–7.

    Article  Google Scholar 

  63. Reimers A, Hari Y, Muller U. Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine: a double-blind, placebo-controlled trial. Allergy. 2000;55:484–8.

    Article  PubMed  CAS  Google Scholar 

  64. Brockow K, Kiehn M, Riethmuller C, Vieluf D, Berger J, Ring J. Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: A prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol. 1997;100:458–63.

    Article  PubMed  CAS  Google Scholar 

  65. Berchtold E, Maibach R, Muller U. Reduction of side effect from rush-immunotherapy with honey bee venom by pretreatment with terfenadine. Clin Exp Allergy. 1992;22:59–65.

    Article  PubMed  CAS  Google Scholar 

  66. Muller U, Hari Y, Berchtold E. Premedication with antihistamines may enhance efficacy of specific-allergen immunotherapy. J Allergy Clin Immunol. 2001;107:81–6.

    Article  PubMed  CAS  Google Scholar 

  67. Muller U, Jutel M, Reimers A, et al. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J Allergy Clin Immunol. 2008;122:1001–7.

    Article  PubMed  Google Scholar 

  68. Ewbank PA, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson HS. A double-blind, placebo-controlled immunotherapy dose–response study with standardized cat extract. J Allergy Clin Immunol. 2003;111:155–61.

    Article  PubMed  CAS  Google Scholar 

  69. Wohrl S, Gamper S, Hemmer W, Heinze G, Stingl G, Kinaciyan T. Premedication with montelukast reduces local reactions of allergen immunotherapy. Int Arch Allergy Immunol. 2007;144:137–42.

    Article  PubMed  Google Scholar 

  70. Heijaioui 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;85:473–9.

    Article  Google Scholar 

  71. • Massanari M, Nelson H, Casale T, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol. 2010;125:383–9. A prospective study which examined the effect of 16 weeks of treatment with omalizumab or placebo on the incidence of SR during cluster immunotherapy in 248 asthmatic subjects.

    Article  PubMed  CAS  Google Scholar 

  72. Calabria CW, Cox L. Accelerated immunotherapy schedules and premedication. Immunol Allergy Clin N Am. 2011;31:251–63.

    Article  Google Scholar 

Download references

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Christopher W. Calabria declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Dilley Allergy and Asthma Specialists LLP, 7835 I-10 West, San Antonio, TX, 78230, USA

    Christopher W. Calabria

Authors
  1. Christopher W. Calabria
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher W. Calabria.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calabria, C.W. Accelerated Immunotherapy Schedules. Curr Allergy Asthma Rep 13, 389–398 (2013). https://doi.org/10.1007/s11882-013-0356-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-013-0356-x

Keywords

Search

Navigation