Advertisement

Benefit of SLIT and SCIT for Allergic Rhinitis and Asthma

  • Giovanni PassalacquaEmail author
  • Giorgio Walter Canonica
  • Diego Bagnasco
Allergies and the Environment (M Hernandez, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Allergies and the Environment

Abstract

Allergen immunotherapy (AIT) has been in use since more than one century, when Leonard Noon experimentally proved its efficacy in hayfever (Noon, in Lancet 1:1572–3, 1911). Since then, AIT was administered only as subcutaneous injections (SCIT) until the sublingual route (SLIT) was proposed in 1986. The use of SLIT was proposed following several surveys from the USA and UK that repeatedly reported fatalities due to SCIT (Lockey et al. in J Allergy Clin Immunol 75(1): 166, 1985; Lockey et al. in J Allergy Clin Immunol 660–77, 1985; Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J, 293: 948, 1986). These reports raised serious concerns about the safety and the risk/benefit ratio of AIT. Many cases of life-threatening events with SCIT were due to avoidable human errors in administration, but a relevant fraction of them remained unexplained and unpredictable (Aaronson and Gandhi in J Allergy Clin Immunol 113: 1117–21, 2014). Subsequently, in a few years, SLIT gained credibility and was included in the official documents and guidelines (Table 1) (Bousquet et al. in J Allergy Clin Immunol 108(5 Supp):S146–S150, 2001; Canonica et al. in Allergy 64 (Supp 91):1–59, 2009) as a viable alternative to traditional SCIT. Of note, the local bronchial (aerosol) and the intranasal route of administration were attempted after the 1970s as alternatives to SCIT: the bronchial route was soon abandoned due to the poor efficacy and/or side effects, and the local nasal route, although effective and safe, was judged substantially impractical (Canonica and Passalacqua in J Allergy Clin Immunol 111: 437–48, 2003). In contrast to SCIT, SLIT was tested in very large clinical trials (need references), including hundreds of patients and with dose-ranging experimental designs, so that some products (tablets) for grass, mite, and ragweed were officially approved as commercial drugs by regulatory agencies such as the Food and Drug Administration and the European Medicines Agency and the optimal content for the maintenance dose was identified for selected allergens. In parallel, the knowledge on the mechanisms of action of AIT was rapidly refined, leading to further improvements, such as the chemically modified extracts and the use of adjuvants to enhance efficacy and safety. In addition, in the last 10 years, there has been an increasing scientific and clinical interest in AIT applied to food allergies, in particular in children, with the use of orally administered extracts (Albin and Nowak-Węgrzyn in Immunol Allergy Clin North Am 35: 77–100, 2015). The results are so far encouraging, at least for cow’s milk, egg, and peanut, although the use of treatment is still restricted to clinical trials or within specialized centers. Finally, the introduction of molecular- or component-resolved diagnosis has allowed detailing the prescription of AIT, by better delineating true sensitization versus cross-reactivity (Canonica et al. in World Allergy Organ J 6(1):17, 2013). This latter point is also in strict relation to the use of recombinant, engineered or highly purified molecules, instead of raw extracts, for the desensitization process.

Keywords

Subcutaneous immunotherapy Sublingual immunotherapy Allergic rhinitis Allergic asthma 

Notes

Compliance with Ethical Standards

Conflict of Interest

Drs. Passalacqua, Canonica, and Bagnasco declare no conflicts of interest relevant to this manuscript.

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.

Funding

The authors have none to declare.

References

  1. 1.
    Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1: 1572–3.Google Scholar
  2. 2.
    BöhmL, Maxeiner J, Meyer-Martin H, et al. IL-10 and regulatory T cells cooperate in allergenspecific immunotherapy to ameliorate allergic asthma. J Immunol. 2015;194:887–97.Google Scholar
  3. 3.
    Fujita H, SoykaMB, AkdisM, Akdis CA. Mechanisms of allergen specific immunotherapy. Clin Transl Allergy. 2012;2:2.Google Scholar
  4. 4.
    Nadeau KC. Immune mechanisms of sublingual immunotherapy. Curr Allergy Asthma Rep. 2014;14:473.Google Scholar
  5. 5.
    Ozdemir C, Kucuksezer UC, Akdis M, Akdis CA. Under the skin or under the tongue: differences and similarities in mechanisms of sublingual and subcutaneous immunotherapy. Immunotherapy. 2013;5:1151–8.Google Scholar
  6. 6.
    Bagnasco M, Altrinetti V, Pesce G, Caputo M, Mistrello G, Falagiani P, et al. Pharmacokinetics of Der p 2 allergen and derived monomeric allergoid in allergic volunteers. Int Arch Allergy Immunol. 2005;138:197–202.Google Scholar
  7. 7.
    Allam JP, Novak N. Immunological mechanisms of sublingual immunotherapy.Curr Opin Allergy Clin Immunol. 2014;14:564–9.Google Scholar
  8. 8.
    Bousquet J, Van Cauwenberge P, editors. Allergic rhinits and its impact on asthma. J Allergy Clin Immunol 2001; 108(5 Supp): S146–S150.Google Scholar
  9. 9.
    Canonica GW, Bousquet J, Casale T, et al., editors. Sub-lingual immunotherapy World Allergy Organization Position Paper 2009. Allergy 2009; 64 (Supp 91):1–59.Google Scholar
  10. 10.
    Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M,Bonini S, et al Sublingual Immunotherapy World Allergy Organization Paper. Update 2013. World Allergy Organiz J 2014; 7(1):6Google Scholar
  11. 11.
    Cox L, Nelson H, Lockey R, Calobria C, Checko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–55.Google Scholar
  12. 12.
    Abramson MJ, Puy RR, WeinerJM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2010;8.Google Scholar
  13. 13.
    Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010;12.Google Scholar
  14. 14.
    Penagos M, Passalacqua G, Compalati E, Baena-Cagnani CE, Orozco S, Pedroza A, et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest. 2008;133(3):599–609.Google Scholar
  15. 15.
    Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G.Efficacy of grass pollen allergen sublingual immunotherapy tablets for seasonal allergic rhinoconjunctivitis: a systematic review and meta-analysis. JAMA Intern Med. 2015;175(8):1301–9.Google Scholar
  16. 16.
    Compalati E, Passalacqua G, Bonini M, Canonica GW. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta-analysis. Allergy. 2009;64(11): 1570–9.Google Scholar
  17. 17.
    Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, doubleblind trials. Ann Allergy Asthma Immunol. 2006;97:141–8.Google Scholar
  18. 18.
    Frew A, Powell JL, Corrigan CJ, Durham SR. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment resistant seasonal allergic rhinoconjunctivitis. JACI. 2006;117: 319–25.Google Scholar
  19. 19.
    Passalacqua G, Albano M, Fregonese L, Riccio A, Pronzato C, Mela GS, et al. Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. Lancet. 1998; 351(9103): 629-632Google Scholar
  20. 20.
    Passalacqua G, Canonica GW. Allergen immunotherapy: history and future developments. Immunol Allergy Clin North Am. 2016;36(1):1–12.Google Scholar
  21. 21.
    Canonica GW, Bagnasco D, Ferrantino G, Ferrando M, Passalacqua G. Update on immunotherapy for the treatment of asthma. Curr Opin Pulm Med. 2016;22(1):18–24.Google Scholar
  22. 22.
    Passalacqua G, Canonica GW. Specific immunotherapy in asthma: efficacy and safety. Clin Exp Allergy. 2011;41(9):1247–55.Google Scholar
  23. 23.
    Mosbech H, Deckelmann R, de Blay F, Pastorello EA, Trebas-Pietras E, Andres LP, et al. Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol.2014;134(3):568–75.Google Scholar
  24. 24.
    Virchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a house dustmite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016;315(16):1715–25.Google Scholar
  25. 25.
    Nolte H, Maloney J, Nelson HS, Bernstein DI, Lu S, Li Z, et al. Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber. J Allergy Clin Immunol. 2015;135(6):1494–501.Google Scholar
  26. 26.
    Lockey RF, Nikoara-Kasti GL, Theodoropoulos DS, Bukantz SC. Systemic reactions and fatalities associated with allergen immunotherapy. Ann Allergy Asthma Immunol 2001; 87 (1 supp): S46-S55 3.Google Scholar
  27. 27.
    Stewart GE, Lockey RF Systemic reactions from allergen immunotherapy. J Allergy Clin Immunol. 1992; 90: 567-78.Google Scholar
  28. 28.
    Committee on the safety of medicines. CSM update. Desensitizing vaccines. Br Med J 1986; 293:948Google Scholar
  29. 29.
    Aaronson DW, Gandhi TK. Incorrect allergy injections: allergists’ experiences and recommendations for prevention. J Allergy Clin Immunol. 2004;113:1117–21Google Scholar
  30. 30.
    Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities associated with immunotherapy and skin testing. J Allergy Clin Immunol 1987; 660–677.Google Scholar
  31. 31.
    Cox L, Jacobsen L. Comparison of allergen immunotherapy practice patterns in the United States and Europe. Ann Allergy Asthma Immunol. 2009;103:451–9.Google Scholar
  32. 32.
    Schiappoli M, Ridolo E, Senna G, Alesina R, Antonicelli L, Asero R, et al. A prospective Italian survey on the safety of subcutaneous immunotherapy for respiratory allergy. Clin Exp Allergy. 2009;39(10):1569–74.Google Scholar
  33. 33.
    Passalacqua G, Nowak-Węgrzyn A, Canonica GW. Local side effects of sublingual and oral immunotherapy. J Allergy Clin Immunol Pract. 2016. doi:10.1016/j.jaip.2016.06.020.Google Scholar
  34. 34.
    Passalacqua G, Baena-Cagnani CE, Bousquet J, Canonica GW, Casale TB, Cox L, et al. Grading local side effects of sublingual immunotherapy for respiratory allergy: speaking the same language. J Allergy Clin Immunol. 2013;132(1):93–8.Google Scholar
  35. 35.
    Pitsios C, Demoly P, Bilò MB, Gerth van Wijk R, Pfaar O, Sturm GJ, et al. Clinical contraindications to allergen immunotherapy: an EAACI position paper. Allergy. 2015;70(8):897–909.Google Scholar
  36. 36.
    Pajno GB, Caminiti L, Crisafulli G, Vita D, Valenzise M, De Luca R, et al. Direct comparison between continuous and coseasonal regimen for sublingual immunotherapy in children with grass allergy: a randomized controlled study. Pediatr Allergy Immunol. 2011;22:803–7.Google Scholar
  37. 37.
    Stelmach I, Kaluzińska-Parzyszek I, Jerzynska J, Stelmach P, Stelmach W, Majak P. Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children. Allergy.2012;67:312–20.Google Scholar
  38. 38.
    Nakonechna A, Hills J, Moor J, Dore P, Abuzakouk M. Grazax sublingual immunotherapy in pre-co-seasonal and continuous treatment regimens: is there a difference in clinical efficacy? Ann Allergy Asthma Immunol. 2015;114:73–4.Google Scholar
  39. 39.
    Passalacqua G. Specific immunotherapy: beyond the clinical scores. Ann Allergy Asthma Immunol. 2011;107:401–6.Google Scholar
  40. 40.
    Canonica GW, Passalacqua G. Noninjection routes for immunotherapy. J Allergy Clin Immunol. 2003;111:437–48.Google Scholar
  41. 41.
    Bernardis P, Agnoletto M, Puccinelli P, Parmiani S, Pozzan M. Injective versus sublingual immunotherapy in Alternaria tenuis allergic patients. J Investig Allergol Clin Immunol. 1996;6:55–62.Google Scholar
  42. 42.
    Quirino T, Iemoli E, Siciliani E, Parmiani S, Milazzo F. Sublingual versus injective immunotherapy in grass pollen allergic patients: a double blind (double dummy) study. Clin Exp Allergy. 1996;26: 1253–61.Google Scholar
  43. 43.
    Mungan D, Misirligil Z, Gurbuz L. Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma—a placebo controlled study. Ann Allergy Asthma Immunol. 1999;82:485–90.Google Scholar
  44. 44.
    Khinchi MS, Poulsen LK, Carat F, André C, Hansen AB, Malling. HJ. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Allergy. 2004;59: 45–53.Google Scholar
  45. 45.
    Calderón MA, Simons FE, Malling HJ, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy:mode of action and its relationship with the safety profile. Allergy. 2012;67(3):302–11.Google Scholar
  46. 46.
    Durham SR, PenagosM. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016;137(2):339–349.Google Scholar
  47. 47.
    Nelson HS, Makatsori M, Calderon MA. Subcutaneous immunotherapy and sublingual immunotherapy: comparative efficacy, current and potential indications, and warnings—United States versus Europe. Immunol Allergy Clin North Am. 2016;36(1):13Google Scholar
  48. 48.
    Passalacqua G, Canonica GW. Sublingual immunotherapy: focus on tablets. Ann Allergy Asthma Immunol. 2015;115(1):4–9.Google Scholar
  49. 49.
    Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol.2010;126(5):969–75.Google Scholar
  50. 50.
    Stelmach I, Sobocinska A, Majak P, Smejda K, Jerzynska J, Stelmach W. Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen immunotherapy. Ann Allergy Asthma Immunol. 2012;109:274–8.Google Scholar
  51. 51.
    Albin S, Nowak-Wegrzyn A. Potential treatments for food allergy. Immunol Allergy Clin North Am. 2015;35:77–100.Google Scholar
  52. 52.
    Anagnostou K, Clark A. Peanut immunotherapy. Clin Transl Allergy. 2014;4:30.Google Scholar
  53. 53.
    Gendelman SR, Lang DM. Sublingual immunotherapy in the treatment of atopic dermatitis: a systematic review using the GRADE system. Curr Allergy Asthma Rep. 2015;15(2):498.Google Scholar
  54. 54.
    Bachert C, Larché M, Bonini S, Canonica GW, Kündig T, Larenas-Linnemann D, et al. Allergen immunotherapy on the way to product-based evaluation—a WAO statement. World Allergy Organ J. 2015;8(1):29.Google Scholar
  55. 55.
    Canonica GW, Ansotegui IJ, Pawankar R, Schmid-Grendelmeier P, van Hage M, Baena-Cagnani CE, et al. AWAO - ARIA - GA2LEN consensus document onmolecular-based allergy diagnostics.World Allergy Organ J. 2013;6(1):17.doi: 10.1186/1939-4551-6-17.
  56. 56.
    Demoly P, Passalacqua G, Pfaar O, Sastre J,Wahn U. Management of the polyallergic patient with allergy immunotherapy: a practicebased approach. Allergy, Asthma Clin Immunol. 2016;12:2.Google Scholar
  57. 57.
    Maloney J, Bernstein DI, Nelson H, Creticos P, Hébert J, Noonan M, et al. Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol.2014;112:146–53.Google Scholar
  58. 58.
    Savi E, Peveri S, Senna G, Passalacqua G. Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach.Allergy. 2013;68(9):1193–5.Google Scholar
  59. 59.
    Passalacqua G, Canonica GW. AIT (allergen immunotherapy): a model for the Bprecision medicine^. Clin Mol Allergy. 2015;13:24.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Giovanni Passalacqua
    • 1
    Email author
  • Giorgio Walter Canonica
    • 1
  • Diego Bagnasco
    • 1
  1. 1.Allergy and Respiratory Diseases, IRCCS San Martino-ISTUniversity of GenoaGenoaItaly

Personalised recommendations