The safety of sublingual immunotherapy, can the rare systemic reactions be prevented?

References

• Update CSM. Desensitising vaccines. Br Med J (Clin Res Ed). 1986 Oct 11;293(6552):948.
   PubMedGoogle Scholar
• Lockey RF, Benedict LM, Turkeltaub PC, et al. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol. 1987 Apr;79(4):660–677.
   PubMed Web of Science ®Google Scholar
• Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin Allergy. 1986 Sep;16(5):483–491.
   PubMedGoogle Scholar
• Passalacqua G, Bagnasco D, Canonica GW. 30 years of sublingual immunotherapy. Allergy. 2020 May;75(5):1107–1120.
   PubMed Web of Science ®Google Scholar
• Passalacqua G, Canonica GW Oral, nasal and sublingual immunotherapy: do they work, are they safe? Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 2003 ( 94):126–130; discussion 130–2.
   Google Scholar
• Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy. 2005 Jan;60(1):4–12.
   PubMed Web of Science ®Google Scholar
• Bousquet J, Khaltaev N, Cruz AA, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008 Apr;63(Suppl 86):8–160.
   PubMed Web of Science ®Google Scholar
• Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy: world allergy organization position paper 2009. Allergy. 2009 Dec;64(Suppl 91):1–59.
   PubMed Web of Science ®Google Scholar
• Bousquet J, Pfaar O, Togias A, et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019 Nov;74(11):2087–2102.
   PubMed Web of Science ®Google Scholar
• Calderon MA, Waserman S, Bernstein DI, et al. Clinical practice of allergen immunotherapy for allergic rhinoconjunctivitis and asthma: an expert panel report. J Allergy Clin Immunol Pract. 2020 Oct;8(9):2920–2936 e1.
   PubMed Web of Science ®Google Scholar
• Bufe A, Ziegler-Kirbach E, Stoeckmann E, et al. Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study. Allergy. 2004 May;59(5):498–504.
   PubMed Web of Science ®Google Scholar
• Rolinck-Werninghaus C, Wolf H, Liebke C, et al. A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen. Allergy. 2004 Dec;59(12):1285–1293.
   PubMed Web of Science ®Google Scholar
• Clavel R, Bousquet J, Andre C. Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis. Allergy. 1998 May;53(5):493–498.
   PubMed Web of Science ®Google Scholar
• Bousquet J, Scheinmann P, Guinnepain MT, et al. Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study. Allergy. 1999 Mar;54(3):249–260.
   PubMed Web of Science ®Google Scholar
• Pradalier A, Basset D, Claudel A, et al. Sublingual-swallow immunotherapy (SLIT) with a standardized five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy. 1999 Aug;54(8):819–828.
   PubMed Web of Science ®Google Scholar
• Ibanez MD, Kaiser F, Knecht R, et al. Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children. Pediatr Allergy Immunol. 2007 Sep;18(6):516–522.
   PubMed Web of Science ®Google Scholar
• Malling HJ, Montagut A, Melac M, et al. Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis. Clin Exp Allergy. 2009 Mar;39(3):387–393.
   PubMed Web of Science ®Google Scholar
• Wahn U, Tabar A, Kuna P, et al. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2009 Jan;123(1):160–166 e3.
   PubMed Web of Science ®Google Scholar
• Bufe A, Eberle P, Franke-Beckmann E, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol. 2009 Jan;123(1):167–173 e7.
   PubMed Web of Science ®Google Scholar
• Blaiss M, Maloney J, Nolte H, et al. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol. 2011 Jan;127(1):64–71, 71 e1–4.
   PubMed Web of Science ®Google Scholar
• Matsuoka T, Bernstein DI, Masuyama K, et al. Pooled efficacy and safety data for house dust mite sublingual immunotherapy tablets in adolescents. Pediatr Allergy Immunol. 2017 Nov;28(7):661–667.
   PubMed Web of Science ®Google Scholar
• Okamoto Y, Fujieda S, Okano M, et al. Efficacy of house dust mite sublingual tablet in the treatment of allergic rhinoconjunctivitis: A randomized trial in a pediatric population. Pediatr Allergy Immunol. 2019 Feb;30(1):66–73.
   PubMed Web of Science ®Google Scholar
• Grosclaude M, Bouillot P, Alt R, et al. Safety of various dosage regimens during induction of sublingual immunotherapy. A preliminary study. Int Arch Allergy Immunol. 2002 Nov;129(3):248–253.
   PubMed Web of Science ®Google Scholar
• Andre C, Perrin-Fayolle M, Grosclaude M, et al. A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship. Int Arch Allergy Immunol. 2003 Jun;131(2):111–118.
   PubMed Web of Science ®Google Scholar
• Durham SR, Yang WH, Pedersen MR, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006 Apr;117(4):802–809.
   PubMed Web of Science ®Google Scholar
• Didier A, Malling HJ, Worm M, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol. 2007 Dec;120(6):1338–1345.
   PubMed Web of Science ®Google Scholar
• Didier A, Worm M, Horak F, et al. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis. J Allergy Clin Immunol. 2011 Sep;128(3):559–566.
   PubMed Web of Science ®Google Scholar
• Nelson HS, Nolte H, Creticos P, et al. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J Allergy Clin Immunol. 2011 Jan;127(1):72–80, 80 e1–2.
   Web of Science ®Google Scholar
• Cox LS, Casale TB, Nayak AS, et al. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE. J Allergy Clin Immunol. 2012 Dec;130(6):1327–34 e1.
   PubMed Web of Science ®Google Scholar
• Armentia A, Carballada F, Carretero P, et al. Postmarketing study for assessment of tolerability of a grass allergen immunotherapy tablet (GRAZAX) in patients with rhinitis or rhinoconjunctivitis. J Investig Allergol Clin Immunol. 2012;22(7):485–490.
   PubMed Web of Science ®Google Scholar
• Creticos PS, Maloney J, Bernstein DI, et al. Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults. J Allergy Clin Immunol. 2013 May;131(5):1342–9 e6.
   PubMed Web of Science ®Google Scholar
• Mosbech H, Deckelmann R, de Blay F, 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 Sep;134(3):568–575 e7.
   PubMed Web of Science ®Google Scholar
• Bergmann KC, Demoly P, Worm M, et al. Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis. J Allergy Clin Immunol. 2014 Jun;133(6):1608–14 e6.
   PubMed Web of Science ®Google Scholar
• Roux M, Devillier P, Yang WH, et al. Efficacy and safety of sublingual tablets of house dust mite allergen extracts: results of a dose-ranging study in an environmental exposure chamber. J Allergy Clin Immunol. 2016 Aug;138(2):451–458 e5.
   PubMed Web of Science ®Google Scholar
• Virchow JC, Backer V, Kuna P, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016 Apr 26;315(16):1715–1725.
   PubMed Web of Science ®Google Scholar
• Yonekura S, Gotoh M, Kaneko S, et al. Treatment duration-dependent efficacy of Japanese cedar pollen sublingual immunotherapy: evaluation of a phase II/III trial over three pollen dispersal seasons. Allergol Int. 2019 Oct;68(4):494–505.
   PubMed Web of Science ®Google Scholar
• Gidaro GB, Marcucci F, Sensi L, et al. The safety of sublingual-swallow immunotherapy: an analysis of published studies. Clin Exp Allergy. 2005 May;35(5):565–571.
   PubMed Web of Science ®Google Scholar
• Blazowski L. Anaphylactic shock because of sublingual immunotherapy overdose during third year of maintenance dose. Allergy. 2008 Mar;63(3):374.
   PubMed Web of Science ®Google Scholar
• Malling HJ, Lund L, Ipsen H, et al. Safety and immunological changes during sublingual immunotherapy with standardized quality grass allergen tablets. J Investig Allergol Clin Immunol. 2006;16(3):162–168.
   PubMed Web of Science ®Google Scholar
• de Groot H, Bijl A. Anaphylactic reaction after the first dose of sublingual immunotherapy with grass pollen tablet. Allergy. 2009 Jun;64(6):963–964.
   PubMed Web of Science ®Google Scholar
• Greenhawt M, Oppenheimer J, Nelson M, et al. Sublingual immunotherapy: A focused allergen immunotherapy practice parameter update. Ann Allergy Asthma Immunol. 2017 Mar;118(3):276–282 e2.
   PubMed Web of Science ®Google Scholar
• Rodriguez Del Rio P, Vidal C, Just J, et al. The European Survey on adverse systemic reactions in allergen immunotherapy (EASSI): A paediatric assessment. Pediatr Allergy Immunol. 2017 Feb;28(1):60–70.
   PubMed Web of Science ®Google Scholar
• Lee TM, Grammer LC, Shaughnessy MA, et al. Modified antigens in the treatment of allergic disease. Year Immunol. 1986;2:338–350.
   PubMedGoogle Scholar
• Compalati E, Incorvaia C, Cavaliere C, et al. The role of allergoids in allergen immunotherapy: from injective to sublingual route. Eur Ann Allergy Clin Immunol. 2020 Sep;52(5):195–204.
   PubMed Web of Science ®Google Scholar
• Nolte H, Casale TB, Lockey RF, et al. Epinephrine use in clinical trials of sublingual immunotherapy tablets. J Allergy Clin Immunol Pract. 2017 Jan - Feb;5(1):84–89 e3.
   PubMed Web of Science ®Google Scholar
• Didier A, Wahn U, Horak F, et al. Five-grass-pollen sublingual immunotherapy tablet for the treatment of grass-pollen-induced allergic rhinoconjunctivitis: 5 years of experience. Expert Rev Clin Immunol. 2014 Oct;10(10):1309–1324.
   PubMed Web of Science ®Google Scholar
• Mosbech H. Tolerability and efficacy of house dust mite AIT. Allergy. 2011 Jul;66(Suppl 95):55–56.
   PubMed Web of Science ®Google Scholar
• Borg M, Lokke A, Hilberg O. Compliance in subcutaneous and sublingual allergen immunotherapy: A nationwide study. Respir Med. 2020 Aug - Sep;170::106039.
   PubMed Web of Science ®Google Scholar
• Kiel MA, Roder E, Gerth van Wijk R, et al. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013 Aug;132(2):353–60 e2.
   PubMed Web of Science ®Google Scholar
• Epstein TG, Liss GM, Murphy-Berendts K, et al. Risk factors for fatal and nonfatal reactions to subcutaneous immunotherapy: national surveillance study on allergen immunotherapy (2008-2013). Ann Allergy Asthma Immunol. 2016 Apr;116(4):354–359 e2.
   PubMed Web of Science ®Google Scholar
• Nurmatov U, Dhami S, Arasi S, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews. Clin Transl Allergy. 2017;7:24.
   PubMed Web of Science ®Google Scholar
• Bernstein DI, Bardelas JA Jr., Svanholm Fogh B, et al. A practical guide to the sublingual immunotherapy tablet adverse event profile: implications for clinical practice. Postgrad Med. 2017 Aug;129(6):590–597.
   PubMed Web of Science ®Google Scholar
• Tankersley M, Han JK, Nolte H. Clinical aspects of sublingual immunotherapy tablets and drops. Ann Allergy Asthma Immunol. 2020 Jun;124(6):573–582.
   PubMed Web of Science ®Google Scholar
• Antico A, Fante R. Esophageal hypereosinophilia induced by grass sublingual immunotherapy. J Allergy Clin Immunol. 2014 May;133(5):1482–1484.
   PubMed Web of Science ®Google Scholar
• Miehlke S, Alpan O, Schroder S, et al. Induction of eosinophilic esophagitis by sublingual pollen immunotherapy. Case Rep Gastroenterol. 2013;7(3):363–368.
   PubMedGoogle Scholar
• Epstein TG, Calabria C, Cox LS, et al. Current evidence on safety and practical considerations for administration of sublingual allergen immunotherapy (SLIT) in the United States. J Allergy Clin Immunol Pract. 2017 Jan - Feb;5(1):34–40 e2.
   PubMed Web of Science ®Google Scholar
• Cosmi L, Santarlasci V, Angeli R, et al. Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma- and interleukin-10-production. Clin Exp Allergy. 2006 Mar;36(3):261–272.
   PubMed Web of Science ®Google Scholar
• Compalati E, Incorvaia C, Urbano S, et al. The safety of carbamylated monomeric allergoids for sublingual immunotherapy. Data from a pharmacovigilance study. Immunotherapy. 2020 Feb;12(3):195–202.
   PubMed Web of Science ®Google Scholar