Skip to main content

Advertisement

Log in

The Future of Sublingual Immunotherapy in the United States

  • Rhinitis (JJ Oppenheimer and J Corren, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

  1. Gentile D, Bartholow A, Valovirta E, Scadding G, Skoner D. Current and future directions in pediatric allergic rhinitis. J Allergy Clin Immunol Pract. 2014;1:214–26.

    Article  Google Scholar 

  2. Tran NP, Vickery J, Blaiss MS. Management of rhinitis: allergic and non-allergic. Allergy Asthma Immunol Res. 2011;3:148–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Lin SY. Sublingual immunotherapy: current concepts for the U.S. practitioner. Int Forum Allergy Rhinol. 2014;4:S55–9.

    Article  PubMed  Google Scholar 

  4. Brehler R, Klimek L, Kopp MV, Christian Virchow J. Specific immunotherapy-indications and mode of action. Dtsch Arztebl Int. 2013;110:148–58.

    PubMed Central  PubMed  Google Scholar 

  5. Linkov G, Toskala E. Sublingual immunotherapy: what we can learn from the European experience. Curr Opin Otolaryngol Head Neck Surg. 2014;22:208–10.

    Article  PubMed  Google Scholar 

  6. Canonica GW, Bousquet J, Casale T, et al. Sub-lingual immunotherapy world allergy organization position paper. WAO J. 2009;2:233–81.

    Google Scholar 

  7. Kim JM, Lin SY, Suarez-Cuervo C, et al. Allergen-specific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review. Pediatrics. 2013;131:1155–67. The authors performed a meta-analysis to study SLIT and the therapy’s effectiveness and safety in asthmatics, rhinitis, conjunctivitis, and children.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Nelson HS. Subcutaneous immunotherapy versus sublingual immunotherapy: which is more effective? J Allergy Clin Immunol Pract. 2014;2:144–9.

    Article  PubMed  Google Scholar 

  9. Didier A, Wahn U, Horak F, Cox LS. Five-grass-pollen sublingual immunotherapy tablet for the treatment of grass-pollen-induced allergic rhinoconjunctivitis: 5 years of experience. Expert Rev Clin Immunol. 2014;10:1309–24. This article summarizes all key parts of grass pollen SLIT including the formulations Oralair® and Grazax™/Grastek® from their efficacy, safety, research trials, and cost-effectiveness.

    Article  CAS  PubMed  Google Scholar 

  10. Creticos PS, Corren J, Feldweg AM. Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. UpToDate. 2014. This article evaluates SLIT completely—from the background to different formulations. It is an all-encompassing article highlighting delivery formulations, doses, and concomitant diseases. The article also goes into detail regarding the FDA-approved SLIT formulations.

  11. Tucker MH, Tankersley MS. Perception and practice of sublingual immunotherapy among practicing allergists. Ann Allergy Asthma Immunol. 2008;101:419–25.

    Article  PubMed  Google Scholar 

  12. Sikora JM, Tankersley MS. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110:194–7.

    Article  PubMed  Google Scholar 

  13. Ryan MW, Marple BF, Leatherman B, et al. Current practice trends in allergy: results of a United States survey of otolaryngologists, allergist-immunologists, and primary care physicians. Int Forum Allergy Rhinol. 2014;4:789–95.

    Article  PubMed  Google Scholar 

  14. Leatherman B, Skoner DP, Hadley JA, et al. The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: provider practices and beliefs about allergen immunotherapy. Int Forum Allergy Rhinol. 2014;4:779–88. The AIRS surveys collected important knowledge of both providers and patients about AR/ARC and immunotherapy. The article highlights the view of providers on allergen immunotherapy.

    Article  PubMed  Google Scholar 

  15. Elenburg S, Blaiss MS. Current status sublingual immunotherapy in the United States. World Allergy Organ J. 2014;7:24.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Durham SR, Nelson HS, Nolte H, et al. Magnitude of efficacy measurements in grass allergy immunotherapy trials is highly dependent on pollen exposure. Allergy. 2014;69:617–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Nelson HS. Sublingual immunotherapy: the U.S. experience. Curr Opin Allergy Clin Immunol. 2013;13:663–8.

    Article  CAS  PubMed  Google Scholar 

  18. Bartholow A, Pleskovic N, Drori J, Skoner DP. Review of the use of sublingual allergen immunotherapy in children. Pediatr Allergy Immunol Pulmonol. 2014;27:3–7.

    Article  Google Scholar 

  19. Cox L. Sublingual immunotherapy for aeroallergens: status in the United States. Allergy Asthma Proc. 2014;35:34–42.

    Article  CAS  PubMed  Google Scholar 

  20. Nelson HS. Is sublingual immunotherapy ready for use in the United States? JAMA. 2013;309:1297–8.

    Article  CAS  PubMed  Google Scholar 

  21. Larenas-Linnemann D, Esch R, Plunkett G, et al. Maintenance dosing for sublingual immunotherapy by prominent European allergen manufacturers expressed in bioequivalent allergy units. Ann Allergy Asthma Immunol. 2011;107:448–58.

    Article  PubMed  Google Scholar 

  22. Bousquet J, Khaltaev N, Cruz AA, Denburg J, et al. Allergic rhinitis and its impact on Asthma (ARIA) 2008 update. Eur J Allergy Clin Immunol. 2008;63:Supplement 86, 8–160.

  23. Compalati E, Braido F, Canonica GW. Sublingual immunotherapy: recent advances. Allergol Int. 2013;62:415–23.

    Article  CAS  PubMed  Google Scholar 

  24. Aboshady OA, Elghanam KM. Sublingual immunotherapy in allergic rhinitis: efficacy, safety, adherence, and guidelines. Clin Exp Otorhinolaryngol. 2014;7:241–9.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol. 2010;126:558–66.

    Article  PubMed  Google Scholar 

  26. Corp MS& D. Biologic License Application (BLA) for Timothy grass pollen allergen extract tablet for sublingual use. FDA Brief Doc. 2013.

  27. 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;114:63–76.

    Article  Google Scholar 

  28. Passalacqua G, Garelli V, Sclifo F, Canonica GW. Sublingual immunotherapy for allergic rhinitis and conjunctivitis. Immunotherapy. 2013;5:257–64.

    Article  CAS  PubMed  Google Scholar 

  29. Canonica GW, Cox L, Pawankar R, et al. Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J. 2014;7:6.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Meltzer EO, Bukstein DA. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy Asthma Immunol. 2011;106:S12–6.

    Article  PubMed  Google Scholar 

  31. Dranitsaris G, Ellis AK. Sublingual or subcutaneous immunotherapy for seasonal allergic rhinitis: an indirect analysis of efficacy, safety, and cost. J Eval Clin Pract. 2014;20:225–38. This is a valuable meta-analysis performed on Oralair®, Grazax™, and SCIT. It examines and compares the efficacy, safety, and cost of the three medications.

    Article  PubMed  Google Scholar 

  32. Incorvaia C, DiRienzo A, Celani C, Makri E, Frati F. Treating allergic rhinitis by sublingual immunotherapy: a review. Ann Ist Super Sanita. 2012;48:172–6.

    Article  CAS  PubMed  Google Scholar 

  33. Hankin CS, Cox L, Bronstone A, Wang Z. Allergy immunotherapy: reduced health care costs in adults and children with allergic rhinitis. J Allergy Clin Immunol. 2013;131:1084–91.

    Article  PubMed  Google Scholar 

  34. Hankin CS, Cox L. Allergy immunotherapy: what is the evidence for cost saving? Curr Opin Allergy Clin Immunol. 2014;14:363–70. This article consisted of a cost-analysis of SLIT, tablets and drops, SCIT, and symptomatic drug treatment.

    Article  CAS  PubMed  Google Scholar 

  35. Bender BG, Oppenheimer J. The special challenge of nonadherence with sublingual immunotherapy. J Allergy Clin Immunol Pract. 2014;2:152–5.

    Article  PubMed  Google Scholar 

  36. Anolik R, Schwartz AM, Sajjan S, Allen-Ramey F. Patient initiation and persistence with allergen immunotherapy. Ann Allergy Asthma Immunol. 2014;113:101–7.

    Article  PubMed  Google Scholar 

  37. Maloney J, Durham S, Skoner D, et al. Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma. Allergy. 2015;70:302–9.

    Article  CAS  PubMed  Google Scholar 

  38. Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010;181:116–24.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Lin SY, Erekosima N, Kim JM, et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA. 2013;309:1278–88.

    Article  CAS  PubMed  Google Scholar 

  40. Nowak-Wgrzyn A, Sampson HA. Future therapies for food allergies. J Allergy Clin Immunol. 2011;127:558–73.

    Article  Google Scholar 

  41. Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126:S1–S58.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Kim EH, Bird JA, Kulis M, et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J Allergy Clin Immunol. 2011;127:640–646.e1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Fleischer DM, Burks AW, Vickery BP, et al. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial. J Allergy Clin Immunol. 2013;131:119–127.e1-e7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Enrique E, Pineda F, Malek T, et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116:1073–9.

    Article  CAS  PubMed  Google Scholar 

  45. Narisety SD, Frischmeyer-guerrerio PA, Keet CA, et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J Allergy Clin Immunol. 2015;135:1275–82.

  46. Burks AW, Wood RA, Jones SM, et al. Sublingual immunotherapy for peanut allergy: long-term follow-up of a randomized multicenter trial. J Allergy Clin Immunol. 2015;1–12.

  47. Leung DYM, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004;113:651–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Qin YE, Mao JR, Sang YC, Li WX. Clinical efficacy and compliance of sublingual immunotherapy with Dermatophagoides farinae drops in patients with atopic dermatitis. Int J Dermatol. 2014;53:650–5.

    Article  PubMed  Google Scholar 

  49. Sánchez-Borges M, Asero R, Ansotegui IJ, et al. Diagnosis and treatment of urticaria and angioedema: a worldwide perspective. World Allergy Organ J. 2012;5:125–47.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Nettis E, Colanardi MC, Soccio AL, et al. Double-blind, placebo-controlled study of sublingual immunotherapy in patients with latex-induced urticaria: a 12-month study. Br J Dermatol. 2007;156:674–81. This study showed the effects or house dust mite SLIT in adults with allergic rhinitis. The 300IR and 500IR levels show a significant improvement in symptoms after 1 year of treatment, and this effectiveness was maintained in the second year without the therapy.

    Article  CAS  PubMed  Google Scholar 

  51. Bergmann K-C, Demoly P, Worm M, Fokkens W, Carrillo T. Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis. Am Acad Allergy Asthma Immunol. 2013;133:1608–14.

    Google Scholar 

  52. Cingi C, Bayar Muluk N, Ulusoy S, et al. Efficacy of sublingual immunotherapy for house dust mite allergic rhinitis. Eur Arch Oto-Rhino-Laryngology. 2014.

  53. Trebuchon F, Lheritier-Barrand M, David M, Demoly P. Characteristics and management of sublingual allergen immunotherapy in children with allergic rhinitis and asthma induced by house dust mite allergens. Clin Transl Allergy. 2014;4:15.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Aydogan M, Eifan AO, Keles S, et al. Sublingual immunotherapy in children with allergic rhinoconjunctivitis mono-sensitized to house-dust-mites: a double-blind-placebo-controlled randomised trial. Respir Med. 2013;107:1322–9.

    Article  PubMed  Google Scholar 

  55. Yukselen A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB. Two year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing subcutaneous and sublingual immunotherapy. Asian Pac J Allergy Immunol. 2013;31:233–41.

    Article  PubMed  Google Scholar 

  56. Nelson HS. Update on house dust mite immunotherapy: are more studies needed? Curr Opin Allergy Clin Immunol. 2014;14:542–8.

    Article  CAS  PubMed  Google Scholar 

  57. Calderon MA, Casale TB, Nelson HS, Demoly P. An evidence-based analysis of house dust mite allergen immunotherapy: a call for more rigorous clinical studies. Am Acad Allergy Asthma Immunol. 2013;132:1322–36.

    CAS  Google Scholar 

  58. Casale TB, Stokes JR. Future forms of immunotherapy. J Allergy Clin Immunol. 2011;127:8–15.

    Article  PubMed  Google Scholar 

  59. Swamy RS, Reshamwala N, Hunter T, et al. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol. 2012;130:215–224.e7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Amar SM, Harbeck RJ, Sills M, Silveira LJ, O’Brien H, Nelson HS. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract. J Allergy Clin Immunol. 2009;124:150–156.e5.

    Article  CAS  PubMed  Google Scholar 

  61. Kavuru M, Melamed J, Gross G, et al. Salmeterol and fluticasone propionate combined in a new powder inhalation device for the treatment of asthma: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2000;105:1108–16.

    Article  CAS  PubMed  Google Scholar 

  62. Creticos PS, Esch RE, Couroux P, et al. Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2014;133:751–8.

    Article  CAS  PubMed  Google Scholar 

  63. Antico A. Long-term adherence to sublingual tablet: literature review and suggestions for management strategies based on patients’ needs and preferences. Clin Exp Allergy. 2014;44:1314–26.

    Article  CAS  PubMed  Google Scholar 

  64. Devillier P, Dreyfus J-F, Demoly P, Calderón MA. A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis. BMC Med. 2014;12:71.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Skoner D, Blaiss M, Dykewicz M, et al. The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: patients’ experience with allergen immunotherapy. Allergy Asthma Proc. 2014;35:219–26.

    Article  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Nicole Pleskovic and Ashton Bartholow declare that they have no competing interests. Deborah A. Gentile reports that she was a speaker for Merck & Co. and Greer. David P. Skoner reports grants from Greer Laboratories, Novartis, Merck & Co., Genentech, GlaxoSmithKline, Sunovion, and Teva, and was a speaker or consultant for Merck & Co., Sunovion, Mylan, Teva, GlaxoSmithKline, Genentech, Novartis, and Sunovion.

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

Authors

Corresponding author

Correspondence to David P. Skoner.

Additional information

This article is part of the Topical Collection on Rhinitis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pleskovic, N., Bartholow, A., Gentile, D.A. et al. The Future of Sublingual Immunotherapy in the United States. Curr Allergy Asthma Rep 15, 44 (2015). https://doi.org/10.1007/s11882-015-0545-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-015-0545-x

Keywords

Navigation