Allergy Drops–Are We Closer to Getting Rid of Shots?

Wouldn’t it be nice to put some drops under your tongue and say goodbye to those painful shots for good?  Allergy treatment under the tongue (sublingual drops and now tablets) have actually been around for a long time.  Until recently, the science behind allergy drops has been lacking.  As you read this review, consider the following:

  1. At the present time, there are no products approved by the FDA for this type of therapy.  It is anticipated that products will be approved within the next 3-5 years, but don’t ever try to predict the FDA!
  2. Most allergy care in the US uses multiple allergens in preparation for allergy shots.  This means a combination of trees, grasses, weeds, molds, dust, cat, dog, and sometimes cockroach. How many of you would be satisfied using only grass pollen or dust mite in your allergy treatment?
  3. Oh, the pain of shots!  There are now high frequency vibrational devices that take the pain out of shots right on the spot.  Ask our nurses to help you try it out.  This might make shots easier to tolerate.
  4. I don’t usually include references in my posts, but there’s only 25; the list is very inclusive for a complete up-to-date review of studies in the United States.
  5. I’ve copied the authors introduction, and conclusions for your review.   I enjoy reading future predictions and we’ll have to see how accurate this is. 

Adult and Pediatric Clinical Trials of Sublingual Immunotherapy in the USA

Dai Park, Nora Daher, Michael S Blaiss. Expert Rev Clin Immunol. 2012;8(6):557-564.

Specific allergen immunotherapy has been practiced for allergic rhinoconjunctivitis for over 100 years and is the only treatment option that is disease modifying. In the USA, immunotherapy is usually administered via subcutaneous injection; this is the only route with a US FDA-approved formulation. There is growing interest in developing US-standardized formulations for the sublingual route, but up until recently there have been few US trials. Most of the experience with sublingual immunotherapy (SLIT) comes from Europe, where it is widely used and there is a large body of literature supporting its use. The purpose of this review is to summarize recent adult and pediatric clinical trials of SLIT in the USA. Most of the trials are for inhalant allergies, but there is some early work on SLIT as a novel therapy for food allergies.


Presently, only subcutaneous immunotherapy is approved by the US FDA for inhalant and stinging insect allergies in the USA. Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is being viewed with increased interest by US allergists as an alternative to subcutaneous immunotherapy.

The first published double-blind, placebo-controlled, randomized clinical trial (DBPC-RCT) with inhalant SLIT came from London, UK in 1986.[1] This was followed by numerous studies from Europe in the last two decades, which confirmed the efficacy and safety of SLIT.[2] Some novel studies include the first DBPC-RCT on allergoid SLIT tablets in 1998[3] and the first DBPC-RCT of SLIT successfully treating atopic dermatitis in dust mite-sensitized children.[4]

Important work has also gone into elucidating the underlying mechanism of SLIT. The current thought is that tolerogenicity is induced by oral dendritic cells, which reside on the uppermost layers of oral tissue and in the context of SLIT, capture allergen and produce IL-10 and IL-12 cytokines. This thereby promotes a tolerogenic pathway and a T-cell shift from a Th2 to a Th1 and Treg phenotype. Treg cells further propagate the Th1 pathway by producing IL-10 and TGF-β that negatively feedback on Th2 cytokines and subsequently cause a decrease in IgE levels and an increase in IgG4 levels.[5]

In the USA, there was early work performed on SLIT for cat allergy in 1993;[6] however, this aside, there were no other published DBPC-RCTs until the past few years. Renewed interest may be, in part, due to the advent of two SLIT grass pollen tablets – Grazax®[7,8] and Oralair®,[9] approved for use in Europe in the late 2000s. These SLIT tablets are currently undergoing trials in the USA. Here we review those and other recent US clinical trials for inhalant and food SLIT.

Expert Review & Five-year View

SLIT has been demonstrated in US studies to be efficacious and safe in the limited number of allergens evaluated so far. Hopefully this will lead to FDA approval for this treatment in the near future. It appears from the studies discussed that SLIT by tablet will have a higher likelihood of FDA approval compared with SLIT drops. We should see the development of other common allergens in tablet form for SLIT, including dust mites, tree pollen and cat hair over the next several years. Studies will need to be performed to determine if mixed unrelated allergens given together by the SLIT method will demonstrate clinical efficacy and safety. We may likely see further studies looking at the disease-modifying aspects of SLIT and whether early treatment with SLIT in children at risk for allergy and asthma may prevent their development. Food studies will continue to assess the role of SLIT versus OIT that will hopefully lead to better and safer means of inducing desensitization and tolerance to improve the lives of the increasing growing population of people with food allergy in the USA.


  1. Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. Clin. Allergy 16(5), 483–491(1986).
  2. Cox LS, Larenas Linnemann D, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J. Allergy Clin. Immunol. 117(5), 1021–1035(2006).
    • A detailed, comprehensive review on Sublingual immunotherapy (SLIT) worldwide and discusses unmet needs.
  3. Passalacqua G, Albano M, Fregonese L et al. Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis. Lancet 351(9103), 629–632(1998).
  4. Pajno GB, Caminiti L, Vita D et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J. Allergy Clin. Immunol. 120(1), 164–170(2007).
  5. Moingeon P, Mascarell L. Induction of tolerance via the sublingual route: mechanisms and applications. Clin. Dev. Immunol. 2012, 623474(2012).
  6. Nelson HS, Oppenheimer J, Vatsia GA, Buchmeier A. A double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized cat extract. J. Allergy Clin. Immunol. 92(2), 229–236(1993).
  7. Durham SR, Emminger W, Kapp A et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J. Allergy Clin. Immunol. 129(3), 717–725.e5(2012).
    • Shows that the grass SLIT tablet, Grazax®, has a sustained disease modifying effect.
  8. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J. Allergy Clin. Immunol. 117(4), 802–809(2006).
  9. 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. 128(3), 559–566(2011).
    • Shows that the grass SLIT tablet, Oralair™, has a sustained disease modifying effect.
  10. Esch RE, Bush RK, Peden D, Lockey RF. Sublingual-oral administration of standardized allergenic extracts: Phase 1 safety and dosing results. Ann. Allergy Asthma Immunol. 100(5), 475–481(2008).
  11. Skoner D, Gentile D, Bush R, Fasano MB, McLaughlin A, Esch RE. Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by ragweed pollen. J. Allergy Clin. Immunol. 125(3), 660–6, 666.e1-e666.e4.(2010).
  12. Bush RK, Swenson C, Fahlberg B et al. House dust mite sublingual immunotherapy: results of a US trial. J. Allergy Clin. Immunol. 127(4), 974–81.e1(2011).
  13. 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. 124(1), 150–156.e1–e5(2009).
  14. Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J. Allergy Clin. Immunol. 127(1), 72–80, 80.e1(2011).
    •• The first study to demonstrate efficacy of grass SLIT tablet in US adults.
  15. Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J. Allergy Clin. Immunol. 127(1), 64–71, 71.e1(2011).
    •• The first study to demonstrate efficacy of grass SLIT tablet in US children.
  16. 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. 123(1), 167–173.e7(2009).
  17. Cox L, Casale TB, Nayak A et al. A US study of 5-grass pollen allergen extract in adults with grass pollen-induced allergic rhinoconjunctivitis – results of secondary efficacy assessments. J. Allergy Clin. Immunol. 129(2), (Abstract AB46) (2012).
  18. Cox L, Casale T, Nayak A et al. Efficacy and safety of sublingual 300IR 5-grass pollen tablets in adult patients with grass-pollen rhinoconjunctivitis in United States. J. Allergy Clin. Immunol. 127(2), (Abstract AB74) (2011).
  19. Berman G, Nolte H, Maloney J et al. Ragweed allergy immunotherapy tablet reduces nasal and ocular symptoms of allergic rhinoconjunctivitis over the peak ragweed pollen season in North America. J. Allergy Clin. Immunol. 129(2), (Abstract AB249) (2012).
  20. Maloney J, Nolte H, Nekam K et al. Dose-related effects of ragweed allergy immunotherapy tablet on nasal and ocular symptoms of allergic rhinoconjunctivitis during the peak ragweed pollen seasons in Europe and North America. J. Allergy Clin. Immunol. 129(2), (Abstract AB47) (2012).
  21. Nolte H, Maloney J, Bernstein D et al. Efficacy and tolerability of a novel ragweed allergen immunotherapy tablet during peak season in North American and European patients. J. Allergy Clin. Immunol. 129(2), (Abstract AB143) (2012).
  22. Kim EH, Bird JA, Kulis M et al. Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization. J. Allergy Clin. Immunol. 127(3), 640–6.e1(2011).
    • This is the first study to demonstrate efficacy of peanut SLIT in US children.
  23. Narisety SD, Keet C, Guerrerio P 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. 129(2), (Abstract AB27) (2012).
  24. Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J. Allergy Clin. Immunol. 129(2), 448–55, 455.e1(2012).
    • This is the first study to compare the efficacy of oral immunotherapy versus SLIT for cow’s milk allergy in children.
  25. Seopaul S, Keet CA, Frischmeyer-Guerrerio PA et al. Prolonged exposure to sublingual immunotherapy improves safety of oral immunotherapy. J. Allergy Clin. Immunol.129(2), (Abstract AB126) (2012).
  26. Website
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