Research regarding the use of sublingual immunotherapy

You'll find the most current understanding of the clinical efficacy, safety and use of sublingual immunotherapy (SLIT) for allergy treatment is embodied in the studies, papers and publications referenced in this document. Over 160 citations are contained in this bibliography, including over 70 peer-reviewed studies published since 1995.
Internationally, SLIT is used widely (50-75% in some European countries), with full regulatory and government backing. U.S. allergy leaders are writing in support of SLIT. (See section 1) The World Health Organization indicated its use in its 1998 position paper. In November 2001, an international workgroup, including U.S. allergists, published the ARIA (Allergy Rhinitis and its Impact on Asthma) guidelines indicating SLIT as an effective alternative as well. Since that time, dozens of well-designed studies (randomized, double-blind, placebo-controlled) have been peer reviewed and published. Cochrane Review has performed a meta-analysis and determined SLIT both safe and effective (see section 1).

Two additional pivotal studies to note are the “10 year study…” showing the long lasting effect of SLIT (see section 1), and the 2004 head-to-head study of SLIT to injection in a double-blind, double-dummy approach (see section 2). Few studies (two) could be found showing that SLIT was not effective, and those results are equivocal and dated.

Additional research efforts are underway in the U.S. and internationally, this document will updated periodically to include further publications.
Comprehensive list of Studies & Papers

1. Recent Major Texts, Guidelines, Papers and Editorials 1. Cox, Linda, et al “Sublingual immunotherapy: A comprehensive review,” J Allergy Clin Immunology, Vol. 117, No. 5, pgs. 1021-1035, May 2006.

2. Nelson, Harold “Advances in upper airway diseases and allergen immunotherapy,” J Allergy and Clin Immunology, Vol. 117, No. 5, pgs. 1047-1053, May 2006.

3. Durham, Stephen et al “Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis,” Vol. 117, No. 4, pgs. 802-809, April 2006.

4. Passalacqua, Giovanni et al “Non-Injection Routes for Allergen Immunotherapy: Focus on Sublingual Immunotherapy,” Inflammation & Allergy – Drug Targets, Vol. 5, pgs. 43-51, 2006.

5. Passalacqua, Giovanni et al “Quantitative assessment of the compliance with once-daily sublingual immunotherapy regimen in real life (EASY Project: Evaluation of A novel SLIT formulation during a Year, ” (Letter to the Editor) J Allergy Clin Immunology, Vol. 117, Number 4, April 2006.

6. Bieber, T. Editorial “Allergen-specific sublingual immunotherapy: less mystic, more scientific,” Allergy, Vol. 61, pgs. 149-150, 2006.

7. Dahl R. et al, “Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis,” Allergy, Vol. 61, pgs. 185-190, 2006.

8. Marogna, Maurizio, et al, “Clinical, functional, and immunologic effects of sublingual immunotherapy in birch pollinosis: A 3-year randomized controlled study,” J Allergy Clin Immunol, Vol. 115, Number 6, pgs. 1184-1188, June 2005.

9. Cingi, C. et al “Efficacy of long-term sublingual-oral immunotherapy in allergic rhinitis,” ACTA Otorhinolaryngol Ital 25, pgs. 214-219, 2005.

10. Gidaro, G.B., et al, “The safety of sublingual-swallow immunotherapy: an analysis of published studies,” Clin Exp Allergy, Vol. 35, pgs. 565-571, 2005.

11. Pajno, Giovanni “Allergen immunotherapy in early childhood: between Scylla and Charybdis!,” Clin Exp Allergy, Vol. 35, pgs. 551-553, 2005.

12. Courtney, A.U, et al, “ Childhood Asthma: Treatment Update,” American Family Physician, Vol. 71, No. 10, pgs. 1959-1968, May 2005.

13. Parks, Kevin “Advances in Immunotherapy: Current Considerations and Beyond,” The Allergy and Immunology Report, Vol. 1 No. 2, Spring 2005.

14. Bousquet, J “Sublingual immunotherapy: from proven prevention to putative rapid relief of allergic symptoms,” Editorial, Allergy, Vol. 60, Issue pgs. 1-3, January 2005.

15. Lambrecht, BN “Dendritic cells in the pathogenesis of asthma” Clinical and Exp. Allergy Rev 2004, 4:123-128.

16. Nelson, Harold “Advances in upper airway diseases and allergen immunotherapy,” Journal of Allergy and Clinical Immunology, Vol. 113, No. 4, Pages 635-42, April 2004.

17. Passalacqua, Giovanni, et al, “Efficacy and safety of sublingual immunotherapy,” Annals of Allergy, Asthma, and Immunology, Vol. 93; 1, pgs. 3-12, 2004.

18. Portnoy J. “Allergen Immunotherapy in the Prevention of Asthma” Current Opinion Allergy Clinical Immunology 4(2): 131-136, 2004.

19. Passalacqua, G, Canonica, GW, “Sublingual or injection immunotherapy: the final answer?” Allergy 2004: 59: 37-38.

20. Malling, Hans-Jorgen “Comparison of the clinical efficacy and safety of subcutaneous and sublingual immunotherapy: methodological approaches and experimental results,” Current Opinion in Allergy and Clinical Immunology, Vol. 4, pgs. 539-542, 2004.

21. Mosages, R “The role of hyposensitization: do we need to start rethinking?” Clinical Opinion in Allergy and Clinical Immunology, 2004, Vol. 4, pgs. 155-157.

22. Norman, Philip S. “Immunotherapy: 1999-2004,” Journal of Allergy and Clinical Immunology, June 2004 Vol. 113, No. 6, pgs. 1013-1023.

23. Passalacqua G, Lombardi C, Canonica GW “Sublingual Immunotherapy: An Update,” Current Opinion in Allergy and Clinical Immunology, Vol. 4 (1), February 2004.

24. Markert, UR and Elsner P. Local Immunotherapy in Allergy, Chemical Immunology and Allergy (lead chapter by D. Morris, et al,) Vol. 82, Karger, Basel, Switzerland 2003.

25. Wilson, DR Torres, LM, and Durham SR “Sublingual immunotherapy for allergic rhinitis” (Cochrane Review), The Cochrane Library, Oxford, England, Issue 2. 2003.

26. Canonica, G. Walter and Passalacqua, G. “Non-injection routes for immunotherapy,” Journal of Allergy and Clinical Immunology, Vol. 111, No. 3 pgs. 437-448, March 2003.

27. Nelson, Harold S. “Advances in upper airway diseases and allergen immunotherapy,” Journal of Allergy and Clinical Immunology, Vol. 111, No. 3, pgs. S793-798, March 2003.

28. Di Rienzo, V., Canonica, GW, and Passalacqua G. “Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10 year prospective study,” Clinical and Experimental Allergy, Vol. 33, pgs. 206-210, 2003.

29. Bielory L. and Heimall “Review of complementary and alternative medicine in treatment of ocular allergies,” Current Opinion in Allergy and Clinical Immunology, Vol. 3, pgs. 395-399, 2003.

30. Passalacqua, G, Baena-Cagnani, Carlos, Berardi, M, Canonica, G Walter “Oral and sublingual immunotherapy in pediatric patients,” Current Opinion in Allergy and Clinical Immunology, Vol. 3(2), pgs. 139-145, April 2003.

31. Li, J et al, “Allergen immunotherapy: a practice parameter,” Journal of Allergy and Clinical Immunology, Vol. 90, January 2003 (see Summary Statement 57, Page 27).

32. Kagi M.K. and B. Wuthrich, Review Article, “Different methods of local allergen-specific immunotherapy,” Allergy, Vol. 57, pgs. 379-388, 2002.

33. Reiber, Mark E. “Sublingual Administration of Allergen Desensitization” Tennessee Medicine, pgs. 465-467, November 2002.

34. Douglass, J. and O'Hehir, R. (Editorial) "Specific allergen immunotherapy: time for alternatives?,” Clinical and Experimental Allergy, Vol. 32, pgs. 1-3, 2002.

35. Bousquet, J. The new ARIA guidelines: putting science into practice, Clin Exp All Rev 2002; 2:38-43.

36. Volpe, A. Della, et al, “Sublingual Allergen-Specific Immunotherapy in Allergic Rhinitis and Related Pathologies: Efficacy in a Paediatric Population” International Journal of Immunopathology and Pharmacology, Vol 15, No. 1, pgs. 35-40, 2002.

37. Malling, H. “Is Sublingual Immunotherapy Clinically Effective?” Current Opinion Allergy and Clinical Immunology, Vol 2, No. 6 pgs. 523-532, 2002.

38. Allergic Rhinitis and its impact on Asthma (ARIA) Workshop Report. ARIA Workshop Group, Journal of Allergy and Clinical Immunology, Supplement, 11/2001:Vol. 108, No. 5.

39. Bousquet, J., ARIA Workshop Group Guidelines J All Clin Immunol pgs S242-S245, 2001.

40. Passalacqua G. & Canonica, G.W. "Allergen-Specific Sublingual Immunotherapy for Respiratory Allergy,” BioDrugs, Vol. 15 (8) pgs. 509-519, 2001.

41. Morris, D.L. "Current use of sublingual-swallow immunotherapy,” Current Opinion in Otolaryngology & Head and Neck Surgery, Vol. 9, No. 3, pgs. 179-180, June 2001.

42. Marogna, M. et al, “Clinical Practice Improvement Program for Immunotherapy of Respiratory Allergic Diseases,” International Journal of Immunopathology and Pharmacology, Vol. 14, No. 2, pgs 93-101, 2001.

43. Allergen Immunotherapy: Guidelines, Update and Recommendations of the World Health Organization, Theodoropoulos & Lockey, Allergy & Asthma Proc. Pg. 159-66, May-June 2000, Vol. 21, No.3.

44. Frew, Anthony, et al, "Sublingual Immunotherapy,” Journal of Allergy Clinical Immunology, pgs. 441-444, March 2001.

45. Brown, J.L. & Frew, A.J. (Editorial) "The efficacy of oromucosal immunotherapy in respiratory allergy,” Clinical & Experimental Allergy, Vol. 31, Is. 1, pg 8-10, January 2001.

46. Editorial, "The efficacy of oromucosal immunotherapy in respiratory allergy,” Clinical and Experimental Allergy, Vol. 31, pgs. 8-10, 2001.

47. Rakoski, Jurgen and Wessner, Dirk "A Short Assessment of Sublingual Immunotherapy,” International Archives of Allergy and Immunology, Vol. 126, pgs. 185-187, 2001.

48. Pineda-Algorta, J. et al, “Study of the efficacy of sublingual immunotherapy in patients with grass pollen sensitization,” (abstract) “Mini Symposium 3 Sublingual Immunotherapy” Allergy 55 Suppl. Vol. 63: pg. 24, 2000.

49. Ano-Garcia, M. et al, “Efficacy and safety of sublingual immunotherapy in patients with sensitization to Dermtophagoides pteronyssinus” (abstract) “Mini Symposium 3 Sublingual Immunotherapy” Allergy 55 Suppl. Vol 63: pg. 24, 2000.

50. Khinchi, M.S. et al, “Clinical efficacy of sublingual-swallow and subcutaneous immunotherapy in patients with allergic rhinoconjunctivitis due to birch pollen. A double-blind, double dummy placebo-controlled study (abstract), “Mini Symposium 3 Sublingual Immunotherapy” Allergy 55 Suppl. Vol 63: pg 24, 2000.

51. Donato, R.M. Patients with allergic rhinitis from Argentine treated with SLIT (sublingual immunotherapy) a non-injective route - Abstract presented October 2000 IACAI Conf.

52. Malling, Hans-Jergen "Allergen-specific immunotherapy. Present state and directions for the future,” Allergy, Vol 54, pgs. 30-33, 1999.

53. Passalacqua, G. et al, "Oral and Sublingual Immunotherapy: General Aspects and Critical Considerations,” WMW Themenheft: Hyposensibilsierung, pgs 433-437, 1999.

54. Donahue, JG et al, “Utilization and cost of immunotherapy for allergic asthma and rhinitis,” Annals of Allergy, Asthma and Immunology, Vol. 82, pgs. 339-347, April 1999.

55. Bousquet J, Lockey R. Malling HJ, Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization Position Paper Allergy Vol 53 Suppl 44 pgs 1-29, 1998.

56. Malling, H.J. Editorial "Sublingual Immunotherapy,” Clinical Experimental Allergy, Vol. 26, pgs. 1228-1231, 1996.

57. Passalacqua G. et and G.W. Canonica “Alternative routes for allergen-specific immunotherapy” J Invest Allergol Clin Immunol, Vol. 6(2) pgs. 81-87, March-April 1996.

58. Creticos, P.S. A review of oral specific immunotherapy, Expressions on allergen specific immunotherapy, Stallergenes S.A., Vol. 1, June 1995. (US Based DBPC Study).

The following pages are a comprehensive bibliography of studies divided into six categories, with citations presented in chronological order;
1. Recent Major Guidelines and Papers; includes over 55 significant position papers;

2. Studies/Abstracts; includes over 70 studies;

3. Comparison Studies of Sublingual and Subcutaneous Antigen Administration; includes 2004 randomized, placebo-controlled, double-blind, double-dummy study;

4. Safety and Quality-of-Life Related Studies;

5. Mechanisms of Sublingual Immunotherapy; current understanding of mucosal immunity;

6. Other Indications for Treatment; other sensitizations where SLIT has been effective.

The scrutiny of SLIT has been intense, particularly in the past five years. The volume of research and its consistency is presented as evidence of the value of SLIT to patients. We thank you for your interest in this topic and invite you to provide us feedback and let us know if you would like to receive updates a new research and publications are added.

2) Studies/Abstracts

1. Niu, Chen-Kuang, et al, “Efficacy of sublingual immunotherapy with high-dose mite extracts in asthma; A multi-center, double-blind, randomized and placebo -controlled study in Taiwan,” Respiratory Medicine, pgs 1-10.

2. Di Rienzo, V. et al, “Post-marketing survey on the safety of sublingual immunotherapy in children below the age of 5 years,” Clinical and Experimental Allergy, Vol. 35, Issue 5, pg. 560, May 2005.

3. Fiocchi, A. et al, “A Prospective Study on Safety of Sublingual Immunotherapy in Children Aged 3 to 6 Years,” Journal of Allergy and Clinical Immunology, Vol. 115, No. 2, pg S265, February 2005.

4. Tesse, R. et al, “Effects of Oral Bacterial Immunotherapy in Children With Atopic Eczema/Dermatitis Syndrome,” Journal of Allergy and Clinical Immunology, Vol. 115, No. 2, pg S266, February 2005.

5. Bahceciler N.N. et al, “Impact of Sublingual Immunotherapy on Specific Antibody Levels in Children Allergic to House Dust Mites, Int Arch Allergy Immunol, Vol. 136, No. 3, pgs. 287-294, February 2005.

6. Wilson, D.R. et al, “Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis*,” Allergy, Vol. 60, Issue 1, page 4, January 2005.

7. Marogna, M et al, “Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more,” Allergy, Vol. 59, No. 11, pgs 1205-1210, November 2004.

8. Novembre, E. et al, “Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis,” Journal Allergy and Clinical Immunology, Vol. 114, No, 4, pgs 851-857, October 2004.

9. Smith, Helen et al, “Randomized controlled trial of high-dose sublingual immunotherapy to treat allergic rhinitis,” Journal Allergy and Clinical Immunology, Vol. 114, No. 4, pgs. 831- 837, October 2004.

10. Savi, E, et al, “A latex-containing hepatitis-B vaccine administered in a severely latex allergic paediatric patient after specific sublingual immunotherapy: a case report. Allergy, Vol. 59, No. 9, pgs. 1014-1015, September 2004.

11. Drachenberg, K.J. et al, “Sublingual specific immunotherapy for adults and children: a post marketing surveillance study” Allergol Immunopathol, Vol. 32, No. 2, pgs 76-81, March-April 2004.

12. Mastrandrea F. “The potential role of allergen-specific sublingual immunotherapy in atopic dermatitis,” Am J Clin Dermatol, Vol. 5, No. 5, pgs 281-294, 2004.

13. Cistero, B.A. et al, “Tolerance and effects on skin reactivity to latex of sublingual rush immunotherapy with a latex extract,” J Investig Alllergol Clin Immunol, Vol. 14, No. 1, pgs 17-25, 2004.

14. Khinchi…Malling, “ 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.

15. Tonnel, A.B. et al, “Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy,” Allergy, Vol. 59, pgs. 491-197, 2004.

16. Bufe, A. et al, “Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study, Allergy, Vol. 59(5), pgs 498-504, May 2004.

17. Pajno, GB, et al, “Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial dagger,” Allergy, Vol. 59(8), pgs. 883-887, August 2004.

18. Pajno, G.B. et al, “Comparisons between injection and sublingual immunotherapy for rhinitis and asthma in allergic children to house dust mite or parietaria pollen. A case controlled study,” Journal of Allergy and Clinical Immunology, February 2004 Supplement, Vol. 113, Number 2. (abs.)

19. Niu, C. et al, “Efficacy and safety of sublingual immunotherapy with high dose house dust mite extract in asthmatic children – a multicenter randomized double-blind, and placebo-controlled study, February 2004 Supplement, Vol. 113, Number 2. (abs.)

20. Mauro, M. et al, “Efficacy and safety of subcutaneous and sublingual immunotherapy in birch pollinosis,” Journal of Allergy and Clinical Immunology, February 2004 Supplement, Vol. 113, Number 2.

21. Melranci, C. Matteoli M. “Efficacy of allergoid sublingual immunotherapy in children with asthma and/or allergic rhinoconjunctivitis: Comparison study with drugs” Journal of Allergy and Clinical Immunology, February 2004 Supplement, Vol. 113, Number 2. (abs.).

22. Bassi M. et al, “High dose sublingual immunotherapy: Economic evaluation from an Italian observational data base study” Journal of Allergy and Clinical Immunology, February 2004 Supplement, Vol. 113, Number 2. (abs.)

23. Pajno, GB “Efficacy of sublingual immunotherapy in asthma and eczema,” Chem Immunol Allergy, Vol. 82, pgs 77-88, 2003.

24. Wuthrich, B et al, “Double-Blind, Placebo-Controlled Study with Sublingual Immunotherapy in Children with Seasonal Allergic Rhinitis to Grass Pollen,” Journal Invest Allergol Clin Immunol, Vol. 13(3), pgs. 145-148, 2003.

25. Andre, et al, “A Double-Blind Placebo-Controlled Evaluation of Sublingual Immunotherapy with a Standardized Ragweed Extract in Patients with Seasonal Rhinitis,” Int Arch Allergy Immunol, 131: pgs. 111-118, 2003.

26. Ippoliti, F, et al, “Immunomodulation during sublingual therapy in allergic children,” Pediatric Allergy and Immunology, Vol. 14, pgs. 216-221, 2003.

27. Pajno, G.B. et al, Abstract “Parietaria Pollen Sublingual Immunotherapy for Asthmatic Children: Seasonal Behavior in Methacholine PC20, Journal of Allergy and Clinical Immunology, February 2003.

28. Mortemousque, B, et al, “House-dust mite sublingual –swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study,” Clinical and Experimental Allergy, Vol. 33, pgs. 464-469, 2003.

29. Gonzalez, E. et al, Abstract “Efficacy and Safety of a Standardized Sublingual Therapeutic Vaccine of Cat Epithelia Extract, Journal of Allergy and Clinical Immunology, page S200, February 2003.

30. Cirla, A.M. et al, “A pre-seasonal birch/hazel sublingual immunotherapy can improve the outcome of grass pollen injective treatment in bisensitized individuals. A case-referent, two year controlled study,” Allergol et Immunopath Vol. 31(1) 31-43, 2003.

31. Madonini, F, et al, “Long-term and preventive effects of Sublingual Allergen Specific Immunotherapy: A retrospective, multicentric study, Int’l Journal of Immunopathology and Pharmacology, Vol.16 no. 1, 73-79 (2003).