100 years of allergen-specific immunotherapy – the future has just begun.

Since 1911, when Noon first administered inoculations of timothy pollen to avoid idiosyncratic reactions, allergen-specific immunotherapy (SIT) has evolved as the key treatment of allergic rhinitis, which is consider a pandemic disease affecting 25% of western populations. A wide range of evidence has been found on the clinical-and immunological efficacy of SIT, its long-term effects as well as its ability to prevent the progression of the disease and to improve the quality of life of our allergic patients. In this year, the 100’s anniversary of this innovative therapy is celebrated by the EAACI.

A new board of the Immunotherapy Interest Group (IT IG) has been elected and officially presented at the last IT IG Business Meeting during EAACI congress in Istanbul 2011. Dr Moises A. Calderon as Chairman and Dr Oliver Pfaar as Secretary will be working with an elected an international and interdisciplinary board: Dr Beatrice Bilo, Dr Constantinos Pitsios, Dr Jorg Kleine-Tebbe, Dr Maia Rukhadze and Dr Gianenrico Senna. The core group is supported by Dr Pablo Rodriguez del Rio as webmaster.

Fifty percent of the active members of the EAACI have signed up for the IT IG. This represents an important challenge and reflects the outstanding importance of this treatment in our medical community and in our daily practice (see table below). Therefore, the aim of the IT-IG is to continue and to coordinate ongoing projects as well as to stimulate cooperation and prospective scientific projects amongst all members. All interested EAACI members are cordially invited to support our group and take part in all our activities.

*Source: EAACI headquarters

Projects for 2011-2012:

1. Task Force on “Dose-Effect of SIT” (already completed)
Coordinator: MA Calderon
Start date: 2009; Finish date: 2011

Rationale: Clinical and immunological efficacy of SIT have been documented in many double-blind, placebo-controlled clinical trials. However, no consensus indication about dose-effect has been established. Different pre-seasonal or perennial schedules of treatment have been proposed and evaluated, all of them using different concentrations of single or multiples allergens. As a consequence, direct comparison of different preparations as reported in clinical trials is not feasible.

Main objectives of the project were:
To collect and compare clinical and immunological data on dose-efficacy of SIT for allergic rhinoconjunctivitis and asthma
To analyse dose-efficacy and dose-safety of venom SCITTo define optimal doses regarding systemic adverse reactions

The results of this TF have already been published in a TF-report in Allergy:

2. Task Force on “European Survey on Systemic Adverse Reactions due to Allergen Immunotherapy in real life setting”

Renamed: "European Adverse Systemic Reactions Survey in Allergen Specific Immunotherapy" EASSI


TF-coordinator: MA Calderon
Start date:  2011
Finish dates:
•    2012 (Phase I): Survey design
•    2013 (Phase II): pilot-study (4 European countries)
•    2016 (Phase III): Pan-European survey

Rationale: To date, clinical trials on SIT are based on carefully controlled clinical protocols in experimental conditions with pre-defined patient numbers and therefore specific information on side-effects. Therefore, the aim of this prospective survey is to collect  on all adverse reactions which may occur on daily practice in the allergy clinics.

Main objective:
To describe the safety profile of immunotherapy, prospectively, in real life setting in Europe.
To estimate the incidence of clinically relevant systemic adverse reactions due to immunotherapy.
To determine the number of systemic, anaphylactic and life-threatening allergic reactions occurring per patient and per treatment-year.

3. Task Force on “Evaluation of adherence to SCIT and SLIT in Europe”


Coordinators: Gianenrico Senna and Giovanni Passalacqua
Start-date: 2011; Finish-date: 2014

Rationale: A good therapy-adherence of patients is essential for the efficacy of both SLIT and SCIT. However, only few clinical reports focus on adherence and underlying factors influencing this issue.

Main objective of this project is:
To evaluate and compare the adherence rate to SLIT and SCIT in Europe and search for the reasons underlying its lack of adherence.
About 100 members from EAACI will be requested to join this study and follow their SIT prescriptions each 4 months and in case of lack of adherence, address the possible reason: lack of efficacy, cost, tolerance, GP acceptance or any other reason. This study will be conducted electronically.

4. Task Force on “Standardization of (Primary) Clinical Outcomes for Clinical Trials in SIT”


TF-Coordinators: Oliver Pfaar and Sabina Rak
Start-date: 2011
Finish date: 2012

Rationale: Generally accepted and authoritative national and international guidelines are still lacking with respect to the assessment of the therapeutic effects of SIT by using clearly-defined symptom- and medication-scores. Therefore, the aim of the task-force will be to propose a position statement clearly defining how symptoms and medications should be assessed, analysed and adequately weighted in prospective clinical trials on both SLIT and SCIT.

Main objectives:
To gather all scoring-systems so far used in trials on SLIT and SCIT.
To l produce a rostrum paper to be published in Allergy.

5. Project on “Seasonal Allergic Rhinitis: In search of the cut-off points”


Coordinator: Glennis Scadding and Moises Calderon
Start date: 2011
Finish date: 2012

Rationale: The evaluation of patient’s assessments of any particular therapeutic intervention during a clinical trial is very important. This can be measured using the validated RQLQ.

Main objective:
To identify the cut-off point between adequately and inadequately controlled rhinoconjunctivitis/rhinitis using the mini Rhinitis-Quality-of-Life-Questionnaire (RQLQ).
Members of the IT IG and EAACI ENT Section will be requested their voluntary participation to take part in a “one” page electronic survey.
Already positive approval has been given by members of the EAACI ExCom.

6. Project “Semantics in SIT”


Coordinator: Pascal Demoly and Moises Calderon
Start date:  2011
Finish date: 2012

Rationale:  Current semantic use to characterize allergen immunotherapy is heterogeneous depending on the countries and/or the scientific societies. 

Main objective:
To create a common language for all audiences regarding immunotherapy and identify semantic keys to reinforce the impact of communication on allergy immunotherapy.

7. Task force on “Contraindications of SIT”


Coordinator: Constantinos Pitsios
Start date:  2011
Finish date: 2012

Rationale: Despite the large number of papers published on SCIT and SLIT, there is still no common agreement on the “contra-indications” for SIT.

Main objective: To collect and compare clinical data on the effect of SIT in the known contraindications.
A systematic literature search will be performed to re-assess SIT contraindications and adapt them to current situation of different diseases, co-morbidities and certain drugs.

8. An “EAACI Scholarship-program on SIT”


Coordinators: Oliver Pfaar and Moises Calderon
Start date:  2011
Finish date: 2012

Rationale: In European countries, there is a broad range of several academic “schools” of IT with different scientific and clinical focuses, these may include SLIT, short-time schedules in SCIT, Cluster-SCIT, adjuvants in SCIT or new innovative forms of IT (ILIT, epicutaneous IT and others).

Main objective:
To coordinate  and support fellowships for young colleagues with outstanding interest in SIT aimed to i) elevate the standards of IT throughout whole Europe and ii) stimulate scientific collaborations and working groups.

9. Reactivation of EAACI IT IG Website
Pablo Rodriguez del Rio and Jorg Kleine-Tebbe (webmasters)
Start date: 2011

Main objective: To establish the IT IG website as a practical tool of communication amongst all members of the EAACI family


General aspects of Allergen-Specific Immunotherapy:

Calderon MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, Varga EM, Valovirta E, Moreno C, Malling HJ, Alvarez-Cuesta E, Durham S, Demoly P. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'. Allergy. 2011 Jun 28. doi: 10.1111/j.1398-9995.2011.02669.x. [Epub ahead of print]

Subcutaneous Immunotherapy:

Cox L, Calderón M, Pfaar O. Subcutaneous allergen immunotherapy for allergic disease: examining efficacy, safety and cost effectiveness of current and novel formulations. Immunotherapy. 2012 Jun; 4(6): 601-16.

Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2010 Mar;125(3):569-74.

Soyer OU, Akdis M, Akdis CA. Mechanisms of subcutaneous allergen immunotherapy. Immunol Allergy Clin North Am. 2011 May;31(2):175-90, vii-vii.

Cox L, Nelson H, Lockey R et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011 Jan;127(1 Suppl):S1-55. Epub 2010 Dec 3

Sublingual Immunotherapy:

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

Scadding G, Durham SR. Mechanisms of sublingual immunotherapy. Immunol Allergy Clin North Am. 2011 May;31(2):191-209, viii.

Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol. 2010 Jan;125(1):131-8.e1-7.

Horak F, Zieglmayer P, Zieglmayer R, et al. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immunol. 2009 Sep;124(3):471-7.

Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010 Dec 8;(12).

Future approaches:

Casale TB, Stokes JR. Future forms of immunotherapy. J Allergy Clin Immunol. 2011 Jan;127(1):8-15;

Valenta R, Linhart B, Swoboda I, Niederberger V.Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. Allergy. 2011 Jun;66(6):775-83.

Moldaver D, Larche M. Immunotherapy with peptides. Allergy. 2011 Jun;66(6):784-91

Senti G, von Moos S, Kundig TM. Epicutaneous allergen administration: is this the future of allergen-specific immunotherapy? Allergy. 2011 Jun;66(6):798-809

Martinez-Gomez JM, Johansen P, Erdmann I, Senti G, Crameri R, Kundig TM. Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150(1):59-65.

Suzuki K, Kaminuma O, Yang L, et al Development of transgenic rice expressing mite antigen for a new concept of immunotherapy. Int Arch Allergy Immunol. 2009;149 Suppl 1:21-4

Non respiratory allergens

Bilo BM, Bonifazi F. Hymenoptera venom immunotherapy. Immunotherapy. 2011 Feb;3(2):229-46.

Niedoszytko M, de Monchy J, van Doormaal JJ, Jassem E, Oude Elberink JN. Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy. Allergy. 2009 Sep;64(9):1237-45.

Nowak-Wegrzyn A, Sampson HA. Future therapies for food allergies. J Allergy Clin Immunol. 2011 Mar;127(3):558-73.

Fernandez-Rivas M, Garrido Fernandez S, Nadal JA et al. Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy. 2009 Jun;64(6):876-83.


Bousquet J, Schunemann HJ, Bousquet PJ et al. How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement. Allergy. 2011 Jun;66(6):765-74.

Ring J, Gutermuth J.100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT). Allergy. 2011 Jun;66(6):713-24

Bousquet PJ, Calderon MA, Demoly P, et al.  The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article. J Allergy Clin Immunol. 2011 Jan;127(1):49-56.

Document was prepared by:

Pablo Rodriguez del Rio
Jorg  Kleine-Tebbe
Oliver Pfaar
Moises Calderon

Last updated 28 July 2014