1. SLIT: dealing with trouble, doing it right. Giovanni B Pajno MD Professor of Pediatrics Department of Pediatrics – Allergy Unit University of Messina Italy Allergy School An Insight into Allergy and Allergen Immunotherapy 11 – 13 September 2014 Athens, Greece

2. FDA Committee Votes to Approve SLIT Treatments Last month, the Allergenic Products Advisory Committee (APAC) of the Food and Drug Administration (FDA) met and voted that the available safety and efficacy data support approval of two sublingual allergy immunotherapy (AIT) products. One is a grass pollen AIT tablet developed by Stallergenes and the other is Merck’s grass pollen AIT tablet. The APAC voted 9-1 regarding approval of the Stallergenes tablet and 9-0 regarding the Merck tablet. The FDA will need to give final approval, but it usually follows the advice of its advisory committees. AAAAI President Linda Cox, MD, FAAAAI, said in an email to members: “There are no FDA-approved forms of sublingual AIT currently available here in the United States, so these products would be the first licensed therapies of their kind. It’s worth noting that the committee felt very strongly about including language in the prescribing instructions for both products that recommended the patient has autoinjectable epinephrine in the event of a severe allergic reaction." Dr. Cox also discusses the news in this month's President's Message.President's Message More information, including a webcast of the meetings, is available from the FDA websiteFDA website

3. 1. Early intervention 2. Long lasting effect 3. Adherence SLIT

4. 1. Early intervention 2. Long lasting effect 3. Adherence SLIT

5. Increasing post-natal age Birth SLITSLIT Hampering the progression and worsening of IgE mediated disorders Allergens Exposure Food Allergens Inhalant Allergens TH2 polarized Immunity Persistent Wheeze Atopic Dermatitis Hay Fever Food Allergy Persistent Allergic Diseases J Allergy Clin Immunol 2007;119:796-801. G.B. Pajno

6. (Di Rienzo V et al. Clin Exp Allergy 2003;33:206-210)

7. Figure 1. Percentage of children in the immunotherapy and control groups who developed asthma after 3 years, in the 3 available trials. In the study by Marogna et al,37 the development of persistent asthma was assessed37 Specific immunotherapy: beyond the clinical scores Passalacqua G Annals of Allergy 2011;107:401-406

9. 1. Early intervention 2. Long lasting effect 3. Adherence SLIT

12. - SLIT

13. 1. Early intervention 2. Long lasting effect 3. Adherence SLIT

14. J Allergy Clin Immunol. 2005;116:1380-1

18. Allergen immunotherapy practice parameter, JACI 2010

19. Discontinuation 52% three y. old 18% four y. " 13% five y. "

20. CONCLUSION

21. Table 1. Comparison between SCIT and SLIT: Similarities and Diversities SharedEffective for both allergic rhino-conjunctivitis and allergic asthma. Disease modifying. - Possible prevention of new sensitivities in patients (mostly children) who are monosensitized to house dust mite. -Persistence of benefit for several years after discontinuation. -Possible prevention of allergic asthma? Immunological mechanisms of action. DifferingSeverity of systemic reactions (favours SLIT) Effectiveness of multiple allergen extracts (favours SCIT) Adherence to therapy (favours SCIT) Treatment of young allergic children (favours SLIT) Exp Review Clin Immunol in press Pajno G et al.