1. EVALUATION OF THREE ALLERGEN SPECIFIC IMMUNOTHERAPY METHODS Standard Injection RUSH Injection Sublingual Abstract# 54 Richard Herrscher M.D. FACAAI Clinical Faculty U.T. Southwestern Medical Center Dallas, Texas Medical Director AIR Care P.A.

2. BACKGROUND RUSH immunotherapy - one day scheduleRUSH immunotherapy - one day schedule –Started using RUSH in 2000 based on description by Sharkey P, Portnoy J. Ann Allergy 1996;76:175-80 –Little is known how this schedule compares to standard immunotherapy in terms of efficacy. SLIT (sublingual immunotherapy)SLIT (sublingual immunotherapy) –Started using SLIT in 2003 based on evidence from European studies reviewed by Canonica and Passalacqua JACI 2003;111:437-48 –Very little data using U.S. extracts.

3. PURPOSE and METHODS Purpose of StudyPurpose of Study –To evaluate how alternative schedules of RUSH and SLIT compare to standard injection immunotherapy (SCIT) in terms of: Compliance - patient acceptanceCompliance - patient acceptance Clinical efficacyClinical efficacy SafetySafety

4. PURPOSE and METHODS MethodsMethods –Observational study. Data collection began in 2005. –Evaluated all patients starting immunotherapy from July 2003 through December 2004. –Data collection is ongoing. –Efficacy data collected prospectively with attempt to collect 6, 12 and 24 month time points. –Efficacy evaluated by patient questionnaire: Symptom and Medication reduction scores 5 point scale 0% - 25% - 50% - 75% - 100%

5. RUSH INJECTION SCHEDULE One - day RUSH protocolOne - day RUSH protocol –Very similar to previously described protocols –Sharkey P, Portnoy J. Ann Allergy 1996;76:175-80 –Harvey SM, Laurie S, Hilton K, Khan DA. Ann Allergy Asthma and Immunology 2004;92:414-9 38% systemic reaction rate during rush protocol38% systemic reaction rate during rush protocol

6. RUSH INJECTION SCHEDULE VialDilution Day 1 Dilution1:11:1 Schedule Vial size 10 ml Dose (ml) Schedule 1X wk monthly 1:10000.070.150.30 Dose (ml) 0.050.070.100.150.200.250.300.400.500.50 1:1000.070.150.3 1:100.070.150.30 1:10.05

7. SLIT SCHEDULE Dilution1:10,0001:10001:1001:101:1 Vial size 5 ml 15 ml schedule qd.- qod. 3X wk Drop dose q.d.- q.o.d. Build-up 3X weekly maintenance 1 (0.05ml) 23456789 10 (0.5ml) 12345678910123456789101234567891012345678910

8. ALLERGEN EXTRACTS/DOSE AllergenTreeGrassWeedMoldMite strength1:20w/v 100k BAU/ml 1:20w/v1:20w/v 10k BAU/ml Major allergen GREER N/AN/A 488  g Amb a1/ml 40  g Alt a1/ml 166  g Der p1f1/ml Std. SCIT 0.5 ml /month.05 ml 6.0k BAU 0.06 ml 29  g 0.06 ml 2.4  g 1.0k BAU 17.3  g RUSH SCIT 0.5 ml /month.05 ml 5.5k BAU 0.06 ml 29  g 0.06 ml 2.4  g 980 BAU 16.3  g SLIT 6.0 ml /month.83 ml 89.0k BAU 0.83 ml 405  g 1.1 ml 44  g 18k BAU 299  g SLIT increase Monthly dose 15X 14X 17X

9. SCHEDULE PERFORMANCE % Patients Achieving Maintenance Doses 1:11:101:1001:1000 Vial dilution 6months 12months 24months 100% 50% 100% 50% 100% 50% Std. SCIT RUSH SCIT SLIT

10. SCHEDULE PERFORMANCE Cumulative Allergen Dose 6months 12months 24months Std. SCIT RUSHSLIT Amb a1 9.3  g 200  g 976  g Effective dose increase (22X) (22X)(105X) Amb a1 234  g 395  g 3.8 mg Effective dose increase (1.7X)(16X) Amb a1 610  g 683  g 8.5 mg Effective dose increase (1.1X)(14X)

11. All patients starting IT July-03 thru Dec-04All patients starting IT July-03 thru Dec-04 COMPLIANCE DATA updated RUSH Std. SCIT SLIT Age yrs. (range) 32.5 (6-60) 24.4 (3-67) 18.2 (4-71) Total starts (M/F) 84 (44/40) 146 (74/72) 97 (56/41) Current on therapy 62 (74%) 92 (63%) 58 (60%) Total evaluated 629258

12. UPDATED EFFICACY DATA Patient starts July 2003 - Dec 2004 75% 25% 50% 43.1% 28.1% 21.4% 50% 34.9%34.7% < 12 months therapy > 12 months therapy No. patients 294931334327 Mean months 9.28.57.817.917.315.0 Std.SCITRUSHSLIT Med/ Sx Medication/ Symptom Reduction Score P=.001 P=.03

13. EFFICACY DATA Patient starts July 2003 - May 2005 75% 25% 50% 39.9% 28.4% 23.2% 43.1% 29.2% 33.9% 6 months 12 months No. patients 216041384234192813 Mean mo’s 7.27.36.912.812.412.921.220.919.1 Std.SCITRUSHSLIT Med/ Sx Medication/ Symptom Reduction Score 56.0% 46.5% 41.4% 24 months P=.025 P=.015

14. SAFETY DATA

15. SYSTEMIC REACTIONS moderate - severe Total patients 99201142 Post Rush 1st or 2nd injection 11N/AN/A Total other 5 (5%) 12 (6%) 1 (0.7%) Total w/reaction 16 (16%) 12 (6%) 1 (0.7%) Total number of reactions 22121 Immediate/ <30min 1481 Delayed / >30min 84 Std.SCIT RUSHSLIT

16. SLITSLIT –Much safer than injection therapy. –Making it feasible for home administration. –Extends immunotherapy to group unable to comply with office injections –Is not a completely benign therapy SUMMARY

17. SLITSLIT –Efficacy appears equal to standard injections. –Optimal dosing? 15X cumulative injection dose performed well in our patients. RUSHRUSH –More efficacious early on (0-18 months), higher compliance, more systemic reactions. SUMMARY