1. Rush and Cluster Immunotherapy Harold S. Nelson, MD Professor of Medicine National Jewish Health University of Colorado Health Science Center Denver, Colorado

2. Immunotherapy with a Standardized Dermatophagoides pteronyssinus Extract: III. Systemic reactions during the rush protocol in patients suffering from asthma.  47/125 experienced systemic reactions: - Urticaria (4) - Anaphylactic shock (8) - Asthma exacerbations (35).  Baseline FEV1 < 80% 73% systemic reactions. Baseline FEV1 ≥ 80% 13% systemic reactions. Difference all due to fewer asthma exacerbations. J Bousquet et al. J Allergy Clin Immunol 1989;83:797-802

3. Immunotherapy with a Standardized Dermatophagoides pteronyssinus Extract: IV. Systemic reactions according to the immunotherapy schedule  To decrease systemic reactions serially introduced: - Premedication: Oral CS, ketotiefen, Theophylline (Group B) - Premedication plus SIT givien only if FEV1 > 70% and stopped for locals > 10 cm (Group C) - Above plus RIT only four doses first day, then single doses days 2, 5, 8, 11, & 14. (D) A Hajjaoui, et al. J Allergy Clin Immunol 1990;85:473-9

4. Systemic reactions according to the immunotherapy schedule A Hajjaoui, et al. J Allergy Clin Immunol 1990;85:473-9 DoseSR’sUrticariaAsthma Anaphyl axis RIT206436%12.7%31%5.1% Pre-Med195416%3.8%14%1.8% FEV1, lg locals 12547.3%0.6%7%0.2% 2-week16625.4%0.4%5%0.4%

5. Double-blind Comparative Study of Cluster and Conventional Immunotherapy Schedules with Dermatophagoides pteronyssinus.  239 patients with allergic rhinitis or asthma sensitive to house dust mites.  Built up to a maintenance dose containing 3.2  g Der p 1 in an alum precipitated extract.  Half by cluster with 15 shots in 6 weeks and half by 13 single weekly injections. AI Tabar, et al. J Allergy Clin Immunol 2005;116:109-18

6. Double-blind Comparative Study of Cluster and Conventional Immunotherapy Schedules with Dermatophagoides pteronyssinus. Systemic reactions, all mild, occurred during the build-up stage in: Cluster: 3% of patients and 0.15% of injections. Weekly: 4% of patients and 0.31% of injections. AI Tabar, et al. J Allergy Clin Immunol 2005;116:109-18

7. P=0.04 Cluster Conventional Weeks Cut Tol Index 10 1 5040200103060 P0P6P12P18 P52 *Difference from P0; p<0.05 Cumlative Dose IT BU Cluster 25.3 25.3 41.3 Conventional 0.85 22.65 48.65 * * * * ** * - Decreased Prick Skin Tests AI Tabar, et al. J Allergy Clin Immunol 2005;116:109

8. Mean global score (standard error) T0T1 TF T1’ N1685655143 * Difference from T0 (wilcoxon, p<0.05) **Difference from T0 (wilcoxon, p<0.001) P=0.001 0.7 0.8 0.9 0.3 0.2 0.1 0 1 0.4 0.5 0.6 * * * ** Cluster Conventional Rhinitis Global Symptom- Medication Score AI Tabar, et al. J Allergy Clin Immunol 2005;116:109

9. Conclusions  Build-up using alum-precipitated D. pteronyssinus extract in a 6 week cluster regimen was as well tolerated as a conventional 12-week program of single injections.  Patients receiving cluster had more rapid onset of immunologic response and more rapid relief of symptoms. AI Tabar, et al. J Allergy Clin Immunol 2005;116:109

10. Experience at National Jewish with Cluster Immunotherapy using Aqueous Extracts

11. Cluster Immunotherapy Schedule: Injections B.I.W. Visit VialDose 11:1000/1:1000.1, 0.4 / 0.1 21:100/1:100.2, 0.4 / 0.07 31:100.1, 0.15, 0.25 41:100.35, 0.5 5Full strength0.07, 0.1 6F.S.0.15, 0.2 7F.S.0.3, 0.4 8F.S.0.5

12. Cluster Immunotherapy: The National Jewish Experience  3 dose-ranging studies, 2 with cat dander extract and 1 with A-P dog extract.  14 subjects received cluster to maintenance dose of 15  g Fel d 1 and 7 to maintenance dose of 15  g of Can d 1.  1 mild systemic reaction (patient reached projected maintenance with one extra injection).

13.  Antihistamine pretreatment with cluster immunotherapy: Premedication with loratadine reduced the percent of patients with systemic reactions from 79% to 33% (p =.002). Systemic reactions were more severe in the placebo group. Nielsen L, et al. JACI 1996;97:1207-13.  Administration of immunotherapy by a cluster regimen: - achieves both clinical and immunologic response more rapidly - does so with little or no increase in the risk of systemic reactions.