1 / 32

Anti-IgE in Asthma and Other Allergic Diseases

Anti-IgE in Asthma and Other Allergic Diseases. Harold S. Nelson. MD Professor of Medicine National Jewish Health And University of Colorado School of Medicine. Denver. Colorado, USA. Pivotal Trials: Study Design . Placebo or Omalizumab + BDP reduction. Placebo or Omalizumab  BDP.

rasha
Télécharger la présentation

Anti-IgE in Asthma and Other Allergic Diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Anti-IgE in Asthma and Other Allergic Diseases Harold S. Nelson. MD Professor of Medicine National Jewish Health And University of Colorado School of Medicine. Denver. Colorado, USA

  2. Pivotal Trials: Study Design Placebo or Omalizumab + BDP reduction Placebo or Omalizumab  BDP Placebo or Omalizumab + Stable BDP BDP Optimization Run-In Phase Stable-Steroid Phase Steroid-Reduction Phase Double-Blind Extension Phase 4-6 Weeks 16 Weeks 12 Weeks 24 Weeks Efficacy 28 Weeks Total Randomization Safety 52 Weeks Total Busse W, et al. J Allergy Clin Immunol. 2001;108:184-190; Soler M, et al. Eur Respir J. 2001;18(2):254-261.

  3. Baseline Asthma Characteristics †Mean (SD) unless otherwise indicated.

  4. Reduction in Asthma Exacerbations Omalizumab Placebo Stable steroid phase16 wk Steroid-reduction phase12 wk P < .001† P < .001† P = .003† P = .006† †van Elteren test; protocol-defined analysis with imputation.

  5. OMAL Placebo Time to First Asthma Exacerbation 009 008 1.0 1.0 0.75 0.75 Proportion of patientsexacerbation free P = .0001† HR = 0.51 0.50 0.50 P = .0067† HR = 0.63 0.25 0.25 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time since randomization

  6. Reduction in Inhaled Steroid Use Studies 008 and 009 (Combined) P < .001† BDP = Beclomethasone dipropionate. †van Elteren test.

  7. Reduction in Albuterol Use Xolair™ Placebo 009 008 NS NS NS * NS NS * Puffs per day, n * * NS * * * * * * * * * * Time, wk Time, wk *P  .05, van Elteren test.

  8. Reduction of Symptoms Omalizumab Placebo Asthma symptom scores Nocturnal symptom scores 008 008 * * * * * * * * * * NS * * * * * * * * * 009 009 * * * * * * * * * * * * * * * * * * * * *P  .05, van Elteren test.

  9. Improvement in Pulmonary Function Omalizumab Placebo 009 008 NS * * * * * * * * * * * * * * * * * * * Mean FEV1 % predicted Time since randomization, wk Time since randomization, wk *P ≤ .05, ANCOVA.

  10. Omalizumab: Mechanisms of Action 1. Omalizumab binds to the IgE molecule preventing its interaction with IgE receptors on inflammatory cells. 2. The fall in free-IgE leads to down regulation of FcεRI on basophils, mast cells and plasmacytoid dendritic cells. 3. The release of pro-inflammatory cytokines from basophils and mast cells is decreased. 4. The effect on pDCs may reduce allergen presentation to T-cells. 4. There is a decrease in levels of blood, tissue and sputum eosinophils. S Holgate, et al. Allergy 2009;64:1728-36

  11. Omalizumab in Patients with Severe Persistent Asthma • Data was pooled from 7 studies, with 4,308 subjects, 93% with severe persistent asthma. • Mean baseline values:ICS 1462 mcg BDP, LABA use by 57%,FEV1 70% predicted • Exacerbations (90% treated with OCS) - 38%Omalizumab 0.91/year Placebo 1.47/year p<.00001 • Emergency Department Visits - 61% 0.026/y vs. 0.066/y p = 0.013 • Hospitalizations- 50%0.03/y vs. 0.06/y p = 0.04 J Bousquet, et al. Allergy 2005;60:302-8

  12. There Are No Predictors of a Good Response to Omalizumab J Bousquet et al. Allergy 2005;60:302-8

  13. Omalizumab in Children • 627 children ages 6 to 11 years with asthma not fully controlled on ≥ 200 mcg FP/d plus history of ≥ 2 exacerbations or ≥ 1 hospitalization in last year. • Randomized 2:1 omalizumab: placebo for 52 weeks, steroid stable first 24 weeks. • Exacerbation defined as doubling dose ICS or oral CS ≥ 3 days. B Lanier, ex al. J Allergy Clin Immunol 2009;124:1210-6

  14. Omalizumab in Children: Exacerbation Rate : 24 WEEKS 52 WEEKS Omalizumab 0.45 0.78 Placebo 0.64 1.36 % reduction / p value -31%/0.007 -43%/0.001 B Lanier, ex al. J Allergy Clin Immunol 2009;124:1210-6

  15. Omalizumab Safety:Anaphylaxis • A joint task force of the AAAAI and ACAAI reviewed all post-marketing reports to the FDA from 1 June 2003 to December 31 2005. • 35 patients experienced 41 episodes of anaphylaxis • This represented 0.09% of patients receiving omalizumab.

  16. Omalizumab Safety:Anaphylaxis L. Cox, ex al. J Allergy Clin Immunol 2007120:1373-7

  17. Omalizumab Safety: Recommendations for Administration • Patient should sign informed consent. • Patient should be instructed in administration of auto-injected epinephrine and carry for 24 hours after each dose of omalizumab • Patients should remain under observation for 2 hours after the first 3 administrations, then 30 minutes after each subsequent administration. L. Cox, ex al. J Allergy Clin Immunol 2007120:1373-7

  18. Omalizumab: Unapproved and Unproven Uses • Seasonal & perennial allergic rhinitis • Chronic urticaria:- Autoimmune (JACI 2008;122:569-73)- Non-autoimmune (JACI 2010;126:664-5)- Delayed pressure, dermagraphism, cholinergic • Food allergy (Allergy Asthma Proc 2010;31:76-83) • Chronicsinusitis (JACI 2008;121:257-8) • Atopic dermatitis (Allergy Asthma Proc 2008;29:530-7) • Allergic bronchopulmonary Aspergillosis (Ped Pulmonol 2009;44:516)

  19. Omalizumab: Unapproved and Unproven Uses • Idiopathic anaphylaxis Ann Allergy Asthma Immunol 2009;102:257-8) • Fire ant anaphylaxis (immunotherapy failure) (JACI 2010;126:664-5) • Occupational latex sensitivity (JACI 2004;113:360-1) • Systemic mastocytosis (JACI 2010;126:415-6) • Systemic mastocytosis plus anaphylaxis to bee sting (Allergy 2009;64:1384-5) • Adjunct to hymenoptera immunotherapy (Allergy 2007;62:963-4). • Insulin allergy (N Engl J Med 2009;360:1045-7)

  20. Omalizumab as an Adjunct in Allergen Immunotherapy

  21. Omalizumab Pretreatment Decreases Acute Reactions after Rush Immunotherapy for ragweed-induced Seasonal Allergic Rhinitis TB Casale, et al J Allergy Clin Immunol 2006;117:134-40 123 adults with ragweed allergic rhinitis Pretreated with 9 weeks of omalizumab or placebo 1 day rush immunotherapy to top dose of 1.2 mcg Amb a 1 Followed by 12 weeks of combined omalizumab or placeb and weekly immunotherapy with increase in dose to 12 mcg Amb a 1.

  22. Reduction of IgE by Pre-Treatment with Omalizumab: Results Anaphylaxis risk vs. placebo during RIT: IT alone OR 12.1 Om plus IT OR 2.1 Anaphylaxis risk vs. placebo during weekly buildup: IT alone 9.7% Om plus IT 0% TB Casale, et al. J. Allergy Clin Imm 20061117:134-40

  23. Effect of Pretreatment with Omalizumab on the Tolerability of Specific Immunotherapy in Patients with Persistent Symptomatic Asthma Inadequately Controlled with Inhaled Corticosteroids Massanari M, Nelson H, Casale T, Busse W, Kianifard F, Geba G, Zeldin R

  24. Omalizumab as an Adjunct to Immunotherapy: Study Design • Subjects with at least moderate persistent allergic asthma. - Symptomatic on inhaled corticosteroids - FEV1 ≥ 75% predicted - Positive prick skin test to cat, dog or house dust mite standardized extract. • Excluded for severe asthma, oral corticosteroid-requiring exacerbation within 3 months, ED visit or hospitalization within 6 months.

  25. Xolair and Immunotherapy: Study Design 275 Patients, Randomized 1:1 Maintenance IT Omalizumab Cluster IT Screening Maintenance IT Placebo Cluster IT 3 wk overlap Period 1 Period 2 Period 3 Period 4 Visit 0 Visit 1 Visit 5 Visit 11 Visit 14 Visit 19 -2wks 0 13wks 16 wks 17 wks 24 wks

  26. Change in Average Total Asthma Symptom Score Before Initiating Immunotherapy Omalizumab Placebo N=124 N=119 Change From Baseline to Visit 5 in Total Average Asthma Symptom Score (Average total symptom score Day 91 to Day 97)

  27. Proportion of Patients Who Experienced a Systemic Allergic Reaction P= 0.017 N = 17 N = 32 N=126 N=122

  28. SARs in Patients According to Average Total Asthma Symptom Scores* Pre Immunotherapy > *Average total symptom score Day 91 to Day 97

  29. Severity of First Systemic Allergic Reaction N=17 N=32

  30. Proportion of Patients Who Experienced a Systemic Allergic Reaction According to Allergen Sensitivity N=16 N=25 N=11 N=15 N=14 N=29 N=209 N=188 N=168 15 g Fel d 1, 15 g Can d 1, 7 g Der p 1

  31. Percent of Patients who Achieved Target Maintenance IT Dose p=0.004

  32. Conclusions • Pretreatment with omalizumab significantly reduced systemic allergic reactions from IT • Pretreatment with omalizumab resulted in a clinically meaningful shift in severity of systemic allergic reactions from IT • A significantly higher proportion of omalizumab patients were able to reach target maintenance dose of IT • Omalizumab was well tolerated

More Related