dr gill allergen immunotherapy apr 2nd, 2014

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  • 1.Allergen Immunotherapy: An Update for Primary-care Physicians

2. Faculty/Presenter Disclosure Faculty/Presenter: [Dr. Shavinder Gill] Relationships with commercial interests: Grants/research support: [None] Speakers bureau/honoraria: Merck, Pfizer, Takeda, Novartis] Consulting fees: [None] Other: [None] 3. Declaration of conflict of interest as per Canada Health. I do not directly owe shares of any of the pharmaceutical company. I have given lectures/talks for pharmaceutical companies in the last several years but have donated that money to non-profitable organizations. 4. Learning Objectives After completing this program, participants will be able to: Discuss the epidemiology and pathophysiology of allergic rhinitis. Understand practice guidelines for the treatment of allergic rhinitis including the role of immunotherapy. Compare subcutaneous and sublingual immunotherapy for allergic rhinitis. Describe the process for initiation and administration of immunotherapy in patients with allergic rhinitis. 5. Lessons learned at recent ACAAI meeting. What is Epigenetics? What is beef-pork syndrome? What is cat-pork syndrome? What is pollen food allergy syndrome? What is allergic eosinophillic oesophagitis? 6. Immunotherapy (IT) Overview Introduction to Allergic Rhinitis (AR) Subcutaneous Immunotherapy (SCIT) Sublingual Immunotherapy Tablet (SLIT-T) Approach in Family Practice 7. What are the two epidemics of last few decades.? ? 8. What are the two epidemics of last few decades? Allergic diseases. There was a 10 fold increase i.e. 1000% increase in allergic diseases in 1960s and 1970s. Metabolic syndrome. 9. What is the prevalence? 10. Epidemiology of Allergic Rhinitis (AR) Affects 10-20% of population Often associated with asthma, atopic dermatitis, food allergy Impacts quality of life, sleep, work National and international guidelines available Small and Kim. AACI Nov 2011. 11. Pathophysiology of Allergic Inflammation: Clinical Disease Early-phase Reaction Max. at 10-30 Minutes American Academy of Otolaryngology, 2006. Adapted from: Naclerio RM. N Engl J Med 1991; 325(12):860-9. Late-phase Reaction Max. at 10-12 Hours Allergens Sneezing Rhinorrhea Congestion Mast cell IgE antibodies Mediator release Blood vessels Nerves Glands Cellular infiltration Eosinophils Basophils Monocytes Lymphocytes Resolution Complications Irreversible disease (?) Late-phase reaction Priming Hyper- responsiveness 12. Allergic Rhinitis (AR) Seasonal Allergic Rhinitis (SAR) Tree, grass and ragweed pollens Triggered by pollen in spring through fall seasons Perennial Allergic Rhinitis (PAR) Dust mites, cockroaches, molds and animal dander Chronic condition 13. AR Guidelines LTRAs: leukotriene receptor antagonsists *Step up if there is no response or incomplete response to treatment, regardless of class LTRAs may be used in class III and IV, but there is less supporting evidence **Oral steroids may be considered for class II (severe intermittent), but there is little supporting evidence * Class I Class II Class III Class IV Allergen / irritant avoidance Oral H1 antihistamines Intranasal corticosteroids LRTAs Oral steroids Immunotherapy Surgery Adapted from: Small P, et al. J Otolaryngol 2007; 36 (Suppl 1):S5-S27. 14. Immunotherapy (IT) Overview Introduction to Allergic Rhinitis (AR) Subcutaneous Immunotherapy (SCIT) Sublingual Immunotherapy Tablet (SLIT-T) Approach in Family Practice 15. Which of the following is true? Immuno-therapy is affective in reducing the incidence of asthma i.e prevent new asthma. It prevents new sensitization. It is more economical than medication. It does not work for food allergy. It has long term efficacy after discontinuing the treatment. 16. Which of the following is true? All of the above are true. 17. Which of the following is true? Immuno-therapy is affective in reducing the incidence of asthma i.e prevent new asthma. True. It reduces the risk by 50%. It prevents new sensitization. True It is more economical than medication. True It does not work for food allergy. True. Except for Oral allergy syndrome. It has long term efficacy after discontinuing the treatment. True. Efficacy remains several years after stopping the vaccine. 18. Subcutaneous Immunotherapy Immunotherapy has been used for 100 years Immune mechanisms of immunotherapy now better defined Effective in AR, asthma, atopic dermatitis and possibly Oral allergy syndrome/Pollen food allergy syndrome. Has disease-modifying benefits Drawbacks: time commitment and very small but significant risk of anaphylaxis. 19. Long-term Clinical Efficacy of Grass-pollen IT RCT of discontinuation of grass-pollen immunotherapy (vs. continuation and vs. controls) in patients with history of severe seasonal AR Conclusion: SCIT for 3-4 years for grass-pollen allergy induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity Durham SR, et al. N Engl J Med 1999; 341:468-75. 20. Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy Initial Placebo Trial Current Trial PollenCount (grains/m3) Symptom Score May June July Aug . May June July Aug . May June July Aug . May June July Aug .1989 1993 1994 1995 Study group Immunotherapy Placebo Immunotherapy Maintenance Discontinuation None (control) 21. Long-term Clinical Efficacy of Grass-pollen IT: Conclusions Immunotherapy for grass-pollen allergy for 3-4 years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity Durham SR, et al. N Engl J Med 1999; 341:468-75. 22. IT With a Standardized D. pteronyssinus Extract Specific IT prevents the onset of new sensitizations in children(< 6 years old, asthma) Des Roches A, et al. J Allergy Clin Immunol 1997; 99(4):450-3. New Sensitivities Initial sensitivity Number of patients None Cat Dog Alt Grass SIT 22 10 6 4 2 1 Control 22 0 12 8 6 6 23. Effects of Specific Immunotherapy in AR Patients With Bronchial Hyper-responsiveness Grembiale RD, et al. Am J Respir Crit Care Med 2000; 162(6):2048-52. PD20FEV1(molofmethacholine) 1 0.1 10 Baseline 1st year 2nd year SIT p = 0.0008 p = 0.0001 PD20FEV1(molofmethacholine) 1 0.1 10 Baseline 1st year 2nd year Placebo p = NS p = NS 24. Children With and Without Asthma 7 Years After Termination of Specific Immunotherapy Jacobsen L, et al. Allergy 2007; 62(8):943-8. Based on patients without asthma before treatment (n = 119), absolute numbers of children shown above bars Mean age 21 years at 10-year follow-up Percentofpatients 90 0 80 70 60 50 100 40 30 20 10 SIT No asthma Asthma Odds-ratio = 2.5 (1.1 5.9) n = 48 n = 16 25% Control n = 29 n = 24 45% 25. (Abramson et al. AARD 1995;151) Meta-Analysis of Immunotherapy for Asthma Mites Smith (n=22) Maunsell (n=34) Werner (n=51) DSouza (n=91) Pauli (n=18) Newton (n=14) BTA (n=56) Other Allergens Frankland (n=57) Ohman (n=17) Sundin (n=39) Valovirta (n=27) Mites Combined (n=286) Other Allergens (n=140) All Studies (n=426)0.1 1 10 100 1000 26. Administering Subcutaneous IT (1) 27. Administering Subcutaneous IT (2) 28. Vial #0 1:1000 Vial #1 1:100 Vial #2 1:10 Vial #3 1:1 Dose mL Dose mL Dose mL Dose mL 1 0.10 6 0.10 11 0.05 17 0.05 2 0.20 7 0.20 12 0.10 18 0.07 3 0.30 8 0.30 13 0.20 19 0.10 4 0.40 9 0.40 14 0.30 20 0.15 5 0.50 10 0.50 15 0.40 21 0.20 16 0.50 22 0.25 ***Hollister-Stier Extract*** Note: Record all injections in the treatment record. Note: This dosage chart is offered as a suggested schedule. However, the degree of sensitivity varies in many individuals. In these cases, the size of the dose and intervals between doses may have to be adjusted and should be regulated by the patients tolerance and reaction. Treatment is normally started with the weakest dilution in the set. Beginning with dose #1 as listed in the schedule. Doses should be administered at weekly or twice-weekly (at least two days apart) intervals while working up. The maintenance level is [] 23 0.30 24 0.35 25 0.40 26 0.45 27 0.50 Gradually increase intervals to monthly maintenance. *Please read text to left* Subcutaneous IT: Sample Dose Chart Dr.: Patient: Content: Lot No.: Expiry Date: This is a suggested dose chart only. Please read the instructions before commencing desensitization. Observe patients for 30 minutes after each injection. Check extract dilution and dose: Check the patient for local or systemic reaction(s) to previous injection. 29. Time to Onset of Systemic Reactions with Allergen Immunotherapy Greineder DK. J Allergy Clin Immunol 1996; 98:S330-S334. [Data from Matloff et al. Allergy Proc 1993; 14:347-50.] Time not recorded 10% 2-24 hours 8% 60-120 minutes minimum 2% 0-30 minutes 72% 30-60 minutes 8% Note: based on this, patients should be advised that they must wait 30 minutes in the clinic after receiving subcutaneous immunotherapy 30. Immunotherapy Overview Introduction to Allergic Rhinitis (AR) Subcutaneous Immunotherapy (SCIT) Sublingual Immunotherapy Tablet (SLIT-T) Approach in Family Practice 31. Sublingual Immunotherapy Tablet (SLIT-T) Novel treatment for AR in Canada Available to treat grass allergy Effective in children and adults Has disease-modifying effects At-home therapy with minimal risk of anaphylaxis 32. Rationale for Treatment with Grass SLIT-T Treatment of Allergic Rhinoconjunctivitis: Reduction of symptoms in first pollen season Reduction of need for pharmacologic treatment Safe for self-administration Sustained Efficacy During Treatment: Maintenance of treatment effect during IT Long-term Efficacy: Disease-modifying effect post-treatment Prevention of disease progression (e.g., asthma)1 Novembre E, et al. J Allergy Clin Immunol 2004; 114(4):851-7. 33. Grass Sublingual Immunotherapy Tablets Grastek (Merck-ALK) Phleum pratense (timothy grass pollen) 75,000 SQ-T (equivalent to 2,800 BAU) for the treatment of Timothy and cross-reactive Rye, Meadow Fescue, Bluegrass,Cocksfoot a

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