Role of Allergen Immunotherapy in Allergic Asthma | Jindal Chest Clinic Chandigarh

Allergen immunotherapy (AIT) is a cost-effective, disease-modifying treatment for allergic diseases like asthma, offering both protective properties and disease-modifying effects against the allergic march. This presentation gives an overview on the topic "Role of Allergen Immunotherapy in Allergic Asthma ". For more information, please contact us: 9779030507.

1. Role of Allergen Immunotherapy in Allergic Asthma

2. Presentation objectives Discuss and define role of allergen immunotherapy in allergic asthma including: Definition Mechanism Inclusion in 10 world asthma guidelines Efficacy studies Safety

3. Definition

4. Definition Allergen immunotherapy is the administration of gradually increasing quantities of an allergen vaccine to an allergic subject, reaching a dose which is effective in ameliorating the symptoms associated with subsequent exposure to the causative allergen. WHO Position Paper 1998

5. History

6. History of Allergen Immunotherapy

7. Major contributors to development of Allergen Immunotherapy Leonard Noon 1877-1913 ROMAGNANI DURHAM

8. Mechanism of action

9. High Dose DC1 IL-12 IgG1 IgA TGF-  B  IFN-  B 1 TGF-  IL-10 IL-10 Allergen Spec . Immunotherapy TH1 B  IL-4,IL-13 THn Allergen Peptide Low Dose DC2 TH2 IL-4 IgG4 Mediators Cytokines IL-5 Inflammation B 4 GM-CSF IL-3 IgE MZ,Ba Allergen Natural Exposition Allergen- Specific Immunotherapy : Mode of Action Tr1 X Tr1 TH3 X TH3 A. Nandy, 2010 Allergen Immunotherapy shifts the T helper cell stimulation from TH2 to TH1

10. Guideline recommendation for Allergen Immunotherapy

11. Allergen Immunotherapy and Asthma Guideline Statement of Recommendation for Allergen Immunotherapy Expert Panel Report 3 U.S. Guidelines Allergen immunotherapy be considered for patients who have persistent asthma if there is clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive GINA Guideline Specific immunotherapy has long term clinical effects and the potential of preventing development of asthma in children with rhino-conjunctivitis up to 7 years after treatment termination European Academy of Allergy and Immunology (EAACI) & Global Allergy and Asthma European Network (GA2LEN) SIT can be used in mild allergic asthma proven to be caused by a well-defined allergen, if asthma is mild, under control and FEV1 is above 70%. Performance of SIT should be based on the allergen sensitization rather than on the disease itself.

12. Allergen Immunotherapy and Asthma Guideline Statement of Recommendation for Allergen Immunotherapy WHO Position Paper There is good evidence that immunotherapy with inhalant allergens used to treat seasonal or perennial allergic rhinitis and asthma is clinically effective American Academy of Allergy, Asthma & Immunology (AAAAI); American College of Allergy, Asthma & Immunology (ACAAI) & Joint Council of Allergy, Asthma & Immunology (JCAAI) Patients with allergic rhinitis/conjunctivitis or allergic asthma whose symptoms are not well controlled by medications or avoidance measures or require high medication doses, multiple medications, or both to maintain control of their allergic disease might be good candidates for immunotherapy World Allergy Organization White Book of Allergy Effects of allergen specific immunotherapy, that are lacking with pharmacological treatment, are the long-lasting clinical effects and the alteration of the natural course of the disease.

13. Allergen Immunotherapy and Asthma Guideline Statement of Recommendation for Allergen Immunotherapy DGAKI, ÄDA, GPA, ÖGAI, SGAI Advised in patients with controlled asthma (acc. to GINA 2008), with intermittent and mild persistent IgE -mediated allergic asthma. Allergic Rhinitis and its Impact on Asthma (ARIA) Management of atopic diseases like allergic asthma is based on allergen avoidance, pharmacotherapy and immunotherapy in selected patients. Performance of SIT should be based on the allergen sensitization rather than on the disease itself. British Society for Allergy and Clinical Immunology (BSACI) Guidelines Immunotherapy for allergic rhinitis has been shown to have a carry-over effect after therapy has stopped. Chronic asthma is a contraindication. Allergen immunotherapy has been included in 10 world wide asthma guidelines

14. Level of Evidence for Allergen Immunotherapy

15. Subcutaneous IT – evidence for efficacy GA 2 LEN/ EAACI SCIT is effective in allergic rhinitis. Long-term benefits were shown. There seems to be a preventive effect on new sensitizations ARIA Conditional recommendation, moderate-quality evidence: SCIT pollen AR adults; SCIT AR + asthma* Conditional recommendation, low-quality evidence: SCIT mites AR adults; SCIT AR children DGAKI, ÄDA, GPA, ÖGAI, SGAI Rhinoconjunctivitis : A,1a for grass pollen A,1b for birch pollen, HDM B,2b for cat, Alternaria , Cladosporium Asthma GINA I/II: A,1a A,1b for asthma prevention B,2c for prevention of new sensitizations BSACI A,1+ for pollen induced rhinitis and/or conjunctivitis 1+ for potential for long-term disease remission EAACI 1a for asthma, 1b for rhinitis, 1b long-term efficacy and preventive capacity WHO No evidence level * For the treatment of asthma not of rhinitis! Conclusion: Efficacy confirmed for various allergens!

16. Cochrane meta-analysis

17. Excerpts from Cochrane database 76 trials with 3,188 patients Significant improvement in asthma symptom scores Significant reduction of allergen specific bronchial hyperreactivity Some reduction also in non-specific bronchial hyperreactivity Abramson, Weiner and Puy, Cochrane Database Systematic Review 2003

18. Excerpts from Cochrane database It would have been necessary to treat 4 (95% CI 3 to 5) patients with immunotherapy to avoid one deterioration in asthma symptoms, and overall to treat 5 (95% CI 4 to 6) patients with immunotherapy to avoid one requiring increased medication. Abramson, Weiner and Puy, Cochrane Database Systematic Review 2003

19. Meta- analysis : SCIT in asthma Data from Abramson MJ, Puy RM, Weiner JM. Cochrane Database Syst Rev 2010;8:CD001186. The effect of mite SCIT on allergen-specific bronchial hyperreactivitiy is even strong with SMD >=0.8.

20. Cochrane Meta analyses SCIT a sthma SMD [95% CI] SCIT 1 Asthma Symptoms (pollen) -0.61 [-0.87, -0.35] Asthma Medication (pollen) -0.52 [-0.91, -0.13] Bronchial Hyperreagibility , unspecific ( metacholine ) -0.25 [-0.51, -0.00] Bronchial Hyperreagibility, specific (pollen) -0.55 [-0.84, -0.27] Bronchial Hyperreagibility, specific (house dust mites) -0.98 [-1.39,-0.58] Abramson MJ et al., Cochrane Database Syst Rev 2010;8:CD001186 88 Studies; 3792 Patients J.C. Cohen, Statistical Power Analysis for the Behavioral Sciences, 1988 no effect small effect medium effect large effect Large effect in controlling bronchial hyper-reactivity seen with house dust mite immunotherapy

21. Whilst inhaled corticosteroid therapy remains the mainstay of asthma management, any reduction in this type of treatment while maintaining good asthma control would be welcome. Abramson MJ et al., Cochrane Database Syst Rev 2010;8:CD001186. New primary end point in asthma studies: Reduction of ICS while maintaing asthma control

22. Meta-analysis on Immunotherapy for Asthma

23. ( Abramson et al. AARD 1995;151) Meta-Analysis of Immunotherapy for Asthma Mites Smith (n=22) Maunsell (n=34) Werner (n=51) D’Souza (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 A meta-analysis of all 20 published prospective, randomized, placebo controlled trials of immunotherapy showed highly statistical significance for efficacy of SIT in asthma

24. Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite   Maestrelli et al, JACI 2004 Significant improvement over 3 years in morning PEF and asthma symptom score

25. SYMPTOMS MEDICATIONS Meta-analysis of the efficacy of immunotherapy in allergic asthma in pediatric patients, 3 to 18 years of age. M Penagos, G Passalacqua, E Compalati, C Baena-Cagnani, S Orozco, A Pedroza GW Canonica Highly significant improvement in symptom score and medication score

26. Efficacy in prevention of new allergen sensitization

27. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study Jacobssen, Allergy 2007 Statistically significant long term preventive benefits of asthma after specific immunotherapy

28. Immunotherapy Prevents the Development of New Allergen Sensitizations A . Des Roches et al. JACI 1998;99:450-453 Group No. of Patients None Cat Dog Alternaria Grass New Allergen Sensitization 22 22 10 Immunotherapy Control group 6 12 4 8 2 6 1 6 10/22 (45%) monosensitized children who received immunotherapy did not develop new sensitivities whereas the entire control group acquired new sensitivities (became polysensitized ) during this period of time.

29. Prevention of Asthma by Immunotherapy 5-Year Follow-Up Jacobsen L Ann Allergy Asthma Immunol 2001; 87: 43-46 Immunotherapy Control Statistically significant increase in development of asthma in the control group only (58% of controls vs. 23% of IT group)

30. Preventative Therapy in Children Moller C et al J Allergy Clin Immunol 2002; 109: 251-256 % Patients Atopic children who were treated with pollen immunotherapy were twice as likely not to develop asthma during corresponding pollen season compared to children not on immunotherapy

31. SLIT NO SLIT 37 8 26 18 NO ASTHMA ASTHMA PRESENCE OF ASTHMA AFTER 3 YEARS Coseasonal SLIT reduces the development of asthma in children with allergic rhinitis. Novembre E. et al, JACI 2004 Randomized, open, controlled 79 children Allergic rhinitis only Follow-up: 3 yrs Significantly less children developed asthma when on immunotherapy

32. Prevention of New Sensitizations by AIT New sensitizations after 3 years: 55% SIT group vs 100% control group. Des Roches et al, JACI 1997 New sensitizations after 3 years: 25% SIT group vs 67% control group. Pajno et al, Clin Exp Allergy 2001 New sensitizations after 4 years 23% SIT group vs 68% control group. Purello D’Ambrosio et al, Clin Exp Allergy 2001 Evidence suggests that allergen immunotherapy prevents the development of new sensitisations

33. Evidence for early intervention in Allergic Rhinitis for prevention of Asthma

34. The nose-lung interaction in allergic rhinitis and asthma: united airways disease G.Passalacqua, G.Ciprandi & G.W.Canonica 2004 Asthma and rhinitis as different Aspects of a single disorder

35. Allergic rhinitis as a predictor for wheezing onset in school-aged children. Rochat et al, JACI 2010 Cohort of 1,314 children followed from birth to 13 yrs Patients with allergic rhinitis have less chances of remaining free of wheezing symptoms

36. MARTINEZ,PEDERSEN Long-Term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma Guilbert T, NEJM 2006 Long term inhaled steroids do not have lasting effects

37. Bousquet , Clin Exp Allergy 2005 asthma Asthma + rhinitis Untreated rhinitis increases the risk of asthma attacks.

38. Bronchial biopsioes after Specific provocation in patients with rhinitis or asthma Crimi E et al, JAP 2001 Allergic Rhinitis and Asthma lead to similar inflammation in bronchial tree

39. Long term Benefits of Allergen Immunotherapy

40. Durham SR et al New Engl J Med 1999;341:468-75 Grass pollen immunotherapy: long-term efficacy Seasonal immunotherapy for 4 years and 7 years showed long term efficacy

41. Long-Lasting Efficacy of Subcutaneous IT: Controlled Studies Author Allergen Duration (yrs) Hedlin, 1995 Cat/dog 3 Ariano, 1999 Parietaria 4 Durham, 2000 Grass 5 Eng, 2002 Grass 3

42. AUTHOR ALLERGEN PATIENTS DURATION SIT LONG-LASTING EFFECT Mosbech Grass 2.5 years 6 years Grammer Ragweed 61 adult/children 4 months 2 years Hedlin Cat/dog 32 adult/chidren 3 years 5 years Des Roches Mite 40 adult 1-4 years 3 years Ariano Parietaria 35 adult 4 years 4 years Durham Grass 52 adult 3-4 years 3 years Eng Grass 25 children 3 years 12 years Long lasting effects of specific immunotherapy has been evaluated in many randomised double bling placebo controlled trials

43. Dust Mite Immunotherapy Trials for Asthma

44. Highlights Significant decrease in asthma symptoms Decrease in asthma medications Decrease in mite-specific immediate and late phase reactions References: Aas K. Acta Paediatr Scand 1971; 60: 264-268 Bousquet J, Calvayrac P, Guerin B, et al. Allergy Clin Immunol 1985; 76: 734-744 Bousquet J, Hejjaoui A, Clauzel AM, et al. J Allergy Clin Immunol 1988; 82: 971-977 Pichler CE, Marquardsen A, Sparholt S, et al. Allergy 1997; 52: 274-283

45. High-dose hypoallergenic SCIT in mite asthma

46. House dust mite SCIT in asthma Zielen S et al., J Allergy Clin Immunol 2010;125:942-9. Daily fluticasone dose reduction after 2 years of SCIT p<0.05 53% stronger daily fluticasone dose reduction vs. control group with ACAROID ® 53% stronger daily fluticasone dose reduction with Acaroid vs. control group

47. House dust mite SCIT in asthma Rudert M et al., EAACI congress 2012 Early onset efficacy: after 9 months of SCIT Children + adults Improvement rate of at least 1 step at least 2 steps SCIT-group (n=60) 55.0% 30.0% SCIT-group (n=60) 32.8% 14.8% Children Improvement rate of at least 1 step at least 2 steps SCIT-group (n=33) 69.7% 36.4% Control-group (n=32) 31.3% 6.3% 69.7% children with asthma saw a 1 step GINA grades asthma improvement with SIT

48. House dust mite SCIT in asthma mod. acc. to Rudert M et al., EAACI congress 2012 Children without need of inhaled steroids 60.6 % of house-dust mite allergic asthmatic children don‘t need any ICS after 3 years of high-dose hypoallergenic SCIT

49. Fluticasone dose ( µg/ day , mean ) p<0.05 p<0.05 p<0.05 330.3 190.9 151.5 124.2 Threshold level , that might reduce growth House dust mite SCIT in asthma mod. acc. to Rudert M et al., EAACI, Genf, 16.-20. Juni 2012:Poster 1400 and Bacharier LB et al., Allergy 2008; 63:5-34 Daily need of fluticasone to retain asthma control during 3 years of SCIT

50. Increase of the morning lung function mod. acc . to Zielen S et al., J Allergy Clin Immunol 2010;125:942-9. Median PEF increase after 2 years of SCIT p < 0.05 Significant increase in morning lung function with add on therapy with Acaroid

51. Safety

52. Allergen Immunotherapy: Safety There is an inherent risk of local allergic reactions (wheal & flare) at the injection site, as well as, systemic anaphylaxis. A prospective study has reported the frequency of systemic reactions to be 0.3% of immunotherapy doses, representing 3.7% of patients. Severe systemic reactions to allergy immunotherapy can be life threatening and fatal reactions do occur. Anaphylactic related fatalities are rare (1 in 2.5 million injections) Bernstein DI, Wanner M, Borish L, Liss GM; Immunotherapy Committee, AAAAI. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001.J Allergy Clin Immunol . 2004 Jun;113:1129-36.

53. Allergen Immunotherapy: Safety Allergy immunotherapy should be administered only in a setting where procedures that can reduce the risk of anaphylaxis are in place and where the prompt recognition and treatment of anaphylaxis is ensured The preferred location for administration of allergy immunotherapy is in the office of the physician who prepared the patient’s allergen immunotherapy extract Because most systemic reactions resulting from SCIT occur within 30 minutes of an injection, the allergen immunotherapy practice parameter recommends that patients should remain in the physician’s office for at least 30 minutes after an injection Joint Task Force on Practice Parameters; AAAAI; ACAAI; JCAAI. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol . 2007;120:S25-85.

54. Conclusion

55. Conclusion There is sufficient evidence to support the overall effectiveness and safety of Allergen Immunotherapy for treating both allergic rhino-conjunctivitis and asthma. It can benefit selected allergic asthma patients by improving symptoms, reducing requirement of medications, improving quality of life, and has long-term benefits. Allergen Immunotherapy has been practiced worldwide for over 100 years Allergen Immunotherapy has been included in over 10 world asthma guidelines

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