Allergy immunotherapy: Who, what, when … and how safe?

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Applied Evidence

Allergy immunotherapy: Who, what, when … and how safe?

J Fam Pract. 2019 June;68(5):270-276

By

Dellyse Bright, MD

Susan M. Pollart, MD, MS

John Franko, MD

The evidence-based answers to these and other questions will help you to update your knowledge of allergy immunotherapy.

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PRACTICE RECOMMENDATIONS

› Diagnose allergies that are amenable to allergy immunotherapy (AIT) using skin prick/puncture allergy testing in conjunction with clinical symptoms, triggers, and exposure. A

› Do not use AIT for urticaria, angioedema, drug hypersensitivity, or latex allergy. A

› Do not initiate AIT during pregnancy or in patients with acquired immune deficiency syndrome or severe asthma. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. US Department of Health and Human Services. Health, United States, 2016: With Chartbook on Long-term Trends in Health. Hyattsville, MD. May 2017. https://www.cdc.gov/nchs/data/hus/hus16.pdf#035. Accessed May 1, 2019.

2. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133:291-307.e1.

3. Tankersley MS, Ledford DK. Stinging insect allergy: state of the art 2015. J Allergy Clin Immunol Pract. 2015;3:315-322.

4. Gupta R, Holdford D, Bilaver L, et al. The economic impact of childhood food allergy in the United States. JAMA Pediatr. 2013;167:1026-1031.

5. Hamad A, Burks WA. Emerging approaches to food desensitization in children. Curr Allergy Asthma Rep. 2017;17:32.

6. Cox L, Nelson H, Lockey R. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(suppl 1):S1-S55.

7. Agache I, Akdis CA, Chivato T, et al. European Academy of Allergy and Clinical Immunology (EAACI) White Paper on Research, Innovation, and Quality of Care. http://www.eaaci.org/documents/EAACI_White_Paper.pdf. Accessed May 1, 2019.

8. Greenhawt M, Oppenheimer J, Nelson M, et al. Sublingual immunotherapy: a focused allergen immunotherapy practice parameter update. Ann Allergy Asthma Immunol. 2017;118:276-282.e2.

9. Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(suppl 3):S1-S148.

10. Burks AW, Calderon MA, Casale T, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131:1288-1296.e3.

11. Khurana T, Bridgewater JL, Rabin RL. Allergenic extracts to diagnose and treat sensitivity to insect venoms and inhaled allergens. Ann Allergy Asthma Immunol. 2017;118:531-536.

12. Tam H, Calderon MA, Manikam L, et al. Specific allergen immunotherapy for the treatment of atopic eczema. Cochrane Database Syst Rev. 2016;2:CD008774.

13. National Heart, Lung, and Blood Institute. National asthma education and prevention program. Expert panel report 3: Guideline for the Diagnosis and Management of Asthma. August 28, 2007. https://www.nhlbi.nih.gov/sites/default/files/media/docs/asthgdln_1.pdf. Accessed May 2, 2019.

14. Ridolo E, Montagni M, Incorvala C, et al. Orphan immunotherapies for allergic diseases. Ann Allergy Asthma Immunol. 2016;116:194-198.

15. Nelson H, Cartier S, Allen-Ramey F, et al. Network meta-analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy. J Allergy Clin Immunol Pract. 2015;3:256-266.e3.

16. Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016;137:339-349.e10.

17. Cox L. The role of allergen immunotherapy in the management of allergic rhinitis. Am J Rhinol Allergy. 2016;30:48-53.

18. Lu Y, Xu L, Xia M, et al. The efficacy and safety of subcutaneous immunotherapy in mite-sensitized subjects with asthma: a meta-analysis. Respir Care. 2015;60:269-278.

19. Mener DJ, Lin SY. The role of allergy immunotherapy in the treatment of asthma. Curr Opin Otolaryngol Head Neck Surg. 2016;24:215-220.

20. Dominguez-Ortega J, Delgado J, Blanco C, et al. Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence. J Investig Allergol Clin Immunol. 2017;27(suppl 1):1-35.

21. Larenas-Linnemann DE, Hauswirth DW, Calabria CW, et al. American Academy of Allergy, Asthma & Immunology membership experience with allergen immunotherapy safety in patients with specific medical conditions. Allergy Asthma Proc. 2016;37:112-122.

22. Dhami S, Zaman H, Varga EM, et al. Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis. Allergy. 2017;72:342-365.

23. Pajno GB, Caminiti L, Chiera F, et al. Safety profile of oral immunotherapy with cow’s milk and hen egg: a 10-year experience in controlled trials. Allergy Asthma Proc. 2016;37:400-403.

24. Yepes-Nunez JJ, Zhang Y, Roque i Figuls M, et al. Immunotherapy (oral and sublingual) for food allergy to fruits. Cochrane Database Syst Rev. 2015;11:CD010522.

25. Nurmatov U, Dhami S, Arasi S, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis. Allergy. 2017;72:1133-1147.

26. PALISADE Group of Clinical Investigators; Vickery BP, Vereda A, Casale TB, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med. 2018;379:1991-2001.

27. Lanser BJ, Wright BL, Orgel KA, et al. Current options for the treatment of food allergy. Pediatr Clin North Am. 2015;62:1531-1549.

28. Nowak-Wegrzyn A. Using food and nutrition strategies to induce tolerance in food- allergic children. Nestle Nutrition Institute Workshop Series. 2016;85:25-53.

29. Tam HH, Calderon MA, Manikam L, et al. Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review. Allergy. 2016;71:1345-1356.

30. Cox L. Allergy immunotherapy in reducing healthcare cost. Curr Opin Otolaryngol Head Neck Surg. 2015;23:247-254.

31. Kristiansen M, Dhami S, Netuveli G, et al. Allergen immunotherapy for the prevention of allergy: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2017;28:18-29.

32. Di Bona D, Plaia A, Leto-Barone MS, et al. Efficacy of allergen immunotherapy in reducing the likelihood of developing new allergen sensitizations: a systematic review. Allergy. 2017;72:691-704.

33. Di Lorenzo G, Leto-Barone MS, La Piana S, et al. The effect of allergen immunotherapy in the onset of new sensitizations: a meta-analysis. Int Forum Allergy Rhinol. 2017;7:660-669.

34. Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126:477-480.

35. Creticos PS, Bernstein DI, Casale TB, et al. Coseasonal initiation of allergen immunotherapy: a systematic review. J Allergy Clin Immunol Pract. 2016;4:1194-1204.e4.

36. Pitsios C, Demoly P, Bilo MB, et al. Clinical contraindications to allergen immunotherapy: an EAAACI position paper. Allergy. 2015;70:897-909.

37. Klimek L, Pfaar O, Bousquet J, et al. Allergen immunotherapy in allergic rhinitis: current use and future trends. Expert Rev Clin Immunol. 2017;13:897-906.

38. Nelson HS. Allergen immunotherapy now and in the future. Allergy Asthma Proc. 2016;37:268-272.

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

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Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT