Subcutaneous and Sublingual Immunotherapy for Allergic Rhinitis and Asthma

1. Subcutaneous and Sublingual Immunotherapy To Treat Allergic Rhinitis/Rhinoconjunctivitis and Asthma Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov

2. Outline of Material • Agency for Healthcare Research and Quality Comparative Effectiveness Review (CER) Process • Background • Clinical Questions Addressed in the CER • Summary of CER Results • Conclusions • Gaps in Knowledge • Resources for Shared Decisionmaking

3. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development • Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, the public, and others. • A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. • The research questions and the results of the report are subject to expert input, peer review, and public comment. • The results of these reviews are summarized into a Clinician Research Summary and a Consumer Research Summary for use in decisionmaking and in discussions with patients. • The Research Summaries and the full report are available at www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

4. Rating the Strength of Evidence From the Comparative Effectiveness Review • The strength of evidence ratings are classified into four broad ratings: AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Available at http://www.effectivehealthcare.ahrq.gov/methodsguide.cfm.Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm. Owens DK, Lohr KN, Atkins D, et al. J Clin Epidemiol. 2010 May;63(5):513-23. PMID: 19595577.

5. Background:Allergic Rhinitis/Rhinoconjunctivitis and Asthma • Allergic rhinitis is a common clinical problem affecting about 20 percent of the general population in North America. • Allergens such as tree, grass, and weed pollens characteristically cause seasonal rhinoconjunctivitis and/or asthma. • Allergens such as cat dander, cockroach, or dust mite may induce symptoms year-round and are associated with perennial rhinitis and/or asthma. • The prevalence of asthma in the general U.S. population is approximately 9 percent, and approximately 62 percent of individuals with asthma have evidence of atopy (i.e., the genetic predisposition to produce elevated immunoglobulin E [IgE] in response to environmental allergens). Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm. Min YG. Allergy Asthma Immunol Res. 2010 Apr;2(2):65-76. PMID: 20358020.

6. Background: Management of Allergy Symptoms • The medical management of patients with allergic rhinitis and allergic asthma includes: • Allergen avoidance • Pharmacotherapy • Immunotherapy • Daily use of pharmacotherapies for allergic asthma and rhinitis symptoms raises issues related to adherence, safety, and cost. • Long-term use of inhaled steroids, long-acting bronchodilators, and leukotriene antagonists for asthma control can have adverse effects. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm

7. Background:Subcutaneous Immunotherapy for Allergies • Allergen-specific immunotherapy is typically used for: • Patients whose allergic rhinoconjunctivitis and asthma symptoms cannot be controlled by medication and environmental control • Patients who cannot tolerate their medications • Patients who do not comply with chronic medication regimens • The U.S. Food and Drug Administration has approved the use of allergen extracts for subcutaneous immunotherapy in treating seasonal and perennial allergic rhinitis and allergic asthma. • In the United States, a patient with allergies undergoing immunotherapy receives subcutaneous injections—in increasing doses until a maintenance dose is found—of an allergen-containing extract comprised of the relevant allergens to which he or she is sensitive in an attempt to suppress or eliminate allergy-related symptoms. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

8. Background:Sublingual Immunotherapy for Allergies • There is considerable interest in using similar allergen extracts as sublingual immunotherapy (SLIT) as an alternative to subcutaneous immunotherapy. • SLIT involves placing drops or tablets with the allergen extract under the tongue for local absorption to desensitize the allergic individual over a period of months to years and to diminish allergic symptoms. • In the United States, there currently are no sublingual forms of immunotherapy approved by the U.S. Food and Drug Administration. • However, some U.S. physicians are using subcutaneous aqueous extracts off-label for sublingual desensitization in the treatment of allergic respiratory conditions. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

9. Systematic Review: Objective and Key Questions • Objective • To evaluate the efficacy, effectiveness, and safety of subcutaneous (SCIT) and sublingual (SLIT) immunotherapies that are presently available for use by clinicians and patients in the United States • Key Questions • For patients with allergic rhinoconjunctivitis and/or asthma: • Efficacy and effectiveness of SCIT, SLIT, and SCIT versus SLIT • Safety of SCIT, SLIT, and SCIT versus SLIT • Safety and effectiveness of SCIT, SLIT, and SCIT versus SLIT in the pediatric subpopulation Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm

10. Outcomes of Interest • Primary Outcomes • Clinical endpoints: • Symptom control • Medication use • Quality of life • Disease evolution/remission • New allergen sensitivities • Overall health care utilization • Missed days of school/work • Secondary Outcomes • Functional tests (pulmonary function test‒forced expiratory volume) • Provocational test • Adherence • Convenience and compliance • Biomarkers • Adverse Effects • Local reactions • Skin, mouth, and throat (including irritation, itching, swelling, or pain in the oral cavity) • General symptoms (such as headache, fatigue, arthritis) • Systemic reactions • Ocular • Rhinitis/nasal • Cutaneous • Rash • Gastrointestinal • Respiratory/asthma • Cardiovascular • Anaphylaxis • Death • Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

11. Overview of Studies Included in theSystematic Review • 142 studies were included in the review with these populations: adults only (52%), children only (24%), and adults and children (22%). • Studies on SLIT mainly included patients with allergic rhinitis and/or mild asthma. • All included studies were randomized controlled trials. • Efficacy and safety of SCIT: n = 74 • Efficacy and safety of SLIT*: n = 60 • Comparisons of SCIT versus SLIT: n = 8 • The types of scales/scoring systems used in the studies were not uniform. • Followup varied and ranged from one pollen season to 6 years. • Standard therapy varied across trials. • Due to heterogeneity in reported outcomes, results often only reflect the percentage of trials in which a significant effect was seen for the immunotherapy arm versus controls and not the magnitude of effect. *SLIT refers to allergen extracts that are administered sublingually in the form of drops. Studies on sublingual tablets are not included here. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

12. Included Studies by Type of Allergen for SCIT, SLIT, and SCIT Versus SLIT SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

13. Included Studies for Subcutaneous Immunotherapy Versus Placebo or Standard Therapy • 74 articles were included with a total of 4,350 patients. • The primary diagnoses were: • Asthma in 19 studies • Asthma with rhinitis in 18 studies • Rhinoconjunctivitis in 14 studies • Asthma with rhinoconjunctivitis in 14 studies • Types of allergens evaluated: • Seasonal allergens such as trees, grasses, weeds, and seasonal molds in 59 percent of studies • Perennial allergens in 38 percent of studies • Seasonal and perennial allergens in 3 percent of studies • The heterogeneity of the data on clinical outcomes precluded pooling of the data for further analysis. Consequently, the results often only reflect the percentage of trials in which a significant effect was seen for the immunotherapy arm versus controls and not the magnitude of effect. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

14. Subcutaneous Immunotherapy Versus Placebo or Standard Therapy: Asthma Outcomes RCT = randomized controlled trial Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

15. SCIT Versus Placebo or Standard Therapy: Rhinitis/Rhinoconjunctivitis Outcomes (1 of 2) RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

16. SCIT Versus Placebo or Standard Therapy: Rhinitis/Rhinoconjunctivitis Outcomes (2 of 2) RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

17. SCIT Versus Placebo or Standard Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

18. Included Studies for Sublingual Immunotherapy Versus Placebo or Standard Therapy • 60 articles on sublingual immunotherapy (SLIT) that included 4,870 patients were eligible for inclusion. • Allergens evaluated included: • Seasonal allergens (66%) • Perennial allergens (31%) • Both seasonal and perennial allergens (3%) • Comparators included: • Placebo (71%) • Another sublingual intervention without a placebo group (15%) • Conventional treatment without placebo (pharmacotherapy or rescue medications; 14%) • Duration of treatment ranged from 3 months to 5 years. • There was great heterogeneity in: • Dosages of maintenance or cumulative treatments • The units to report dosing • Standard therapy used across trials • Reported results often only reflect the percentage of trials in which a significant effect was seen for the immunotherapy arm versus controls and not the magnitude of effect. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

19. Sublingual Immunotherapy Versus Placebo or Standard Therapy: Asthma Outcomes • Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm. RCT = randomized controlled trial

20. SLIT Versus Placebo or Standard Therapy: Rhinitis/Rhinoconjunctivitis Outcomes • Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm. RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire

21. SLIT Versus Placebo or Standard Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

22. Subcutaneous Versus Sublingual Immunotherapy: All Outcomes RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

23. Included Studies for SCIT Versus Placebo or Standard Therapy in the Pediatric Population • Thirteen studies on subcutaneous immunotherapy included 920 pediatric patients. • The pediatric population ranged in age from 3 to 18 years. • Primary diagnoses included: • Asthma in 7 studies • Asthma with rhinitis in 3 studies • Asthma with rhinoconjunctivitis in 2 studies • Rhinoconjunctivitis in 1 study • All studies allowed either conventional pharmacotherapy or rescue allergy medications during the study. • Standard therapy varied across studies. • Due to heterogeneity in reported clinical outcomes, results often only reflect the percentage of trials in which a significant effect was seen for the immunotherapy arm versus controls and not the magnitude of effect. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

24. Pediatric Patients—SCIT Versus Placebo or Standard Therapy: Asthma Outcomes RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

25. Pediatric Patients—SCIT Versus Placebo or Standard Therapy: Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial ; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

26. Pediatric Patients—SCIT Versus Placebo or Standard Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

27. Included Studies for SLIT Versus Placebo or Standard Therapy in the Pediatric Population • 18 studies including 1,583 pediatric patients (≤ 18 years of age) • Primary diagnoses: • Asthma (n = 3 studies) • Rhinitis (n = 2 studies) • Rhinoconjunctivitis (n = 4 studies) • Asthma and rhinitis (n = 4 studies) • Asthma with rhinoconjunctivitis (n = 5 studies) • Perennial and/or seasonal allergies were included • Comparator groups included: • Placebo (n = 15 studies) • Sublingual immunotherapy (SLIT) comparator group (n = 3 studies) • Pharmacotherapy/symptomatic therapy (n = 2 studies) • Due to heterogeneity in reported clinical outcomes, results often only reflect the percentage of trials in which a significant effect was seen for the immunotherapy arm versus controls and not the magnitude of effect. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

28. Pediatric Patients—SLIT Versus Placebo or Standard Therapy: Asthma Outcomes RCT = randomized controlled trial; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

29. Pediatric Patients—SLIT Versus Placebo or Standard Therapy: Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

30. Pediatric Patients—SLIT Versus Placebo or StandardTherapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes RCT = randomized controlled trial; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

31. Pediatric Patients—SCIT Versus SLIT:All Outcomes RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

32. Adverse Effects:Subcutaneous Immunotherapy in Adults • Local reactions (such as redness, swelling, pruritus, or induration at the injection site) were usually mild and occurred in 5 to 58 percent of patients and 0.6 to 54 percent of injections and were more common than systemic reactions. • The most common systemic reactions were respiratory reactions, occurring in up to 46 percent of patients and in up to 3 percent of injections. • General symptoms (such as headache, fatigue, and arthritis) occurred in up to 44 percent of patients and were usually mild or unspecified. • Gastrointestinal reactions were reported in only one study. • Thirteen anaphylactic reactions were reported in four trials. • No deaths were reported in the included studies. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

33. Adverse Effects:Sublingual Immunotherapy in Adults • Local reactions (such as irritation, itching, swelling, or pain in the oral cavity) were common and usually mild and occurred in 0.2 to 97 percent of patients receiving sublingual immunotherapy (SLIT). • Systemic reactions occurred more frequently in the SLIT arm versus controls and included ocular, rhinitis/nasal, respiratory/asthma, cutaneous, gastrointestinal, and cardiovascular adverse effects. • No life-threatening reactions, anaphylaxis, or deaths were reported in the included trials. • SLIT studies mainly include patients with allergic rhinitis and/or mild asthma. Safety outcomes should not be extrapolated to more severely affected patients. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

34. Adverse Effects: Subcutaneous Versus Sublingual Immunotherapy in Adults • The recording and reporting of the adverse events was neither uniform nor comparable across studies. • Local reactions were common and were all of mild or moderate severity. • There was one report of anaphylaxis with subcutaneous immunotherapy. • There were no reported deaths in the included studies. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

35. Adverse Effects: Subcutaneous Immunotherapy in Pediatric Patients • Local reactions were the most common adverse reactions in the pediatric population receiving subcutaneous immunotherapy. • There were no reports of anaphylaxis or deaths. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

36. Adverse Effects: Sublingual Immunotherapy in Pediatric Patients • Local reactions (such as irritation, itching, swelling, or pain in the oral cavity) were common but mild. • No life-threatening reactions, anaphylaxis, or deaths were reported in these trials. • The strength of evidence for all other adverse effects is insufficient. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

37. Adverse Effects: Subcutaneous Versus Sublingual Immunotherapy in Pediatric Patients • Local reactions were reported in both patient groups. • No systemic reactions were reported in patients receiving sublingual immunotherapy. • In the pediatric population taking subcutaneous immunotherapy, one anaphylaxis event and three respiratory systemic reactions were reported. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

38. Overview of Conclusions (1 of 2) • There is sufficient evidence to support the overall effectiveness and safety of both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for treating allergic rhinoconjunctivitis and asthma. • However, there is not enough evidence to determine if either SCIT or SLIT is superior. • SCIT and SLIT are usually safe, although local reactions are commonly reported regardless of the mode of delivery. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

39. Overview of Conclusions (2 of 2) • Serious, life-threatening reactions are rare, although they can occur. • Studies of sublingual immunotherapy (SLIT) mainly include patients with allergic rhinitis and/or mild asthma. • Safety outcomes should not be extrapolated to more severely affected patients. • Most of the studies in the review used a single allergen for immunotherapy, and it may be difficult to extrapolate these results to the use of multiple-allergen regimens, which are commonly used in clinical practice in the United States. • Due to the wide variety of reported regimens, the target SLIT maintenance dose and duration of therapy are unclear. Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

40. Gaps in Knowledge • Additional studies are needed on: • The efficacy and safety of multiple-allergen subcutaneous (SCIT) and sublingual (SLIT) immunotherapy • The effectiveness of single-allergen versus multiple-allergen SCIT and SLIT for desensitization • The efficacy and safety of SCIT and SLIT in specific subpopulations (pregnant women, monosensitized vs. polysensitized patients, patients with severe asthma, and urban vs. rural patients) • Whether or not SCIT and SLIT can prevent or modify the atopic march in pediatric patients at high risk for allergic rhinitis and asthma, as well as the optimal age to initiate therapy • Determining the target maintenance dose, dosing strategies, and the necessary durations of treatment for SCIT and SLIT • Direct comparisons of SCIT to SLIT in pediatric and adult patients • Optimizing allergen standardization for subcutaneous and sublingual regimens Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

41. Shared Decisionmaking: What To Discuss With Your Patients • The benefits and adverse effects of subcutaneous (SCIT) or sublingual (SLIT) immunotherapy for them or their child • Any comorbid conditions that they or their child may have that would affect their ability to take SCIT or SLIT • Other prescription or over-the-counter medications they are taking during SCIT or SLIT treatment • What adverse effects to look for and when to call their doctor • How often they should be taking SCIT or SLIT • How long they can expect to take SCIT or SLIT • The costs of SCIT and SLIT Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

42. Resource for Patients • Allergy Shots and Allergy Drops for Adults and Children, A Review of the Research is a free resource that can help patients talk with their health care professionals about treatment options. It provides information about: • Allergies in general • How allergies are treated • Allergy shots and allergy drops • The benefits of allergy shots and allergy drops for adults and children • Possible side effects of allergy shots and allergy drops for adults and children • Questions to discuss with their doctor • Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.