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Context: Treatment options for allergic asthma include allergen avoidance, pharmacotherapy, and allergen immunotherapy., Objectives: Summarize and update current evidence for the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in pediatric allergic asthma., Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials (January 1, 2005, through May 8, 2017), ClinicalTrials.gov, and the US Food and Drug Administration Adverse Event Reporting System. We reevaluated trials from our 2013 systematic review., Study Selection: We included studies with children ≤18 years of age in which researchers reported on prespecified outcomes and had an intervention arm receiving aeroallergen SCIT or SLIT. Only randomized controlled trials (RCTs) were included for efficacy. RCTs and non-RCTs were included for safety outcomes., Data Extraction: Two reviewers extracted data. We included 40 studies (17 SCIT trials, 11 SLIT trials, 8 non-RCTs for SCIT safety, and 4 non-RCTs for SLIT safety)., Results: We found moderate-strength evidence that SCIT reduces long-term asthma medication use. We found low-strength evidence that SCIT improves asthma-related quality of life and forced expiratory volume in 1 second. There was also low-strength evidence that SLIT improves medication use and forced expiratory volume in 1 second. There was insufficient evidence on asthma symptoms and health care use., Limitations: There were no trials in which researchers evaluated asthma symptoms using a validated tool. Study characteristics and outcomes were reported heterogeneously., Conclusions: In children with allergic asthma, SCIT may reduce long-term asthma medication use. Local and systemic allergic reactions are common, but anaphylaxis is reported rarely., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objectives/hypothesis: To systematically review the effectiveness and safety of subcutaneous immunotherapy (SCIT) for treatment of allergic rhinoconjunctivitis and asthma, using formulations currently approved in the United States., Study Design: We searched the following databases up to May 21, 2012: MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials., Methods: We included randomized controlled trials published in English comparing SCIT to placebo, pharmacotherapy, or other SCIT regimens that reported clinical outcomes of interest. Studies of adults or mixed age populations were included. Studies were excluded if the diagnosis of allergy and/or asthma was not confirmed with objective testing. Paired reviewers selected articles for inclusion and extracted data. We assessed the risk of bias for each study and graded the strength of evidence for each outcome as high, moderate, or low., Results: Sixty-one studies met our inclusion criteria. Majority of the studies (66%) evaluated single-allergen immunotherapy regimens. The literature provides high-grade evidence that SCIT reduces asthma symptoms, asthma medication usage, rhinitis/rhinoconjunctivitis symptoms, conjunctivitis symptoms, and rhinitis/rhinoconjunctivitis disease-specific quality of life in comparison to placebo or usual care. There is moderate evidence that SCIT decreases rhinitis/rhinoconjunctivitis medication usage. Respiratory reactions were the most common systemic reaction. There were few reports of anaphylaxis; no deaths were reported., Conclusions: Generally moderate to strong evidence supports the effectiveness of SCIT for treatment of allergic rhinitis and asthma, particularly with single-allergen immunotherapy regimens. Adverse reactions to SCIT are common, but no deaths were reported in the included studies., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Allergen-specific immunotherapy is widely used in the management of patients with allergic rhinoconjunctivitis and asthma, but the best route of delivery is unclear., Objective: We performed a systematic review of studies with head-to-head comparison of effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in the treatment of allergic rhinoconjunctivitis and asthma., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched through December 21, 2012. We included English language randomized controlled trials that enrolled patients with allergic rhinoconjunctivitis and/or asthma with head-to-head comparisons of SCIT with SLIT. Paired reviewers extracted detailed information from included articles on standardized forms and assessed the risk of bias in each article., Results: Eight trials compared the effectiveness and safety of SCIT and SLIT. The effectiveness of the 2 forms of immunotherapy in managing allergic asthma and rhinoconjunctivitis were reported in 4 and 6 clinical trials, respectively. Low-grade evidence supports greater effectiveness of SCIT than SLIT for asthma symptom reduction and also at reducing a combined measure of rhinitis symptoms and medication use. Moderate-grade evidence supports greater effectiveness of SCIT than SLIT for nasal and/or eye symptom reduction. All 8 trials reported on adverse events with an episode of anaphylaxis reported in a child treated with SCIT., Conclusion: Our review provides low-grade evidence to support that SCIT is superior to SLIT for reduction in asthma symptoms and moderate-grade evidence for reduction of allergic rhinoconjunctivitis. Additional studies are required to strengthen this evidence base for clinical decision making., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Subcutaneous immunotherapy (SCIT) is approved in the United States for the treatment of pediatric asthma and rhinitis; sublingual immunotherapy (SLIT) does not have regulatory approval but is used in clinical practice. The objective of this study was to systematically review the evidence regarding the efficacy and safety of SCIT and SLIT for the treatment of pediatric asthma and allergic rhinoconjunctivitis., Methods: Two independent reviewers selected articles for inclusion, extracted data, and graded the strength of evidence for each clinical outcome. All studies were randomized controlled trials of children with allergic asthma or rhinoconjunctivitis treated with SCIT or an aqueous formulation of SLIT. Data sources were Medline, Embase, LILACS, CENTRAL, and the Cochrane Central Register of Controlled Trials through May 2012., Results: In 13 trials, 920 children received SCIT or usual care; in 18 studies, 1583 children received SLIT or usual care. Three studies compared SCIT with SLIT head-to-head in 135 children. The strength of evidence is moderate that SCIT improves asthma and rhinitis symptoms and low that SCIT improves conjunctivitis symptoms and asthma medication scores. Strength of evidence is high that SLIT improves asthma symptoms and moderate that SLIT improves rhinitis and conjunctivitis symptoms and decreases medication usage. The evidence is low to support SCIT over SLIT for improving asthma or rhinitis symptoms or medication usage. Local reactions were frequent with SCIT and SLIT. There was 1 report of anaphylaxis with SCIT., Conclusions: Evidence supports the efficacy of both SCIT and SLIT for the treatment of asthma and rhinitis in children.

Importance: Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization., Objective: To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma., Evidence Acquisition: The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence., Results: Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported., Conclusions and Relevance: The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.