UNASSIGNED: Asthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma.
UNASSIGNED: We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case-control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool.
UNASSIGNED: The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference -0.05 [95% CI: -0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference -1.60 [95% CI: -6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]).
UNASSIGNED: SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches.

House dust mite (HDM) allergen immunotherapy (AIT) has an established role in the treatment of perennial allergic rhinitis (AR) and allergic asthma (AA) triggered by HDM sensitization. We aimed to identify all double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AR and AA in humans and to summarize the evidence for AIT products that are currently manufactured and available for clinical use. A total of 56 eligible double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AA and/or AR in humans fit the inclusion criteria and investigated a total of 14 commercial AIT products; together, the 56 studies enrolled a total of 14,619 patients. Of the 56 studies, 39 studies investigated the current manufacturer-recommended maintenance dose (MRMD) of the product, and 17 investigated other doses. We identified 39 studies (12,539 patients randomized) for 8 sublingual immunotherapy (SLIT) products and 17 studies (2,080 patients randomized) for subcutaneous immunotherapy products. For AR, 3 products, the ALK 12 standardized-quality (SQ-HDM) SLIT tablet, the ALK 6 SQ-HDM tablet, and the SG 300 index of reactivity SLIT tablet, had both dose-finding studies (DFSs) and phase III definitive studies (DSs) to demonstrate efficacy of the MRMD of the product. For AA, 2 products, the ALK 12 SQ-HDM SLIT tablet and the ALK 6 SQ-HDM tablet, had both DFSs and DSs for the MRMD. No subcutaneous immunotherapy product had a paired DFS and DS supporting the MRMD. A total of 30 studies of products no longer commercially manufactured were excluded. This study will help to inform clinical care and product selection for the treatment of HDM-induced AR and AA.

暂无摘要。

Objective: Sublingual immunotherapy (SLIT) has emerged as a potentially safe and convenient option for allergen immunotherapy for patients with inhalant allergy. Larger studies on the overall side effects and severe reactions anaphylaxis are still lacking. Study Design: Systematic review and meta-analysis. Setting: Author\'s review was completed in the University of Texas Medical Branch. Methods: A systematic review and meta-analysis of prospective clinical trials focusing on SLIT safety published from January 1, 2001, to December 31, 2021, was conducted. Results: Twenty-six studies were included with analysis of 7827 patients, representing over 2.7 million SLIT doses. All studies focused on single-antigen immunotherapy. The mean duration of treatment was 11.54 months. Local side effects were present in 40.83% of patients [95% confidence interval (CI) 24.78-57.96]. Systemic side effects were encountered in 1.09% of SLIT patients (95% CI 0.57-1.78). Anaphylaxis was reported in 0.13% of patients (95% CI 0.06-0.22). Discontinuation rates due to side effects were low, at 4.32% of patients (95% CI 3.28-5.49). Conclusion: This meta-analysis shows that single-antigen SLIT is well-tolerated, with overall low rates of systemic side effects including anaphylaxis. Although there is a high rate of minor local side effect, the treatment attrition during the first year is low. With growing allergy burden worldwide, SLIT is a convenient and economically feasible option for immunotherapy. Further work is needed to evaluate long-term safety and efficacy of single as well as multi-antigen SLIT, including quality of life assessments.

To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma.
PubMed searches were conducted and unpublished data were included if necessary.
Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials.
Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

UNASSIGNED: Although randomized controlled trials (RCT) are the reference standard of evidence in allergen immunotherapy (AIT), nonrandomized studies (NRS) are needed to confirm their results in more representative populations, particularly for treatment duration and persistence. However, when discrepancies are observed between RCT and NRS, NRS reliability decreases because these discrepant results are generally attributed to the methodologic flaws of NRS.
UNASSIGNED: We compared the benefit of sublingual AIT (SLIT) for allergic rhinoconjunctivitis in NRS versus RCT focusing on a single product/allergen to reduce heterogeneity.
UNASSIGNED: For meta-analysis, house dust mite (HDM) SLIT liquid formulation studies were sourced from computerized (Medline, Web of Science, and LILACS databases, to January 2023) and manual literature searches. Populations, treatments, and outcome data were combined (DerSimonian-Laird method). Noncomparative NRS were compared to RCT\' SLIT arm before and after treatment. Efficacy was determined as the standardized mean difference (SMD) in symptom score (SS) and medication score (MS).
UNASSIGNED: Data from 12 NRS (682 patients) and 8 RCT (176 patients) were analyzed. The benefit with index of reactivity (IR)-HDM SLIT liquid formulation was found significant for, first, SS in both NRS (SMD = -1.27; 95% confidence interval [CI], -1.64, -0.90) and RCT (SMD = -0.56; 95% CI, -0.90, -0.21), and second, MS with SMD equal to -1.35 (95% CI, -1.77, -0.93) and -0.46 (95% CI, -0.67, -0.25), respectively. Metaregression showed that symptom improvement was correlated with treatment duration with consistent results in NRS and RCT with 12-month SS data: -0.87 (interquartile range, -1.02, -0.77) and -0.75 (interquartile range, -0.93, -0.41), respectively.
UNASSIGNED: This meta-analysis showed comparable clinical benefit of IR-HDM SLIT liquid formulation increasing over time in both NRS and RCT, suggesting that NRS may reliably integrate RCT results and be considered for guidelines.

To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).
PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.
Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).
Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.
PROSPERO (CRD42023460693).

OBJECTIVE: Sublingual immunotherapy (SLIT) has been widely applied to treat patients with allergic rhinitis (AR). However, meta-analyses on the efficacy of SLIT in AR patients with asthma are still limited.
METHODS: Literature without language limitation published before October 28, 2022, were retrieved from PubMed, EMBASE, and Cochrane Library. STATA 16.0 software was used for the meta-analysis of the extracted data. The results reported were symptom scores, drug scores, adverse effects rates, and cost of treatment.
RESULTS: Ten studies involving 1722 patients met the inclusion criteria. The total rhinitis score (TRSS) (weighted mean difference [WMD] = -1.23, 95% CI: -1.39--1.06, P < .001) and total asthma symptom score (TASS) (WMD = -1.00, 95% CI: -1.12-0.89, P < .001) were significantly lower in the SLIT group than the placebo group. The SLIT group had higher rates of treatment-related adverse events (relative risk [RR] = 2.82, 95% CI: 1.77-4.48, P < .001) and total costs of treatment (standardized mean difference [SMD] = 0.71, 95% CI: 0.45-0.97, P < .001). There was no significant difference in inhaled corticosteroids (ICS) dose (P = .195), fractional exhaled nitric oxide (FeNO) (P = .158), forced expiratory volume in 1 s (FEV1) (P = .237), and direct costs of treatment (P = .630) between the SLIT and placebo groups.
CONCLUSIONS: SLIT may be a therapeutic method for improving rhinitis symptoms and asthma symptoms in AR patients with asthma. However, as there was significant heterogeneity in results, more high-quality and well-designed studies are needed in the future to elucidate the efficacy of SLIT.

Most patients with allergic rhinitis are polysensitized. The efficacy of house dust mite (HDM) allergen immunotherapy (AIT) compared between monosensitized and polysensitized patients remains limited.
To systematically review the efficacy and safety of HDM AIT compared between monosensitized and polysensitized patients with allergic rhinitis.
We searched PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane central register of Controlled Trials (CENTRAL) until June 2022. The primary outcome was the changes from baseline in total nasal symptom score (TNSS). Secondary outcomes were changes from baseline in total medication score (TMS), combined symptom medication score (CSMS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, immunological parameters, and adverse events (AEs).
Of 13 eligible studies, 10 prospective cohorts, 2 retrospective cohorts, and 1 matched cohort, we identified 10 studies for quantitative synthesis. There were 1,113 patients with allergic rhinitis, 566 with HDM monosensitization and 547 with polysensitization to HDM and other allergens. There was no significant difference in the pooled mean changes of the 2 groups in TNSS (SMD -0.05, 95%CI: -0.22 to 0.11, p = 0.532) and VAS (SMD -0.20, 95%CI: -0.42 to 0.01, p = 0.060) with moderate certainty of evidence. The changes in TMS, CSMS, and RQLQ were similar between the 2 groups with very low certainty of evidence. The AEs were mild and comparable between the 2 groups. The immunological indices remained inconsistent and were not predictive of clinical responses.
A single HDM AIT similarly improved clinical outcomes in monosensitized and polysensitized patients with allergic rhinitis.

Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT\'s effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.