Clinical efficacy of Dermatophagoides farina drops on allergic rhinitis in children sensitized by dust mites combined with different allergens.

OBJECTIVE: This study aimed to investigate the clinical efficacy and safety of sublingual immunotherapy (SLIT) using standardized dermatophagoides farina drops for the treatment of allergic rhinitis (AR) in children sensitized to dust mites combined with different allergens. The findings contribute to establishing a preliminary foundation for future in-depth studies on AR treatment. METHODS: A total of 152 AR children undergoing SLIT were categorized into two groups based on serological test results: the inhalation group (dust mite combined with inhalation allergy) and the ingestion group (dust mite combined with ingestion allergy). The clinical efficacy and safety were evaluated by assessing the total nasal symptoms score (TNSS), total medication scores (TMS), visual analog scale scores (VAS scores), and the incidence of adverse reactions before treatment and after two years of treatment. RESULTS: After two years of treatment, TNSS, TMS, and VAS scores significantly improved compared to pre-treatment values in both the inhalation and ingestion groups (p < 0.05). However, there were no significant differences in efficacy between the two groups after two years of treatment (p > 0.05). During the treatment period, only 15 cases (10.9 %, 9 cases in the inhalation group and 6 cases in the ingestion group) experienced mild adverse reactions. There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). CONCLUSION: SLIT using standardized dermatophagoides farina drops demonstrates long-term efficacy in children with AR, regardless of whether they belong to the inhalation or ingestion group, without significant differences in treatment outcomes.

Allergen Immunotherapy: The Evidence Supporting the Efficacy and Safety of Subcutaneous Immunotherapy and Sublingual Forms of Immunotherapy for Allergic Rhinitis/Conjunctivitis and Asthma.

Allergen immunotherapy (AIT) is a recognized key therapeutic modality for the treatment of allergic respiratory disease. Definitive studies have provided evidence-based data to demonstrate its effectiveness in allergic rhinitis and asthma due to the inhalation of proteinaceous allergic substances from specific seasonal pollens, dust mites, animal allergens, and certain mold spores. Over the ensuing decades, laboratory investigations have provided objective evidence to demonstrate immunologic changes, including production of protective IgG antibody, suppression of IgE antibody, upregulation of regulatory T cells, and induction of a state of immune tolerance to the offending allergen(s). Tangential to this work were carefully designed clinical studies that defined allergen dose and duration of treatment, established the importance of preparing extracts with standardized allergens (or well-defined extracts) based on major protein moieties, and used allergen provocation models to demonstrate efficacy superior to placebo. In the United States, the use of subcutaneous immunotherapy extracts for AIT was grandfathered in by the Food and Drug Administration based on expert literature review. In contrast, sublingual tablet immunotherapy underwent formal clinical development programs (phase I-III clinical trials) that provided the necessary clinical evidence for safety and efficacy that led to regulatory agency approvals for the treatment of allergic rhinitis in properly characterized patients with allergy. The allergy specialist's treatment options currently include traditional subcutaneous AIT and specific sublingual tablets approved for grass, ragweed, house dust mites, trees belonging to the birch-homologous group, and Japanese cedar. Tangential to this are sublingual drops that are increasingly being used off-label (albeit not approved by the Food and Drug Administration) in the United States. This article will review the evidence-based literature supporting the use of these forms of AIT, as well as focus on several current controversies and gaps in our knowledge base that have relevance for the appropriate selection of patients for treatment with specific AIT.

The Relationship Between Eosinophilic Esophagitis and Immunotherapy.

Immunotherapy is a treatment approach based on the principle of incremental allergen exposure to achieve desensitization. Recently, oral immunotherapy has been introduced as a treatment of IgE-mediated food allergy. Some patients receiving oral immunotherapy for food allergy may develop eosinophilic esophagitis. Here, we summarize the literature examining this association, its treatment, and outcomes and discuss possible explanations for this clinical phenomenon. We further identify potential associations with aeroallergen sensitivity and other forms of immunotherapy including subcutaneous immunotherapy and sublingual immunotherapy. Finally, we discuss management of immunotherapy-induced eosinophilic esophagitis. Epicutaneous immunotherapy is highlighted as an area of therapeutic investigation.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Increased Nasal Blimp1 + Treg Cells After Sublingual Immunotherapy Reflect the Efficacy of Treatment in Allergic Rhinitis.

INTRODUCTION: Allergen-specific immunotherapy (AIT) plays a pivotal role in altering the immune status and tissue responses in allergic rhinitis (AR). This study focuses on the impact of sublingual immunotherapy (SLIT) involving dust mite drops, exploring the modulation of regulatory T cells (Treg) and their specific marker, BLIMP1, in the nasal mucosa. METHODS: Immune cells were isolated from nasal lavage fluid of patients with AR undergoing SLIT (n = 94). Treg cells were analyzed for BLIMP1 expression, and chemokine levels associated with Treg recruitment were assessed using Luminex assay. Patients were categorized on the basis of SLIT efficacy and followed for changes after discontinuation. RESULTS: SLIT induced a significant increase in nasal Treg cells (7.09 ± 2.59% vs. 0.75 ± 0.27%, P < 0.0001). BLIMP1 expression in Treg cells notably increased after SLIT (0.36 ± 0.22% to 16.86 ± 5.74%, P < 0.0001). Ineffective SLIT cases exhibited lower levels of nasal Treg and Blimp1 + Treg cells (both P < 0.0001). Receiver operating characteristic (ROC) analysis confirmed their potential as efficacy predictors (AUC = 0.908 and 0.968, respectively). SLIT discontinuation led to a significant reduction in Treg and Blimp1 + Treg cells (P < 0.001), emphasizing their maintenance during treatment. Pro-inflammatory cytokines decreased (P < 0.001), while CCL2 associated with Treg recruitment increased (P = 0.0015). CONCLUSION: Elevated nasal Blimp1 + Treg cells serve as a predictive biomarker for SLIT responsiveness in pediatric AR. Their influence on immunotherapy effectiveness contributes to a nuanced understanding of SLIT mechanisms, allowing for disease stratification and personalized treatment plans. This study offers scientific support for predicting SLIT efficacy, enhancing the prospects of improved treatment outcomes in AR.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: 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. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: 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. CONCLUSION: 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.

[TWO CASES OF LARYNGEAL EDEMA CAUSED BY SUBLINGUAL ALLERGEN IMMUNOTHERAPY].

Sublingual immunotherapy is a widely used treatment, and serious adverse reactions such as anaphylaxis are rare. We report two cases of laryngeal edema as adverse reactions to sublingual immunotherapy, which could be continued due to a change in the administration method. Case 1 presents a 15-year-old male suspected to have had anaphylaxis due to the dust at the age of 6 years. He started treatment with Miticure® and developed laryngeal edema 30 minutes after taking the 10000JAU dose on the 10th day. laryngeal edema was treated with intravenous infusion. Case 2 presents a 48-year-old woman. She started treatment with Cidacure® and developed respiratory distress and laryngeal edema 1 hour after taking the 5000JAU dose on the 5th day. she had resolved mildly without therapeutic intervention. In both cases, the patients were switched to sublingual spitting, resumed with the initial dose cautiously, and were able to continue. Sublingual immunotherapy is a safe treatment, but sudden adverse reactions may occur. Laryngeal symptoms may be treated by changing to the sublingual spitting method, but laryngeal findings should be examined, and the dosage should be carefully increased.

Baseline Severity and Disease Duration Can Predict the Response to Allergen-specific Immunotherapy in Allergic Rhinitis.

Allergen-specific immunotherapy (AIT) has confirmed its efficacy in improving the symptoms of allergic rhinitis. However, no reliable biomarkers have been identified to predict the efficacy of AIT were found. We aimed to find clinical and immunological markers to predict efficacy in children after 2 years of sublingual immunotherapy (SLIT). A total of 285 children diagnosed with allergic rhinitis were recruited. The clinical efficacy was evaluated by comparing endpoint and baseline symptom and medication scores (SMS). Baseline clinical and immunological markers (serum total and specific immunoglobulin [Ig]E) and their correlation with clinical efficacy were analyzed. Of the 285 children recruited, 249 completed the 2-year SLIT program. After 2 years of SLIT, 68.3% of the children showed a significant response. Children in the Remarkable Response Group had the highest baseline SMS and most extended disease duration, followed by the Effective Relief and Unresponsive Group. Correlation analysis demonstrated that SMS improvement was positively correlated with baseline SMS (r=0.67) and disease duration (r=0.35). SMS improvement was not correlated with age, body mass index, total or specific IgE levels, or their ratios. Our results show that baseline SMS and disease duration can predict the efficacy of SLIT. Our study can guide the selection of suitable candidates for SLIT.

Sublingual Tablet Immunotherapy Improves Quality of Life in Adults With Allergic Rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis with or without conjunctivitis can negatively impact many aspects of quality of life (QoL). The efficacy and safety of standardized quality (SQ) sublingual immunotherapy (SLIT) tablets have been confirmed across large clinical trials in adults with grass, tree, ragweed, and house dust mite (HDM) allergic rhinitis with or without conjunctivitis. OBJECTIVE: This pooled analysis investigates whether the reduction in symptom burden found across the clinical trials is supported by improvements in QoL. METHODS: A total of 11 phase II/III randomized placebo-controlled trials across the SQ grass, tree, ragweed, and HDM SLIT tablets (grass: N = 3179; ragweed: N = 767; tree: N = 634; HDM: N = 2221) were included. QoL was assessed using the standardized Rhinitis Quality of Life Questionnaire (RQLQ), with the exception of 3 grass trials, which used the nonstandardized version. The overall RQLQ scores were expressed as a mean of 7 domains. In the pooled analysis, treatment was used as fixed effect; and the trial, and the interaction between region/country and trial as random effects. RESULTS: The pooled analysis showed consistent and statistically significant improvements in overall RQLQ scores across all 4 SQ SLIT tablets versus placebo (pooled estimate [95% CI], P value-grass: -0.20 [-0.28 to -0.12], P < .001; tree: -0.42 [-0.58 to -0.26], P < .001; ragweed: -0.36 [-0.55 to -0.17], P < .001; HDM: -0.28 [-0.39 to -0.17], P < .001). Furthermore, significant improvements versus placebo for all 4 SQ SLIT tablets were seen across the 7 individual domains. CONCLUSIONS: The proven efficacy of SQ SLIT tablets to reduce symptoms across 4 of the most common respiratory allergens is supported by concurrent significant improvements in RQLQ scores overall and for all 7 domains.

Efficacy of Adjuvant Sublingual Immunotherapy After Septomeatoplasty.

BACKGROUND: The efficacy of adjuvant sublingual immunotherapy (SLIT) in correcting structural problems in patients with allergic rhinitis (AR) caused by mite who have undergone septomeatoplasty (SMP) has not been studied. METHODS: This non-randomized controlled study recruited patients with AR (caused by mite) and concurrent septal deviation and inferior turbinate hypertrophy, at a tertiary hospital in Taiwan. SMP was performed on all patients as a surgical intervention. The patients were then divided into two groups: the control group, which underwent surgery only, and the experimental group, which received SLIT as an adjuvant treatment. Demographic data and rhinitis control assessment test (RCAT) results were analyzed. RESULTS: A total of 96 patients were enrolled in the study (SMP + SLIT group, n = 52; SMP only group, n = 44). No significant differences were observed in any of the variables between the two groups before and one month after surgery. However, during evaluations at the third and sixth month, the SMP + SLIT group showed significant improvement in the total RCAT scores compared to the SMP only group (28.6 ± 1.56 vs. 24.5 ± 3.66, p < 0.001; 27.1 ± 2.87 vs. 19.9 ± 5.56, p < 0.001). In addition, significantly better control of all RCAT sub-categories was observed in the SMP + SLIT group at the third and sixth month evaluations. CONCLUSIONS: SLIT may serve as an ideal adjuvant therapy after SMP in patients with AR. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3073-3079, 2024.

Safety and Effectiveness of Bypassing Oral Immunotherapy Buildup With an Initial Phase of Sublingual Immunotherapy for Higher-Risk Food Allergy.

BACKGROUND: Because of its favorable safety, sublingual immunotherapy (SLIT) for food allergy has been proposed as an alternative treatment for those in whom oral immunotherapy (OIT) is of higher risk-older children, adolescents, adults, and those with a history of severe reactions. Although safe, SLIT has been shown to be less effective than OIT. OBJECTIVE: To describe the safety of multifood SLIT in pediatric patients aged 4 to 18 years and the effectiveness of bypassing OIT buildup with an initial phase of SLIT. METHODS: Patients aged 4 to 18 years were offered (multi)food SLIT. Patients built up to 2 mg protein SLIT maintenance over the course of 3 to 5 visits under nurse supervision. After 1 to 2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC) (cumulative dose, 300 mg protein) with the goal of bypassing OIT buildup. RESULTS: Between summer 2020 and winter 2023, 188 patients were enrolled in SLIT (median age, 11 years). Four patients (2.10%) received epinephrine during buildup and went to the emergency department, but none experienced grade 4 (severe) reaction. A subset of 20 patients had 50 low-dose OFCs to 300 mg protein and 35 (70%) OFCs were successful, thereby bypassing OIT buildup. CONCLUSIONS: In combination with very favorable safety of SLIT, with no life-threatening reactions and few reactions requiring epinephrine, we propose that an initial phase of SLIT to bypass supervised OIT buildup be considered for children in whom OIT is considered to be of higher risk.

Effectiveness of sublingual immunotherapy in pediatric cedar pollinosis: A real-world database study.

BACKGROUND: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real-world settings, on children with CP. METHODS: This retrospective cohort study used a claim database in 2018-2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. RESULTS: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non-SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was -0.62 (95% confidence interval: -0.86 to -0.39, p < .0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. CONCLUSION: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases.

Modelling the impact of sublingual immunotherapy versus subcutaneous immunotherapy on patient travel time and CO2 emissions in Sweden.

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients.

Effect of sublingual immunotherapy on clinical and laboratory autoimmunity.

Background: There still are few data on the long-term safety of sublingual immunotherapy (SLIT). The aim of this study was to assess the appearance of autoimmune diseases in patients before and after SLIT. Materials & methods: New cases of autoimmune diseases were monitored. Patients in the SLIT group (n = 816) were compared with controls (n = 1096). Results: The new incidences of autoimmune diseases in the SLIT group were lower compared with the control group: 18 (2.2%) versus 58 (5.3%); p < 0.05. Systemic lupus erythematosus, psoriasis and Hashimoto appeared much more often in the control group. Conclusion: SLIT had no significant effect on the induction of autoimmune diseases.

The therapy for allergic people is named allergen-specific immunotherapy, and one of the ways of administering this therapy is sublingual immunotherapy (SLIT), which means that the medication is kept in the mouth under the tongue. The authors assessed the safety of SLIT in terms of the risk of inducing autoimmune diseases, which means that the immune system is overactive, causing it to attack and damage the body's own tissues. Analysis of medical history for autoimmune diseases, clinical examinations and laboratory diagnostic tests were performed. SLIT did not significantly increase the incidences of autoimmune disease in the study group. SLIT is a safe therapy in long-term observation.

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy.

INTRODUCTION: Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy. METHODS: A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial's initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells. RESULTS: Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 ß (GSKß) and mammalian target of rapamycin (mTOR) expression after SLIT. CONCLUSION: Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT's effectiveness.

The Art of Dosing for Subcutaneous Immunotherapy in North America.

Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.

Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites.

BACKGROUND: Allergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease-modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT. METHODS: The authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM-specific IgA, IgE, and IgG4 antibodies, and HDM-induced production of interleukin (IL) 5 and IL-10 from cultured PBMCs were evaluated by enzyme-linked immunosorbent assay. RESULTS: Following 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM-specific IgG4 was significantly increased; and HDM-induced production of IL-5 from PBMCs was significantly decreased, while that of IL-10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores. CONCLUSION: An increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT.

Anaphylaxis in Clinical Trials of Sublingual Immunotherapy Tablets.

BACKGROUND: There is no consensus method to identify anaphylaxis in sublingual immunotherapy (SLIT) trials. Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQs) are standardized groupings of MedDRA terms used in drug safety monitoring. OBJECTIVE: To develop a method to identify potential anaphylaxis in SLIT-tablet trials using SMQ searches and case definitions of anaphylaxis adopted from the National Institute of Allergy and Infectious Disease. METHODS: The SMQ search tool contained 2 criteria including treatment-emergent adverse events (AEs): (1) narrow MedDRA terms related to anaphylaxis and (2) all AEs with broad MedDRA terms from at least 2 of 3 categories (respiratory/skin/cardiovascular) occurring on the same day. Criteria were applied to a pooled data set of all subjects from 48 timothy grass, ragweed, house dust mite, and tree SLIT-tablet trials (SLIT-tablet, N = 8200; placebo, N = 7033). Additional search strategies were any treatment-emergent AE with MedDRA preferred term "hypersensitivity" and epinephrine administrations. Identified potential cases underwent blinded independent medical expert review. Nonanaphylaxis cases were designated local AEs or mild to moderate systemic reactions. RESULTS: Using the SMQ search tool and after subsequent medical review, 8 anaphylaxis cases were identified; 3 were considered treatment-related, resulting in a proportion of anaphylaxis cases/subject of 0.02% (2 of 8200) with SLIT-tablet and 0.01% (1 of 7033) with placebo. One additional anaphylaxis case related to SLIT-tablet was identified by the preferred term "hypersensitivity." The 3 anaphylaxis cases associated with SLIT-tablet treatment were not life-threatening. The epinephrine administration rate was 17 of 8200 (0.2%) with SLIT-tablet treatment and 2 of 7033 (0.03%) with placebo. CONCLUSIONS: SMQ search criteria for identifying potential anaphylaxis related to SLIT were developed. Anaphylaxis was rare for SLIT-tablets.