Allergen immunotherapy in asthma.

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses.

Dendritic Cells in Food Allergy, Treatment, and Tolerance.

Food allergy is a growing problem with limited treatment options. It is important to understand the mechanisms of food tolerance and allergy to promote the development of directed therapies. Dendritic cells are specialized antigen presenting cells that prime adaptive immune responses, such as those involved in the development of oral tolerance and food allergies. The dendritic cell subsets in the gut and skin are defined by their surface markers and function. The default response to an ingested innocuous antigen is oral tolerance, which requires either gut dendritic cells or a subset of newly identified RORγt+ antigen presenting cells to induce the development of gut peripheral T regulatory cells. However, dendritic cells in the skin, gut, and lung can also promote allergic sensitization when they are activated under certain inflammatory conditions, such as with alarmin release or gut dysbiosis. Dendritic cells also play a role in the responses to the various modalities of food immunotherapy. Langerhans cells in the skin appear to be necessary for the response to epicutaneous immunotherapy. It will be important to determine which real-world stimuli activate the dendritic cells that prime allergic sensitization and discover methods to selectively initiate a tolerogenic program in antigen presenting cells.

Evaluation and Comparison of the Efficacy of Subcutaneous and Sublingual Immunotherapy for the Treatment of Allergic Asthma in Children.

Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually (SLIT). The aim of the current study was to evaluate and compare the efficacy of SCIT and SLIT for the treatment of allergic asthma in children. Our study included 69 children with allergic asthma who underwent immunotherapy for house dust mites or pollen for at least 3 consecutive years. After 3 years of SCIT and SLIT, the median number of asthma exacerbations in the last three months decreased from 2 to 0 (p < 0.01) and from 1 to 0 (p < 0.01), respectively. When comparing the efficacy of SCIT and SLIT, our study revealed a significantly better efficacy of SCIT only in terms of increasing lung function. The median increase in forced expiratory volume in one second (FEV1) after 3 years was 8% with SCIT and -1% with SLIT (p < 0.01). Daily controller therapy could be withdrawn or reduced in 9 out of 16 (56.3%) children who received it before SCIT (p < 0.01) and in 19 of 29 (65.6%) children who received it before SLIT (p < 0.01), but the difference in efficacy was not significant (p = 0.88). Both SCIT and SLIT are effective treatments for allergic asthma in children.

Satisfaction, Qol and adherence of patients allergic to dust mites and/or pollens undergoing sublingual immunotherapy.

Aim: Sublingual immunotherapy (SLIT) changes history of allergic respiratory disease (ARD). However, adherence is a barrier for optimal outcomes. Patients & methods: In the QUALI study, 859 patients with house-dust mite (HDM) and/or pollen induced ARD uncontrolled with symptomatic treatment and undergoing SLIT for at least 6 months or including one pre-coseason (pollen) were collected. Results & conclusion: SLIT significantly improved allergic rhinoconjunctivitis (ARC) and asthma symptom control, leading to reduced medication, meaningful health-related quality of life gain, improved nasal, ocular and bronchial symptoms and everyday life activities. Patients were highly satisfied and most of them adhered to SLIT, being forgetfulness the main non-adherence motive. SLIT is a quick effective treatment against persistent moderate-to-severe symptoms in ARC and asthma but it should been improve forgetfulness, as non-adherence reason.

Sublingual immunotherapy (SLIT) has really changed how we deal with allergic respiratory disease. But there's a catch: sticking to the treatment can be tough.In the QUALI study, we looked at 859 patients dealing with dust mite and/or pollen allergies who were not getting relief from the usual treatments. We put them on SLIT for at least 6 months or during pollen season.This treatment made a big difference. Symptoms got better, people needed less medication and they felt better in their day-to-day lives. Most patients were happy with the treatment and stuck to it well, but some forgot sometimes.In short, SLIT works fast and works well for moderate to severe allergies and asthma. But we need to help people remember to stick with it.

Modelling the Costs of Sublingual Immunotherapy versus Subcutaneous Immunotherapy Based on Clinical Appointments and Impacts of Patient Travel in Sweden.

Aim: 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 direct and indirect annual costs stemming from treatment-related travel, appointments, waiting times and medication costs, before exploring likely CO2 emission-related cost-savings for 20,330 patients receiving SCIT or SLIT-tablets in Sweden. Methods: A model was developed in Python to capture each category of costs in the target patient population. Absenteeism costs arising from treatment-related travel were determined by obtaining average hourly pay data from Swedish Government sources. Absenteeism costs were also calculated for 30-minute post-dose observation times, which occurred during one clinical appointment for SLIT patients, and all clinical appointments for SCIT patients. Clinical appointment costs were obtained from healthcare price lists for Sweden. Medication costs were retrieved from the Pharmaceutical Specialities in Sweden (Fass) website, and treatment doses required for SCIT and SLIT-tablets were determined based on product labels and previously-calculated dosage regimes. High-cost protection and reimbursement scheme payment caps were applied when determining patient appointment and medication costs, respectively, and when identifying financial burdens for individual payers. Results: Mean total annual costs for SCIT were Swedish Krona (SEK) 604.1 million (m), with clinical appointments contributing the largest share of these costs (52.7%), followed by medication (34.4%), travel-related absenteeism (8.9%), waiting time-related absenteeism (2.7%) and private transportation (1.3%). Mean total annual costs for SLIT-tablets were SEK 336.2m. Medication contributed the most to these costs (72.3%), followed by clinical appointments (22.7%), travel-related absenteeism (3.8%), waiting time-related absenteeism (0.6%) and private transportation (0.6%). Conclusion: For patients with moderate-severe AR receiving AIT in Sweden, SLIT-tablets displayed large potential cost savings to patients, the healthcare system, and the government, whilst possessing reduced societal costs of carbon emissions relative to SCIT.

Exploring Side Effects of Sublingual Immunotherapy: A Systemic Review and Meta-Analysis.

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.

The effect of subcutaneous and sublingual birch pollen immunotherapy on birch pollen-related food allergy: a systematic review.

Background: Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen-specific subcutaneous or sublingual immunotherapy in treating BPFA. Methods: A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized. Results: Ten studies were selected that included 475 patients in total. Seven studies were categorized into "high risk of bias" and three into "moderate risk of bias." The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL. Conclusion: This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.

Impact of liquid sublingual immunotherapy on asthma onset and progression in patients with allergic rhinitis: a nationwide population-based study (EfficAPSI study).

Background: The only disease-modifying treatment currently available for allergic rhinitis (AR) is allergen immunotherapy (AIT). The main objective of the EfficAPSI real-world study (RWS) was to evaluate the impact of liquid sublingual immunotherapy (SLIT-liquid) on asthma onset and evolution in AR patients. Methods: An analysis with propensity score weighting was performed using the EfficAPSI cohort, comparing patients dispensed SLIT-liquid with patients dispensed AR symptomatic medication with no history of AIT (controls). Index date corresponded to the first dispensation of either treatment. The sensitive definition of asthma event considered the first asthma drug dispensation, hospitalisation or long-term disease (LTD) for asthma, the specific one omitted drug dispensation and the combined one considered omalizumab or three ICS ± LABA dispensation, hospitalisation or LTD. In patients with pre-existing asthma, the GINA treatment step-up evolution was analysed. Findings: In this cohort including 112,492 SLIT-liquid and 333,082 controls, SLIT-liquid exposure was associated with a significant lower risk of asthma onset vs. control, according to all definitions (combined: HR [95% CI] = 0.62 [0.60-0.63], sensitive: 0.77 [0.76-0.78], and specific: 0.67 [0.61-0.72]). Exposure to SLIT was associated with a one-third reduction in GINA step-up regardless baseline steps. Interpretation: In this national RWS with the largest number of person-years of follow-up to date in the field of AIT, SLIT-liquid was associated with a significant reduction in the risk of asthma onset or worsening. The use of three definitions (sensitive or specific) and GINA step-up reinforced the rigorous methodology, substantiating SLIT-liquid evidence as a causal treatment option for patients with respiratory allergies. Funding: Stallergenes Greer.

Real-world assessment of anaphylaxis and eosinophilic esophagitis with 12 SQ house dust mite SLIT-tablet sublingual immunotherapy.

Background: Sublingual immunotherapy (SLIT) with 12 SQ house dust mile SLIT-tablet (HDM SLIT-tablet) for dust mite-induced perennial allergic rhinitis is reported as effective and safe. Although serious allergic reactions (SARs) and eosinophilic esophagitis (EoE) have infrequently occurred under trial conditions, the safety of HDM SLIT-tablet challenge under real-world conditions is unknown. Objective: Our aim was to estimate the incidence of SARs and EoE due to HDM SLIT-tablet challenge. Methods: Through use of administrative data from Kaiser Permanente Southern California, this prospective observational study identified patients newly administered HDM SLIT-tablet with follow-up until SLIT discontinuation or end of study. Suspected cases of SARs and EoE were detected by using International Classification of Diseases, 10th Revision, diagnosis and Current Procedural Terminology procedure codes and medication dispensing records. A 3-member clinical review committee of allergists adjudicated suspected reactions. The incidence rate of confirmed SARs and EoE per 1000 person years of exposure were determined. Results: A total of 521 patients (93.9% adult and 6.1% pediatric) were exposed to HDM SLIT-tablet challenge from January 2018 through May 2023, for 440.4 person years of exposure. The patients' average age (SD) was 39.3 (14.1) years, 58.7% were female, 44.3% were non-Hispanic White, 40.3% had asthma, and 15.0% had gastroesophageal reflux disease. A SAR occurred in 1 adult patient, and during initial HDM SLIT-tablet challenge, SARs occurred in 2 pediatric adolescents, for an overall incidence of 6.8 SARs per 1000 patient years (95% CI = 2.2-21.1). EoE occurred in 1 adult patient, for an overall incidence of 2.3 cases of EoE per 1000 patient years (95% CI = 0.3-16.1). Conclusions: This real-world study demonstrated that SARs and EoE were infrequent events with HDM SLIT-tablet use, supporting the safety of HDM SLIT-tablets and need for physician supervision with initial challenge.

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.

Clinical efficacy and safety evaluation of Dermatophagoides farinae drops in the treatment of allergic rhinitis with epistaxis.

Summary: Background. Epistaxis is frequently observed in allergic rhinitis (AR) patients. However, few studies focus on the outcome of epistaxis with treatment of AR patients. This study aimed to retrospectively analyze the efficacy and safety of AR patients with epistaxis treated with sublingual immunotherapy (SLIT). Methods. A total of 74 patients aged 4-60 years with house dust mite (HDM)-induced AR accompanied by epistaxis and who completed 1 year of SLIT treatment with standard Dermatophagoides farinae (D. farinae) drops were enrolled in this study. The symptom scores, total medication scores (TMS), combined symptom and medication score (CSMS), visual analog scales (VAS), and bleeding score (BS) were assessed, as well as the nasal endoscopic examinations were performed to observe nasal signs. Results. The levels of symptom scores, TMS, CSMS, VAS, and BS at 0.5 year and 1 year of SLIT treatment were significantly lower than those at the baseline (all p less than 0.01). Also, statistical differences were seen in CSMS (p less than 0.05) and VAS (p less than 0.01) between 0.5 year and 1 year. As expected, BS was positively correlated with CSMS (r = 0.617, 95% CI 0.517-0.699) and VAS (r = 0.777, 95% CI 0.719-0.822) at all three time points. Conclusions. SLIT with D. farinae drops was effective and safe for AR patients with epistaxis, resulting in improving the symptoms of rhinitis while relieving the symptoms of epistaxis.

Food Sublingual Immunotherapy: Safety and Simplicity of a Real Food Updosing Protocol.

BACKGROUND: Sublingual immunotherapy (SLIT) using food extracts is safe and effective in desensitizing patients with food allergy, yet not often used in clinical practice. OBJECTIVES: To propose a cost-effective, expedited SLIT protocol using real food. METHODS: Patients with food allergy aged 5 to 50 years (median, 11 years) initiated food SLIT in a single-clinic setting. The daily maintenance dose was 4 to 11 mg protein in 0.1 to 0.5 mL volume, depending on the food. Some foods were available in liquid form at the local grocery (milk, egg white liquid, and cashew/walnut/sunflower/hazelnut milk), whereas others were prepared in the office using flour and 50% glycerin saline (peanut/sesame/wheat). The first cohort of 20 patients began dosing at a 1:1000 dilution, the next 30 patients at 1:100 dilution. An exercise challenge was performed in a subset of patients on maintenance dosing to evaluate the need for a predose or postdose rest period. RESULTS: The 1:1000 and 1:100 cohorts both completed day 1 without adverse reactions beyond itchy mouth. There were no systemic reactions requiring epinephrine throughout the study period and 88% reached their maintenance dose. Skin testing of 6-month-old peanut flour solution was not diminished from fresh solution and similar to food extract. Exercise challenge test results in 12 patients were negative. CONCLUSIONS: Allergen extract food SLIT as used in published trials has limitations of cost and multiple office visits. Inexpensive real food, at the same or slightly higher protein dose, was well tolerated in 4 updose visits, a minimum of a week apart. Unlike food oral immunotherapy, a predose or postdose rest period may not be necessary.

Eosinophilic esophagitis improved by the discontinuation of sublingual immunotherapy for aeroallergens: a case report.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammation of the esophagus, characterized by symptoms related to esophageal dysfunction, resulting from severe eosinophilic infiltration of the esophageal mucosa. It is common in atopic subjects and food antigens have been identified as the most common triggers. However, a seasonal variation in EoE prevalence, correlated with air pollen levels, is reported, suggesting that also aeroallergens may play a role. Little is known about the interplay between EoE and concomitant atopy treatment for aeroallergens. Case presentation: We describe the case of an 11-year-old boy who presented dysphagia, vomiting, drooling, and chest pain while eating meat, developed 15 months after receiving sublingual immunotherapy (SLIT) for Alternaria (SUBLIVAC®). He underwent esophagogastroduodenoscopy (EGD) revealing severe eosinophilic predominant inflammation (100 eos/HPF), consistent with the diagnosis of EoE, not improving at the EGDs performed after both omeprazole and topical corticosteroids treatment, despite symptom improvement. Afterward, immunotherapy was switched from sublingual to injective form. At the EGD performed 1 month later, macroscopic examination of the esophageal mucosa was normal and eosinophilic infiltration was significantly decreased (5-10 eos/HPF). Conclusions: SLIT may induce EoE by chronic antigenic exposure of oral mucosa in patients with a robust allergic susceptibility: while attenuating the IgE-mediated immune reactions, the progressive contact with the causative allergen might induce a chronic stimulation of the immune system with the consequent activation of tissue eosinophils. Our data suggest monitoring patients receiving SLIT for EoE symptoms and to discontinue SLIT on their earlier appearance, possibly as a first-line treatment.

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.

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.

Effectiveness of allergen immunotherapy with house dust mite extract for pediatric bronchial asthma.

Aim: We compared the effectiveness of rush subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) using standardized house dust mite (HDM) extract for pediatric bronchial asthma (BA). Methods: We followed the pediatric BA treatment score during 3 years of treatment. We assessed the median time to no longer requiring long-term control pharmacotherapy (LTCP) for BA (LTCP-free). We compared the outcomes after adjustment for confounding factors and propensity score matching. Results: Patients in the HDM SCIT group achieved the LTCP-free status significantly earlier than those in the HDM SLIT group after adjustment for confounding factors and propensity score matching. Conclusion: Patients treated for pediatric BA with rush HDM SCIT had earlier onset of therapeutic effects than those with HDM SLIT.

[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.

House dust mite sublingual allergen immunotherapy tablet is safe and well-tolerated in Dutch clinical practice.

Background: Half (49%) of clinically diagnosed allergic rhinitis (AR) patients are sensitized to house dust mite (HDM). If allergen avoidance and symptomatic medication fail, allergen immunotherapy may be indicated. Objective: We investigated safety and tolerability of HDM-sublingual immunotherapy by HDM-SLIT tablets in Dutch daily clinical practice. Methods: Daily intake of 12 SQ-HDM SLIT-tablet was investigated in a prospective, multicenter, observational study (EUPAS43753). It comprised 4 consultations in 1 year. Data on safety, tolerability, treatment satisfaction, symptomatic medication, compliance, and clinical effectiveness (Control of Allergic Rhinitis and Asthma Test; CARAT) were collected. Descriptive and longitudinal regression data analysis were performed. Results: Adult patients (n = 415), mean (SD) age 36.6 (12.2) years, 61.4% female and 36% asthmatic were included. The preponderance (65.1%) experienced adverse events (AEs). These, mostly mild (67%), AEs comprised: oral allergic reactions (58.6%), respiratory (12.4%) and gastrointestinal symptoms (9.4%). Sixty (14.5%) patients stopped due to AEs and 76 (18.3%) for non-AE reasons. CARAT scores improved clinically significant by 6 points and symptomatic medication use decreased from 96.1% to 77.4%. Most patients (74.5%) tolerated the treatment and were compliant (>86.5%). The majority of patients (62.4%) and investigators (69.4%) were satisfied with treatment. Conclusions: HDM SLIT-tablet is a safe and well-tolerated AR treatment. AEs occur often but are mostly mild and decreasing during the first year. CARAT scores improved and symptomatic medication use decreased suggesting better control of AR with treatment. Compliance, tolerability, and treatment satisfaction are good. However, patient follow-up and compliance remain important points of attention when initiating treatment.

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.