Dataset Information

Effects of house dust mite subcutaneous immunotherapy in real-life. Immunological and clinical biomarkers and economic impact analysis.

ABSTRACT:

Background

Etiology of allergic rhinitis and asthma is frequently associated with house dust mite sensitization and allergen immunotherapy (AIT) represents the only disease modifying treatment. In a real world setting, clinicians would benefit from biomarkers to monitor or predict response to AIT.

Methods

Twenty-four consecutive house dust mite (HDM) mono-sensitized rhinitic patients, treated with subcutaneous immunotherapy (SCIT) as per clinical practice, were enrolled. Multiple in vitro biomarkers such as basophil activation (BAT), IL-10 levels, and molecular allergen-specific IgE were performed during HDM SCIT, to monitor the effects of AIT and then correlated to in vivo scores (VAS, CMSS, RQLQ). Nasal cytology was performed at baseline and after 6 and 12 months of treatment. Finally, the economic impact of SCIT in this cohort of patients was evaluated.

Results

Clinical biomarkers confirmed to be useful to monitor AIT efficacy. As for laboratory biomarkers, BAT showed a reduction trend, particularly for D2C1, suggesting that this is a useful parameter in monitoring patients. IL-10 levels tend to remain stable or slightly decrease during treatment. The economic analysis confirmed the favorable impact of immunotherapy.

Conclusions

In this cohort of patients, SCIT confirmed its effectiveness in reducing symptoms and drug utilization. Clinical scores confirmed to be valid in monitoring patients and their response. BAT demonstrated to be useful in monitoring more than predicting response. Further studies are needed to better explore the usefulness of these biomarkers in AIT.

SUBMITTER: Caruso C

PROVIDER: S-EPMC10362513 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Effects of house dust mite subcutaneous immunotherapy in real-life. Immunological and clinical biomarkers and economic impact analysis.

Caruso Cristiano C Colantuono Stefania S Tolusso Barbara B Di Mario Clara C Fancello Giovanni G La Sorda Marilena M Celi Giorgio G Caringi Mario M Volterrani Anna A Descalzi Desideria D Gremese Elisa E Sanguinetti Maurizio M Gasbarrini Antonio A Canonica Giorgio Walter GW

The World Allergy Organization journal 20230615 6

<h4>Background</h4>Etiology of allergic rhinitis and asthma is frequently associated with house dust mite sensitization and allergen immunotherapy (AIT) represents the only disease modifying treatment. In a real world setting, clinicians would benefit from biomarkers to monitor or predict response to AIT.<h4>Methods</h4>Twenty-four consecutive house dust mite (HDM) mono-sensitized rhinitic patients, treated with subcutaneous immunotherapy (SCIT) as per clinical practice, were enrolled. Multiple ...[more]

PMID: 37484874

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Project description:Purpose: Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are effective in reducing symptoms and medication scores and inducing long-term efficacy in patients with allergic rhinitis (AR). However, SLIT has been associated with poor patient adherence. This study investigates the factors impacting dropout rates from SLIT in house dust mite (HDM)-sensitized AR patients. Methods: A retrospective study was performed to analyze dropout rates and reasons in AR patients receiving Dermatophagoides farinae (Der f) SLIT with a follow-up period of 2 years. Results: A total of 719 HDM-sensitized AR patients received Der f-SLIT. Dropout rates increased with time and most occurred after 1 year of SLIT. By month 24, 654 (91%) patients had discontinued SLIT. The dropout rates by month 24 were 100, 90.1, and 91.1% in children <5 years old, children aged 5-18 years old, and adults ≥ 18 years old, respectively. Combination with allergic asthma and mono- or multi-sensitization to other aeroallergens did not affect the dropout rates. The most common self-reported reasons for dropouts were refusal of continuation, dissatisfaction with the efficacy, transition to SCIT, and adverse effects. Refusal of continuation increased with age, whereas transition to SCIT decreased with age. Ninety-seven cases transitioned from SLIT to SCIT, and the transition rates increased with time. Comorbid allergic asthma did not affect the transition rates. However, multi-sensitization was associated with a slightly higher rate of transition to SCIT. The most common reason for the transition was dissatisfaction with the efficacy (54.6%), which was only reported by patients older than 5 years. For children who began SLIT at younger than 5 years old, the most common reason (81.2%) for transition was age reaching 5 years. Conclusions: HDM-SLIT has a very high dropout rate, which is mainly due to refusal of continuation and dissatisfaction with the efficacy. Transitioning from SLIT to SCIT may help keep these patients on AIT and thus increase adherence and long-term efficacy.

Project description:BACKGROUND:The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines on immunotherapy products, a study was conducted to evaluate the safety, tolerability and short-term treatment effects of up-dosing regimens with high doses (up to 40,000 AUeq) of allergoid HDM immunotherapy. METHODS:In total 48 patients with HDM-allergic rhinitis or rhinoconjunctivitis (29 M/19 F; 18-53 years) were included and enrolled into one of three up-dosing regimens (1:4:4): 1) a regular regimen with up-dosing to 40,000 AUeq followed by two maintenance doses (total duration 17 weeks), 2) an intermediate regimen (14 weeks) or 3) a fast regimen (11 weeks). Safety and tolerability were evaluated by monitoring of early and late local reactions and systemic reactions. In addition, short-term effects were assessed by conjunctival provocation test (CPT) and levels of serum allergen-specific IgE, IgG and IgG4. RESULTS:Thirty-nine patients completed the study according to protocol. No early local reactions occurred. Late local reactions (LLR) were observed in 12% of the injections. In total, 31 systemic reactions, all grade 1, were reported of which two needed oral antihistamine treatment. No grade 2 or higher systemic reactions were observed. Six patients (15%) did not reach the highest dose due to LLR and/or systemic reactions needing antihistamines (20% in the regular regimen, 16% in the intermediate regimen and 13% in the fast regimen). At the end of the study, an improvement in the CPT was observed in 82.1% of patients, indirectly indicating an early treatment effect at the current dose and higher doses. In addition, IgG4 immunoglobulin levels were significantly increased in all groups following treatment. CONCLUSIONS:In this open-label study, allergoid HDM immunotherapy in doses up to 40,000 AUeq was generally well tolerated and no clinically relevant safety issues were identified. In the safety aspects of the three up-dosing regimens no clinically relevant differences were encountered. Therefore, these dose ranges and up-dosing regimens can be safely included in future dose-finding efficacy studies.

Project description:BackgroundAllergen immunotherapy (AIT) aims at modulating the immune response by administration of allergen preparations at regular intervals over several years (1). For subcutaneous AIT (SCIT), the treatment is initiated with a dose escalation phase followed by a maintenance dose administration. Over the last decade, there has been a trend towards shortening dose escalation regimens to increase patient adherence. This open-label, phase II trial aimed to investigate the safety and tolerability of a house dust mites (HDMs) SCIT product when used in a newly designed one-strength dose escalation scheme.MethodPatients, aged 12-65, suffering from HDM-allergic rhinitis/rhinoconjunctivitis ± asthma were included. Patients were randomized to the one-strength (6 injections from the highest strength 3) or the Standard dose escalation regimen (14 injections from strengths 1 to 3) using the HDMs-SCIT product. All adverse events were reported. Tolerability was assessed on the Likert scale.ResultsOne hundred and forty-three patients were randomized, 79 adults and 64 adolescents. In total, the one-strength regimen caused more adverse drug reactions (ADRs) than the Standard regimen (p = .0457). With both regimens most ADRs were local reactions which occurred more often in the one-strength group (p = .0393). But there was no significant difference in the number of patients affected by systemic or serious ADRs between both regimens. No relevant differences occurred between the two age groups and no other risks were observed for adolescents compared to adults.ConclusionThe safety and tolerability of both regimens can be considered comparable, as most ADRs were local reactions, primarily rated as mild in intensity. Nevertheless, the one-strength regimen caused more ADRs. Reducing the number of injections from 14 to 6 while using only one strength offers the potential to improve patient adherence which further might increase clinical efficacy. Future trials could confirm this hypothesis.

Project description:BackgroundSubcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.MethodsWe prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.ResultsSixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.ConclusionOur discover-validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.

Project description:BackgroundSubcutaneous immunotherapy (SCIT) has been proved to be effective and safe in adult asthma. But it is still controversial in children.ObjectTo evaluate the efficacy and safety of SCIT in asthmatic children with allergy to house dust mite.MethodWe searched the databases of Cochrane Library, EMBASE and MEDLINE (from 1 January 1990 to 1 December 2022). Two reviewers independently screened studies, extracted data and critically appraised the risk of bias. We used the Revman 5 to synthesize the effect sizes.ResultsWe finally selected 38 eligible studies including 21 randomized controlled trials to evaluate the efficacy and safety of SCIT and 17 observational studies to assess the safety. The results revealed that short-term asthma symptom scores were declined with a standardized mean difference (SMD) of -1.19 (95% CI: -1.87, -0.50) in 12 researches with high heterogeneity. Short-term asthma medication scores were decreased with SMD -1.04 (95% CI: -1.54, -0.54) in 12 heterogeneous researches. One study showed no significant reduction in combined symptom and medication scores without providing details. No studies we reviewed reported long-term efficacy. SCIT resulted in an obviously increased risk of adverse reactions compared with placebo. For secondary outcomes, SCIT improved life quality and reduced the numbers of annual asthma attacks and allergen-specific airway hyperreactivity, but without significant improvement in pulmonary function, asthma control or hospitalization.ConclusionsSCIT can reduce the short-term symptom scores and medication scores regardless of different treatment duration or mono/polysensitization, but with an increased incidence of local and systemic adverse effects. Further studies on pediatric asthma are needed to evaluate the long-term efficacy, and clarify the effectiveness of SCIT in specific population using mix allergen extracts or with severe asthma. Overall, it is recommended for children with mild-moderate HDM-driven allergic asthma.

Project description:BackgroundAllergen immunotherapy (AIT) is a specific treatment of administering clinically important allergens to patients who have allergic diseases. In Japan, the standardized house dust mite (HDM) allergen for subcutaneous immunotherapy (SCIT) was approved in 2015, and we then introduced rush-immunotherapy (rush-IT) using the standardized HDM allergen for HDM-sensitive asthmatics. However, little data are available on the safety and effectiveness of rush-HDM-IT, especially for Japanese asthmatics.ObjectiveThe objective of this study was to examine the safety and clinical effectiveness of rush-IT using the standardized HDM for HDM-sensitive Japanese asthmatics.MethodsThirteen HDM-sensitive asthmatics who received rush-HDM-IT and 12 HDM-sensitive asthmatic controls were enrolled. To evaluate the safety, the number of systemic reaction (SR) events, including anaphylaxis, was assessed. To evaluate the effectiveness, changes in the treatment step, dose of inhaled corticosteroid, and asthma control after rush-HDM-IT and the subsequent maintenance SCIT were assessed. Changes in the HDM-induced production of type 2 cytokines from peripheral blood mononuclear cells were also evaluated.ResultsAmong the 12 patients who received rush-IT, 4 (30.7%) experienced a SR and 3 (23.1%) experienced anaphylaxis. However, the anaphylaxis was not severe (grade 3) in all cases, and they recovered in a short time. The treatment step of asthma was better and the dose of inhaled corticosteroid was lower in the rush-HDM-IT group than in the control group. The HDM-induced production of both interleukin (IL)-5 and IL-13 from peripheral blood mononuclear cells was significantly lower in the rush-HDM-IT group than in the control group.ConclusionRush-HDM-IT can be performed relatively safely in Japanese asthmatics. Furthermore, rush-HDM-IT and the subsequent maintenance SCIT provided clinical improvement in asthma patients, and was accompanied by the suppression of HDM-specific Th2-mediated systemic immune responses.

Dataset Information

Effects of house dust mite subcutaneous immunotherapy in real-life. Immunological and clinical biomarkers and economic impact analysis.

Background

Methods

Results

Conclusions

Publications

Effects of house dust mite subcutaneous immunotherapy in real-life. Immunological and clinical biomarkers and economic impact analysis.

Similar Datasets

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