Effect Of Allergen Immunotherapy Research Articles

Allergen immunotherapy effectiveness in specific nasal reactivity of children with local allergic rhinitis.

Background.Allergen immunotherapy (AIT) is the only disease-modifying treatment in allergy. Its efficacy has been demonstrated in the treatment of Local Allergic Rhinitis (LAR) in adults. This study intends to evaluate the effectiveness of AIT in specific nasal reactivity of paediatric patients with LAR. Methods.Patients diagnosed with LAR to Dermatophagoides pteronyssinus (Dp) were submitted to subcutaneous AIT (SCIT) (depigmented-polymerized Dp allergen extracts) for 3 years. Nasal allergen challenge (NACs) with Dp extract were performed before and 3 years after AIT. NAC response was assessed with peak nasal inspiratory flow (PNIF) and symptom score of Lebel. NACs were considered positive when there was a flow decrease of ≥ 20% in PNIF and a score of symptoms ≥ 3 points. Demographic data and NAC results were analysed. Results.We included 32 paediatric patients (mean age 9.9±3.08 years, 18 female) and 10 adult patients, (mean age 30.4±12.2 years, 7 female). The symptom score obtained at the 1st minute, 5th minute, 15th minute and 30th minute in response to NAC, were reduced after AIT. The nasal inspiratory flow decrease induced by NAC was also reduced after AIT. This reduction in nasal reactivity was observed in paediatric and in adult patients, both with statistical significance. Conclusions.AIT induced a decrease in Dp-nasal specific reactivity in children with LAR. This decline of nasal response to allergen exposure, after AIT treatment, emphasis the interest of this therapeutic approach in LAR, even in paediatric patients.

Real-world evidence of allergen immunotherapy.

The full understanding of the long-term effectiveness and safety of allergen immunotherapy (AIT) for allergic respiratory diseases cannot be achieved through randomized controlled trials (RCTs) alone. However, real-world studies designed as registries can complement RCTs. The significance of registries is highlighted by their potential to reassess contraindications and collect data on adult and pediatric patients with multiple comorbidities who are often excluded from RCTs. AIT is the sole disease-modifying therapeutic approach capable of inducing tolerance and offering a long-term response to allergens. AIT has been shown to play a role in arresting the 'allergic march' in young people, which reduces the risk of developing asthmatic clinical manifestations. Although RCTs are considered the gold standard for evaluating the efficacy and safety of AIT, their duration is usually too short (seldom lasting more than 1 year) to assess the long-term effects of AIT. Several long-term studies show that AIT's effect depends strongly on its use duration.

The feasibility of allergen-specific immunotherapy for bronchial asthma in children with polysensitization

Relevance. There is a shortage of studies that would evaluate the effectiveness of allergen immunotherapy (AIT) in children with bronchial asthma (BA) and polysensitization.The aim of the study: to evaluate AIT effectiveness with house dust mite (HDM) allergens in the treatment of BA in children polysensitized to perennial allergens, based on the dynamics of the symptoms and medications score.Materials and methods. The open prospective controlled study included 36 children aged 9,6 [6,9; 12,3] years (from 6 years 1 months to 14 years 3 months) with moderate atopic asthma (21 children (58%) and mild asthma (15 children (42%) and polysensitization to household allergens. Each patient was observed in the study for 4 years: 1 year of preliminary observation and 3 years of sublingual AIT with D. pteronyssinus and D. farinae (Staloral, Stallergenes Greer, France). For each year of observation, asthma symptoms and medications used were assessed, and the combined Score was calculated. To confirm sensitization, a prick test was performed using a standard method with allergens: house dust, D. pteronyssinus, D. farinae, cat, dog, horse, pillow feather (Biomed, Russia).Results. Over 2 years of AIT, the decrease in the symptom and medication Score was 46,9%, and at the end of 3rd year of therapy, 59,8% (р = 0,0001 from baseline). A decrease in the combined Score exceeding 34.9% compared to baseline was noted in all patients in the study.Conclusion. Sublingual AIT with HDM allergens is highly effective in the treatment of asthma in children with domestic polysensitization, in terms of reducing symptoms of the disease, the need for pharmacotherapy and the combined Score of symptoms and medications. A significant positive effect was registered already from the first year of AIT and continues to increase over subsequent years of therapy.

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

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. 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. 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. 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.

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.

Advocacy of Precision Allergy Molecular Diagnosis in Decision Making for the Eligibility of Customized Allergen Immunotherapy.

Allergen immunotherapy (AIT) with aeroallergens is the only disease-modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT having been proven in both randomized controlled trials and real-world studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a precision allergy molecular diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects' basal atopic condition. No solely specific IgE-binding responses to Der p 1, Der p 2, and/or Der p 23 were found in the studied cohort. Despite the patients with A and atopic dermatitis showing significantly higher serum titers to six mite allergens than subjects with AR, no specific molecular profile was regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

Progressive clinical effects of the combination omalizumab and HDM – allergen immunotherapy in asthma

Objective The combination of allergen immunotherapy (AIT) and omalizumab is used to treat patients at risk of anaphylaxis. There is currently a very little evidence that this combination increases the effectiveness of AIT in patients with inhalant allergies. The study aimed to evaluate the effectiveness of HDM-SCIT therapy (injection immunotherapy for house dust mites) in combination with omalizumab in treating HDM-induced asthma. Methods This study was a placebo-controlled, randomized, multicenter trial including 82 patients with HDM-driven mild to moderate asthma. Omalizumab alone (A), HDM SCIT + omalizumab (B), SCIT alone (C), or placebo (D) for 24 months were applied. All patients received asthma treatment in accordance with GINA recommendations. The treatment efficacy was defined by a reduction in the daily dose of inhaled steroids (ICS) and a reduction in the number of asthma exacerbations (AX). Results After 24 months of therapy, a statistically significant reduction in the daily doses of ICS in groups A and B was observed (p = 0.021 and p = 0.008). Daily ICS reduction was considerably more significant in group B (p = 0.01). During 24 months of observation, the AX was significantly reduced in all study groups, with the greatest significant difference observed between groups A and B and groups C and D (placebo) as follows: 0.42 patient/per year vs. 0.39 vs. 0.84 vs. 0.91 (p = 0.023). Conclusion The combination of HDM SCIT and omalizumab is significantly and progressively reducing ICS use and AX in a 24-month study. The combination is significantly more effective than the single treatments or placebo.

Effects of allergen immunotherapy on follicular regulatory T cells.

Emerging evidence indicating that the dysfunction of T follicular regulatory (T FR ) cells contributes to excessive immunoglobulin E (IgE) production and the development of allergic diseases. Conversely, allergen immunotherapy (AIT) modulates T FR cells abundance and function to promote immune tolerance. This review focus on the role of T FR cells in allergic diseases and AIT, with the objective of providing novel insights into the mechanisms underlying immune tolerance of AIT and proposing the potential targeting of T FR cells in the context of allergic diseases. Numerous studies have consistently demonstrated that T FR cells play a pivotal role in the inhibition of class switch recombination to IgE in both humans and specific murine models. This suppression is attributed to the actions of neuritin and IL-10 secreted by T FR cells, which exert direct and indirect effects on B cells. In patients with allergic rhinitis, reduced frequencies of circulating or tonsillar T FR cells have been reported, along with impaired functionality in suppressing IgE production. AIT, whether administered subcutaneously or sublingually, reinstates the frequency and functionality of T FR cells in allergic rhinitis patients, accompanied by changes of the chromatin accessibility of T FR cells. The increase in T FR cell frequency following AIT is associated with the amelioration of clinical symptoms. T FR cells exert an inhibitory effect on IgE production and demonstrate a correlation with the clinical efficacy of AIT in patients with allergic rhinitis, suggesting T FR cells hold promise as a therapeutic target for allergic diseases and potential biomarker for AIT.

Аллерген-специфическая иммунотерапия в сочетании с иммунобиологической терапией у пациентов, страдающих среднетяжелой и тяжелой бронхиальной астмой

Background. Allergen immunotherapy (AIT) is a pathogenetic substantiated method for the allergic disease’s treatment, which allows reducing the symptom severity and decreasing the medication use. Uncontrolled severe asthma is a contraindication for AIT. The appointment of biological therapy helps to improve the asthma control, but their cancellation is impossible. The combined use of the biological therapy and AIT makes it possible to achieve the long-term symptoms control in patients with severe asthma, increase the AIT safety, and probably stop biological therapy. Aim. To evaluate the efficacy and safety of combination therapy with dupilumab and AIT in patients with severe asthma. Materials and methods. The study involved 30 adult patients with moderate to atopic severe asthma. Patients was randomized for 3 groups: group 1: standard therapy (0–52 weeks) + dupilumab (0–16 weeks) + AIT (12–16 weeks); group 2: standard therapy without biological therapy (0–52 weeks) + AIT (12–16 weeks); group 3: standard therapy without biological therapy, without AIT (0–52 weeks). We evaluated the asthma control and comorbidities using questionnaires (ACQ, AQLQ, TNSS, SNOT-22, DQLQ), respiratory function (FEV1), the number of exacerbations and adverse events At control points (initially, after 12, 20 and 52 weeks). Results. As a result of the appointment of dupilumab it was possible to quickly achieve asthma control and comorbidities (12 wk), which made it possible to successfully conduct AIT. In the first group, symptom control is maintained even after discontinuation of both dupilumab and AIT. ACQ-6 52 wk: 1 group – 0.30±0.21; 2 group – 1.62±0.51; 3 group – 2.76±0.85. FEV1 52 wk: group 1 – 81.47±7.48%; group 2 – 73.99±6.17%; group 3 – 65.02±7.23% for 3 group (р<0.01). In the first group, there weren’t adverse events that allowed complete AIT successfully, unlike for the second group, where, maximum tolerated allergen dose was lower due to development of systemic reactions. Conclusion. Combined treatment with dupilumab and AIT allows to quickly achieve a control, decrease a background therapy and adverse events during the AIT. The control of asthma symptoms and the effect of AIT were maintained even after the end of dupilumab therapy.

Vitamin D Role in Childhood Mite Allergy and Allergen Immunotherapy (AIT).

The post hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid immunotherapy (AIT). Previously, we have shown that in allergic children, after 12 months of this immunoactive treatment, functionally potentiated memory regulatory T cells are identified. Indeed, AIT is the only known treatment that is able to reshape the detrimental immune response against the allergen into a non-noxious one. Besides, VD is widely considered an immunoregulatory molecule that is endogenously produced and exogenously provided by foods and supplements that might interact with the AIT mechanism, thus affecting its outcome. Therefore, a post hoc analysis of the clinical and immunological data from three different cohorts of allergic patients was performed. One cohort (N = 70) was on a standard symptom-controlling pharmacological treatment, while the other two (N = 60 and N = 35) were treated with AIT for 12 months. In the first cohort, a lower mean endogenous VD level (<22 ng/mL) was observed along with worse symptoms and a greater use of medications. Remarkably, the comparison between two sub-cohorts of patients with a serum VD level above (N = 32) or below (N = 28) a cut-off value set at the mean value (27 ng/mL) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected from effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients that were also concomitantly taking VD3 as a food supplement (N = 19), was distinguished by an uppermost overall treatment outcome (the amelioration of symptoms, the lowest medication requirements, and a reduction in the total and allergen-specific IgE levels), as well as an increase in the allergen-specific tolerogenic memory T regulatory cells. These findings suggest that the endogenous VD level affects the allergy severity and allergen immunotherapy effectiveness. In addition, VD3 might be investigated as an add-on supplement to obtain the best out of immunotherapy in VD-deficient/-insufficient allergic patients. The immunogenic, but low-allergenic, mite allergoid used as the bioactive agent might have contributed to minimizing the allergic response and highlighting the immunological effects described here.

Potential Effects of AIT on Nonspecific Allergic Immune Responses or Symptoms.

Allergen immunotherapy (AIT) is a treatment in which clinically corresponding allergens are administered to patients with allergic diseases, either by subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT), or by oral immunotherapy (OIT) in the case of food allergy. Since etiological allergens are administered to patients, AIT is presumed to modify mainly allergen-specific immune responses. In bronchial asthma, AIT with house dust mites (HDM) alleviates clinical symptoms, suppresses airway hyperresponsiveness, and reduces medication doses of HDM-sensitive asthmatics. Moreover, AIT can suppress the symptoms of other allergic diseases associated with asthma including allergic rhinitis. However, AIT sometimes reduces allergic symptoms not induced by the responsible allergens, such as non-targeted allergens, in clinical settings. Furthermore, AIT can suppress the spread of sensitization to new allergens that are not targeted allergens by AIT, suggesting the suppression of allergic immune responses in an allergen-nonspecific manner. In this review, the nonspecific suppression of allergic immune responses by AIT is discussed. AIT has been reported to increase regulatory T cells that produce IL-10, transforming growth factor-β, and IL-35, IL-10-producing regulatory B cells, and IL-10-producing innate lymphoid cells. These cells can suppress type-2 mediated immune responses mainly through the production of anti-inflammatory cytokines or a cell-cell contact mechanism, which may be involved in the nonspecific suppression of allergic immune responses by AIT.

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy.

Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.

Allergic asthma: An indication for allergen immunotherapy.

. Allergen immunotherapy (AIT) as a validated, disease-modifying treatment is nowadays a widely recommended therapy option for allergic rhinitis and allergic asthma. The registration of allergen extracts used for AIT is based on allergen standardization, dose finding trials, and phase 3 trials proving their efficacy in high-quality, statistically significant randomized clinical trials. Real-world evidence (RWE) studies confirm the clinical relevance of these findings. The most data are available for the treatment of patients suffering from allergic rhinitis. Due to the similar inflammatory mechanisms, allergic rhinitis is often associated with allergic asthma. AIT, which induces tolerance against individual allergens, is the approach to treat the underlying mechanisms of these two interrelated respiratory diseases. Some trials have been published focusing primarily on the effect of AIT on parameters of allergic asthma. Here we give a summary of the evidence for the efficacy of AIT in the indication of allergic asthma.

Molecular profiling of allergen-antibody IgE might decide about the efficacy of allergen immunotherapy in a patient with atopic dermatitis and allergy to house dust mites.

Allergen immunotherapy (AIT) has no clear recommendation for atopic dermatitis (AD). To evaluate the effect of AIT on house dust mites (HDM) in AD patients sensitised to HDM with different baseline molecular profiles of antigens. In this placebo-controlled study, 61 patients with moderate-to-severe AD allergy symptoms and HDM allergy were included. They received a 12 months' AIT with the use of HDM allergen extract or placebo. The authors adopted their AD improvement criterion after 1 year of AIT as a reduction of all examined indicators by at least 50% from the baseline for %BSA, TMS, and EASI scores. Additionally, the influence of individual HDM molecules on the final AIT effect was analysed. Finally, from the 24 desensitised patients, 15 achieved a positive expected effect after 12 months of HDM AIT. None of the patients who received a placebo had an improvement in AD of at least 50% after 1 year of follow-up. Patients with polysensitisation less frequently achieved the expected HDM AIT effect than patients monosensitised to mites (p < 0.05). The presence of sensitisation to rDer p 1 (odds ratio = 4.35, 95% CI: 4.01-4.56) and/or rDer p 2 (OR = 2.16, 95% CI: 1.98-2.33) and/or rDer f 2 (OR = 1.41, 95% CI: 1.55-1.78) molecules significantly increased the efficacy of AIT. HDM AIT could be helpful for patients with moderate-to-severe AD and sensitised to HDM as an add-on therapy. Various HDM molecules may affect the effectiveness of the expected AIT effect. The presence of sensitisation to rDer p 1 (OR = 4.35, 95% CI: 4.01-4.56) and/or rDer p 2 (OR = 2.16, 95% CI: 1.98-2.33) and/or rDer f 2 (OR = 1.41, 95% CI: 1.55-1.78) molecules significantly increased the efficacy of AIT. HDM AIT could be helpful for patients with moderate-to-severe AD and sensitised to HDM as an add-on therapy. Various HDM molecules may affect the effectiveness of the expected AIT.

Long-term benefit after allergen immunotherapy to HDM in elderly patients with allergic rhinitis.

Allergen immunotherapy (AIT) is an effective therapy for allergic rhinitis and may have long-term benefits. However, these benefits have not been strictly defined for older people. The evaluation of the effectiveness of AIT in patients over 60 with allergic rhinitis and house dust mites (HDM) allergy over a period of 7 years was performed. Patients after three years of HDM-AIT were observed to assess the sustained clinical effect of treatment. The average adjusted symptom score (AAdSS) and sIgG4 were monitored for 7 years after sublingual (SLIT) and injection AIT (SCIT). After 3 years of HDM-AIT, a significant clinical effect was observed in the group after SLIT and SCIT based on AAdSS compared to the baseline and the placebo group (p < 0.05). After 7 years of follow-up, there was a sustained trend of decrease in clinical symptoms in desensitized patients relative to placebo. Serum sIgG4 was constantly present in all desensitized patients. AIT may be beneficial for treating seniors with allergic rhinitis and allergies to house dust mites.

Allergen immunotherapy enhances the immunosuppressive effects of Treg cells to alleviate allergic rhinitis by decreasing PU-1+ Treg cell numbers

ObjectiveTo investigate the role of Tregs and their subtypes in the treatment of allergic rhinitis with allergen immunotherapy (AIT) as well as the underlying mechanism. Methods1. Thirty-one healthy controls, 29 Allergic rhinitis (AR) patients and 16 AR patients treated with AIT were recruited. The total nasal symptom scores (TNSSs) were calculated. The serum levels of IgE, IL-2, TNF-α, IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-17 were measured. 2. Changes in the proportions of CD4+ T cells, Treg cells, Treg subtypes and Th1/Th2/Th9/Th17/Tfh cells in the peripheral blood of the subjects in the three groups were measured. 3. The correlations of Treg cells, Treg subtypes and TNSS with the levels of various cytokines in the AR group and AIT group were analysed. Results1. Compared with the control group, the TNSS and IgE, IL-5 and IL-6 levels in the AR group were significantly increased, while the IL-2, IFN-γ and IL-10 levels were significantly decreased (P < 0.05). Compared with the AR group, the TNSS and IgE, IL-5 and IL-6 levels in the AIT group were significantly decreased, while the IL-2, IFN-γ and IL-10 levels were significantly increased (P < 0.05). 2. Compared with the control group, the proportions of Tregs, GATA3+ Tregs and Th1 cells in the AR group were significantly reduced, while the proportions of PU-1+ Tregs, T-bet+ Tregs and Th2 cells were significantly increased (P < 0.05). Compared with the AR group, the proportions of Tregs and Th1 cells in the AIT group were significantly increased, while the proportions of PU-1+ Tregs and Th2 cells were decreased (P < 0.05). 3. Correlation analysis showed that Treg cell proportions were negatively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but positively correlated with the IL-2 and IL-10 levels (P < 0.05). PU-1+ Treg cell proportions were positively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but negatively correlated with the Treg cell proportions, IL-2 levels and IL-10 levels (P < 0.05). ConclusionsAIT can reduce the proportions of PU-1+ Treg subtypes in AR patients. PU-1+ Treg cell numbers can potentially be used as an indicator to monitor the therapeutic effect of AIT on AR.

Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference.

Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. We assessed the MASK-air® app data (May 2015-December 2020) by users self-reporting AR (16-90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR=0.75; 95% CI=0.71-0.80). Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines.

Allergen immunotherapy for asthma prevention: A systematic review and meta-analysis of randomized and non-randomized controlled studies.

Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated diseases. Randomized controlled trials (RCTs) support AIT's potential role in asthma prevention but evidence from non-randomized studies of interventions (NRSI) and longitudinal observational studies has been poorly addressed. Therefore, we aimed to conduct a systematic review and meta-analysis to assess clinical data from all study types to evaluate quantitatively the preventive role of AIT in asthma onset. We search three databases. Studies were screened, selected and evaluated for quality using risk-of-bias (ROB) tools. Data were descriptively summarized and meta-analysed using random effects. We performed a sensitivity, influence and subgroup analyses. Publication bias and heterogeneity were assessed. From the 4549 identified studies, 24 (12 RCTs and 12NRSI) were included in the qualitative synthesis and 18 underwent meta-analysis. One study was at low ROB, seven had moderate ROB, and 15 were proven of high ROB. Random-effects analysis showed a significant decrease in the risk of developing asthma following AIT by 25% (RR, 95% CI: 0.75, 0.64-0.88). This effect was not significant in the sensitivity analysis. Publication bias raised concerns, together with the moderate heterogeneity between studies (I2 =58%). Subgroup analysis showed a remarkable preventive effect of AIT in children (RR, 95% CI: 0.71, 0.53-0.96), when completing 3years of therapy (RR, 95% CI: 0.64, 0.47-0.88), and in mono-sensitized patients (RR, 95% CI: 0.49, 0.39-0.61). Our findings support a possible preventive effect of AIT in asthma onset and suggest an enhanced effect when administered in children, mono-sensitized, and for at least 3years, independently of allergen type.

Allergen immunotherapy in MASK‐air users in real‐life: Results of a Bayesian mixed‐effects model

BackgroundEvidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies.ObjectiveTo compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT.MethodsWe assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season.ResultsWe analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2).ConclusionIn patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.

Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study.

SummaryBackgroundAllergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs).MethodsREACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888).Findings46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT.InterpretationThe study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia.FundingThe study was funded by ALK A/S.