Background Allergic rhinitis (AR) with/without allergic asthma (AA) can be treated with sublingual allergen immunotherapy (SLIT). The PRACTIS study evaluated the short-term benefits of SLIT in AR patients in current practice in France. Here are specifically described the observed modalities of use and treatment plan. Methods This prospective, non-interventional, longitudinal, multicentre study was conducted in patients ≥5-years-old, with clinically significant confirmed AR to one or more allergens and eligible for SLIT. Patients’ data were recorded at inclusion and after 6 (seasonal allergy) or 12 (perennial allergy) months of SLIT. Results SLIT was prescribed in 1587 patients (mean age 25.8 ± 15.6 years, 52.7% female) and 1047 (66.0%) attended the end-of-study visit to assess the benefits and satisfaction with SLIT. Most (87.4%) patients had moderate-to-severe persistent AR, 31.8% had AA and 50.8% were poly-allergic. The main reasons for prescribing SLIT were discomfort severity (85.4%) and type of allergic symptoms (80.2%). Patients were involved in the treatment choice in 68.7% of cases. A single SLIT was prescribed to 88.0% of patients, mainly in liquid form (71.8%), most frequently house dust mite or grass pollen allergen extracts. Physician-patient agreement on satisfaction with SLIT was >80% for mono-allergic and poly-allergic patients at end-of-study. Overall, 85.7% of patients planned to continue treatment and 78.8% would recommend SLIT to someone else. Discussion-Conclusion SLIT availability in tablet or liquid form, comprising a large number of allergen extracts and dose flexibility, enables treatment personalisation. The shared decision with the patients in the prescription type may improve SLIT adherence and satisfaction.

BACKGROUND:House dust mite (HDM) allergic rhinitis (HDM-AR) fluctuates over time with exposure conditions, making disease activity assessment essential when demonstrating treatment efficacy. We conducted post hoc tertile analyses to more accurately assess the efficacy of 300 IR HDM sublingual immunotherapy (SLIT) tablet in moderate-to-severe HDM-AR pediatric patients during periods of increased disease activity. METHODS:Data from two Japanese randomized controlled trials of 300 IR HDM SLIT-tablet were used to assess the average adjusted symptom score (AASS) and average combined symptom and medication score (ACSMS). To determine the impact of HDM-AR activity, placebo group scores during the primary period (end of treatment) at each center were ranked from lowest to highest to establish three tertiles. Scores differences between SLIT and placebo were analyzed in each tertile using ANCOVA. RESULTS:The first analysis included patients aged 5-16 years (300 IR = 193, placebo = 210). During the primary period, the effect of the SLIT-tablet, estimated at -13.1% (AASS) and -12.9% (ACSMS) versus placebo overall, was more pronounced in the highest tertile (relative differences -27.3% and -28.5%, respectively), with similar results across age groups. The second analysis including a pool of adolescents (300 IR = 120, placebo = 135) showed an overall effect of -19.9% (AASS) and -21.2% (ACSMS) with 300 IR versus placebo, with again greater improvements in the highest tertile (-32.5% and -34.1%, respectively). CONCLUSION:The greatest improvements occurred in the tertile where pediatric patients exhibited higher disease activity. This underscores the true efficacy of 300 IR HDM SLIT-tablet during periods when patients experience the most troublesome symptoms.

BACKGROUND:Patients with allergic rhinitis (AR) and/or mild or moderate asthma derived from birch-family pollen allergy can be treated with liquid sublingual immunotherapy (SLIT-liquid). This study evaluated the impact of two SLIT extracts on AR and asthma progression or onset in these patients. METHODS:This was a sub-analysis of a retrospective, longitudinal comparative cohort study that used a German prescription database. Patients treated with 3-tree (birch/alder/hazel) or birch-only SLIT-liquid and followed up for up to 6 years after treatment were compared with controls dispensed symptomatic medications. Multiple regression analysis compared dispensation data as a proxy for disease status and progression. RESULTS:A total of 493 patients treated with 3-tree SLIT-liquid and 311 treated with birch SLIT-liquid were analysed vs. 44,835 patients included as controls. Overall, 70.5 % of patients presented solely AR, 24.2 % solely asthma, and 5.3 % both diseases. Compared with controls, patients treated with 3-tree SLIT-liquid had reduced risk of AR [odds ratio (OR) = 3.21, 95 % CI 2.54-4.06, p < 0.001], asthma progression (OR = 2.03, 95 % CI 1.43-2.89, p < 0.0001), or asthma onset (OR = 0.592, 95 % CI, 0.408-0.860, p = 0.006). Birch-only SLIT-liquid showed similar effectiveness in reducing AR and asthma medication dispensation but no significant effect in reducing new-onset asthma. CONCLUSIONS:This real-world study demonstrated the effectiveness of treatment with 3-tree SLIT-liquid or birch SLIT-liquid in slowing the progression of birch-family pollen allergy. 3-tree SLIT-liquid covering a broader repertoire of epitopes mimicking natural exposure throughout the year may be valuable for patients sensitised to birch and/or alder and/or hazel pollen suffering from overlapping tree-pollen seasons.

[This corrects the article DOI: 10.3389/falgy.2025.1597003.].

Respiratory allergy (RA), one of the most prevalent global chronic diseases, is often suboptimally managed by both patients and healthcare professionals (HCPs). This qualitative survey investigated the RA healthcare journey from the patient perspective to better understand the challenges faced at key stages and the unmet needs for potential improvements in physician-patient relationship, shared decision-making and patient quality of life outcomes. The survey employed an ethnographic approach consisting of getting rid of any preconceived ideas and adopting an attitude of listening and empathy devoid of any prejudices. It involved 105 participants distributed across 3 countries (France, Germany, and Italy) who took part in a 2-h interview. All were diagnosed with intermittent or persistent RA and were at different stages of the journey/treatment (without treatment, antihistamine, undergoing Allergen Immunotherapy [AIT], completed AIT, reluctant to AIT, or discontinued AIT). Regional differences and variations related to medical subspecialties are considered, offering a comprehensive and nuanced perspective on RA management at an international level. The examination of a complex and lengthy journey revealed 4 key stages and explored the corresponding emotional experiences. Physician-patient communication, clinical and emotional support and timing are found to be crucial factors in treatment choice, adherence and the psychological impact of the journey. Additionally, the data collected identified 4 distinct profiles related to AIT, based on their approach to managing RA and their level of access to treatment information: the "skeptic", the "skittish", the "determined", and the "convinced". This patient stratification can help physicians tailor their strategies and adopt more personalized approaches.

BACKGROUND AND OBJECTIVE:The retrospective study EfficAPSI explored the real-world impact of liquid sublingual allergen immunotherapy (AIT; Staloral® SLIT-liquid) on health care resource utilization (HCRU) in allergic rhinitis (AR) patients with/without asthma. METHODS:In the EfficAPSI cohort, patients dispensed SLIT-liquid and AIT-naïve controls taking symptomatic drug treatment (SDT) were compared using propensity score weighting. A total of 5 periods were analyzed, namely, the historical pre-SLIT period (HP, 2 years before the index dose of SLIT/SDT [first dispensation]) and four 2-year follow-up periods (FUPs) after the index dose, with the latter 2 periods corresponding to post-treatment years. HCRU was analyzed using a Poisson model with generalized estimating equations. RESULTS:The study population comprised 112 492 SLIT and 333 082 control patients. Dispensations of antihistamines and intranasal corticosteroids decreased by 28% to 49% during the FUPs (IRR from 0.51 [0.50-0.52] to 0.69 [0.67-0.71]) and after treatment (IRR from 0.62 [0.59-0.65] to 0.72 [0.69-0.74]), favoring SLIT-exposed patients. In patients with asthma, a 17%-29% reduction in asthma medication dispensations also favored SLIT-liquid (IRR, 0.83 [0.78-0.88] to 0.71 [0.68-0.74] during treatment; 0.82 [0.77-0.88] to 0.78 [0.72-0.85] after treatment). For oral corticosteroids, the between-group difference in change from the HP was in favor of SLIT-liquid for all FUPs (IRR for doses, 0.66 [0.64-0.69] to 0.79 [0.73-0.85]). The decrease in medical consultations and hospitalizations was consistently more frequent over time in SLIT patients than in controls. CONCLUSIONS:In this national real-world study involving the largest number of person-years followed in the field of AIT to date, SLIT-liquid was associated with a reduction in AR and dispensation of asthma medication, including systemic corticosteroids, and medical consultations. The results recorded in the last 2 post-treatment FUPs suggest a sustained effect of SLIT-liquid.

Introduction Although cat allergy is highly prevalent in the French population, it is often underdiagnosed and undertreated. Allergen immunotherapy (AIT) can be an effective etiological treatment for cat allergy, but there is limited data on its effectiveness. To investigate patients' perceptions of AIT effectiveness, a survey was conducted in France in a cohort of patients with cat-associated allergic rhinitis with/without mild-to-moderate allergic asthma and treated with cat allergen liquid sublingual immunotherapy (SLIT). Methods Patients (5-65 years old) registered in the Stallergenes Greer SLIT dispensation database and treated with 300 IR cat allergen SLIT-liquid for more than 12 months were invited to participate in the survey. Data were collected on the patient’s socioeconomic characteristics, past or current cat exposure, allergy history and treatment, and perception of SLIT treatment’s impact on the patient’s health status. Data were analyzed descriptively. Results Of 617 patients invited to participate in the survey, 197 responded (31.9%). Most respondents were adults (78.6%) living in urban areas (64.0%). The majority (89.8%) have been suffering from cat allergy for ≥3 years, 86.8% declared being poly-allergic (mainly to house dust mites and pollen), and 63.2% were receiving multiple treatments. Most respondents (80.8%) had lived with or were currently living with cats (72.0% for more than 5 years). Before SLIT initiation, 92% of patients were using symptomatic medications. The prescription of SLIT was primarily driven by the presence of allergic asthma (61.9%), followed by allergic rhinitis (54.8%). Most patients (86.8%) reported an improvement within the first year of SLIT, particularly regarding rhinitis symptoms (63.2%), the ability to pet a cat without experiencing symptoms (51.5%), and a reduction in asthma exacerbations (48.0%). A significant percentage of patients (59.9%) reported an improvement in their health status following the initiation of SLIT. Conclusion The findings from this survey support the clinical benefit of cat SLIT as a valuable therapeutic option for patients with persistent cat allergy symptoms, demonstrating rapid symptom relief and a meaningful improvement in quality of life.

[This corrects the article DOI: 10.1016/j.lanepe.2024.100915.].

Background: In the realm of allergen immunotherapy (AIT), the quality of evidence varies across different products, making it unjustifiable to extend overall conclusions to all AIT products, as highlighted by WAO and EAACI. Objective: To confirm the efficacy of the 300 IR 5-grass pollen sublingual AIT (SLIT)-tablet through a specific meta-analysis of randomized controlled trials (RCTs) involving patients with allergic rhino-conjunctivitis (ARC) with/without mild/intermittent asthma. Methods: Data from published RCTs on the 300 IR 5-grass SLIT-tablet were gathered from electronic databases (MEDLINE, ISI Web of Science, LILACS, the Cochrane Library and ClinicalTrial. gov) and manual searches up to November 2023. Populations, treatments, and outcome data were combined. Efficacy was assessed based on symptom score (SS) and medication score (MS), measured as standardized mean difference (SMD) or mean difference (MD). Results: Results from 5 RCTs comprising 1468 patients revealed a significant reduction in SS (SMD,-0.36; 95%confidence interval [CI],-0.52 to-0.19; P < 0.05) and MS (SMD,-0.29; 95% CI,-0.40 to-0.19; P < 0.05) compared to placebo. The difference of-0.36 SMD for SS corresponds to a MD of-1.26 SS points, greater than the minimal important difference. Subgroup analysis did not show differences in efficacy according to age, asthma status, and geographic location of the study (USA, Canada, Europe, Russia). No safety issues were reported. Conclusion: This product-specific meta-analysis reinforces the evidence of clinical benefits associated with the 300 IR 5-grass SLIT-tablet, suggesting its appropriateness as a therapeutic choice for patients with ARC, irrespective of concurrent asthma, and exhibiting a favorable safety profile.

•What is already known about this topic

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 fi rst dispensation of either treatment. The sensitive de fi nition of asthma event considered the fi rst asthma drug dispensation, hospitalisation or long-term disease (LTD) for asthma, the speci fi c 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 signi fi cant lower risk of asthma onset vs. control, according to all de fi nitions (combined: HR [95% CI] = 0.62 [0.60 - 0.63], sensitive: 0.77 [0.76 - 0.78], and speci fi c: 0.67 [0.61 - 0.72]). Exposure to SLIT was associated with a onethird 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 fi eld of AIT, SLIT -liquid was associated with a signi fi cant reduction in the risk of asthma onset or worsening. The use of three de fi nitions (sensitive or speci fi c) and GINA step-up reinforced the rigorous methodology, substantiating SLITliquid evidence as a causal treatment option for patients with respiratory allergies. Copyright (c) 2024 Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

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.

BACKGROUND:The only causal treatment for allergic rhinitis (AR) is allergen immunotherapy (AIT) including personalized liquid sublingual AIT (SLIT). We present the methodology for establishing the EfficAPSI cohort to further evaluate the real-life effectiveness and use of SLIT liquid. RESEARCH DESIGN AND METHODS:The EfficAPSI cohort was constituted by deterministic linkage of Stallergenes Greer dispensing and nationwide French healthcare insurance system (SNDS) databases. Data from 2006 to 2018 were extracted. All patients who initiated Stallergenes Greer SLIT liquid between 2010 and 2013 were considered as exposed and those dispensed with AR symptomatic treatment only as control. To limit the impact of confounding, the models will be weighted using the inverse probability of treatment weighting (IPTW). RESULTS:A total of 445,574 patients were included; median age was 38 years; 59.1% were female. Exposed patients (n = 112,492) were significantly younger, more frequently males, and less likely to have comorbidities than controls (n = 333,082). After IPTW, patients' characteristics from both groups were similar. CONCLUSIONS:To date, the EfficAPSI cohort has the largest number of person-years of follow-up in the field of AIT. The completeness of the data allows to evaluate SLIT liquid effectiveness with rigorous methodology, leading to important insights on personalized medicine in real-life.

Sublingual allergen immunotherapy (SLIT) is a safe, effective, disease-modifying treatment for moderate-to-severe respiratory allergies. The function and responsiveness of the immune system components underlying the effects of allergen immunotherapy may vary from one patient to another. Furthermore, the severity of the symptoms of allergic disease can fluctuate over time, due to changes in environmental allergen exposure, effector cell responsiveness, and cell signaling. Hence, the allergen dose provided through SLIT can be fine-tuned to establish an optimal balance between effectiveness and tolerability. The objective of the MaDo study was to describe and understand dose adjustments of SLIT liquid formulations in France. We performed a retrospective, observational, cross-sectional, real-life study of allergists and other specialist physicians. Physicians described their patients via an anonymous case report form (CRF). The main patient inclusion criteria were age 5 years or over, at least one physician-confirmed IgE-driven respiratory allergy, and treatment for at least 2 years with one or more SLIT liquid preparations. A nationally representative sample of 33 specialist physicians participated in the study. The physicians' main stated reasons for dose adjustment were adverse events (according to 90.9% of the physicians), treatment effectiveness (60.6%), sensitivity to the allergen (42.4%) and other characteristics (30.3%: mainly symptom severity, type of allergen, and asthma). 392 CRFs (mean ± standard deviation patient age: 27.8 ± 17.5; under-18s: 42.1%; polyallergy: 30.9%) were analyzed. Respectively 53.6%, 25.8%, 15.3%, and 8.7% of the patients received house dust mite, grass pollen, birch pollen and cypress pollen SLIT. Dose adjustments were noted in 258 (65.8%) patients (at the start of the maintenance phase for 101 patients (39.2%) and later for 247 (95.7%)). Dose adjustment was not linked to sex, age, or the number of allergens administered. All measures of disease severity (including symptom severity noted on a 0-to-10 visual analogue scale by the physician) decreased significantly during SLIT. Notably, the mean AR symptom severity score decreased to a clinically relevant extent from 7.6 at SLIT initiation to 2.4 at last follow-up, and the mean asthma symptom severity score decreased from 5.0 to 1.3. The few differences in effectiveness between patients with vs. without dose adjustment were not major. For about one patient in five, a specialist physician decided to reduce or increase the SLIT liquid dose at the start of maintenance treatment and/or during maintenance treatment. This decision was influenced by a broad range of patient and treatment factors, mainly to improve tolerability to treatment and/or enhance effectiveness. In France, dose adjustment of SLIT liquid preparations as a function of the patient profile and/or treatment response is anchored in clinical practice. Precision dosing might optimize the overall benefit-risk profile of AIT for individual patients throughout their entire treatment course, enabling them to achieve both short- and long-term treatment goals, whilst maximizing the safety and tolerability.

The concept of personalized medicine as a diagnostic and therapeutic approach tailored to the medical needs of each patient is currently revolutionizing all fields of medicine and in particular allergology. Allergen immunotherapy (AIT) meets the three main needs for precision medicine: identification of molecular mechanism of disease, diagnostic tools for the mechanism and treatment blocking the mechanism itself. AIT adapts to the spectrum of specific IgE of each individual subject, changing the course and natural history of the disease, so is a clear model of precision and personalized medicine. This first step before the prescription of AIT is to define the sensitization profile of the patient; after that, the healthcare professional has numerous levers for adapting the treatment to the physio-pathological mechanisms involved. AIT allows to adapt treatments to the profile of the patients, but also to the its preferences, to ensure optimal treatment efficacy, resulting in an agile and personalized approach, with the aim to ensure adherence to the treatment, which is usually quite low. AIT also broadens the field of possibilities for healthcare professionals and patients, by allowing to choose the galenic formulation according to patient preferences and on the basis of their clinical history, adapting the product composition to the patient’s sensitization profiles and the underlying biological mechanisms identified at the diagnostic stage, while guaranteeing quality of the prescribed product as the production of allergens and allergoids is today more regulated than in the past years. In the management of AIT, it is also possible to involve patients in decisions throughout their care pathway thanks to multiple services, offering personalized follow-up and support, to ensure the highest treatment efficacy levels, and recalling medication intake, medical appointments and prescription renewals.

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3-5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with mite-induced respiratory allergy.

Introduction: Polysensitization, that is, sensitization to more than one allergen family, is a common feature of patients with allergic rhinitis (AR) and significantly impairs their quality of life (QoL). Allergen-specific immunotherapy is the only causal treatment for AR. However, the polysensitization phenomenon may represent a crucial obstacle as far as it concerns the choice of the allergen extract to be used for immunotherapy. Areas covered: A series of real-life based multi-center studies, named POLISMAIL (Polysensitization Impact on Allergen Immunotherapy), have been designed with the aim of evaluating the behavior of allergists in managing polysensitized AR patients. The effect of immunotherapy treatment in these patients was also evaluated. A single allergen extract was used in two-thirds of patients, whereas a mix of two allergens was chosen in the remaining. The severity grade of AR and the QoL were significantly improved by immunotherapy. Both outcomes confirmed that immunotherapy with one or two allergen extracts achieves a significant improvement in polysensitized patients. Expert opinion: In conclusion, POLISMAIL studies demonstrate that polysensitization should not represent a counter-indication for prescribing immunotherapy. The choice of limiting sublingual immunotherapy to one to two allergen extracts, preferably separated and at high dosages, is sufficient and effective in improving symptoms and QoL.