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Background: Diet restrictions and fear of adverse reactions put a significant burden on the nutrition, growth and life style of children and adults with food allergies. While various disease-modifying options are pursued, there are so far no published clinical data on immunotherapy for crustaceans. The efficacy and safety of desensitization to crustaceans by means of sublingual immunotherapy is assessed for the first time in this study with a view of validating it as a clinical-practice modality. Methods: Charts of a Midwest Allergy-Immunology practice from the period January 2014–June 2023 were reviewed to identify patients with allergy to shrimp treated with sublingual immunotherapy and to retrospectively evaluate their responses to oral challenge. Results: Sixty-six patients were identified who had been treated by sublingual immunotherapy for either systemic or localized reactions to shrimp. Demographics and relevant comorbidities were consistent with those of the atopic population. Sublingual immunotherapy with serially diluted mixtures was initiated at 64–320 ng/dose and was gradually escalated to 0.5 mg/dose three times a day. The sublingual immunotherapy course ranged from 5 to 72 months (average: 51 months), following which, 18 patients underwent shrimp oral challenge. No systemic reactions occurred upon challenge; no patient required epinephrine. Tolerance of target dose equal to or exceeding 42 g shrimp was achieved in 11 patients (61%), seven of whom had originally presented with systemic reactions to crustaceans. Seven patients (38%) developed one or more of the following localized reactions: oral itching, nasal symptoms, localized perioral hives, localized hives at pressure points, nausea, vomiting, abdominal pain upon exposure to a cumulative dose of 39.2–148.2 g of shrimp during the 4 h of the challenge. Five of these patients had originally presented with systemic reactions to crustaceans. Five of the 7 patients who developed localized symptoms during the challenge were subsequently placed on routine exposure to 12–20 g shrimp every other day. Two patients continued sublingual immunotherapy but declined routine exposure to shrimp every other day because they had no intention to incorporate crustaceans to their routine diet. On repeat challenge 6–9 months after original challenge, all five patients who had routine exposure to 12–20 g shrimp every other day tolerated the procedure to target dose without any symptoms. Conclusions: Desensitization to shrimp by sublingual immunotherapy appears to be safe and effective as shown in this study. Whether the immune modification induced by sublingual immunotherapy is permanent resulting in sustained tolerance, or the achieved degree of desensitization depends on regular exposure is not known; therefore, following challenge, regular consumption three-four times per week was recommended. [ABSTRACT FROM AUTHOR]

Background: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC. Methods: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes. Results: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios. Conclusions: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is frequent in children and adolescents and can severely affect their lives. This article describes the development and validation of a questionnaire to assess treatment needs and benefits in children and adolescents, the PBI-AR-K, in a sample of patients receiving grass pollen sublingual immunotherapy. Patients and methods: The PBI-AR-K was developed based on an open survey including children and adolescents and expert consensus between methodologists, patients, and physicians. The PBI-AR-K assesses patient needs before the treatment and perceived benefit during or at the end of a treatment. A weighted benefit score can be calculated ranging from 0 to 4 (4 = highest possible benefit). The validation was conducted in children (5–12 years) and adolescents (13–17 years) receiving sublingual immunotherapy. Subscales were developed based on factor analysis. Psychometric properties of items and scales were assessed with descriptive statistics, internal consistency, and convergent validity. Results: The final PBI-AR-K consists of 19 items. For validation, data from 345 patients (mean age 11.1; 60.9% male; n = 223 children; n = 122 adolescents) was analysed. Factor analyses resulted in four subscales for children and three subscales for adolescents. The items with the highest importance ratings were about choice of leisure activities (mean value in children: 3.5) and about being free of AR symptoms (adolescents: 3.3). The weighted PBI-AR-K scores reflected considerable patient-reported benefit (2.08–2.82) in both children and adolescents. Internal consistency of all scales was good or acceptable. In the children's sample, the global scale and three of four subscales were quite consistently correlated with convergent variables, while the subscale 'treatment burden' was significantly correlated only with change in average impairments due to rhinitis symptoms. The adolescents' sample showed more inconsistent results with only change in rhinitis severity being significantly associate with all subscales. Conclusion: The newly developed PBI-AR-K is a reliable and valid questionnaire for use in children; for the use in adolescents, it should be further elaborated. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear. Methods: This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire. Results: Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141). Conclusions: AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs. [ABSTRACT FROM AUTHOR]

Background: Post hoc analyses of randomized placebo-controlled trials have demonstrated efficacy and tolerability of the ragweed sublingual immunotherapy (SLIT)-tablet in Canadian adults with ragweed pollen-induced allergic rhinitis/conjunctivitis (AR/C). This post hoc analysis evaluated the efficacy and tolerability of the ragweed SLIT-tablet in the subpopulation of Canadian children and adolescents with AR/C in a previously described randomized, double-blind, placebo-controlled trial. Methods: The trial (NCT02478398) was conducted in North American and European children/adolescents ages 5–17 years with ragweed pollen-induced AR/C with or without asthma (FEV1 ≥ 80% predicted). Participants were randomized to daily ragweed SLIT-tablet (12 Amb a 1-U) or placebo for up to 28 weeks. The primary endpoint was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary endpoints were TCS during the entire RPS, and DSS and DMS during peak RPS. Post hoc analyses of the primary and key secondary endpoints were conducted in the subpopulation of Canadian participants. Results: Of the 1025 randomized participants, 246 (SLIT-tablet, n = 116; placebo, n = 130) were in the Canadian subpopulation. In the total study population, relative TCS (95% CI) improvement with ragweed SLIT-tablet versus placebo was − 38.3% (− 46.0%, − 29.7%; least square [LS] mean difference, − 2.73; P < 0.001) during peak RPS. In the Canadian subpopulation, relative TCS improvements with ragweed SLIT-tablet versus placebo were − 40.8% (− 54.5%, − 20.2%; LS mean difference, − 1.59; P = 0.001) during peak RPS and − 36.6% (− 50.2%, − 16.5%; LS mean difference, − 1.36; P = 0.002) during the entire RPS. DSS and DMS during peak RPS in the Canadian subpopulation improved with SLIT-tablet versus placebo by − 30.6% (− 45.2%, − 7.7%; LS mean difference, − 0.94; P = 0.010) and − 77.2% (− 97.5%, − 44.2%; LS mean difference, − 0.66; P = 0.003), respectively. No events of anaphylaxis, airway compromise, intramuscular epinephrine administration, eosinophilic esophagitis, or severe treatment-related systemic allergic reactions were reported in the overall population or Canadian subpopulation. Conclusion: Efficacy and safety of the ragweed SLIT-tablet in Canadian children/adolescents with ragweed pollen-induced AR/C was consistent with the total study population. The ragweed SLIT-tablet resulted in clinically meaningful improvement in symptoms, decreased symptom-relieving medication use, and was well tolerated in Canadian children/adolescents. Trial registration: clinicaltrials.gov, NCT02478398. Registered June 23, 2015, https://clinicaltrials.gov/ct2/show/NCT02478398?term=NCT02478398&draw=2&rank=1 [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy tablets (SLIT-T) are an effective treatment for allergic rhinitis (AR), but some patients experience local allergic reactions (LAR) in the first few weeks of treatment that can lead to treatment discontinuation. Although oral antihistamines are recommended for the treatment and pretreatment of LAR associated with SLIT-T, there are no clinical trial data to support this recommendation. Rupatadine is an H1 antihistamine that also inhibits platelet activating factor activity. The objective of this case series is to describe real-world clinical situations in which rupatadine was used to treat or mitigate SLIT-T–related LAR. Case presentations: Five cases are presented by the managing allergist and off-label use of rupatadine is their expert opinion only. Patients in all 5 cases were treated with a SLIT-T (e.g. ragweed, tree, grass, or house dust mites) for the management of allergic rhinitis and experienced bothersome LAR with the first SLIT-T administration. In 3 cases, rupatadine 10 mg was administered for the immediate treatment of LAR (either in-office with the first SLIT-T dose or for subsequent LAR experienced at home) and the symptoms resolved. In 3 cases, pretreatment with other second-generation H1 antihistamines was unable to prevent LAR and the patients discontinued the SLIT-T. In these 3 cases, switching to pretreatment with rupatadine allowed the patients to restart and tolerate SLIT-T treatment with minimal or no LAR. In these patients with an established history of LAR, proactive pretreatment with rupatadine in subsequent seasons or with initiation of a different SLIT-T mitigated the previously experienced LARs. Conclusions: In the cases presented, treatment with rupatadine resolved LAR associated with SLIT-T treatment and rupatadine pretreatment appeared to mitigate subsequent LAR. Rupatadine may be an option to treat or improve the tolerability of the SLIT-T, potentially improving early treatment persistence. [ABSTRACT FROM AUTHOR]

Background: A cost-minimization analysis (CMA) was performed to evaluate the economic implications of introducing the SQ Tree sublingual immunotherapy (SLIT)-tablets marketed as ITULATEK® (Health Canada regulatory approval in April 2020) for the treatment of pollen-induced (birch, alder and/or hazel) seasonal allergic rhinitis in Canada (Ontario and Quebec), where Tree Pollen subcutaneous immunotherapy (SCIT) is already an available treatment option. Methods: A CMA was deemed appropriate and was based on the assumption that the SQ Tree SLIT-tablets have comparable efficacy to Tree Pollen SCIT. A societal perspective was adopted in the model, including relevant costs of medications, costs of health care services, and productivity losses. The time horizon in the model was three years, which corresponds to a minimal treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where available, and validated by Canadian specialist clinicians (allergists) in active practice in Ontario and in Quebec, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, scenario analyses were performed by testing alternative assumptions for selected parameters (e.g., Tree Pollen SCIT resource use, discount rates, number of injections, annual SCIT dosing with maintenance injections, and nurse time support), to evaluate their impact on the results of the analysis. Results: The direct costs, including the drug costs, and physician services costs, for three years of treatment, were similar for both SQ Tree SLIT-tablets vs. Tree Pollen SCIT in both Ontario and Quebec ($2799.01 and $2838.70 vs. $2233.76 and $2266.05 respectively). However, when the indirect costs (including patient's travel expenses and lost working hours) are included in the model, total savings for the treatment with SQ Tree SLIT-tablets of $1111.79 for Ontario and $1199.87 for Quebec were observed. Scenario analyses were conducted and showed that changes in assumptions continue to result in the savings of SQ Tree SLIT- tablets over Tree Pollen SCIT. Conclusions: The CMA indicates that SQ Tree SLIT-tablets are a cost-minimizing alternative to Tree Pollen SCIT when considered from a societal perspective in Ontario and Quebec. [ABSTRACT FROM AUTHOR]

Background: The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. Methods: Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. Results: The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver. Conclusions: SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations. [ABSTRACT FROM AUTHOR]

Background: Air pollution may be associated with increased airway responsiveness to allergens in allergic rhinitis (AR). Ozone-aged environmental black carbon (O3BC) is an important constituent of atmospheric particulate matter (PM), for which the mechanisms underlying its effects have not been fully elucidated in AR. The objective of the present study was to determine the O3BC and pollen-induced alterations in the transcriptome in human nasal epithelial cells (hNECs) in vitro. Methods: hNECs from nasal epithelial mucosal samples of healthy individuals undergoing nasal surgery (turbinoplasty or septoplasty) were established as air–liquid interface (ALI) cultures and exposed to O3BC, pollen, or a combination of O3BC+ pollen. Changes in cell viability were analyzed by fluorescence and changes in the transcriptome by high-throughput RNA sequencing (RNA-seq). Several differentially expressed genes were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Enrichment analysis, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, was performed to determine major biological functions and pathways involved. Results: Exposure to ≥ 50 μg/ml O3BC or 25 μg/ml O3BC+ 200 μg /ml pollen significantly decreased cell viability of the hNECs compared to control (p < 0.05) or 25 μg/ml O3BC alone (p < 0.05); whereas exposure to pollen alone did not alter cell viability at any concentration investigated. High-throughput RNA sequencing analysis indicated that there was significant difference in gene expression between pollen or O3BC alone and O3BC+ pollen exposed cells. Exposure to 200 μg/ml O3BC was associated with hypoxia stress response GO terms, whereas exposure to 25 μg/ml O3BC+ 200 μg/ml pollen was associated with inflammatory response GO terms; including regulation of neutrophil migration and chemotaxis, macrophage differentiation and chemotaxis, mast cell activation, and phagocytosis. KEGG pathway analysis indicated the top 10 upstream regulators to be IL1B, CSF1, CCL2, TLR2, LPL, IGF8, SPP1, CXCL8, FCER1G and IL1RN; of which expressions of inflammation-related genes IL1B, CSF1 and FCER1G were significantly increased. Conclusion: O3BC and pollen allergen combined exposure may induce innate immune and allergic inflammation in hNECs, and therefore potentially exacerbate the symptoms of AR in affected individuals. [ABSTRACT FROM AUTHOR]

Background: Worldwide, allergy affects more than one billion people, with particularly rising prevalence in industrialised areas. Specifically, young adults appear to be predominantly targeted for an allergy diagnosis. Allergic diseases in pregnancy are mainly pre-existing but could also occur de novo. The immunological changes while pregnant, with increased Th2 lymphocyte activity, can facilitate allergen sensitisation. Objective: The aim of this study was to evaluate the pattern of specific IgE (sIgE) sensitisation to common inhalant and food allergens in pregnancy, and assess its relationship to self-reported allergic disease. Methods: We assessed 200 pregnant women, aged 20–38 years (mean age = 29 years), participant of ELMA (Epigenetic Hallmark of Maternal Atopy and Diet) study, living in a metropolitan area, with no pregnancy associated metabolic complications, for total IgE and allergen specific IgE to 20 allergens. Results: 48% of pregnant women were sensitised to at least one allergen, at a cut-off point of 0.35 kU/L and they were assigned as atopic. However 42% in atopic group were not reporting any allergic disease. The most common inhalant allergens were: pollen (24.5%) and animal dander (23.5%). The most common food allergens were: cow's milk (5.5%) and apples (4.5%). 7.5% of women reported asthma, 21.5% allergic rhinitis, 11.5% atopic dermatitis and 18.5% food allergy. 8.5% of were taking medication for asthma or allergies. Atopic dermatitis had the highest tendency to become more severe during pregnancy. Total IgE values were significantly higher in atopic women. Conclusions: Allergic sensitisation is a common phenomenon in pregnancy. Some sensitisations could be asymptomatic. Further studies should investigate if sensitisation in mothers confers risks for immune alterations in their children. [ABSTRACT FROM AUTHOR]

Background: Egg allergy is one of the most common food allergies in children. To date, oral immunotherapy (OIT) has been considered as a promising treatment option for egg allergy. However, safety issues remain concerning severe adverse events requiring epinephrine injection. Hence, establishing a safer method to treat egg allergy would be beneficial. We report here two children with egg allergy who were safely treated with sublingual immunotherapy (SLIT) before transitioning to OIT. Case presentation: Patient 1 was a 7-year-old girl and Patient 2 was a 5-year-old girl. Although OIT for egg had been attempted in both patients, severe anaphylactic symptoms were induced by ingesting only 0.1 g of heated whole egg. Therefore, SLIT was conducted with aqueous suspensions consisting of water and heated whole egg powder. Suspensions were administered sublingually, kept in the mouth for 2 min, and spat out immediately thereafter. SLIT was continued for 7 months for Patient 1 and 8 months for Patient 2 due to the exploratory character of the study. Afterwards, the patients successfully transferred to low-dose OIT with 1 g of heated whole egg (≒170 mg of egg protein) daily, and are continuing the therapy as of June 2020. As for adverse reactions, Patient 1 expressed oral cavity itchiness once at the beginning of SLIT. Patient 2 had no adverse reaction. The levels of antigen-specific IgE decreased in both patients after SLIT, and further decreased after switching to OIT. Conclusions: Few clinical studies have evaluated the efficacy and safety of SLIT for egg allergy. Although the treatment was conducted in only two patients, our results have shown that SLIT is a promising treatment procedure for egg allergy. Further clinical trials will be needed to additionally assess the efficacy and safety of SLIT in children with food allergy. [ABSTRACT FROM AUTHOR]

Background: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. Methods: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms. Discussion: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication. Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301 [ABSTRACT FROM AUTHOR]

Background: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. Methods: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms. Discussion: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication. Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301 [ABSTRACT FROM AUTHOR]

Background: The Allergy Patient Identification for Immunotherapy (AsPIRe) program was a parallel physician and patient survey. The objectives were to examine physician and patient perceptions of seasonal allergy symptoms and their impact on patients, and to examine patient and physician attitudes to allergen immunotherapy (AIT) for seasonal allergies. AsPIRe was led by a steering committee and received research ethics board clearance from Queen's University. Methods: Allergists (17) from across Canada enrolled in the AsPIRe program and completed an on-line survey to collect demographic information and baseline perceptions. Allergists then recruited patients and completed paper-based parallel physician and patient questionnaires. Patients received an AIT informational booklet with their questionnaire. Patients who were AIT-naïve with no contraindication to AIT and 12 years of age and older met the inclusion criteria. Results: The survey was in field from February 2018 to June 2018. A total of 141 allergist surveys and 136 patient surveys were completed. Mean age of patients was 30 years old (range 12–70). Fifty-seven percent of patients reported prior knowledge of AIT. Seventy-two percent of patients reported seasonal allergies of longer than 5 years duration and in this subset of patients, 46% were at their first allergist visit. Seventy-three percent of all patients indicated they would be likely or very likely to try sublingual immunotherapy (SLIT), if recommended by their allergist compared to 36% for subcutaneous immunotherapy (SCIT). Conversely, 10% of patients reported they would be unlikely or very unlikely to try SLIT compared to 46% of patients who would be unlikely or very unlikely to try SCIT if recommended by their allergist. Conclusions: In this particular study cohort, there was a gap in perception between allergists and their patients as to the impact of allergy symptoms on daily life. Patients reported being more frequently impacted vs. their physician's assessment. When asked about preference for AIT options, Canadian patients reported they were more likely to follow their allergists' recommendation for initiation of SLIT compared to SCIT. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis is estimated to affect 20-25% of Canadians and has a significant impact on quality of life, with many patients reporting inadequate control of their symptoms [1]. Mainstays of treatment for allergic rhinitis include avoidance, intranasal steroids, oral antihistamines and leukotriene receptor antagonists [2]. Specific immunotherapy offers disease-modifying treatment for those uncontrolled by, intolerant to, or averse to pharmacotherapy [3]. Currently two types of aeroallergen immunotherapy are used in clinical practice: subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). SLIT was first accepted as an alternative to SCIT by the WHO in 1998, and was then introduced into the ARIA guidelines [4, 5]. While SLIT has been available in Europe for some time, Canada first approved a sublingual grass immunotherapy tablet in 2012. At present, there are three sublingual tablet immunotherapy products on the market in Canada (Table 1). There will be other allergens for SLIT available soon. The sublingual route of immunotherapy offers multiple potential benefits over the subcutaneous route including the comfort of avoiding injections, convenience of home administration and a favourable safety profile. In addition, SLIT tablets appear to be economically favourable to standard drug therapy, and possibly also to SCIT [6, 7]. This position statement discusses SLIT tablets only, as SLIT drops are not approved by Health Canada. [ABSTRACT FROM AUTHOR]

Introduction: To assess the safety and efficacy of an oral immunotherapy regimen in patients with allergy to lipid transfer proteins (LTPs). Materials and methods: Prospective study of 24 patients allergic to LTP with positive skin test and a history of anaphylaxis. All patients underwent a desensitization protocol with commercial peach juice. Rising doses of peach juice were administered, starting with an initial dose of seven drops of a 1/1000 dilution and finishing with a dose of 5 ml at visit 17. At visit 18, all patients performed an open challenge with whole juice at a cumulative dose of 200 ml. All adverse reactions occurring during the administration of the different doses were recorded. Levels of rPru p 3 in the juice were quantified. Results: There were no severe reactions during the desensitization process in the 24 patients. Seven patients (29%) reported mild oral symptoms, and two patients (8%) had urticaria associated with co-factors (one due to exercise and another due to non-steroidal anti-inflammatory drugs). Nineteen patients were able to swallow 5 ml of juice and five withdrew from the study. In two pregnant patients the final challenge was not performed. In all, 17/24 patients were able to consume 200 ml peach juice without developing symptoms. Conclusions: Oral immunotherapy with the regimen used in this study is an effective and safe short-term therapeutic option for patients with allergy to LTPs. Commercial peach juice appears to be suitable for this treatment. [ABSTRACT FROM AUTHOR]

Background: A cost-minimization analysis (CMA) was performed to estimate the economic impact of introducing the SQ house dust mite sublingual immunotherapy (SQ HDM SLIT)-tablet marketed as ACARIZAX™ (regulatory approval May 2017) for the treatment of HDM-induced allergic rhinitis in Canada (Ontario and Quebec), where house dust mite subcutaneous immunotherapy (HDM SCIT) is already an available treatment option. Methods: A CMA was deemed appropriate and was based on the assumption that the SQ HDM SLIT-tablet has comparable efficacy to HDM SCIT. A societal perspective was adopted in the model, including relevant costs of medications, health care services and productivity loss. A 3 year time horizon was used corresponding to a recommended treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where possible, and validated and complemented by a Canadian specialist clinician (allergist) in active practice in Ontario and in Quebec, respectively, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, sensitivity analyses were performed by testing alternative assumptions for selected parameters, to understand their impact on the results of the analysis. Results: The direct treatment costs for a 3-year treatment with SQ HDM SLIT-tablets were higher than for HDM SCIT for both provinces, Ontario and Quebec ($4732.12 and $4829.03 vs. $3434.51 and $2987.74). However, when adding the indirect costs to the model, total savings for the treatment with SQ HDM SLIT-tablets of $1833.00 for Ontario and $769.03 for Quebec were observed. Sensitivity analyses with varying HDM SCIT resource use, discount rates, titration and maintenance injections, nurse time, and number of injections per vial resulted in savings of SQ HDM SLIT-tablets over HDM SCIT in all scenarios analysed. Conclusions: The CMA indicates that SQ HDM SLIT-tablets are a cost-minimizing alternative to HDM SCIT when considered from a societal perspective in Ontario and Quebec. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-grass pollen extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to grass pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information. Methods: This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 pollen season were eligible. Data was collected at the inclusion visit and at the end of the pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the pollen season and any modifications to treatment or adverse events were documented. Results: 280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3–5 months before the pollen season for 85.3%. Treatment was discontinued before the start of the pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus. Conclusions: 5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated. Trial registration EUPAS9358. Registered 13 May 2015. Not prospectively registered. http://www.encepp.eu/encepp/viewResource.htm?id=16229 [ABSTRACT FROM AUTHOR]