PQ Grass 27600 SU (PQ Grass) cumulative dose is a pre-seasonal, six-injection, aluminium-free, modified subcutaneous immunotherapy product under development for the treatment of allergic rhinitis (AR). A pivotal Phase III randomiseddouble-blind, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of PQ Grass in subjects with seasonal AR.

An adaptive group sequential trial PQGrass306 (G306) with one pre-defined interim analysis was designed, using 2 parallel groupsapplying a 1:1 active versus placebo randomisationof patients aged 18-65. The primary efficacy endpoint was the EAACI (European Academy of Allergy and Clinical Immunology) Combined Symptom and Medication Score (EAACI-CSMS0-6) averaged over the peak grass pollen season (GPS).

858 subjects were screened and 555 subjects were randomised. Based on the results of the pre-defined interim analysis, the trial was stopped for success showing superiority in favourof PQ Grass. The primary endpoint EAACI-CSMS0-6(peak GPS) demonstrated a highly significant and clinically meaningful point difference of PQ Grass over placebo of -0.27 points (95% CI: -0.42 to -0.12), corresponding to arelative difference of -20.3% (p = 0.0005). Highly consistent and beneficial results were obtained for PQ Grass for all key secondary endpoints. Significant induction of blocking IgG4 and IgAantibody subclasses occurred. PQ Grass was well tolerated, and no unexpected safety signals occurred.

This pivotal Phase III trial demonstrated a significant and clinically meaningful effect on the primary endpoint as well as highly consistent secondary endpoint results and a supportive safety profile.

Long-term evidence on maintenance doses of oral immunotherapy (OIT) for anaphylactic cow's milk allergy is insufficient.

We retrospectively compared the three-year safety, efficacy, and adherence between OIT with a maintenance dose of 200 mLof cow's milk (HOIT, 2009-2013) and 3 mLof cow's milk (LOIT, 2013-2019). Patients aged 6-18 years with a history of anaphylaxis reacting to ≤3 mLof cow's milk during oral food challenge (OFC) were included. Adverse symptoms, OFC negative rate after 2 weeks of avoidance, dropout rate, and immunological changes were compared.

The median ages in the HOIT (n = 78) and LOIT (n = 99) groups were 8.1 and 7.8 years, with milk-specific IgElevels of 56.5 and 49.2 kUA/L, respectively. The percentages of doses triggering symptoms were 20.88%, 13.73%, and 7.31% in the HOIT group and 11.81%, 8.15%, and 6.30% inthe LOIT group during years 1, 2, and 3, respectively. After 3 years, 29% of patients in the HOIT group passed the OFC with 200 mL, and 47%, 18%, and 5% of patients in the LOIT group passed the OFC with ≥25 mL, ≥50 mL, and 100 mLof cow's milk, respectively. After 3 years, the dropout rates were 24% and 11% in the HOIT and LOIT groups and milk-specific IgElevels decreased by 88% and 78% in the HOIT and LOIT groups, respectively.

HOIT enables higher dose consumptions. LOIT might be safer and have higher adherence in patients with anaphylactic cow's milkallergy.

Peanut oral immunotherapy (POIT) has promising potential of disease modification, but there are no studies to date evaluatinghigh-dose POIT, leading to ad libitum(ad lib) consumption of peanut products, especially in children 6 months to 4 years of age.

To report real-world outcomes of high-dose POIT in children 6 months to 4 years of age, including adverse events, achievement ofad lib consumption, and the impact of age on these outcome measures.

Patients 6 months to 4 years of age with a diagnosis of peanut allergy were enrolled in a POIT protocol with a goal dose of 3000mg. Demographics along with POIT and clinical outcomes 6 months after POIT are reported.

Sixty children, with a median age of 16 months, started POIT. Three (5%) were lost to follow-up, and 6 (10%) discontinued POIT because of recurrent adverse events or the inability to consume daily peanut protein. Fifty-one (85%) children completed POIT in a median of 7 monthsand were consuming ad lib peanut products for a duration of 6 months after completion of the POIT protocol. Sixteen (26.7%) children experienced a total of 22 adverse reactions during POIT. Initiating POIT before 24 months of age increased the likelihood of ad lib peanut consumption by an odds ratio of 11.69(1.19-114.31, P = .035).

Our study demonstrates that high-dose POIT in infants and toddlers is well tolerated and can lead to ad lib introduction of dietary peanut products into the diet, especially if initiated before 2 years of age.

To observe and assess the efficacy and safety of Artemisia annua(A. annua)-sublingual immunotherapy (SLIT) in patients with mild-moderate allergic asthma (AS).

In this retrospective study, the complete data of 60 patients with mild-moderate AS from October 2022 to October 2023 was included. Patients were stratified into two different groups based on treatment regimens: the SLIT group, 30 individuals who underwent standardized A. annua-SLIT for at least 6 months before pollen season, and the control group, the other 30 patients only received the symptomatic drug. During the 2022 and 2023 pollen season, asthma daytime symptom score (ADSS), asthma nighttime symptom score (ANSS), total medicine score (TMS), asthma control test score (ACT), forcedexpiratory volume in one second (FEV1), and FEV1/forced vital capacity (FVC) were measured to evaluate the efficacy, and adverse events (AEs) were used to assess its safety.

There were no significant differences in all clinical outcomes between the two groups during the 2022 pollen season (all P > 0.05). However, after SLIT treatment, the level of ADSS, ANSS, TMS, ACT, FEV1, and patients' number of well controlled AS significantly improved compared with the control group (all P < 0.01). Notably, all the clinical outcomes significantly improved compared with the baseline only in the SLIT group (all P < 0.001). No severe AEs were reported, and all AEs were mild.

Pre-seasonal treatment of A. annua-SLIT for at least 6 months could relieve daytime and nighttime symptoms, reduce medication use, and improve asthma control and lung function in mono-and poly-sensitized patients with mild-moderate AS.

Data on anaphylaxis due to allergen immunotherapy (AIT) are limited. This study assessed AIT-induced anaphylaxis using data fromthe European Anaphylaxis Registry.

To analyze the characteristics, symptoms, severity and emergency management of AIT-induced anaphylactic reactions across age groups and the administered allergenic source.

Data for this analysis were contributed by 54 allergy centers across ten European countries from 2007 to 2023. Anaphylactic reactions involving at least two organ systems were analyzed for symptoms, severity, associated diseases, administration routes, and emergency treatment. Statistical methods included chi-squared and Fisher's exact tests.

AIT accounted for 1.1% cases in the anaphylaxis registry (173/15,748), of these 1.8% were pediatric and 0.7% adult. Respiratory symptoms were more frequent in children/adolescents (92%) than in adults (66%) among AIT-related anaphylaxis, while cardiovascular and gastrointestinal symptoms occurred more common in adults (40% vs. 78% and 20% vs. 42%). Only a few SLIT related cases were documented including 2 grade III reactions, with no fatalities (SLIT n=8 vs. SCIT n=153). One fatality due to SCIT was reported (grass pollen). Delayed reactions (>30 minutes) were reported in 22 cases,predominantly after SCIT. All delayed grade III reactions beyond 120 minutes occurred in children. Adrenaline was underused in the emergency management andadministered in 30% of grade II and 50% of grade III reactions.

Our study highlights the importance of age-specific monitoring, and appropriate emergency treatment to enhance patient safety during AIT.

Allergen immunotherapy is the only treatment that may modify the natural course of allergic diseases. Sublingual immunotherapy (SLIT) is a promising treatment, especially for children. Few studies currently exist related to optimal dosing forBlomiatropicalis.

This was a double-blind, randomized, placebo-controlled trial of SLIT to treat house dust mite-induced Allergic Rhinitis (AR). Atotal of 65 patients, ages 12-16 years, were treated for 12 months and randomized into SLIT versus placebo. The SLIT group received a combination ofDermatophagoidespteronyssinusandBlomiatropicalisallergens. Sensitization was confirmed by skin prick test or serum specific IgE. Total Nasal Symptom Score (TNSS), RhinoconjunctivitisQuality of Life Questionnaire (RQLQ), current treatment, and need for medication to control symptoms were ascertained during the study. Total serum IgE, serum specific IgE, and IgG4 levels forDerp1 andBlotwere assessed at baseline and, 6 and 12 months after treatment.

There was no significant difference in the number of adverse events between groups. The SLIT group showed a significant reduction in antihistamine use to control symptoms (p < 0.0001) compared to placebo. There was no significant change in serum total IgE, serum specific IgE, and IgG4 for either allergen when comparing the SLIT and placebo groups.

After 1 year, SLIT using a dose of 1 mcg of Derp 1/day and 753 UBE of Blot/day lowered the need for medications for break-through symptoms, with a good safety profile.

Omalizumabenables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumabtreatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Approved therapeutics for peanut allergy are not designed for the many patients with allergic reactions to more than one peanut.

We randomly assigned (1:1) participants 4 to 14 years of age reacting to a challenge of between 443 mg and 5043 mg of peanut protein to peanut oral immunotherapy (P-OIT) using home-measured peanut butter versus peanut avoidance. The primary end point was the difference between groups in the proportion tolerating a two-dose-level increase or 9043 mg of peanut protein. For ingestion participants tolerating 9043 mg, sustained unresponsiveness (tolerance off treatment) was tested after 16 weeks of ad lib ingestion followed by 8 weeks of abstinence.

Of 73 participants, 38 were randomly assigned to P-OIT and 35 to avoidance. Thirty-two of 38 participants in the ingestion group(84.2%) and 30 of 35 in the avoidance group (85.7%) underwent the primary outcome food challenge. The primary analysis with prespecifiedmultiple imputation for missing values showed 100% success for ingestion versus 21.0% for avoidance (between-group difference, 79.0 percentage points; 95% confidence interval [CI], 64.6 to 93.5; P<0.001). All 32 treated and 3 out of 30 avoiders (10%) tolerated 9043 mg. In the intention-to-treat analysis, sustained unresponsiveness occurred in 68.4% (26/38) on P-OIT versus 8.6% (3/35) tolerating 9043 mg among those avoiding (between-group difference, 59.9 percentage points; 95% CI, 42.4 to 77.3). No dosing reactions were greater than grade 1 severity, and no serious adverse events were reported.

In this trial of P-OIT using store-bought, home-measured peanut versus peanut avoidance in high-threshold peanut allergy, those treated achieved significantly higher rates of desensitization with a durable response off treatment.

Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifoodoral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight.

The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC).

Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders).

In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both thehigh-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominalP= .048,P= .306, respectively; adjusted for multiple comparisons,P= .097,P= .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths.

The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the

To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery.

A retrospective cohort of surgically treated, HDM-sensitized CRSwNPpatients phenotypedas CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use ( 100/HPF), and serum IgE(kU/L) were also recorded.

Eighty-six CCAD patients were assessed (41 ±14 yrs, 64% female). AIT was applied in 37% (n = 32). Baseline features were similar apart from greater conjunctivalsymptoms (72 vs. 45%, p = 0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (% ≥ diffuse 15.6 vs. 52.9, p < 0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (% ≥ 4/week, 37.5 vs. 79.6%, p < 0.01). The rhinologicsymptoms were similar (21.1 ±17.1 vs. 20.1 ±21.6, p = 0.83).

Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.