The dominant allergen in cat dander, Felis domesticus allergen 1 (Fel d 1), is a persistent trigger for allergic rhinitis and asthma symptoms.

Evaluate the efficacy of Fel d 1 monoclonal antibodies (REGN1908/1909) in preventing cat allergen-induced early asthmatic responses (EAR) in cat-allergic patients with mild asthma.

Patients were randomized to single-dose REGN1908/1909 600 mg (n = 29) or placebo (n = 27). Forced expiratory volume in 1 second (FEV1) was measured for up to 4 hours in a cat allergen environmental exposure unit (EEU) up to 85 days after dosing. Assessments included between-group differences in change from baseline in FEV1 area under the curve (AUC; 0-2 hours) and incidence of EAR (FEV1 reduction ≥20%).

Single-dose REGN1908/1909 significantly prevented reductions in FEV1 on days 8, 29, 57, and 85. Most REGN1908/1909 patients did not have an EAR by 4 hours (last timepoint tested). In contrast, placebo-treated patients experienced ≥20% mean FEV1 reduction on days 8, 29, 57, and 85 post-dosing, with most experiencing an EAR within 1 hour. REGN1908/1909-treated patients tolerated 3-fold higher allergen quantities (P < .05 at all timepoints) versus placebo. REGN1908/1909 substantially reduced skin test reactivity to cat allergen versus placebo at all timepoints tested (nominal P < .001). REGN1908/1909 was generally well tolerated; no serious adverse events or deaths were reported.

Single-dose REGN1908/1909 significantly prevented reductions in FEV1 in cat-allergic patients with mild asthma upon cat-allergen EEU exposure at 8 days and up to 85 days post-dose.

Severe asthma (SA) has been identified as a risk factor for severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT). However, the incidence and characterization of SRs in SA in comparison to less severe or no asthma is not known. Objective: The objective of this study was to characterize the incidence of SRs in SA patients receiving SCIT in comparison to patients with no asthma or less severe asthma.

A retrospective cohort study was performed of patients receiving SCIT from a multicenter national network of private allergy practices between January 2015 to December 2019. Demographics, asthma severity (ICD-10 codes), concomitant medications, aeroallergen skin testing, measures of asthma control with the asthma control test (ACT) and FEV1 values, SCIT prescription, and a SR standardized form were assessed.

65,855 patients, with 1072 SA patients, receiving SCIT were included with a total of 4415 SRs (19.9 SR per 10,000 injection visits). SA had 23.9 SRs per 10,000 injection visits (incidence rate 0.239; 95% CI [0.189, 0.298). There were 155 grade III/IV SRs; 5 (3.2%) occurred in SA group. There was no difference in rates of grade III/IV SRs between SA and no asthma as well as in rates of total SRs between SA and less severe asthma.

In a large cohort of patients with SA undergoing multi-allergen SCIT drawn from a diverse outpatient allergy population, the diagnosis of SA was not associated with increased moderate-severe SRs compared to patients without asthma and any severity of asthma.

Antigen-specific immunoglobulin responses have yet to be studied at the oral mucosal surface during peanut oral immunotherapy (PnOIT).

We aimed to quantify salivary peanut-specific IgG4 (PNsIgG4) and IgA (PNsIgA) and total IgG4 and IgA in participants from the Immune Tolerance Network's IMPACT study, a phase 2 PnOIT trial.

Peanut-allergic children, aged 12 months to younger than 48 months at screening, were enrolled and randomized to PnOIT or placebo oral immunotherapy (OIT) for 134 weeks. Per-protocol analysis included 69 PnOIT and 23 placebo participants. Double-blind, placebo-controlled food challenges were conducted at weeks 134 and 160 to assess desensitization and remission, respectively. Saliva samples were collected at baseline and 30, 82, 134, and 160 weeks to quantify PNsIgG4, PNsIgA, and total IgG4 and IgA.

Participants who received PnOIT experienced significant increases in PNsIgG4 in saliva, whereas participants on placebo did not (P < .01 at all time points). The PNsIgA/total IgA ratio was also significantly increased in participants treated with PnOIT when compared with those receiving placebo at 30 and 82 weeks (P < .05). During PnOIT, desensitized participants had increased PNsIgA that plateaued, whereas the not desensitized/no remission group did not change over time. Interestingly, when the PnOIT group was evaluated by clinical outcome, PNsIgA was higher at baseline in the not desensitized/no remission group than in the desensitized/remission group (P < .05).

PnOIT induces substantial increases in allergen-specific IgG4 and IgA in saliva. These data provide insight into OIT-induced mucosal responses and suggest the utility of these easily obtained samples for biomarker development.

Clinical trials (PALISADE [ARC003], ARTEMIS [ARC010]) proving efficacy and safety of peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) used double-blind, placebo-controlled food challenges (DBPCFCs) to screen for eligibility and to evaluate efficacy. In routine clinical practice, individuals with peanut allergy do not always undergo food challenges to confirm diagnosis or determine candidacy for treatment.

To describe PTAH safety/tolerability in participants selected by clinical history and peanut sensitization parameters not undergoing DBPCFC during trails and to compare findings with previously published data.

RAMSES (ARC007) was a 6-month, phase 3, randomized, double-blind, placebo-controlled trial in children aged 4 to 17 years with physician-confirmed peanut allergy. ARC011 was the subsequent 6-month follow-on maintenance PTAH study. The primary endpoint for RAMSES and ARC011 was frequency of treatment-emergent adverse events (AEs). We descriptively compared baseline characteristics and safety outcomes from RAMSES/ARC011 to participants undergoing DBPCFCs in phase 3 PALISADE/ARTEMIS trials.

In 506 patients randomized to study treatment, baseline characteristics appeared balanced between groups. Proportion of participants with ≥1 AE was 55% for PTAH versus 33.9% for placebo during initial dose escalation and 98.8% versus 94.0%, respectively, during updosing. Most participants with AEs had mild/moderate events. The most common AEs were gastrointestinal. Comparisons to pooled PALISADE and ARTEMIS data showed higher baseline median peanut-specific immunoglobulin E and skin prick test values for RAMSES participants. Safety outcomes during trial periods were comparable.

Safety data from clinically selected children with peanut allergy receiving PTAH do not appear different from those in phase 3 trials requiring DBPCFC to enter trials.

Asthma and allergic disease impact millions of patients and are associated with high costs. Up to 30% of all medical care involves wasted spending. Across the spectrum of care provided by the allergist-immunologist, there are opportunities to improve value and reduce medical waste. Several examples highlight this reality. Evidence suggests that most patients may receive cost-effective care in the management of chronic spontaneous urticaria without the need for laboratory testing. For patients with asthma, although a single maintenance and reliever therapy approach may be cost-effective, insurance-mandated therapy changes are not, and may harm patients. Biologics may be very effective in improving asthma control but are too expensive for this indication-as demonstrated by cost-effectiveness analyses and highlighted by the Institute of Clinical and Economic Review, which concluded that the value-based price for asthma biologics ranges between $6500 and 14,3000 per year. Early introduction may prevent food allergy, but screening before first introduction is neither necessary nor cost-effective, although early salvage food oral immunotherapy may result in improved quality of life and cost savings. Evidence does not support the presence of allergic disease as a risk factor for anaphylaxis to coronavirus disease 2019 vaccination, and risk-stratified vaccination approaches do not appear cost-effective. Allergen immunotherapy is a very cost-effective treatment option. The practice of allergy-immunology has continued to evolve in recent years and can provide a leading example of high-value practice.

Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients.

We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated.

The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT.

Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.

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 current review describes the incidence and risk for anaphylaxis due to allergy injections.

The incidence of fatal anaphylaxis occurs with approximately one in 7.2 million injection visits. Severe anaphylaxis may occur once in every 160 000 visits. The major risk for fatal anaphylaxis is severe and uncontrolled asthma.

Understanding risk factors for anaphylaxis to allergy injections has led to clinic protocols aimed at preventing such events. The efficacy of these preventive measures remains to be determined in future studies.

Adverse reactions, which are mostly local and rarely systemic, can be seen during subcutaneous immunotherapy (SCIT). It was not possible to continue SCIT at times due to systemic reactions. The purpose of the present study was to identify the incidence and risk factors associated with adverse reactions during subcutaneous allergen-specific immunotherapy (AIT).

A total number of 344 patients under 18 years old with allergic rhinitis and/or asthma who underwent SCIT between 2005 and 2021 were included in the study. Demographic characteristics of the patients, laboratory findings [Total Immunglobulin E(IgE), aeroallergen prick test, inhaler, and allergen specific IgE(sIgE) and eosinophil counts], and adverse events observed during AIT were recorded retrospectively. Descriptive and univariate/multivariate logistic regression analyses were used to identify risk factors for adverse events

Among 344 patients, 33.4% (n = 115) were female, mean age was 133.1 ± 41.0 months, and 42.2% (n = 145) were >12 years old. One hundred-thirty eight (40.1%) of the patients were mono-sensitized, 47 (13.7%) had asthma, 207 (60.2%) allergic rhinitis, and 90 (26.2%) asthma and allergic rhinitis. Single allergen content was administered to 187 (54.4%) patients (62 mite, 114 grass mix, 11 olea), and multiple allergens to 157 (45.6%) patients (121 pollen mix, 36 other (mite/alternaria)]. A total number of 33.008 injections were administered. 840 adverse reactions (262 (31.1%) at up-dosing phase, 578 (68.8%) at maintenance phase) in 195 (56.7%) patients were observed. Among the adverse reactions, 632 (75.2%) were local, 160 (19%) large local, and 48 (5.7%) (39 at maintenance, 9 at up-dosing) (in 31 patients) were systemic (28 Grade 1, 12 Grade 2, 8 Grade 3). Adrenalin was administered to 8 patients with Grade 3 systemic reaction (8/33008; %0.024). Adverse reactions, especially local ones, were seen more frequently in children under 12 years old (p < 0.001). Patients sensitized with grass pollen (p:0.01) and mite (p:0.004), and those who had received SCIT with pollen mixture had more adverse reactions than the others. More adverse reactions were observed in SCIT containing calcium-phosphate as adjuvant (p: 0.01). Local reactions were risk factors for large local (OR = 3.591, %95 CI:2.064-6.247, p < 0.001) and systemic (OR = 2.190, %95 CI:1.005-4.722 p = 0.046) reactions at univariate analyses. Total nasal symptom scores, Visual Analog Scale and asthma symptom control test decreased after one year of treatment (p < 0.01).

SCIT is a safe and effective treatment method in childhood that leads to improvements in all nasal symptoms and asthma after one year of treatment.

Allergic rhinitis (AR) is very commonly caused by pollens. The symptoms of AR consist of sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. The diagnosis has long been based on clinical history, skin prick tests and in vitro measurement of specific IgE, but the innovative approach of precision medicine has made diagnostic tools of much greater accuracy available.

This review covers the advances in the treatment of seasonal AR concerning the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy (AIT), which is the only treatment capable of acting, in addition to the symptoms, on the cause of AR and therefore to modify its natural history.

Drug treatment of AR include a large number of agents, the choice of which depends on the severity of the disease. AIT has high evidence of efficacy demonstrated by meta-analyses, and further improvement is currently apparent, as for diagnosis, applying the means of precision medicine. However, when AIT is performed in current practice, without the strict rules of controlled trials, long-term low adherence is a major problem to be solved.