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Background: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. Methods: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4, IgA1 and IgA2) and their inhibitory capacity were measured at multiple timepoints. Results: The allergen concentration tolerated increased significantly at 6 months (Group A; p =.047) and 24 months (Group B; p =.049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71‐fold, p =.027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p =.047 and p =.0039) and sIgA2 to Phl p in Group B (p =.032 and p =.0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen–IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra‐nasally in Group A (serum; 휌 = −.47, p =.0006, nasal; 휌 = −.38, p =.0294). Conclusions: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy (SCIT) can induce systemic reactions (SRs) in certain patients, but the underlying mechanisms remain to be fully elucidated. Methods: AR patients who were undergoing standardized HDM SCIT (Alutard, ALK) between 2018 and 2022 were screened. Those who experienced two consecutive SRs were included in the study group. A control group was established, matched 1:1 by gender, age, and disease duration with the study group, who did not experience SRs during SCIT. Clinical and immunological parameters were recorded and analyzed both before SCIT and after 1 year of treatment. Results: A total of 161 patients were included, with 79 (49.07%) in the study group. The study group had a higher proportion of AR combined asthma (26.8% vs. 51.8%, p < 0.001) and higher levels of sIgE to HDM and HDM components (all p <.001). Serum IL‐4 and IL‐13 levels in the study group were higher than those in the control group (p <.05). The study group received a lower maintenance dosage of HDM extracts injections than control group due to SRs (50000SQ vs. 100000SQ, p <.05). After 1 year of SCIT, the VAS score, the lung function parameters of asthmatic patients over 14 years old significantly improved in both groups (all p <.05). After a 7‐day exposure to 20 μg/mL HDM extracts, the percentages of Th1, Th17, Tfh10, and Th17.1 in PBMCs decreased, while the Tfh13 cells significantly increased in the study group (p <.05). Conclusion: The type 2 inflammatory response is augmented in HDM‐induced AR patients who experienced SRs during SCIT. Despite this, SCIT remains effective in these patients when administered with low‐dosage allergen extracts. [ABSTRACT FROM AUTHOR]

Background: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long‐term effectiveness of HDM AIT are rare. We evaluated real‐world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long‐term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. Methods: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non‐AIT group); the evaluation period for up to 6 years of follow‐up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. Results: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non‐AIT group. During the follow‐up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p <.0001) for AR medication and by 42.4% for asthma medication (p =.0003). New‐onset asthma risk was significantly reduced in the SCIT vs non‐AIT group by 27.0% (p =.0212). The asthma‐preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non‐AIT group (p =.0010). Conclusion: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a common condition that is frequently associated with atopic inferior turbinate hypertrophy (ITH) resulting in nasal obstruction. Current guidelines support the use of subcutaneous allergen immunotherapy (SCIT) when patients fail pharmacologic management. However, there is a lack of consensus regarding the role of inferior turbinate reduction (ITR), a treatment that we hypothesize is cost‐effective compared with other available treatments. Methods: We conducted a cost‐effectiveness analysis comparing the following treatment combinations over a 5‐year time horizon for AR patients presenting with atopic nasal obstruction who fail initial pharmacotherapy: (1) continued pharmacotherapy alone, (2) allergy testing and SCIT, (3) allergy testing and SCIT and then ITR for SCIT nonresponders, and (4) ITR and then allergy testing and SCIT for ITR nonresponders. Results were reported as incremental cost‐effectiveness ratios (ICERs). Results: For patients who fail initial pharmacotherapy, prioritizing ITR, either by microdebrider‐assisting submucous resection or radiofrequency ablation, before SCIT was the most cost‐effective strategy. Probabilistic sensitivity analysis demonstrated that prioritizing ITR before SCIT was the most cost‐effective option in 95.4% of scenarios. ITR remained cost‐effective even with the addition of concurrent septoplasty. Conclusion: For many AR patients who present with nasal obstruction secondary to atopic inferior turbinate hypertrophy that is persistent despite pharmacotherapy, ITR is a cost‐effective treatment that should be considered prior to immunotherapy. Level of Evidence: NA – Laryngoscope, 2023 Laryngoscope, 134:1572–1580, 2024 [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

The plain language summary explains allergen immunotherapy to patients, families, and caregivers. The summary is for patients aged 5 years and older who are experiencing symptoms from inhalant allergies and are considering immunotherapy as a treatment option. It is based on the 2024 "Clinical Practice Guideline: Immunotherapy for Inhalant Allergy." This plain language summary is a companion publication to the full guideline, which provides greater detail for health care providers. Guidelines and their recommendations may not apply to every patient, but they can be used to find best practices and quality improvement opportunities. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of dust mite subcutaneous immunotherapy (SCIT) in monosensitized and polysensitized children with allergic rhinitis (AR). Study Design: Prospective cohort study. Setting: Tertiary referral center. Methods: One hundred thirty children were enrolled and categorized into 2 groups: monosensitized to only dust mites and polysensitized to at least 1 additional allergen beyond dust mites. All patients received SCIT targeting dust mites for 3 years, followed by a 5‐year monitoring period. The Total Nasal Symptom Score (TNSS), Symptom and Medication Score (SMS), Visual Analogue Scale (VAS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were assessed before SCIT (T0); at 1 (T1) and 2 (T2) years of SCIT; immediately after SCIT (T3); and 2 years post‐SCIT (T5). Safety was assessed based on adverse events (AEs). Results: Fifty‐one monosensitized and 50 polysensitized children completed the study. At T3, 47 monosensitized and 46 polysensitized children were effectively treated, with no significant between‐group difference in efficacy (P >.05). The TNSS, SMS, VAS scores, and RQLQ score were significantly lower at T1, T2, T3, and T5 than at T0 in both groups (P <.05). The differences in the TNSS, SMS, VAS score, and RQLQ score between the 2 groups were nonsignificant at T0, T1, T2, and T3 (P >.05), but significant at T5 (P <.05). No serious AEs were reported. Conclusion: Monosensitized and polysensitized children exhibited similar beneficial efficacy and safety after 3 years of dust mite SCIT. Monosensitized children derived more benefits 2 years after discontinuation. [ABSTRACT FROM AUTHOR]

Background: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid‐A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short‐course treatment of grass‐pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. Methods: In this exploratory, randomized, double‐blind, placebo‐controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre‐seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18–65 years) with moderate‐to‐severe SAR with or without asthma that was well‐controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ‐S) and allergen‐specific IgG4 response. Results: The mean CSMS compared to placebo was 33.1% (p =.0325) and 39.5% (p =.0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p <.01) as well as an improvement in total RQLQ‐S for the extended regimen (mean change −0.72, p =.02). Both regimens were well‐tolerated. Conclusions: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well‐tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial. [ABSTRACT FROM AUTHOR]

Background: Maintenance doses for allergen immunotherapy (AIT) have been recommended for at least 3 years but little data on long‐term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented‐polymerized house dust mite (dpg‐pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. Methods: Patients included in a double‐blind placebo‐controlled AIT study with dpg‐pol HDM allergen extract were reviewed at completion of the perennial treatment and 10‐year follow‐up (10y‐FU). Change in symptom and rescue medication score was the primary objective. Visual analog scale (VAS), asthma control test (ACT), and degree of disease control were the secondary objectives. A comparative analysis between patients who underwent AIT treatment for <3 years and ≥3 years was performed. Results: Data from 31 patients (mean age 38 years) were available at 10y‐FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty‐three patients were treated ≥3 years and 8 for <3 years. Seventeen (55%) patients were asymptomatic at completion of AIT, with significant differences for nasal, conjunctival, and bronchial symptoms (p <.0001) compared with baseline only in those patients treated ≥3 years. Nine (52.9%) patients remained completely asymptomatic at 10y‐FU, all were treated for ≥3 years. Moreover, significant reduction in the number of patients with rhinitis (p =.0117), conjunctivitis (p <.0001), and bronchial (p =.0005) symptoms was observed at 10y‐FU compared with baseline only in the ≥3 years treated. Ten (32.3%) patients did not require any rescue medication at 10y‐FU, all had been treated for ≥3 years. ACT at 10y‐FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared with VAS at 10y‐FU. Conclusions: Sustained clinical efficacy is achieved 10 years after completion of depigmented‐polymerized HDM, however, these findings were observed only if patients are treated for at least 3 years. Key Messages: A minimum of 3 years AIT treatment is required to obtain a sustained long‐term effectiveness.Dpg‐pol HDM is able to remove allergic rhinitis and asthma symptoms completely.Three‐year treatment with dpg‐pol HDM is able to maintain effectiveness 10 years after treatment. [ABSTRACT FROM AUTHOR]

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation fromthe full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based reviewwith recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensuswas performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment. [ABSTRACT FROM AUTHOR]

Background: Given that subcutaneous immunotherapy (SCIT) adherence in the literature is often studied in closely monitored trials, few studies report real‐world SCIT adherence. The purpose of this review is to assess SCIT adherence in real‐world settings. Methods: A literature search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus for real‐world studies examining SCIT adherence was performed. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow‐up after initiating SCIT, and "adherence" defined as persistence in accordance with prescribed SCIT dose, dosing schedule, and duration. Article quality was first assessed using a modified Newcastle‐Ottawa scale and then converted to Agency for Healthcare Research and Quality standards (good, fair, and poor). Results: The search yielded 1596 nonduplicate abstracts, from which 17 articles (n = 263,221 patients) met inclusion criteria. Fourteen (82%) studies reported persistence rates, ranging from 16.0% to 93.7%. Seven (41%) studies reported adherence rates, ranging from 15.1% to 99%. Five (29%) studies (n = 416 patients) collected original data on reasons for discontinuing SCIT, of which inconvenience was most cited. All studies were Oxford level of evidence 2b and of good (n = 10) to fair (n = 7) quality. Conclusion: Real‐world SCIT persistence and adherence rates are poor, with the majority of included studies reporting rates <80%; however, they range widely, explained in part by inter‐study differences in measuring and reporting adherence‐related findings. Future studies on SCIT adherence may benefit from following concordant definitions of persistence and adherence in addition to standardized reporting metrics. [ABSTRACT FROM AUTHOR]

Patients with moderate to severe allergic rhinitis may benefit from subcutaneous immunotherapy (SCIT), despite the risk of systemic allergic reaction. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin‐4 and interleukin‐13, key drivers of the type 2 inflammation seen in allergic rhinitis, thereby inhibiting their signaling. In the LIBERTY Grass AID trial (NCT03558997), 16 weeks of treatment with 300 mg of dupilumab every 2 weeks plus timothy grass (TG) SCIT did not reduce TG allergen challenge nasal symptom scores compared with SCIT only but did improve tolerability of SCIT up‐titration in patients with a history of grass pollen–induced seasonal allergic rhinitis. Here, we present the pharmacokinetics of functional serum dupilumab and concentration‐response relationships in 52 patients enrolled in this trial. Functional dupilumab concentrations and concentrations of TG‐specific IgE and IgG4 were assessed in blood samples collected from dupilumab‐only and SCIT + dupilumab–treated groups. Mean functional dupilumab concentrations were similar in both groups and reached a steady state of ≈70–80 mg/L at week 5. One week after the end of treatment, TG‐specific IgG4 concentrations were increased in the SCIT + dupilumab group, but not in the dupilumab‐only group, over the range of dupilumab concentrations evaluated, whereas no changes were seen for TG‐specific IgE concentrations. This study demonstrates that SCIT does not alter functional concentrations of serum dupilumab, and the impact of SCIT on TG‐specific immunoglobulins is not affected by functional dupilumab concentrations over the range studied, indicating that maximum response was achieved in all patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma. Methods: Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta‐analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta‐analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1. Results: Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta‐analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n = 13) and SLIT versus placebo (n = 33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD] = 0.40; 95% confidence interval [CI] = 0.31–0.49), MS (SMD = 0.26; 95% CI = 0.14–0.39), CSMS (SMD = 0.42; 95% CI = 0.17–0.67), and RQLQ (MD = 0.24; 95% CI = 0.04–0.44). Statistically significant results favoring SLIT were found for SS (SMD = 0.42; 95% CI = 0.32–0.53), MS (SMD = 0.40; 95% CI = 0.28–0.53), CSMS (SMD = 0.37; 95% CI = 0.29–0.45), and RQLQ (MD = 0.32; 95% CI = 0.20–0.43). No significant differences were found between SCIT and SLIT for SS (SMD = −0.02; 95% CI = −0.15 to 0.11), MS (SMD = −0.14; 95% CI = −0.31 to 0.03), CSMS (SMD = 0.05; 95% CI = −0.21 to 0.31), or RQLQ (MD = −0.08; 95% CI = −0.31 to 0.15). Conclusion: SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two. Laryngoscope, 132:499–508, 2022 [ABSTRACT FROM AUTHOR]

Background: This study investigated patients' preference for allergy immunotherapy (AIT) administered as either sublingual immunotherapy‐tablets versus monthly or weekly subcutaneous immunotherapy (SCIT) from a Spanish patient perspective. Methods: A discrete choice experiment (DCE) consisting of two blocks with eight choice sets in each was constructed to elicit the preferences for AIT. Three attributes were included in the DCE for the mode of administration, including the frequency of administration, the risk of systemic reactions and the co‐payment. Adults and caregivers of children with moderate to severe allergic rhinitis (AR) were included if they were not currently receiving or had not previously received AIT. Results: In total, 587 adults and 613 caregivers started the survey. Of those, 579 adults and 611 caregivers completed the survey and were included in the study. Both adults and caregivers had a significant preference for tablets compared with both monthly and weekly injections (p ≤ 0.0001). Furthermore, the respondents showed a significant preference for reducing the risk of systemic reactions. Subgroup analyses showed that caregivers of polyallergic children and female caregivers were significantly less price sensitive when choosing their preferred treatment. Conclusion: Our study demonstrated that both adults with AR and caregivers of children with AR prefer daily SLIT‐tablets to SCIT with either a weekly or monthly dose schedule. [ABSTRACT FROM AUTHOR]

Background: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID‐19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. Methods: Visual analogue scale for quality of life (VAS‐QoL), VAS for symptom scores (VAS‐symptom), medication scores (MSs), and total symptom scores (TSS‐6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre‐pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2‐month intervals (Group 3). Results: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS‐symptom, and TSS‐6 scores of Group 3 patients during the pandemic were higher than the pre‐pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS‐QoL scores of Group 3 during the pandemic were lower than the pre‐pandemic scores (p < 0.001). Median TSS‐6 and VAS‐symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS‐QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). Conclusion: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. Objective: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. Methods: Untargeted metabolomics using ultra‐high‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR‐DDT‐13003728). Results: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)‐hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p <.0001) and 15(S)‐HETE (AUC = 0.89, p =.0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels. Conclusion: 12(S)‐ and 15(S)‐HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Although there is a considerable body of knowledge about allergen immunotherapy (AIT), there is a lack of data on the reliability of real‐world evidence (RWE) in AIT, and consequently, a lack of information on how AIT effectively works in real life. Methods: To address the current unmet need for an appraisal of the quality of RWE in AIT, the European Academy of Allergy and Clinical Immunology Methodology Committee recently initiated a systematic review of observational studies of AIT, which will use the RELEVANT tool and the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE) to rate the quality of the evidence base as a whole. The next step will be to develop a broadly applicable, pragmatic "real‐world" database using systematic data collection. Based on the current RWE base, and perspectives and recommendations of authorities and scientific societies, a hierarchy of RWE in AIT is proposed, which places pragmatic trials and registry data at the positions of highest level of evidence. Key Results: There is a need to establish more AIT registries that collect data in a cohesive way, using standardized protocols. Conclusions: This will provide an essential source of real‐world data that can be easily shared, promoting evidence‐based research and quality improvement in study design and clinical decision‐making. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL‐4) and IL‐13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS‐24/SINUS‐52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery. Methods: Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co‐primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund‐Mackay (LMK), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), and smell scores. Results: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile. Conclusion: Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery. [ABSTRACT FROM AUTHOR]

Introduction: Humulus pollen is an important cause of allergic asthma in East Asia. There have been some murine models for Humulus pollen allergy established by intraperitoneal (IP) sensitization and nasal drip stimulation, but they were not comprehensive enough. Here, we used atomized inhalation for challenge and compared the subcutaneous (SC) and IP sensitization routes to determine the optimal method to establish a model of asthma induced by Humulus pollen. Subsequently, we tried to develop a rapid subcutaneous immunotherapy (SCIT) model for Humulus allergy. Methods: BALB/c Mice were sensitized through the SC or IP route, with respective reference to previously established sensitization methods and allergen dosing, and challenged with nebulized Humulus pollen extract to induce asthma. To compare the two sensitization methods, airway hyperresponsiveness (AHR), inflammatory cell infiltration, allergen‐specific serum immunoglobulin (Ig)E (sIgE) levels, cytokine levels, and lung histopathology were assessed. The effects of SCIT (once every other day for 16 days) on airway inflammation, AHR, sIgE, and allergen‐specific serum IgG2a (sIgG2a) levels were evaluated by using the model established in this study. Results: Although mice sensitized by the SC or IP routes both showed AHR and airway inflammation, the SC route elicited significantly higher levels of sIgE, eosinophil inflammation, and T helper type 2 cytokines, compared with the IP route. SCIT in the treatment group significantly reduced the titers of sIgE, enhanced the titers of sIgG2a, and effectively alleviated pulmonary inflammation and AHR, compared with the vehicle group. Conclusions: The SC route can be used to establish a murine model of Humulus pollen allergy that recapitulates the characteristics of clinical allergic asthma. Short‐term SCIT can significantly improve symptoms and pathophysiology in asthmatic mice. [ABSTRACT FROM AUTHOR]

Keywords: allergen immunotherapy; allergy; asthma; subcutaneous immunotherapy; sublingual immunotherapy EN allergen immunotherapy allergy asthma subcutaneous immunotherapy sublingual immunotherapy 1070 1072 3 03/02/22 20220301 NES 220301 Allergen immunotherapy (AIT) has gained a permanent place in the therapeutic arsenal for the patient with allergic rhinitis. Provided the diagnosis of asthma is correct, and the specific allergy is present, and a therapeutic extract containing the relevant allergen components is used, then AIT may result in clinical improvement of asthma. The recent EAACI guideline about HDM driven asthma recommends AIT as an add-on to regular asthma therapy for adults with controlled or partially controlled allergic asthma. Allergen immunotherapy, allergy, asthma, subcutaneous immunotherapy, sublingual immunotherapy. [Extracted from the article]

Background: Although previous studies had confirmed the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), respectively, direct head‐to‐head comparison of SCIT vs SLIT is sparse. We aimed to compare the efficacy, safety, and compliance of SCIT and SLIT in allergic rhinitis (AR) children. Methods: This study is a prospective, open‐label, and single‐center study performed between June 2017 and June 2018. A total of 325 children were grouped into SLIT, Alutard (SCIT1), and NovoHelisen Depot (NHD) (SCIT2) according to the parents' wishes. The adherence and reasons for dropout were recorded. The efficacy of SLIT and SCIT was evaluated by a combined symptom medication score. Adverse events (AEs) were recorded and graded during the whole treatment. Results: The compliance rate was higher in the SCIT group compared with the SLIT group (P <.05). The total nasal symptom score (TNSS), rescue medication score (RMS), and symptom medication score (SMS) after 6‐month, 12‐month, and 2‐year treatment were lower in the SCIT group compared with the SLIT group (P <.05). But the scores between the Alutard and NHD groups were not significantly different. The occurrence of AEs in the SCIT group was significantly higher compared with the SLIT group (P <.05). Conclusion: Our results suggested SCIT is more effective compared with SLIT to a certain degree, whereas SLIT had less AEs compared with SCIT. The AIT routes can be chosen according to personal specific conditions. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Recent research has examined the nasal microbiome in rhinosinusitis and nondiseased states. Given immunologic alterations in allergic rhinitis (AR) and after allergen immunotherapy (IT), we evaluated the nasal microbiome in these conditions.Study Design: Cross-sectional comparison.Methods: In this cross-sectional study, nasal swabs for microbiome analysis were collected from three patient groups: IT-naïve AR patients, AR patients undergoing IT for greater than 12 months, and a control group without sinonasal inflammatory disease.Results: Nasal swabs were successfully collected for 14 IT-naïve AR patients, 20 post-IT patients, and 17 controls. The α diversity showed a statistical difference in evenness but not in richness amongst samples, whereas the β-diversity was significantly different between groups. Corynebacterium and Staphylococcus were the most prevalent bacteria across all groups.Conclusions: β-diversity was found to be significantly different across the three groups, but the AR groups were found to be more similar to each other than to the controls. Although there is symptomatic improvement in the AR group undergoing IT, the microbiome does not appear to transition to a healthy microbiome composition.Level Of Evidence: 4 Laryngoscope, 2020. [ABSTRACT FROM AUTHOR]

Keywords: allergen immunotherapy; COVID-19 vaccination; subcutaneous immunotherapy; adverse effects; allergenimmuntherapie; COVID-19 impfungen; subkutane immuntherapie; nebenwirkungen EN allergen immunotherapy COVID-19 vaccination subcutaneous immunotherapy adverse effects DE allergenimmuntherapie COVID-19 impfungen subkutane immuntherapie nebenwirkungen 1 3 3 02/01/22 20220101 NES 220101 To the Editor, Allergen-specific immunotherapy (AIT) is an important therapeutic option for allergic diseases mediated by IgE. Real-life data on inactivated COVID-19 vaccination in patients with subcutaneous allergen immunotherapy Seventy-seven (54%) patients did not change their SCIT schedule during vaccination, but only five patients were administered the two types of injections simultaneously because they did not inform doctors that they had received another injection on the same day. [Extracted from the article]

Background and Objective: Nasal symptoms were reduced following allergen‐specific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis. Methods: Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54). Results: SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P <.001, the Mann‐Whitney U test), and (P <.00001) in season. Metachromatic cell counts in nasal swabs of SLIT subjects in preseason and in season were lower than those of untreated subjects (P =.014, the Mann‐Whitney U test) and (P =.00001) respectively. Eosinophil numbers in SLIT subjects were not significantly different than in untreated subjects in both preseason (P =.29) and in season (P =.09). However, when SLIT subjects in season were divided into those with greater than or equal to 1.5 years, or <1.5 years of SLIT duration, the degree of eosinophilia in those with SLIT greater than or equal to 1.5 years was significantly lower (P =.011) than in untreated patients, but not in those with SLIT less than 1.5 years (P =.9). There were no significant differences in neutrophil numbers in nasal swabs between untreated and SLIT subjects in preseason and in season. Conclusion: One of mechanisms underlying the effectiveness of sublingual drop immunotherapy for Japanese cedar pollinosis is a reduction of the number of metachromatic cells in preseason and in season. Eosinophilia was also reduced in season in those given SLIT for greater than or equal to 1.5 years. [ABSTRACT FROM AUTHOR]

Background and objective: Nasal symptoms of allergic rhinitis can be reduced with allergen‐specific subcutaneous immunotherapy (SCIT). However, the mechanisms underlying the effectiveness of SCIT for Japanese cedar pollinosis are not well understood. We studied changes in the numbers of metachromatic cells, eosinophils and neutrophils in nasal swabs following SCIT for Japanese cedar pollinosis. Methods: Subjects were either untreated or given SCIT for 0.5 to 13 years duration. For the 2019 seasons, nasal swabs were taken in the pollinosis preseason (immunotherapy n = 36; untreated control, n = 62) and in the pollinosis season (immunotherapy n = 45; untreated control n = 46) and the numbers of mast cells, eosinophils and neutrophils assessed by microscopy. Results: There were significant improvements in symptom severities following SCIT in comparison to untreated subjects (P <.0003, the Mann‐Whitney U test) in preseason, and (P <.00001) in season. Metachromatic cell counts from nasal swabs of SCIT subjects in preseason and in the season were lower than those of untreated subjects (P =.0029 and P =.031, respectively). Eosinophil numbers in nasal swabs of subjects given SCIT were lower than in untreated subjects (P =.0031) in season, but not in preseason. There were no significant differences in degrees of neutrophilia between untreated and SCIT subjects in preseason and in season. Conclusion: One mechanism underlying the effectiveness of SCIT for Japanese cedar pollinosis involves a reduction in the number of metachromatic cells in nasal swabs in the preseason and an inhibition of increases in the number of metachromatic cells and eosinophils in season. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy (SCIT) is the allergen‐specific curative treatment of allergic rhinitis. Adverse effects, most of which are local, can be observed during the immunotherapy. These adverse effects have been reported more frequently during the pollen season. The purpose of this study was to estimate the rate of local, large local, and systemic reactions during the treatment, to determine the relationship between adverse reactions and the season in which these reactions occur, as well as the risk factors for adverse reactions during the grass pollen–specific SCIT treatment in children. Methods: We retrospectively collected and analyzed the data of 261 children who administered grass pollen SCIT between 2008 and 2018. Results: A total of 261 children (177, 67.8% male), who received grass pollen SCIT, with a mean (±SD) age of 12.0 ± 3.0 years at the initiation of SCIT were enrolled to the study. The number of the patients who experienced local and large local reactions was 109 and 30, respectively. In addition, the number of the patients with systemic reactions was 35. After the 12 284 injections, local reactions occurred in 357 (2.9%), and this was followed by systemic reaction as 55 (0.4%) and large local reactions as 40 (0.3%). Frequency of local (P <.001) and systemic reactions (P =.003) was higher during grass pollen season than out of the grass pollen season. In multivariate analysis, initiation of SCIT during the grass pollen season [OR:7.351, 95%CI:1.532‐35.279, P =.013] and experiencing local reactions [OR:4.214, 95%CI:2.159‐8.224, P <.001] were independent predictors for the development of large local and systemic reactions. Conclusion: SCIT, in which only mild‐to‐moderate systemic reactions occurred, is safe for the treatment of allergic rhinitis in children. Our study revealed that previous local reactions and initiation of immunotherapy during the grass pollen season were the predictors for large local and systemic reactions during SCIT in children. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to analyze the effectiveness of allergen immunotherapy (AIT) with an allergoid in the treatment of house dust mites (HDM)‐induced allergic rhinitis and/or asthma based on recent real‐life data. The outcomes were measured using asthma incidence and consumption of corresponding medications as the indicator of persisting symptoms. Methods: In this retrospective cohort analysis of a German longitudinal prescription database, patients who received at least two relevant mite AIT prescriptions in two different successive seasonal cycles were compared with non‐AIT patients who received at least three symptomatic allergic rhinitis (AR) prescriptions in successive mite seasons. Study endpoints included AR progression, asthma progression, asthma occurrence, and therapy adherence. We used multivariate regression analyses to estimate the effects of AIT, adjusting for relevant variables. Results: This study included 2350 patients receiving a mite allergoid and 64 740 control patients. After up to 6 years of follow‐up, patients treated with mite allergoid required significantly fewer AR and asthma prescriptions (59.7% vs 10.8%) than the control group, and the probability of asthma development was significantly lower. The adherence of patients receiving allergoid was 63.8% at the end of the second year and 38.6% at the end of the third year. Conclusions: This real‐world evidence confirms the good efficacy of subcutaneous AIT with HDM mite allergoid in the treatment of allergic rhinitis and/or asthma. Up to 6 years of follow‐up revealed significant effects in allergic rhinitis by measuring the number of AR medications and demonstrating significant reductions in asthma medications. [ABSTRACT FROM AUTHOR]

Background: Peanuts are most responsible for food‐induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well‐characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)3. Methods: Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut‐allergic patients, competitive IgE‐binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE‐specific T‐cell lines and the induction of PE‐specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)3 was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut‐allergic mice. Results: Compared to PE, the IgE‐binding and capacity to induce allergic symptoms of MPE were lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)3. Both PE and MPE + Al(OH)3 showed to be efficacious in a model for immunotherapy. Conclusion: In our studies, an Al(OH)3 adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT. [ABSTRACT FROM AUTHOR]

Background: Real‐world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only disease‐modifying intervention for allergic rhinitis (AR) with long‐term efficacy. This real‐life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen‐associated AR and/or asthma. Methods: In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received ≥2 successive seasonal treatment cycles; non‐AIT patients had ≥3 AR prescriptions in three seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple regression analysis compared prescription data in AIT and non‐AIT groups as proxy for clinical status/disease progression. Results: Up to 6 years of follow‐up, significantly more AIT (65.4%) vs non‐AIT (47.4%) patients were AR medication‐free; odds ratio (OR) [95% confidence interval (CI)]: 0.51 [(0.48‐0.54); P < 0.001] (28.6% covariate‐adjusted reduction vs non‐AIT; P < 0.001), and significantly more AIT (49.1%) vs non‐AIT (35.1%) patients were asthma medication‐free [OR (95% CI): 0.59 (0.55‐0.65); P < 0.001] (32% reduction vs non‐AIT; P < 0.001), or reduced existing asthma medication use (32% covariate‐adjusted reduction vs non‐AIT; P < 0.001). During treatment, new‐onset asthma risk was significantly reduced in the AIT vs non‐AIT group (OR: 0.83; P = 0.001). Conclusions: Birch pollen AIT demonstrated real‐world benefits up to 6 years post‐treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new‐onset asthma medication use on‐treatment. In this retrospective, real‐world study in Germany, birch pollen allergen immunotherapy (AIT) demonstrated significant benefits up to 6 years post‐treatment in patients with birch pollen‐associated allergic rhinitis (AR) and/or asthma. AIT was associated with significantly improved AR and asthma symptoms as the medication dispensing decreased; nearly two‐thirds and one‐half of patients initially using AR or asthma medications, respectively, no longer required them at study end. During the period in which they were receiving AIT, patients with AR but not asthma had a significantly decreased risk of new‐onset asthma medication dispensing. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is still the only causal treatment for allergic diseases. However, conventional subcutaneous immunotherapy (SCIT) administration schedules are time‐consuming and patient nonadherence is a major barrier to achieving a satisfactory therapeutic effect. Our study aimed to analyze the causes leading to discontinuation of SCIT and to determine risk factors associated with nonadherence in respiratory allergies. Methods: This was a prospective study. Patients with respiratory allergies who had received standardized dust mite SCIT were enrolled from January 2012 to January 2014. And a follow‐up study on these subjects was conducted via telephone interviews on an interval of 3 months and online communication through social network applications. Reasons for discontinuation were documented when patients claimed to stop treatment. Results: A total of 311 patients were enrolled in the study. The adherence rate at year 3 was 64.6%. Fifty‐nine patients (19.0%) dropped out in year 1, 31 (10.0%) in year 2, and 20 (6.4%) in year 3. Reasons for nonadherence included inconvenience (32.7%), ineffectiveness (25.5%), improvement of symptoms (22.7%), and adverse reactions (14.5%). Children had higher adherence than adults (70.7% vs 55.0%) (p < 0.05). The dropout reasons were different among the children and adults groups (p < 0.005). The follow‐up work was carefully and thoroughly done. All the 311 (100%) patients accepted the telephone interview, and 296 (95.2%) patients submitted questions and got rapid replies from doctors online. Conclusion: Adherence to SCIT was less than satisfactory in the real‐life study. A close communication between doctors and patients is helpful in enhancing adherence with AIT in clinical practice. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy (AIT) represents at present the unique disease‐modifying treatment strategy for IgE‐mediated allergic diseases. AIT can induce clinical improvement of allergic asthma, including reduced symptoms, medication use, and improvement of quality of life, with a long‐lasting effect after cessation of treatment. Notably, the current asthma guidelines are now recommending sublingual immunotherapy as an add‐on therapy for asthma in adults and adolescents with house dust mite allergy. Clinical indications of AIT, with particular reference to pediatric asthma, mechanisms of clinical and immunological tolerance to allergens, and the potential biomarkers predicting clinical response are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks. Methods: In a randomized, double‐blind, placebo‐controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints. Results: The mean reduction in CSMS in the LPP vs placebo group was −15.5% (P = .041) during the peak period and −17.9% (P = .029) over the entire pollen season. LPP‐treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP‐treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication. Conclusion: Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well‐tolerated. [ABSTRACT FROM AUTHOR]

Summary: Background: Both subcutaneous and sublingual allergen immunotherapy (SCIT and SLIT) have been shown to effectively suppress allergic manifestations upon allergen exposure, providing long‐term relief from symptoms in allergic disorders including allergic asthma. Clinical studies directly comparing SCIT and SLIT report a different kinetics and magnitude of immunological changes induced during treatment. Comparative studies into the mechanisms underlying immune suppression in SCIT and SLIT are lacking. Objective: We aimed to establish an experimental model for grass pollen (GP) SCIT and SLIT that would allow a head‐to‐head comparison of the two treatments. Methods: BALB/c mice were sensitized with GP extract, followed by SCIT and SLIT treatments with various GP dosages. Subsequently, we challenged mice with GP and measured airway responsiveness (AHR), GP‐specific immunoglobulins, ear swelling tests (EST), eosinophilic inflammation in bronchoalveolar lavage fluid (BALF), and T cell cytokine release after restimulation of lung cells (IL‐5, IL‐10, and IL‐13). Results: We find that SLIT treatment was able to suppress allergen‐induced AHR, while allergic inflammation was not effectively suppressed even at the highest GP dose in this model. In contrast, SCIT treatment induced higher levels of GP‐specific IgG1, while SLIT was superior in inducing a GP‐specific IgG2a response, which was associated with increased Th1 activity in lung tissue after SLIT, but not SCIT treatment. Interestingly, SCIT was able to suppress Th2‐type cytokine production in lung cell suspensions, while SLIT failed to do so. Conclusions and clinical relevance: In conclusion, GP‐SCIT suppresses Th2 inflammation and induced neutralizing antibodies, while GP‐SLIT suppresses the clinically relevant lung function parameters in an asthma mouse model, indicating that the two application routes depend on partially divergent mechanisms of tolerance induction. Interestingly, these data mirror observations in clinical studies, underscoring the translational value of these mouse models. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy is an effective allergy treatment only if properly dosed. In this article we review the data on the probable effective dose range for subcutaneous immunotherapy and convert the recommended doses into a clinically relevant format. Methods: A comprehensive literature search of dose‐response subcutaneous immunotherapy studies was done of EBM databases, Medline database, PreMedline, and the National Guideline Clearinghouse for the period 1980–2016. Recommended doses were converted to the volume of allergen extract that should be added to a 5‐mL maintenance vial. Results: A safe and effective dose for subcutaneous immunotherapy is likely 5–20 μg of major allergen per injection. A 0.5‐mL injection from a 5‐mL maintenance vial containing 0.2 mL of manufacturer's extract of each allergen should reach the lower end of the probable effective dose range for most allergens. A larger volume of extract is required to reach that range when treatment includes cat, dog, or only 1 dust mite. Increasing beyond the commonly prescribed 0.2 mL of manufacturer's extract added to a 5‐mL treatment vial is reasonable for nearly all allergens to achieve a maintenance dose higher in the probable effective dose range. Conclusion: Current otolaryngic allergy practice usually escalates patients to 0.5‐mL injections from 5‐mL maintenance vials containing 0.2 mL of manufacturer's extract of each allergen. With the main exceptions of cat and dog, those injections administered 1 or 2 times per month likely provide an efficacious dose of allergen and are consistent with published guidelines. A larger volume of extract should be considered in certain clinical situations. [ABSTRACT FROM AUTHOR]

Abstract: Background: Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short‐course treatment with adjuvant‐free Lolium perenne peptides (LPP) following a 6‐week dose‐escalation protocol. Methods: In a prospective, dose‐escalation study, 61 grass pollen–allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8). Results: No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1‐fold, P < .001) and V8 (12.2‐fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (−54.6%, P < .001) and V8 (−71.6%, P < .001) compared to V1. The absolute decrease in IgE‐facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8. Conclusion: Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Allergen‐specific immunotherapy is the only causal form of therapy for IgE‐mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. Methods: A non‐interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. Results: A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Conclusions: Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. [ABSTRACT FROM AUTHOR]

Abstract: Background: Since 1988, numerous allergen immunotherapy guidelines (AIT‐GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely underused. Objective: To evaluate AIT‐GLs with AGREE‐II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. Methods: Allergist, from different continents, knowledgeable in AIT and AGREE‐II trained were selected into the project team. The project received methodologists’ guidance. AIT‐GLs in any language were sought from 1980 to 2016; AIT‐GLs were AGREE II‐evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists’ consulting. Results: We found 31 AIT‐GLs (15 post‐2010), ranging from local consensus reports to international position papers (EAACI, AAAAI‐ACAAI, WAO). Pre‐2010 GLs scored 1.6‐4.6 (23%‐67%) and post‐2010 GLs scored 2.1‐6 (30%‐86%), on a 7‐point Likert scale. The highest scores went to: German‐Austrian‐Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT‐GL (4.7). These were also the only 3 GLs that received “yes” of both evaluators to the item: “I would recommend this GL for use.” The domains of “Stakeholder involvement” and “Rigor of Development” only scored 3/7, and “Applicability” scored the lowest. Strikingly, newer GLs only scored clearly better in “Editorial independence” and “Global evaluation.” Conclusions: In AIT‐GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the “Scientific rigor” domain flawed. When resources are limited, transculturizing a high‐quality GL might be preferable over developing a GL from zero. Our study and AGREE‐II could help to select the best candidate. Clinical Implications: We here evaluate allergen immunotherapy guideline (AIT‐GL) quality. Only high‐quality AIT‐GLs should be consulted for AIT management decisions. In low‐resource settings, transculturization of these is preferred over developing low‐quality guidelines. [ABSTRACT FROM AUTHOR]

Background: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). Methods: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence‐based review (EBR), or evidence‐based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. Results: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. Conclusion: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding. [ABSTRACT FROM AUTHOR]

Background Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture. Objective To find the optimal dose of a Phleum pratense ( P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation. Methods In this double-blind, placebo-controlled study (Eudra CT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units ( TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing ( ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score ( TNSS) assessed in the allergen exposure chamber ( AEC), the changes in P. pratense-serum-specific IgG4 and the incidence of adverse events ( AEs). Results All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation. Conclusions & Clinical relevance The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured. [ABSTRACT FROM AUTHOR]

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa. [ABSTRACT FROM AUTHOR]

Background The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy ( SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite ( HDM)-induced allergic rhinoconjunctivitis ( ARC) using a titrated nasal provocation test ( TNPT). Methods In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. Results After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of ≥20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups. Conclusion In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of ≥20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development. [ABSTRACT FROM AUTHOR]

Background Allergen-specific immunotherapy (IT) is a disease-modifying treatment for allergic rhinitis, and adherence to the treatment schedule is important for a successful outcome. Several methods for delivering IT are now available, but little information is known concerning patient preference for these options. Methods Over a 12-month period, 228 adults scheduled to undergo outpatient allergy testing were offered a survey to rank 4 different IT delivery methods: subcutaneous IT (SCIT), sublingual IT using liquid extracts (SLIT), sublingual allergy immunotherapy tablets (AIT), and oral mucosal immunotherapy (OMIT) using a toothpaste delivery vehicle. Results Of the participants who completed the survey, ranking scores (mean ± SD) for SCIT, SLIT, AIT, and OMIT, with 1 being the highest rank, were 3.36 ± 1.02, 2.03 ± 0.92, 2.30 ± 1.02, and 2.32 ± 1.05, respectively. The number of participants who ranked SCIT, SLIT, AIT, or OMIT as their number 1 choice was 24 (10.5%), 79 (34.6%), 61 (26.8%), and 64 (28.1%), respectively. When comparing first choice rankings, there were no statistically significant differences between SLIT, AIT, or OMIT, yet all 3 groups ranked higher than SCIT ( p < 0.0001). Conclusion SCIT earned the lowest mean rank and had the least number of participants rank it as the most preferred method. Among the other 3 choices, by mean scores, SLIT was preferred most compared to either AIT or OMIT; but when considering first choices only, there were no significant differences in preference. Most of the study participants identified the convenience of home IT administration as the most important factor in their ranking. [ABSTRACT FROM AUTHOR]

Background Patient compliance is critical for successful allergen immunotherapy (AIT). Previous studies suggest that AIT compliance is worse outside of controlled clinical trials, with reported subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) noncompliance at 11% to 50% and 3% to 25%, respectively. Methods A retrospective review of 384 AIT patients at a single, tertiary care otolaryngic allergy practice evaluated SCIT and SLIT compliance, based on treatment stage. SCIT compliance was defined as the number of 2-week breaks per year or in compliance with their defined schedule: excellent = 2 or fewer; good = 3 to 4; fair = 5 to 6; and poor = 7 or more. Compliance with SLIT was defined as the number of days vials were refilled within the defined expiration date: excellent = 10 days or fewer; good = 11 to 15 days, fair = 16 to 20 days; and poor = 25 or more days. Fisher exact and chi square tests were used for statistical analysis. Results Seventy-four SCIT and 200 SLIT patients had data appropriate for analysis. Compliance rates were excellent (62%) or good (22%) in 62 SCIT patients and excellent (31%) or good (35%) in 131 SLIT patients. Comparing excellent compliance rates, SCIT patients had a higher rate of excellent compliance at all stages of treatment compared to SLIT patients ( p < 0.05). For SCIT patients there was no significant difference in excellent compliance rates between escalation, first year of maintenance, and greater than 1 year of maintenance ( p > 0.05). Conclusion The results of this study showed higher rates of patient adherence to treatment protocols among SCIT patients. There was no decrease in SCIT compliance rates across treatment stages. [ABSTRACT FROM AUTHOR]

Background: The majority of allergic patients are poly-sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ® grass SLIT-tablet and were treated with concomitant AIT products. Methods: In a non-interventional, open-label, observational study in Germany treatment of patients with the SQ® grass SLIT-tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ® grass SLIT-tablet and after 1-3 months of treatment. Tolerability of the treatment with the SQ® grass SLIT-tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities. Results: In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3%) patients with concomitant AIT, and AEs considered related with the SQ® grass SLIT-tablet in 49 (30.6%) and with concomitant AIT in 18 (11.3%) patients. Treatment was discontinued due to ADRs in 12 (7.5%) patients and severity of ADRs was assessed mild or moderate in 29 (18.1%), and severe in 20 (12.5%) patients. Most common reactions were localised at the application site of the SQ® grass SLIT-tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ® grass SLIT-tablet if given with concomitant AIT was assessed as "good" or "very good" by 91.0% of patients and 91.6% of physicians. Conclusions: In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ® grass SLIT-tablet was administered with concomitant SCIT or SLIT. [ABSTRACT FROM AUTHOR]

Background: The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. Methods: In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Results: Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". Conclusions: The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation. [ABSTRACT FROM AUTHOR]

Background We previously reported the safety of a self-administered subcutaneous immunotherapy (SCIT) protocol. Here we report the results of the retrospective efficacy trial of the United Allergy Service (UAS) self-administered SCIT protocol. We hypothesized that by utilizing a slow SCIT buildup phase, designed to attain recommended allergen concentrations on a cumulative basis, efficacious outcomes and clinical relevance would be achieved. Methods We enrolled 60 SCIT patients and 56 control patients. The study contrasted baseline and treatment period combined symptom plus medication scores (CSMS) as the primary outcome measure and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores as the secondary study outcome measure. Changes in pollen counts were also examined with regard to effects on these efficacy parameters. Results The treatment group showed significantly improved CSMS (standardized mean difference [SMD]: −1.57; 95% confidence interval [CI], −1.97 to −1.18; p < 0.001) and RQLQ (SMD: −0.91; 95% CI, −1.23 to −0.59; p < 0.001). These treatment group outcome measures were respectively improved by 33% and 29% compared to baseline and greater than 40% in comparison to the control group ( p < 0.0001). Significant results were also shown when examining these outcome measures with regards to either monotherapy or poly-allergen SCIT. Furthermore, a comparison to recent meta-analyses of SCIT studies showed equivalent efficacy and clinical relevance. Assessment of pollen counts during the baseline and treatment periods further corroborated the efficacy of the UAS SCIT protocol. Conclusion These efficacy results, and our previous safety results, show that a carefully designed and implemented self-administered SCIT protocol is efficacious and safe. [ABSTRACT FROM AUTHOR]

Background: The majority of allergic patients are poly‐sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ® grass SLIT‐tablet and were treated with concomitant AIT products. Methods: In a non‐interventional, open‐label, observational study in Germany treatment of patients with the SQ® grass SLIT‐tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ® grass SLIT‐tablet and after 1–3 months of treatment. Tolerability of the treatment with the SQ® grass SLIT‐tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities. Results: In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3 %) patients with concomitant AIT, and AEs considered related with the SQ® grass SLIT‐tablet in 49 (30.6 %) and with concomitant AIT in 18 (11.3 %) patients. Treatment was discontinued due to ADRs in 12 (7.5 %) patients and severity of ADRs was assessed mild or moderate in 29 (18.1 %), and severe in 20 (12.5 %) patients. Most common reactions were localised at the application site of the SQ® grass SLIT‐tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ® grass SLIT‐tablet if given with concomitant AIT was assessed as "good" or "very good" by 91.0 % of patients and 91.6 % of physicians. Conclusions: In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ® grass SLIT‐tablet was administered with concomitant SCIT or SLIT. [ABSTRACT FROM AUTHOR]

Background: The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. Methods: In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Results: Treatment‐related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty‐eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". Conclusions: The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation. [ABSTRACT FROM AUTHOR]

Background Asthma and allergic rhinitis are 2 of the most prevalent chronic medical diseases. Asthma is estimated to affect 8% of adults and 9% of children, with nearly 300 million people affected worldwide. Poorly controlled allergic rhinitis may be associated with worsening asthma symptoms over time. Various treatments have been proposed in the improvement and prevention of asthma in children and adults with allergic symptoms, which have included pharmacotherapy with antihistamines and topical intranasal corticosteroids, as well as allergen-specific immunotherapy. Methods Articles were selected through PubMed and personal knowledge of the authors based on a comprehensive literature review examining whether treatment of allergic rhinitis improves and/or prevents concomitant symptoms of asthma. The largest and highest-quality studies were included in the literature review. The search selection was not standardized. Articles written in a language other than English were excluded. Results Clinical trials have showed improvement in asthma symptoms with concomitant treatment of allergic rhinitis with antihistamines and topical intranasal corticosteroids, though improvement in objective pulmonary function parameters has not been uniformly demonstrated with antihistamine use alone. There is very strong evidence to suggest that subcutaneous and sublingual immunotherapy may in addition prevent the progression of asthma in high-risk atopic patients by inducing immunological tolerance. Conclusion Traditional pharmacotherapy with antihistamines and topical intranasal steroids has been shown to improve allergic rhinitis symptoms with concomitant allergic asthma; however, only allergen-specific immunotherapy offers long-term control in improving asthma symptoms, exacerbations, and likely ultimate prevention in developing asthma. [ABSTRACT FROM AUTHOR]