Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

Introduction: The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. Materials and Methods: A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Result: Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. Conclusions: The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

Efficacy and safety of Artemisia annua sublingual immunotherapy in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons.

OBJECTIVE: This study investigates the efficacy and safety of sublingual immunotherapy (SLIT) with A. annua allergens in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons. METHODS: Seventy patients with moderate-severe seasonal allergic rhinoconjunctivitis were divided evenly into the SLIT and control groups. The SLIT last from 3 months before the summer-autumn pollen season in 2021 till the end of the summer-autumn pollen season in 2022. The daily individual symptom score, total rhinoconjunctivitis symptom score (dTRSS), total medication score (dTMS), combined score of medication and rhinoconjunctivitis symptom (dCSMRS), visual analog scale (VAS) score, and adverse events (AEs) were evaluated. RESULTS: The average pollen concentration in 2022 was twice that previous two-year during the pollen season. Fifty-six patients completed treatments (SLIT group: 29, control group: 27). Compared with baseline, the individual symptoms, dTRSS, dTMS, dCSMRS, and VAS scores of SLIT group declined in 2021. After 16 months of SLIT, all efficacy indexes in 2022 were still lower than baseline and equivalent to those in 2021. In control group, the efficacy indexes in 2022 were higher than that in 2020 and 2021. The efficacy indexes of SLIT group were lower than those of control group in 2021 and 2022. SLIT is effective for both mono- and poly-sensitized patients. AEs incidence in SLIT group was 82.7% without severe AEs. CONCLUSIONS: The A. annua-SLIT can obtain efficacy and safety over two pollen seasons for patients with moderate-severe seasonal allergic rhinoconjunctivitis.

Double-Blind, Placebo-Controlled Study of E-B-FAHF-2 in Combination With Omalizumab-Facilitated Multiallergen Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.

Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. METHODS: Thirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abelló) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. RESULTS: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-γ levels increased only in the actively treated group. CONCLUSION: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

Off-label Use of Oral Immunotherapy for Rhinoconjunctivitis and Asthma due to Grass Pollen: A Safe and Effective Alternative in Patients over 65 Years Old: A Series of Case Reports.

INTRODUCTION: Allergic rhinoconjunctivitis and asthma are the most common IgE-mediated diseases worldwide. Allergen-specific immunotherapy (AIT) is currently the only modifying treatment for these IgE-mediated diseases in both children and adults. Subcutaneous immunotherapy is widely used, but in patients over 65 years old, there may be an increased risk of adverse reactions and a worse response to treatment. Oral immunotherapy (OIT) has been proven to be effective and safe, but currently, in most countries, it has been licensed only for patients up to 65 years old based on its technical datasheet. So far, no studies on the efficacy and safety of this type of immunotherapy in patients older than 65 years old have been published. CASE PRESENTATION: We present four patients older than 65 years old with a diagnosis of moderate seasonal rhinoconjunctivitis and moderate-persistent seasonal pollen-induced asthma. Off-label use of oral immunotherapy (OIT) for grass pollen was prescribed due to the severity of their rhinoconjunctivitis symptoms and the worsening of asthma symptoms during the spring. Improvement in the rhinoconjunctivitis and asthma symptoms was reported by all patients since the first spring season and was maintained during the following two years of follow-up. There were no systemic reactions, and only two patients initially had self-limiting oral pruritus. CONCLUSION: Oral immunotherapy for pollens appears to be a convenient, effective, and safe option in older patients (>65 years) with comorbidities after a three-year treatment. This is, to the best of our knowledge, the first report on the off-label use of OIT in patients over 65 years old with symptoms of allergic rhinoconjunctivitis and asthma.

Efficacy and safety of sublingual versus subcutaneous immunotherapy in children with allergic rhinitis: a systematic review and meta-analysis.

Aim: To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison. Results: Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26). Conclusion: Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians. Systematic review registration: PROSPERO (CRD42023460693).

Safety of subcutaneous immunotherapy with carbamylated allergoids based on data from a pharmacovigilance database.

Aims: Allergen immunotherapy aims to induce tolerance, which persists after its discontinuation, to targeted allergens. However, concern exists regarding the use of subcutaneous immunotherapy with whole extracts due to frequently reported events of anaphylactic reactions. Materials & methods: In this pharmacovigilance study, the authors assessed the safety of subcutaneous immunotherapy with the monomeric allergoid Lais-in using a database of adverse reactions documented in real-world postmarketing reports from 2010 to 2020. Results & conclusion: The results showed that more than 171,916 doses of Lais-in were administered from 2010 to 2020, resulting in five adverse drug reactions. Nonserious adverse events, including hives, eye irritation and skin reactions, were reported. These data indicate that monomeric allergoids prevent serious reactions to subcutaneous immunotherapy.

Effectiveness and adverse reactions to subcutaneous immunotherapy in children with allergic rhinitis/asthma.

OBJECTIVE: Adverse reactions, which are mostly local and rarely systemic, can be seen during subcutaneous immunotherapy (SCIT). It was not possible to continue SCIT at times due to systemic reactions. The purpose of the present study was to identify the incidence and risk factors associated with adverse reactions during subcutaneous allergen-specific immunotherapy (AIT). METHODS: A total number of 344 patients under 18 years old with allergic rhinitis and/or asthma who underwent SCIT between 2005 and 2021 were included in the study. Demographic characteristics of the patients, laboratory findings [Total Immunglobulin E(IgE), aeroallergen prick test, inhaler, and allergen specific IgE(sIgE) and eosinophil counts], and adverse events observed during AIT were recorded retrospectively. Descriptive and univariate/multivariate logistic regression analyses were used to identify risk factors for adverse events. RESULTS: Among 344 patients, 33.4% (n = 115) were female, mean age was 133.1 ± 41.0 months, and 42.2% (n = 145) were >12 years old. One hundred-thirty eight (40.1%) of the patients were mono-sensitized, 47 (13.7%) had asthma, 207 (60.2%) allergic rhinitis, and 90 (26.2%) asthma and allergic rhinitis. Single allergen content was administered to 187 (54.4%) patients (62 mite, 114 grass mix, 11 olea), and multiple allergens to 157 (45.6%) patients (121 pollen mix, 36 other (mite/alternaria)]. A total number of 33.008 injections were administered. 840 adverse reactions (262 (31.1%) at up-dosing phase, 578 (68.8%) at maintenance phase) in 195 (56.7%) patients were observed. Among the adverse reactions, 632 (75.2%) were local, 160 (19%) large local, and 48 (5.7%) (39 at maintenance, 9 at up-dosing) (in 31 patients) were systemic (28 Grade 1, 12 Grade 2, 8 Grade 3). Adrenalin was administered to 8 patients with Grade 3 systemic reaction (8/33008; %0.024). Adverse reactions, especially local ones, were seen more frequently in children under 12 years old (p < 0.001). Patients sensitized with grass pollen (p:0.01) and mite (p:0.004), and those who had received SCIT with pollen mixture had more adverse reactions than the others. More adverse reactions were observed in SCIT containing calcium-phosphate as adjuvant (p: 0.01). Local reactions were risk factors for large local (OR = 3.591, %95 CI:2.064-6.247, p < 0.001) and systemic (OR = 2.190, %95 CI:1.005-4.722 p = 0.046) reactions at univariate analyses. Total nasal symptom scores, Visual Analog Scale and asthma symptom control test decreased after one year of treatment (p < 0.01). CONCLUSION: SCIT is a safe and effective treatment method in childhood that leads to improvements in all nasal symptoms and asthma after one year of treatment.

An overview of the current state of food desensitization.

PURPOSE OF REVIEW: To highlight the current evidence on food desensitization in children with food allergy. RECENT FINDINGS: Food Allergen Specific Immunotherapy (FA-AIT) is currently recognised as a treatment option for treating children with allergy at least to the main common foods (i.e. milk, egg and peanut). The oral route of administration has been proven to be the most effective in achieving desensitisation. Efforts are devoted to overcome the current unmet needs mainly related to safety issues and long-term efficacy, as well as adherence to the treatment and improvement of health-related quality of life. In this perspective, alternative routes of administration and adjunctive treatments are under investigation. SUMMARY: The future of food allergy management is a personalised approach based on a shared decision-making that takes into account the needs of patients and families. Health professionals will be able to offer multiple treatment options, including FA-AIT with adjunctive or alternative therapies. Thus, patients should be correctly identified, using validated predictive factors, in order to select appropriate candidates for these therapies.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid immunotherapy in adult patients with allergic asthma and rhinitis: A real-life prospective observational study.

INTRODUCTION: Although clinical trials have shown the efficacy and safety of allergen-specific immunotherapy (AIT) in the treatment of allergic asthma, there is a need for real-life studies. We aimed to assess the effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid (Acarovac Plus®) in patients with house dust mite (HDM)-induced allergic asthma in a real-life study. METHODS: A subanalysis of a multicenter, prospective, observational, real-life study. Patients with rhinitis and allergic asthma caused by HDMs were assessed before AIT with Acarovac Plus® and at 6 and 12 months after this treatment. Assessment parameters were percentage of days with asthma symptoms, percentage of days on asthma medication, classification of asthma according to Spanish guidelines for the management of asthma, asthma-related quality of life (quality of life in adults with asthma questionnaire [QLAAQ]), perception of symptoms (visual analog scale [VAS]), and treatment satisfaction (treatment satisfaction questionnaire for medication [TSQM]). Safety was assessed by the number and severity of adverse reactions. RESULTS: This subanalysis included 55 patients. Treatment with Acarovac Plus® showed significant differences in the analyzed variables when the baseline visit was compared with the 12-month visit: reduction of the mean (SD) percentage of days with asthma symptoms (23.9 [9.2] vs. 5.1 [12.8]; p = .002), of the mean [SD] percentage of days on asthma medication (67.6 [42.9] vs. 45.1 [46.8]; p = .002), and of the percentage of patients with persistent asthma (78.2% vs. 38.9%; p = .009). Acarovac Plus® significantly improved asthma-related quality of life, as shown by a decrease of 1.39 points in QLAAQ score at 12 months (p < .001), and in the subjective perception of symptoms on the VAS (-3.50, p < .0001). Patients showed high treatment satisfaction according to the TSQM, and it was well tolerated. No serious adverse events were reported. CONCLUSIONS: Acarovac Plus® was effective and safe for the treatment of patients with HDM-induced allergic asthma in a real-life study.

Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study.

OBJECTIVES: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. METHODS: The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. RESULTS: The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of >0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of >0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. CONCLUSION: Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.

High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase.

BACKGROUND: The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. METHODS: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. RESULTS: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. CONCLUSION: Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.

Accelerated Dose Escalation with 3 Injections of an Aluminum Hydroxide-Adsorbed Allergoid Preparation of 6 Grasses Is Safe for Children and Adolescents with Moderate to Severe Allergic Rhinitis.

A high-dose, accelerated escalation schedule during subcutaneous allergen-specific immunotherapy (AIT) is safe and well-tolerated in adults. However, there are no data in children and adolescents. The aim of the present trial was to assess safety and tolerability of an accelerated dose escalation schedule of an AIT with a grass pollen allergoid in children and adolescents with moderate to severe seasonal rhinoconjunctivitis in a multicenter, open-label, randomized phase II trial. The dose escalation scheme for patients in the One Strength Group included 3 injections with 1 strength B (10,000 TU/mL), whereas the dose escalation scheme for the Standard group included 7 injections with 2 strengths A (1,000 TU/mL) and B (10,000 TU/mL) of an allergoid grass pollen preparation. Overall, n = 50 children (n = 25 in each group; mean age 8.9 + 1.54 years) and n = 37 adolescents (n = 20 and n = 17; 14.2 + 1.62 years) were randomized. For all patients, the mean treatment duration was 59.4 days in the One Strength group and 88.6 days in the Standard group. Treatment-emergent adverse events (TEAEs) related to AIT were reported in 52 and 40% in children and 35 and 35.3% in adolescents, respectively. Systemic allergic reactions occurred in about 5% of our patients and were reported in more patients of the One Strength group (6.7 vs. 2.4%). All systemic reactions were classified as WAO Grade 1. Accelerated high-dose escalation with an aluminum hydroxide-adsorbed grass pollen allergoid can be initiated with a safety and tolerability profile comparable to the standard dose escalation schedule in children and adolescents with allergic rhinitis with or without asthma.

Principles of Allergen Immunotherapy and Its Clinical Application in China: Contrasts and Comparisons with the USA.

Allergen immunotherapy (AIT) for allergic rhinitis (AR), asthma, and other allergic diseases has developed quickly. House dust mite (HDM), Artemisia (wormwood), Humulus japonicus (Japanese hop), Alternaria alternata, and Cladosporium herbarum are the five most common inhalant allergens in China. AIT has been performed in China for over 60 years. With the support of the Chinese Medical Association (CMA) and the Chinese Medical Doctors Association (CMDA), the Chinese College of Allergy and Asthma (CCAA) was established in 2016 as a specialized branch of CDMA and is the main certification authority for AIT. Chinese allergists and scientists have made tremendous progress in the development of AIT. There have been many publications by Chinese allergists and scientists worldwide encompassing original research studies, systematic reviews, case studies, and clinical trials. Currently, conventional subcutaneous immunotherapy (SCIT) is the preferred AIT in China, but sublingual immunotherapy (SLIT) is beginning to gain recognition. An increasing number of clinical trials have been conducted to investigate the clinical efficacy and side effects of SLIT and SCIT. In China, HDM is the only commercial standardized allergen extracts in clinical use, whereas the others are crude allergen extracts. Besides standardized allergen extracts, other forms of hypoallergenic extracts are still being investigated and developed in China. Immunotherapy in China is similar to that in the USA in which allergen extracts can be mixed for SCIT. However, allergen extracts cannot be mixed for SCIT in Europe.

Acupuncture as an add-on therapy to sublingual allergen-specific immunotherapy for patients with allergic rhinitis.

This study retrospectively analyzed the effectiveness of acupuncture as add-on therapy (AAOT) to sublingual allergen-specific immunotherapy (SASIT) for patients with allergic rhinitis (AR). A total of 120 eligible cases of adult patients with AR were included in this retrospective study. Of these, 60 patients received AAOT plus SASIT and were assigned to a treatment group, while the other 60 subjects underwent SASIT only, and were assigned to a control group. Primary outcome was AR symptoms. The secondary outcome was quality of life, as evaluated by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). In addition, adverse events were also recorded during the study period. All outcomes were assessed before and after 8 weeks treatment. After 8 weeks treatment, patients in the treatment group had much better effectiveness in symptoms relief (P <.05), and quality of life improvement (activity domain, P = .04; practical domain, P = .03), compared with patients in the control group. In addition, although patients in the treatment group reported more mild pain at local area after the treatment than that in the control group (P <.01), no patients stopped the treatment. The results of this study showed that AAOT plus SASIT achieved more benefits in patients with AR than SASIT alone.

Efficacy and safety of birch pollen allergoid subcutaneous immunotherapy: A 2-year double-blind, placebo-controlled, randomized trial plus 1-year open-label extension.

BACKGROUND: Previous clinical trials with birch pollen subcutaneous immunotherapy have been conducted over a 1- to 2-year treatment period and involved mostly a single geographic location. OBJECTIVE: This study (EudraCT-Number: 2005-000025-35) intended to evaluate the effect of subcutaneous immunotherapy with high-dose hypoallergenic birch pollen allergoid in patients with confirmed moderate to severe seasonal allergic rhinitis/rhinoconjunctivitis over a 3-year course in 19 European centres. METHODS: Adults with confirmed birch pollen allergy (n = 253) were randomized to preseasonal placebo (n = 129) or active treatment (n = 124). Primary endpoint was change in Symptom Medication Score after 2 years treatment (2007). RESULTS: The change in Symptom Medication Score of active- vs placebo-treated patients for the Full Analysis Set (n = 227, 15.2% reduction, P = 0.0710) and Per-Protocol Set (n = 216, 16.7% reduction, P = 0.0523) showed a positive trend, although significance was not achieved. The primary endpoint, assessed in 2007, coincided with the lowest pollination during the study period. In a subgroup analysis of patients in the north-eastern region (n = 102), where birch is the major tree and consequently patients' exposure is higher, changes in Symptom Medication Score (32.7% reduction, P = 0.0034) and median number of well days (P = 0.0232) were highly significant in favour of the active group. During the open-label third year of treatment, the mean Symptom Medication Score of active-treated patients was further reduced despite an increased pollen count. Subcutaneous immunotherapy was well tolerated and consistent with the known safety profile. CONCLUSIONS AND CLINICAL RELEVANCE: Although the primary endpoint was not reached for the Full Analysis Set, a significant and clinically relevant effect on Symptom Medication Score was clearly demonstrated for the subgroup of patients in the north-eastern region of Europe, where birch is the predominant tree species. Proving efficacy of birch allergen subcutaneous immunotherapy is challenging due to the numerous factors influencing birch pollen allergen exposure in field studies.

Birch pollen-specific subcutaneous immunotherapy reduces ILC2 frequency but does not suppress IL-33 in mice.

BACKGROUND: The underlying mechanism of allergen-specific subcutaneous immunotherapy (SCIT) is not yet fully understood, but suppression of allergen-specific Th2 cells and production of allergen-specific IgG4 antibodies are two hallmarks. The impact on the innate arm of the immune system is far less clear. OBJECTIVE: The aim of this study was to investigate the effect of birch pollen (BP) SCIT on the innate immune response in a BP SCIT mouse model. METHODS: Mice with birch pollen-induced allergic airway inflammation received weekly subcutaneous immunotherapy injections with birch pollen extract (BPE) adsorbed to alum. The effect of the BP SCIT on innate cytokine levels in lung, the number and the functionality of ILC2s and the airway inflammation was determined. RESULTS: Mice with BP allergy had an increased level of the innate cytokines IL-33, IL-25, GM-CSF and IL-5+ ILC2s in the lungs. BP SCIT suppressed the number of IL-5+ ILC2s, mast cell tryptase release, Th2 cytokine production, eosinophil recruitment and peribronchial inflammatory infiltrates. In contrast, innate cytokine production and collagen deposition in the airways were not affected. CONCLUSION AND CLINICAL RELEVANCE: BP SCIT is able to suppress the adaptive and part of the innate immune response, but this is not sufficient to inhibit collagen deposition and the IL-33 expression in the airways in mice.

Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy.

BACKGROUND: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose. METHODS: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED50 ), a measure of potency. RESULTS: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups. CONCLUSION: Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.