House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

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.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

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; 𝜌 = -.47, p = .0006, nasal; 𝜌 = -.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.

Is It Possible to Predict Systemic Adverse Effects in Subcutaneous Allergen Immunotherapy? Single-Center Experience.

INTRODUCTION: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. METHODS: The files of 295 patients who had received SCIT were evaluated retrospectively. RESULTS: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). CONCLUSION: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

Does skin prick test response intensity predict symptom severity and efficacy of subcutaneous immunotherapy in allergic rhinitis?

OBJECTIVES: To investigate the effect of response intensity of allergen skin prick test (SPT) on symptom severity and long-term efficacy of dust mite subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR). METHODS: AR Patients diagnosed with dust mite allergy and completed 3 years of SCIT were collected and classified into three groups: grade 2 (SPT of + +), grade 3 (SPT of + + +) and grade 4 (SPT of + + + +). Comparisons between groups were performed to examine the associations of SPT categories and symptom severity and the long-term efficacy of SCIT in AR. RESULTS: 181 AR patients were included. There was no significant difference in the baseline TNSS, SMS, RQLQ and VAS, and particularly to symptom severity grading among three SPT grade groups (P > 0.05). The moderate-severe AR was more likely to be smoking and accompany with asthma and had higher prevalence of sensitization to cockroach, mixed grass and tree pollen than mild AR (P < 0.05). Prevalence of sensitization to cockroach, mixed grass, ragweed and animal dander was increased in AR patients with asthma and allergic conjunctivitis (P < 0.05). Furthermore, after 3 years of SCIT, no statistical differences in TNSS, SMS, RQLQ, VAS and long-term efficacy were observed among the three SPT grade groups (P > 0.05). Similarly, long-term outcomes of patients with different SPT grades did not differ among different clinical characteristics and different efficacy determination criteria (P > 0.05). CONCLUSIONS: The SPT response intensity cannot be used as an objective evaluation index for symptom severity and the long-term efficacy of SCIT in AR patients.

Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year. OBJECTIVE: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response. METHODS: We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16. RESULTS: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response. CONCLUSIONS: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Allergen immunotherapy in asthma.

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses.

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OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.

Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

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.

Evaluation of Safety, Efficacy, and Compliance of Intralymphatic Immunotherapy for Allergic Rhinoconjunctivitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Intralymphatic immunotherapy (ILIT) is an emerging type of allergen immunotherapy with fewer injections and shorter course for allergic rhinoconjunctivitis (ARC). The efficacy and safety have not been confirmed by informative and powerful evidence yet. METHODS: A systematic review and meta-analysis were conducted through electronic searching with PubMed, Web of Science, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). The safety (incidence of adverse events [AEs]), compliance (percent of patients completing treatment), and clinical efficacy of ILIT were evaluated. Clinical efficacy could be assessed by improvement of subjective symptom and rescue medication use or the nasal tolerance to specific allergen. This study is registered with PROSPERO (CRD42022353562). RESULTS: 12 randomized controlled trials (RCTs) comparing ILIT with placebo and 3 trials (2 RCTs and one case-control study) comparing ILIT and SCIT were included in this review. Totally, 582 patients diagnosed as AR or ARC were enrolled. Almost all the AEs were mild-to-moderate reactions except 2 patients developed anaphylactic reactions at the intralymphatic injection dose 5,000 SQ-U in one study. ILIT got higher incidence of local AEs than placebo, but their incidence of systemic AEs was similar. ILIT was safer than SCIT (p < 0.05). Almost all the patients could complete ILIT treatment, and the most common reason for discontinuation of ILIT was AEs. The compliance of patients receiving ILIT seemed higher than patients receiving SCIT. ILIT could significantly ameliorate subjective allergic symptoms, especially for seasonal ARC, and increase nasal tolerance, similar to SCIT. CONCLUSION: ILIT was a safe and effective treatment for ARC and could achieve comparable clinical improvement with SCIT with shorter duration and higher compliance. Moreover, ILIT was safer than SCIT.

Efficacy and safety of house dust mite subcutaneous immunotherapy in polysensitized children with allergic asthma.

INTRODUCTION: The aim of this study was to compare the efficacy and safety of 3 years of HDM subcutaneous immunotherapy (HDM-SCIT) in allergic asthma (AA) children with mono- and polysensitized. METHODS: This was a retrospective observational study, 51 AA children (aged 4-14 years) who had completed 3 years of standardized HDM-SCIT were enrolled in. Based on skin prick tests (SPT) and allergen-specific IgE antibody (sIgE) test results, children were classified into two groups: the monosensitized group (n = 31) and the polysensitized group (n = 20). Total asthma symptoms score (TASS), total medication score (TMS), visual analog scale (VAS) scores, fractional exhaled nitric oxide (FeNO), lung function parameters, and adverse reactions were evaluated before treatment and at 6 months, 1, 2, 3 years of HDM-SCIT. RESULTS: In terms of effectiveness, compared to baseline, TASS, TMS, VAS, FeNO and lung function parameters were significantly improved in both groups after 3 years of HDM-SCIT (all P < 0.05). The comparison between the two groups showed that efficacy indicators were no statistically significant difference at follow-up time points (all P > 0.05) except PEF%pred at 6 months (P = 0.048). In terms of security, the number of adverse reactions in both groups also no statistical difference between the two groups (all P > 0.05). CONCLUSION: This study confirmed that no significant difference was observed in the clinical efficacy and safety of HDM-SCIT between mono-and polysensitized children with allergic asthma.

Effects of subcutaneous immunotherapy in allergic rhinitis children sensitive to dust mites.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is now the only treatment that can modify the natural course of allergic rhinitis (AR). However, not all children with AR benefit from SCIT. OBJECTIVE: To evaluate the efficacy of SCIT in dust-mites-induced AR children and explore correlative factors predicting treatment response to SCIT. METHODS: 225 children aged 4-17 years old with AR were recruited from January 2016 to September 2019, and monitored at baseline, 4, 12, and 24 months after the start of SCIT treatment. The visual-analogue-score (VAS) was used to assess the clinical symptoms. Multivariate binary logistic regression analyses and receiver operating characteristic curves were used to explore correlative factors in predicting the efficacy of SCIT. RESULTS: The significant declines in VAS started after 4 months of SCIT and continued to improve throughout the study compared with baseline. An increase in children's age (OR=0.688, 95%CI: 0.479-0.988) and those with allergic history (OR=0.097, 95%CI: 0.009-1.095) were negatively associated with the risk of poor efficacy. Polysensitized children were more likely to suffer poor efficacy (OR=15.511 95%CI: 1.319-182.355). The clinical response at month 4 (r=0.707) and month 12 (r=0.925) was related to that at month 24. The area under the curve (AUC) for improvement at month 4 and month 12 was 0.746 and 0.860, respectively. CONCLUSION: Our study confirmed the clinical efficacy of SCIT in AR children. Children with younger age, negative allergic history, and multiple allergens may predict a worse efficacy. The onset of action and the clinical response to SCIT in the second year can be predicted as early as by month 4.

Evaluation of pain-alleviating strategies during allergy shots (subcutaneous immunotherapy): a randomized controlled pilot study.

Summary: Background. Subcutaneous immunotherapy (SCIT) is a potential disease-modifying therapy effective for treatment of various allergic disorders. Pain and fear are common concerns of children, which can pose stress and result in negative experiences. The purpose of this study was to evaluate and compare the effectiveness of three marketed distraction devices and ethyl chloride spray (a routinely used topical anesthetic agent for painful procedures), the current clinical standard of care in reducing the perception of needle pain during SCIT administration in children. Methods. 40 children, aged 4-17 years, receiving SCIT with use of one of three alternative pain therapies or with standard practice were enrolled. Participants were randomly assigned to one of the pain-modifying interventions. The three interventional groups were ShotBlocker® (Bionix, Toledo, OH, USA), Buzzy® I (Pain Care Labs, Atlanta, GA, USA) (vibration only), and Buzzy® II (vibration with ice). Control group was ethyl chloride spray. The study consisted of two visits during SCIT administration process. Results. Of these 40 children, 12 received the ShotBlocker, 8 received the Buzzy I, 11 received the Buzzy II, and 9 received ethyl chloride spray (control group). Conclusions. There were no significant differences found between each of the distraction devices and between the control group. Type II error/false negative finding cannot be ruled out because of a small sample. Therefore, we cannot conclude that no true difference exists between each distraction device and the control group simply because of occurrence of a non-significant P-value in our study.

Clinical evaluation of subcutaneous immunotherapy with a polymerized molecular allergoid of Alt a 1 in patients with allergic rhinoconjunctivitis and/or allergic asthma caused by the mould Alternaria alternata.

Summary: This is a retrospective analysis of the clinical evolution of 14 patients diagnosed with allergic rhinoconjunctivitis (AR) and/or allergic asthma (AA) caused by Alternaria alternata, who were attended by the allergology service of Vega Baja Hospital of Orihuela (Alicante, Spain). The purpose was to assess the clinical impact and safety of 1-year of subcutaneous immunotherapy with a polymerized molecular allergoid of Alt a 1. Impact of the treatment on allergic diseases (mean number AR/AA episodes and ARIA/GINA classifications), changes in symptoms and prescribed medication, change in the global subjective clinical status of patients and satisfaction with the treatment were also evaluated. Adverse reactions were also recorded and analyzed. After 1-year of treatment, fewer AR and AA episodes (p less than 0.05) and improvements in ARIA/GINA classifications were observed. Significant improvements of symptoms (p less than 0.05) and a resulting general reduction of the medication prescribed was also detected. Improvements in the global subjective clinical status and good satisfaction rates were observed. Only 1 patient presented a local and not clinically relevant adverse reaction. The treatment showed promising effects with a significant improvement in the clinical status of all patients with a good safety profile.

Allergen immunotherapy for long-term tolerance and prevention.

Allergen immunotherapy is effective for the treatment of allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. In view of potential side effects, cost, and the necessary patient commitment, an important question is whether allergen immunotherapy provides persistent clinical benefits after treatment discontinuation. Here, we appraise the existing evidence for long-term effects of both subcutaneous and sublingual immunotherapy in terms of clinical efficacy, immune mechanisms, prevention of asthma development, and prevention of new allergen sensitizations. Evidence from large, randomized, double-blind, placebo-controlled clinical trials that include a follow-up phase after treatment cessation demonstrate long-term efficacy. The data strongly support recommendations in international guidelines that both sublingual and subcutaneous immunotherapy should be continued for a minimum of 3 years to achieve disease modification and long-term tolerance. Grass pollen immunotherapy for seasonal rhinitis may inhibit the onset of asthma symptoms and requirements for asthma medication. Whether early intervention in infancy with mite sublingual immunotherapy may prevent asthma remains to be tested.

Comparison of rush-subcutaneous and sublingual immunotherapy with house dust mite extract for pediatric allergic rhinitis: A prospective cohort study.

BACKGROUND: We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis. METHODS: Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors. RESULTS: After propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment. CONCLUSIONS: The HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase.

Can development of asthma and bronchial hyperreactivity be reduced by subcutaneous immunotherapy in adult patients with allergic rhinitis?

BACKGROUND: Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. METHODS: The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. RESULTS: A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). DISCUSSION: In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

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.

Safety of allergen-specific immunotherapy in children.

Allergic respiratory diseases, such as asthma and allergic rhinitis, are global health issues and have had an increasing prevalence in the last decades. Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic rhinitis and asthma, as it has a disease-modifying effect. AIT is generally administered by two routes: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Local side effects are common, but usually well-tolerated and self-limited. However, systemic side effects are rare, and associated with uncontrolled asthma and bronchial obstruction, or related to errors in administration. Physicians should constantly assess potential risk factors for not only reporting systemic reactions and fatalities but also implementing other therapies to improve AIT safety. This paper highlights recent evidence on local and systemic reactions related to SCIT and SLIT in children.

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.