Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis.

PURPOSE: Sublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. MATERIALS AND METHODS: This study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. RESULTS: After SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3-4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). CONCLUSION: Different duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

BACKGROUND: Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). OBJECTIVE: To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. METHODS: MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. RESULTS: An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers. CONCLUSIONS: HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. TRIAL REGISTRATION NUMBER: NCT01433523.

Long-Term Efficacy and Safety of Subcutaneous Immunotherapy in Monosensitized and Polysensitized Children With Allergic Rhinitis.

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.

Effect of intralymphatic allergen-specific immunotherapy on house dust mite in a murine model of allergic rhinitis.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a promising alternative for the treatment of patients with allergic rhinitis, providing similar therapeutic efficacy to conventional allergen-specific immunotherapy (AIT). However, the allergic mechanism of ILIT is not completely known. AIM: The aim of this study was to determine the efficacy of ILIT in a house dust mite (HDM) mouse model of allergic rhinitis. METHODS: BALB/c mice were divided into four groups: G1, control without allergy; G2, allergy sensitized with HDM; G3, allergy with ILIT (starting with HDM 1.25 µg/mL); and G4, allergy with ILIT (starting with HDM 2.5 µg/mL). After the murine model of allergic rhinitis with HDM was established, mice were administered an intralymphatic injection through the inguinal lymph nodes with HDM. RESULTS: ILIT decreased serum total IgE level and eosinophil infiltration in the nasal mucosa. ILIT also decreased the expression levels of IL-13, IL-25, IL-33, IFN-γ, IL-6, and IL-17, and increased the expression of FoxP3(+) T reg cells. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that ILIT regulates the specific immunotherapy immunologic mechanism by downregulating Th1, Th2, and Th17 cytokines and upregulating FoxP3(+) T reg cells in the HDM allergic mouse model.

Safety and effectiveness of a 300 IR house dust mite sublingual tablet: descriptive 4-year final analysis of a post-marketing surveillance in Japan.

Background: Data are limited for clinical outcomes with house dust mite (HDM) allergen immunotherapy beyond 2 years' observation. Materials & methods: A post-marketing drug-use survey assessed the safety and effectiveness of the 300 index of reactivity (IR) HDM tablet during use for up to 4 years in Japan. Results: 538 patients were evaluable for safety and 383 for effectiveness. Most adverse drug reactions (ADRs) occurred early and were local reactions; 5.6% of 249 total events were reported during years 2 to 4 as new ADRs after the interim analysis. The CAP-RAST score was identified as a potential risk factor for ADRs. The proportion of evaluable patients with severe allergic rhinitis symptoms decreased from 46.4% at baseline (n = 317) to 1.0% at 4 years (n = 104). Patients (n = 16) who discontinued 300 IR HDM tablet due to symptomatic improvement had sustained improvement relative to baseline 1 to 2 years later. Conclusion: Long-term use of the 300 IR HDM tablet is safe and effective.

The 300 index of reactivity house dust mite (HDM) sublingual tablet (Actair^®) is a treatment option for people with HDM allergy. A Japanese study investigated the safety and effectiveness of the HDM sublingual tablet during its use for up to 4 years. Less than a third of patients (29%) reported adverse effects, mainly itching or irritation in the mouth. The percentage of patients with no allergic rhinitis symptoms increased from 0.3% before treatment to 57.7% after 4 years of use. The percentage of patients who perceived that their allergic rhinitis had improved 'substantially' compared with before treatment increased from 22.3% at 6 months to 73.5% at 4 years. Patients who ended treatment with the HDM sublingual tablet because their symptoms had improved continued to perceive benefit 1 to 2 years later. Clinical Trial Registration: University hospital Medical Information Network (UMIN) Clinical Trials Registry identifier: UMIN000042840.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

[Compliance and withdraw reason of sublingual immunotherapy in 245 patients with allergic rhinitis].

Objective:To investigate the compliance of patients with allergic rhinitis（AR） receiving sublingual immunotherapy and its influencing factors. Methods:The clinical data of 291 AR patients who received sublingual immunotherapy for dust mites at the First Hospital of Peking University from January 2016 to January 2018 were retrospectively analyzed, and their outpatient or telephone follow-up was conducted. For patients whose treatment time was less than 2 years, the time and reason for the loss were recorded, and the factors affecting their compliance were discussed from the aspects of gender, age, and education. Results:Among the 291 patients, 245 cases（84.2%） were successfully followed up, and 193 cases（78.8%） fell off midway（treatment time<2 years）. The overall compliance rate was 21.22%（52/245）. The compliance rate of children is higher than that of adults（χ²=21.306, P<0.05）, and gender and education level have no significant effect on the compliance rate. The time period for the largest number of shedding was 6-<12 months after treatment（68 cases, 27.8%）. The main cause of shedding was symptom relief, which was considered cured（16.7%）. Secondly, within 3 months after treatment, a total of 61 patients（24.9%） fell off, of which 34 cases（13.9%） fell off because of troublesome medication, often missed medication, and simply stopped taking the drug. Statistics on the overall reasons for shedding in 193 patients, the top three shedding reasons were: cured after symptom relief（59 cases, 30.6%）, troublesome medication, discontinuation after missed dose（44 cases, 22.8%）, slow onset or ineffectiveness（26 cases, 13.5%）. Conclusion:The overall compliance of sublingual immunotherapy in patients with allergic rhinitis is poor, and the compliance of children is better than that of adults. Clinicians should focus on the reasons for patients to fall off at various times, strengthen patient education, enhance patient confidence in treatment, and improve the compliance of patients.

Real-world study: drug reduction in children with allergic rhinitis and asthma receiving immunotherapy.

Background: The reduction of pharmacological treatment after allergen immunotherapy (AIT) for house dust mites (HDMs) has been little studied in children. Objective: To evaluate the reduction of pharmacological treatment comparing children that receive HDM immunotherapy (AIT group) versus only pharmacotherapy. Methods: A historic cohort of children with rhinitis or asthma was assessed. The main outcome was the frequency of complete drug discontinuation. Results: 100% drug reduction was higher for rhinitis (4-year cumulative incidence: 30 vs 10.7%) and asthma (24.1 vs 10.5%) in the AIT group (n = 987) than in the pharmacotherapy group (n = 2012). Conclusion: Immunotherapy is associated with a significant reduction of pharmacotherapy in children. This is a marker of clinical control and could be associated with positive economic impact.

The benefits of allergen immunotherapy for house dust mites has been little studied in children. The usefulness of this treatment in asthma over the use of pharmacotherapy has also not been clearly evaluated. The use of immunotherapy allowed greater reductions in pharmacological treatment in children with rhinitis and asthma. Immunotherapy is a useful treatment for childhood rhinitis and asthma and reduces the risk of adverse effects from pharmacological treatments.

Current advances in house dust mite allergen immunotherapy (AIT): Routes of administration, biomarkers and molecular allergen profiling.

Allergy to house dust mites (HDM) is a perennial respiratory disease that affect more than half a billion people worldwide. Dermatophagoides pteronyssinus and D. farinae, two HDM species, are major sources of indoor allergens triggering allergic inflammation. Although symptomatic drugs are widely used to block the allergic reaction, allergen immunotherapy is the only curative treatment of IgE-mediated type I respiratory allergies. In this article, we review recent advances in various routes of allergen immunotherapy. We particularly focus on subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, used as a reference therapy since they have transformed allergic treatments by improving symptoms (asthma and rhinitis) as well as the quality of life of patients. We also highlight recent data in more exploratory routes (i.e., oral, intralymphatic, epicutaneous and intradermal) and discuss respective advantages of various route, as well as their foreseen modes of action. Finally, we provide an update on biomarkers as well as on the relevance of the molecular profiling of allergic individuals related to treatment efficacy or asthma prediction.

Allergen immunotherapy for allergic asthma: The future seems bright.

Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data.

Recombinant T-cell epitope conjugation: A new approach for Dermatophagoides hypoallergen design.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. METHODS: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. RESULTS: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL- 2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. CONCLUSIONS: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.

Compliance and withdraw reason of sublingual immunotherapy in 245 patients with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the compliance of patients with allergic rhinitis（AR） receiving sublingual immunotherapy and its influencing factors. Methods:The clinical data of 291 AR patients who received sublingual immunotherapy for dust mites at the First Hospital of Peking University from January 2016 to January 2018 were retrospectively analyzed, and their outpatient or telephone follow-up was conducted. For patients whose treatment time was less than 2 years, the time and reason for the loss were recorded, and the factors affecting their compliance were discussed from the aspects of gender, age, and education. Results:Among the 291 patients, 245 cases（84.2%） were successfully followed up, and 193 cases（78.8%） fell off midway（treatment time<2 years）. The overall compliance rate was 21.22%（52/245）. The compliance rate of children is higher than that of adults（χ²=21.306, P<0.05）, and gender and education level have no significant effect on the compliance rate. The time period for the largest number of shedding was 6-<12 months after treatment（68 cases, 27.8%）. The main cause of shedding was symptom relief, which was considered cured（16.7%）. Secondly, within 3 months after treatment, a total of 61 patients（24.9%） fell off, of which 34 cases（13.9%） fell off because of troublesome medication, often missed medication, and simply stopped taking the drug. Statistics on the overall reasons for shedding in 193 patients, the top three shedding reasons were: cured after symptom relief（59 cases, 30.6%）, troublesome medication, discontinuation after missed dose（44 cases, 22.8%）, slow onset or ineffectiveness（26 cases, 13.5%）. Conclusion:The overall compliance of sublingual immunotherapy in patients with allergic rhinitis is poor, and the compliance of children is better than that of adults. Clinicians should focus on the reasons for patients to fall off at various times, strengthen patient education, enhance patient confidence in treatment, and improve the compliance of patients.

[Efficacy comparison and safety analysis of subcutaneous specific immunotherapy with standardized house dust mite allergen in patients with single and multiple allergic rhinitis].

Objective: To investigate the efficacy and safety of house dust mite (HDM) allergen subcutaneous specific immunotherapy (SCIT) in patients with allergic rhinitis (AR) with single dust mite allergy and multiple allergen allergy. Methods: A retrospective study was conducted. A total of 372 patients with allergic rhinitis induced by house dust mite were diagnosed in the allergy clinic of General Hospital of North Theater Command from January 2013 to January 2018.They were treated with house dust mite allergen preparation for standardized SCIT for 3 years or more, and had complete follow-up data. The age ranged from 5 to 55 years, the median age was 13 years, and the average age was (19.4±14.7) years; 216 males and 156 females. According to their age, they were divided into the older group (age >14 years) and younger group (age ≤ 14 years). According to the number of allergens, they were divided into single group (only HDM group allergic to house dust mites) and multi recombination (including 2 or more allergens including house dust mites). The multi recombination was further divided into HDM+1 group, HDM+2 group, HDM+3 group, HDM+4 and above group. Before treatment (T0), 1 year (T1) and 3 years (T2) after SCIT treatment, the patients in each group established files, analyzed and compared the average total nasal symptoms score (TNSS), total non nasal symptoms score (TNNSS), visual analogue scale (VAS), total medicine score (TMS) and rhinoconjunctivitis quality of life questionnaire (RQLQ), and evaluated the clinical efficacy of the treatment and the comparison of various scores in the efficacy of SCIT with different allergens and ages. Record the occurrence of local and systemic adverse reactions of all patients during treatment, and evaluate the safety of SCIT. All scores are measurement data that do not conform to normal distribution. Mann-Whitney U and Kruskai-Wallis test of independent samples are used for inter group comparison, and Bonferroni correction is used for further pairwise comparison; Chi square test and continuity correction method were used for the comparison between count data groups such as the incidence of adverse reactions and the effective rate of TNSS, and a-division method was used for further pairwise comparison. Results: After SCIT treatment, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in T1 and T2 were significantly lower than those in T0, and the scores in T2 were significantly lower than those in T1 (Z=-11.168, -4.786, -6.639, -13.012, -10.652 in T0 vs T1; Z=-13.527, -8.746, -13.397, -14.477, -11.833 in T0 vs T2; Z=-4.721, -4.607, -10.020, -7.180, -5.721 in T1 vs T2; P<0.05). In T1 and T2, compared with the older group, the scores of TNSS, TNNSS, TMS, VAS and RQLQ in younger group were lower, and the differences of various indexes were statistically significant(the median scores of T1: Myounger=3.0, 1.0, 2.0, 4.0, 2.6, Molder=5.0, 2.0, 3.0, 5.0, 3.2; the median scores of T2: Myounger=3.0, 1.0, 0, 2.0, 1.3, Molder=4.0, 1.0, 1.5, 3.0, 2.3; ZT1=-4.525, -5.830, -4.061, -3.608, -2.785; ZT2=-3.847, -4.055, -2.820, -2.998, -3.418; P<0.05). In T1 and T2, the scores of TNSS, VAS and RQLQ in a single group after SCIT treatment were lower than those in multiple recombination(the median scores of T1:Msingle=4.0, 4.0, 2.6, Mmultiple=5.0, 5.0, 3.2; the median scores of T2: Msingle=3.0, 2.0, 1.4, Mmultiple=4.0, 3.0, 2.1), and the difference was statistically significant (ZT1=-3.002, -2.092, -1.977; ZT2=-3.354, -2.469, -2.116; P<0.05). There was no significant difference in TMS (the median score during T1 period: Msingle=2.0, Mmultiple=3.0, ZT1=-1.130; the median score during T2 period: Msingle=1.0, Mmultiple=1.0, ZT2=-1.544; P>0.05). Further comparison within the group showed that there was no significant difference in the improvement rate of TNSS during T2 period among HDM group, HDM+1 group, HDM+2 group and HDM+3 group (HDM vs HDM+1 group χ2=0.277, HDM vs HDM+2 group χ2=0.78, HDM vs HDM+3 group χ2=0.075, HDM+1 vs HDM+2 group χ2=0.057, HDM+1 vs HDM+3 group χ2=0.019, HDM+2 vs HDM+3 group χ2=0.003; P>0.005), the improvement rates were 92.5%, 90.3%, 89.1% and 89.5%. Respectively in HDM group,HDM+1 group, HDM+2 group, HDM+3 group, compared with HDM+4 and above group, the difference was statistically significant (χ2=26.144, 13.254, 15.144, 8.808; P<0.005). The improvement rate of TNSS in HDM+4 and above group was 60.9%. 122 patients had local adverse reactions during the treatment of SCIT, accounting for 32.8%. The local adverse reactions were 759 injections (15 336 injections in total), accounting for 4.95%. Most of them were swelling, dizziness, induration and pruritus at the injection site, which could be relieved by oral antihistamines or within 2 hours. There were 2 cases of local urticaria, once for each case. The symptoms were relieved within 1 week after oral antihistamine. No serious systemic adverse reactions occurred. Conclusion: Standardized SCIT may be a safe and effective treatment for AR patients, and the type of allergen may be one of the important factors affecting the efficacy of SCIT. The efficacy of SCIT was significant in AR patients with three or less allergens other than house dust mite.

Omalizumab added to allergen immunotherapy increased the effect of therapy in patients with severe local allergic rhinitis.

BACKGROUND: Allergen immunotherapy (AIT) is effective in patient with local allergic rhinitis (LAR). However, AIT may not always achieve the optimal treatment effect. OBJECTIVE: To present short study with clinical cases of LAR combined therapy with sublingual immunotherapy (SLIT) and omalizumab in patients with house dust mite (HDM) allergy and compared it to therapy with omalizumab alone. METHODS: Patients with severe LAR and hypersensitivity to HDMs were included. SLIT for HDMs was launched in a perennial protocol using SQ-HDM SLIT tablets with omalizumab. The total rhinitis symptom score (TRSS), total medication score (TMS) and combined total score (CTS) were assessed after one year. RESULTS: After 12 months, significant improvements in all analyzed parameters in the patients on SLIT+ omalizumab therapy were observed: a reduction in the TRSS from 1.21 ± 0.33 to 0.6 ± 0.28 (p < .05), a reduction in the TMS from 2.25 ± 1.05 to 0.88 ± 0.31 (p < .05) and a reduction in the CTS from 3.46 ± 0.57 to 1.48 ± 0.51 (p < .05). This improvement in TRSS, TMS also in CTS was significantly greater than in the rest of the group with SLIT alone or omalizumab alone. CONCLUSION: Omalizumab may be a valuable treatment that increases the effectiveness of immunotherapy in patients with severe LAR.

Circulating MMP-12 as Potential Biomarker in Evaluating Disease Severity and Efficacy of Sublingual Immunotherapy in Allergic Rhinitis.

Background: Allergic rhinitis (AR) is a highly heterogeneous disease, and allergen-specific immunotherapy (AIT) is an effective treatment. This study aims to evaluate the circulating mas-related G protein-coupled receptor-X2 (MRGPRX2) and matrix metalloproteinase-12 (MMP-12) levels in evaluating disease severity and predicting efficacy of SLIT in AR patients. Methods: We enrolled 110 moderate-severe persist AR patients (AR group) and 40 healthy controls (HC group). Circulating levels of MRGPRX2 and MMP-12 were measured, and their associations with disease severity were evaluated. All AR patients were assigned to receive sublingual immunotherapy (SLIT), and the efficacy was evaluated, and serum samples were collected at 1 year and 3 years after treatment. The correlations between serum MRGPRX2 and MMP-12 and clinical efficacy were assessed. Results: The serum concentrations of MRGPRX2 and MMP-12 were significantly higher in the AR group than the HC group, and the elevated MMP-12 levels were correlated with VAS and TNSS, and serum MRGPRX2 levels were correlated with VAS. Finally, 100 and 80 patients completed 1-year and 3-year follow-up and were classified into effective and ineffective groups. Serum MRGPRX2 and MMP-12 levels were lower in the effective group than the ineffective group. Although serum MRGPRX2 and MMP-12 levels did not significantly change after 1 year SLIT, serum MMP-12 levels were decreased 3 years post-SLIT than baseline and 1 year post-SLIT levels. Receiver operating characteristic (ROC) showed that serum MMP-12 was a potential biomarker for predicting the efficacy of SLIT. Conclusion: Serum MRGPRX2 and MMP-12 appeared to be promising biological indicators in reflecting disease severity in AR patients. Moreover, circulating MMP-12 might serve as a reliable predictor for clinical responsiveness of SLIT.

Efficacy of subcutaneous house dust mite immunotherapy in patients with moderate to severe allergic rhinitis.

Aim: To evaluate the efficacy of subcutaneous immunotherapy (SCIT) for the treatment of allergy to house dust mites (HDM) in adults with moderate/severe allergic rhinitis (AR). Methods: Patients sensitized to HDM were randomized to SCIT plus rescue medication (Group A, n = 38) or rescue medication alone (Group B, n = 18), and assessed at baseline and 2, 6 and 12 months. Results: At month 12, Group A presented significant improvement with respect to baseline as evaluated by a visual analogue scale at three concentrations of antigen (0.1, 1 and 10 IR/ml; p < 0.0001). Group A presented significant decreases in symptom scores after 2 months of treatment, which were maintained after 1 year. After 12 months of treatment, Group A showed rescue medication consumption reductions (p < 0.001) and quality of life improvements (p < 0.0001). SCIT elicited a strong immunological response and was well tolerated. Conclusion: SCIT is efficacious for HDM allergy in patients with AR, generating a strong immunological response. Trial Registration Number: EUCTR2009-018155-16-ES (Cochrane Central Register of Controlled Trials).

Allergic rhinitis is a common disease that can be treated by exposing the patient to small quantities of the agents triggering the allergy. In this study, allergic patients were injected with extracts of house dust mites over a period of 12 months, and the status of the patient was evaluated at the initiation of treatment and at 2, 6 and 12 months. The study showed that the allergic rhinitis symptoms improved after only 2 months of treatment with the extract and were sustained after 1 year. Also, other medication to treat the rhinitis was reduced with the treatment, and quality of life improved. Overall, the study suggests that treatment with injections of extracts of house dust mites can help patients with allergic rhinitis.

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.

Efficacy and Safety of House Dust Mite Sublingual Immunotherapy Tablet in Allergic Asthma: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: House dust mite sublingual immunotherapy (HDM SLIT) effectively treats allergic rhinitis (AR). However, the evidence of HDM SLIT for allergic asthma remained limited. OBJECTIVE: To systematically review the efficacy and safety of HDM SLIT tablets in patients with allergic asthma. METHODS: We performed a systematic search through PubMed, Scopus, EMBASE, Web of Science, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM SLIT tablets compared with placebo or no intervention in allergic asthma from their inception date until September 2021. The primary outcome was the reduction in inhaled corticosteroids (ICS) dose. Additional outcomes were asthma control, exacerbation, lung function, quality-of-life, and adverse events. RESULTS: There were 7 RCTs, 5 studies in allergic asthma (4 in adults and 1 in children), and 2 in AR with or without asthma. The 6 standardized quality (SQ) HDM effectively reduced ICS dose in well- to partly controlled mild-to-moderate asthma in 1 RCT. Two RCTs evaluated the efficacy of 6 SQ and 12 SQ HDM in reducing asthma exacerbation in partly controlled moderate-to-severe asthma, and their results were inconsistent. One study in children with mild-to-moderate asthma found no benefit of HDM SLIT. Two RCTs in AR with or without mild-to-moderate asthma showed improvement of asthma symptoms. Adverse events were primarily local, and anaphylaxis treated with epinephrine was reported in 3 patients. CONCLUSIONS: The HDM SLIT tablets tend to effectively reduce ICS use in adults and adolescents with well- to partly controlled mild-to-moderate allergic asthma with a favorable safety profile.

Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. OBJECTIVE: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. RESULTS: A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. CONCLUSIONS: Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.

Nasal Nitric Oxide and Nasal Cytology as Predictive Markers of Short-Term Sublingual Allergen-Specific Immunotherapy Efficacy in Children with Allergic Rhinitis.

BACKGROUND: Few studies have been conducted on the short-term response to sublingual immunotherapy (SLIT). OBJECTIVE: The purpose of our experimental trial was to evaluate if two markers such as nasal nitric oxide (nNO) and nasal cytology could be useful to identify a precocious clinical efficacy of SLIT treatment. METHODS: We enrolled 34 children aged 6 to 14 years old with diagnosis of allergic rhinitis (AR) and documented sensitization towards house dust mites. We started allergoid-monomeric tablets immunotherapy along with any conventional therapy for AR and we evaluated at baseline (T0), after one (T1), two (T2), three (T3), and six months (T6) the effects of the treatment through the study of: i) a visual analogue scale (VAS 1-10); ii) measurement of nNO; iii) measurement of FeNO; iv) nasal cytology; v) spirometry; and vi) evaluation of any conventional therapy. RESULTS: We observed an improvement in symptoms evaluated by global VAS (T0 vs. T6: 47.13 vs. 17.57; p < .05) and a statistically significant reduction of nNO (1035.2 ± 956.08 vs. 139.2 ± 59.01; p < .05). In this case, significance was reached when the patients completed the 6 months of treatment. Cytological evaluation revealed significant reduction in nasal eosinophils (T0 vs. T6: 87% vs. 16%; p < .01). Moreover, at T0, 56% of patients had also neutrophils that were reduced up to the 8% at T6 (p < .05). CONCLUSIONS: Our data confirm the effectiveness of SLIT treatment from a clinical perspective and identifies two biomarkers, such as nNO and nasal cytology, as predictive of treatment efficacy in the short term.