The Efficacy of Sublingual Immunotherapy in Patients With House Dust Mite Allergic Asthma—A Systematic Review

Abstract

Background and objective

Patients’ with allergy-driven symptoms of asthma may not achieve adequate symptom control on inhaled pharmacotherapy alone, therefore, allergen-immunotherapy may be a relevant add-on treatment. The aim of the present review is to provide an update on the current evidence of efficacy of sublingual immunotherapy (SLIT) for the treatment of house dust mite (HDM)-driven allergic asthma.

Methods

Systematic review performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses-Statement (PRISMA) guidelines.

Results

A total of 15 studies fulfilled the predefined criteria and were included, all assessing the efficacy of the HDM SLIT-tablet in patients with HDM-driven asthma. Of the 15 studies, 13 reported significant improvements in asthma symptoms, while 2 found no changes. Ten studies assessed lung function (that is FEV₁, PEF and FEV₁/FVC) with 6 reporting significant improvements and 4 reporting no significant changes. Eight of the 15 studies measured the impact on prescribed asthma controller medication, of which 6 studies reported a significant reduction in daily mean dose of inhaled corticosteroid (ICS) (up to a reduction of 300+ µg/day), 1 found a significant reduction in medication use (according to the GINA steps), while 1 showed no significant reduction.

Conclusion

In the majority of studies, HDM SLIT was associated with improvements in asthma symptom control and a reduction in daily dose of ICS. On the other hand, the findings addressing treatment induced changes in lung function are conflicting.

Introduction

Asthma is among the most common chronic illnesses. World-wide it is estimated that 300 million people have asthma and, by 2025, it is predicted that an additional 100 million people will suffer from this illness.¹ Asthma is characterized by chronic airway inflammation, variable airflow limitation and airway hyperresponsiveness that may lead to airway remodeling and, by that, fixed airflow limitation.² Asthma is a heterogeneous disease with several pheno- and endotypes and one of these endotypes is allergic asthma.³ Especially in children and younger adults, allergy to common aeroallergens may be an important trigger of asthma symptoms and, in general, individuals sensitized to aeroallergens have a higher risk of subsequently developing asthma. Moreover, a substantial proportion of patients with asthma triggered by allergens are allergic to house dust mites (HDM).⁴

The Global Initiative for Asthma (GINA) recommends a stepwise approach to the management of asthma based on the frequency and severity of the symptoms and use of rescue medication.⁶ Overall, the aim of asthma management is to achieve and maintain asthma control at the lowest possible level of asthma medication. Patients with asthma should be assessed for concomitant allergic rhinitis (AR), as best possible management of AR may help improve asthma control. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommends the use of intranasal corticosteroids and oral antihistamines as first-line treatment for AR, also in patients with asthma.⁵ Controller therapy, including ICS in combination with long-acting beta₂-agonists, may not always lead to adequate symptom control for asthma patients. In cases where symptom control is not achieved, allergen-specific immunotherapy (AIT) becomes a potential option. Recent GINA guidelines suggest considering AIT as an add-on treatment, particularly for patients with allergy-triggered asthma who do not achieve adequate asthma control with standard pharmacotherapy alone.⁶ At present, AIT is marketed in 2 forms: subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). The aim of the present review is to provide an update on the current evidence of primarily efficacy of sublingual immunotherapy (SLIT) for the treatment of asthma patients with house dust mite (HDM) allergy.

Methods

The present review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses-Statement (PRISMA) guidelines. With the aim of collecting all relevant literature and studies regarding SLIT and asthma, we conducted a broad search using the PubMed database with the following Medical Subject Headings (MeSH) terms: ((“Hypersensitivity” [Mesh]) AND (“Asthma/therapy” [Mesh]) AND (“Desensitization, Immunologic” [Mesh]). The search algorithm yielded 1.091 hits of which 45 articles advanced through the screening phrase based on title and abstract to the full-text screening phase. Similar search conducted in EMBASE did not reveal further potentially eligible studies. The search was last updated January22nd 2025. Covidence was used for selection, which enabled all authors to systematically review all of the yielded hits/articles; first based on title and abstract, then followed by full-text screening. All conflicts were resolved by at least two of the authors, debating for and against inclusion/exclusion of the study.

The inclusion criteria were (1) intervention administered as SLIT tablets, and (2) studies enrolling patients with HDM-allergy and asthma.

For the present review, only administration of the SLIT tablet formulations was included as these are standardized formulations marketed in a large number of countries following clinical trials according to standard procedures, and by that, facilitating broader collection of findings from reported studies. Focusing exclusively on the tablet formulation also enhances the comparability of outcomes and reduces variability that may be caused by administration method.

The exclusion criteria were: (1) pediatric studies, (2) studies not reporting original data, including reviews, (3) intervention towards other allergies than HDM, (4) non-English studies, (5) intervention administered as SCIT, (6) nonhuman studies, (7) articles published before 2000. Further details are provided in Figure.

Fig.

Flow chart depicting the selecting procedure of studies for the present systematic review of the efficacy of sublingual immunotherapy for house dust mite allergy in adults with asthma.

Results

A total of 15 studies met the predefined criteria and were included in the present review. The included studies, comprising a total of 43.700 individuals, evaluated the efficacy of the HDM SLIT-tablet in patients with HDM-driven asthma.

Mosbech et al investigated, in a phase II/III, randomized, double-blind, placebo-controlled (RCT) 12-months trial, the efficacy of the HDM SLIT-tablet.⁷ A total of 604 patients were included and allocated (1:1:1:1) to treatment with 1, 3, or 6 standardized quality (SQ)-HDM SLIT-tablets, respectively, or placebo. The study showed that treatment with 6 SQ-HDM SLIT-tablets resulted in a significant reduction in daily ICS dose while maintaining asthma control (81 µg/day, [95% Cl: 27–136 µg/day], P = 0.004), compared to placebo. However, no significant differences were found in Asthma Control Questionnaire (ACQ) score, Asthma Quality of Life Questionnaire (AQLQ), Forced Expiratory Volume in 1. Second (FEV₁), or Peak Expiratory Flow (PEF) between the groups.

In a post hoc analysis, de Blay et al subsequently reported on a subgroup of participants in the Mosbech et al trial, including participants with an ICS dose of 400 to 800 ug/day, defined as medium-to-high dose, and an ACQ score of 1 to 1.5 at randomization.^8,7 The analysis revealed a statistically significant reduction in daily ICS dose in the 6 SQ-HDM treated group at the end of trial ICS stable period compared to the placebo treated group with a difference of 327 µg/day (95% CI: 182–471 µg/day, P < 0.0001). Furthermore, a significant improvement from baseline in overall ACQ and AQLQ scores, respectively, were found in the 6 SQ-HDM group at the end of trial ICS stable-dose period, which followed the ICS tapering period, during which the lowest ICS dose was found (P = 0.0002 and P = 0.010, respectively). The improved AQLQ score in the 6 SQ-HDM group was primarily related to the symptom (P = 0.006) and activity limitation (P = 0.011) domains. However, no significant changes were observed for the treatment groups receiving either 1, 3 SQ-HDM, or placebo.

Tanaka et al conducted a RCT in Japan investigating the efficacy and safety of SQ-HDM SLIT-tablets.⁹ The trial comprised 3 periods; screening (baseline/ period 1), treatment maintenance (period 2) and ICS reduction (period 3). After the 4-week screening period, a total of 826 individuals were randomly allocated (1:1:1) to receive either 10.000 JAU (6 SQ-HDM), 20.000 JAU (12 SQ-HDM) HDM SLIT-tablets, or placebo, respectively. These treatments were administered for a duration of 7 to 13 months. All participants with an ACQ score of ≤ 1.5 after period 2 were eligible to proceed into the final part of the trial with ICS dose reduction. No significant differences were found between the SLIT groups and the placebo group in terms of lung function, asthma symptom score, quality of life, or in moderate or severe asthma exacerbations. A further post hoc analysis of the subgroup of patients (n = 391) who required short acting beta₂-agonist (SABA) during the baseline period (daily dose of SABA 1.32 ± 1.63) was conducted, and by that a mean total asthma symptom score of 2.64 ± 1.98 classified as having not well-controlled asthma. The analysis showed that treatment with the SQ HDM SLIT-tablet significantly lowered the risk for a moderate or severe asthma exacerbation during the ICS dose reduction phase (P = 0.044). Furthermore, the subgroup of patients requiring SABA during the baseline period in the 20.000 JAU group had fewer exacerbations compared to the placebo group (P = 0.04997).

Nolte et al conducted from January 2013 to April 2015, a RCT trial in North America investigating the efficacy and safety of the SQ-HDM SLIT-tablet.¹⁰ Out of 1.482 participants, 31% had a history of asthma (28% reported ICS use at baseline). The participants were randomly allocated to either 12 SQ-HDM or placebo with an intervention period of up to 52 weeks. The study showed that treatment with 12 SQ-HDM led to a 19% improvement in mean asthma daily symptom score (DSS) (from 2.95 to 1.26) compared with placebo (from 3.12 to 1.56; P = 0.002). No details about the calculation of these numbers were provided. A post hoc analysis of participants with asthma showed, in the least-square mean asthma DSS, a difference of −0.46 (95% CI: −0.83 to −0.10) between 12 SQ-HDM (from 3.45 to 1.37) and placebo (from 3.86 to 1.83), corresponding to a 25% improvement compared to placebo.

In a prospective case-control study in Hong Kong, Chan et al investigated the effectiveness of the HDM SLIT-tablet, from January 2016 to December 2017.¹¹ Patients who had inadequate response to pharmacotherapy and had received SLIT for 12 months were defined as the case group (n = 80), whereas the control group (n = 40) was age- and sex-matched patients who had not been treated with SLIT for personal financial reasons (prevalence of asthma 32.5% and 22.5%, respectively). The study revealed that the total symptom score for asthma in the SLIT group decreased from 17.79 to 8.80 (P < 0.0001) compared to 19.70 to 18.30 in the control group (NS). Furthermore, for participants with asthma, the study showed a significant reduction in the symptom scores of shortness of breath (P = 0.0246) and wheezing (P = 0.0189) in the SLIT group compared to the controls.

In a randomized, double-blind, placebo-controlled parallel-group 12-months study from China, Wang et al investigated the efficacy and safety of HDM SLIT-tablets.¹² After a 12-week baseline period a total of 484 patients with mild (taking 200–400 µg/day budesonide) or moderate (taking 401–800 µg/day budesonide) asthma were allocated 2:1 to 2 treatment groups receiving either SLIT (n = 322) or placebo (n = 162). During the baseline period, patients who were later assigned to either of the treatment groups showed noticeable improvements in overall AQLQ scores, increasing from 4.5 at screening to 5.9 at randomization. Furthermore, over 80% of patients had an ACQ score < 1.5 at randomization. The treatment compliance during the study was reported as being high. The study reported that a higher proportion of the patients in the actively treated group achieved well-controlled asthma (WCA), or totally controlled asthma (TCA) (definitions based on GINA/National Institutes of Health guideline aims of treatment) at the end of the study period compared to the placebo group, but the difference was not statistically significant.^13,14 A post hoc analysis revealed that the subgroup of patients with moderate asthma, but not mild asthma, in the active group (n = 175) had a higher success rate in achieving WCA (P = 0.021) and TCA (P = 0.008) compared to those in the placebo group. Furthermore, a significant reduction was observed in daily dose of budesonide (P = 0.004) and proportion of patients with ACQ score < 0.75 (P = < 0.05) in the subgroup of patients classified as having moderate asthma in the active group compared to the placebo group with moderate asthma. The mean FEV_1% predicted remained above 80% during the treatment period in both groups with no significant change from baseline.

Bozek et al enrolled 32 patients with allergic rhinitis (AR) and concomitant asthma in a prospective, double-blind, randomized, placebo-controlled trial in Poland to investigate the effectiveness of the HDM SLIT-tablets.¹⁵ After a 12-month intervention period, patients receiving SLIT treatment (n = 16) showed a significant reduction in the monthly total asthma symptom score (TASS) (P < 0.05) compared with the control group (n = 14). Furthermore, the SLIT group also had a significant reduction in mean daily dose of budesonide both compared to baseline (from 450 µg to 250 µg) and the dosage taken by the control group. Lastly, 9 patients (56%) from the SLIT group had a statistically significant increase in mean FEV₁ from baseline to 12 months of treatment (P = 0.03), whereas 1 patient from the control group showed statistically significant improvement.

Hoshino et al, in an open study published in 2022, investigated the effectiveness and safety of the addition of SLIT in patients with severe asthma treated with dupilumab in a real-life setting.¹⁶ All participants enrolled to the study had received dupilumab for a mean duration of 12.6 months. The treatment period, with 6 SQ-HDM, lasted 48-weeks and was completed by 41 patients. The study revealed an improvement in ACQ-5 score from 1.80 at baseline to 1.28 at week 48 (P = 0.045), and AQLQ scores from a mean score of 5.53 at baseline to 6.07 at week 48 (P = 0.044). Furthermore, an improvement at week 48 was seen in FEV₁/FVC (Forced Vital Capacity) (P = 0.048) and FEV₁ percent predicted (P = 0.035), with FEV₁ values increasing from least-square mean of 1748 mL to 1860 mL.

Baba et al conducted a prospective, parallel-group, RCT to evaluate and compare the long-term efficacy of 36 months of SLIT and/or pharmacotherapy (PT).⁴ Out of 332 patients, 168 had allergic rhinitis and 164 had allergic asthma. All patients included were allocated into 3 treatment groups receiving either SLIT only (n = 164), SLIT + PT (n = 88), or PT only (n = 80).

Out of the patients from the combined SLIT + PT and PT only groups (n = 168), 81 patients with allergic rhinitis were given daily dosage of intranasal mometasone (50 µg), with a few patients also receiving montelukast 10 mg and antihistamine. Additionally, 80 patients with allergic asthma were treated with daily dosage of inhaled budesonide (200–400 µg) and formoterol (6 µg). Seven patients from these groups had both asthma and allergic rhinitis and received a combination of the before mentioned treatments. The study found a significant improvement in Asthma Control Test (ACT) score at months 12, 24 and 36 within the SLIT group, where 70 out of the total 164 patients had asthma (17.97 ± 5.65, 19.85 ± 7.42, 21.74 ± 7.35, respectively), compared with baseline (14.14 ± 6.12) (P = 0.006). The SLIT+PT group (n = 88), including 60 asthma patients with or without allergic rhinitis, experienced a significant improvement after 36 months of treatment (21.36 ± 6.73), compared to baseline (14.35 ± 3.65) (P = 0.007). No significant differences were observed in the PT only group, where 34 patients had asthma with or without allergic rhinitis (P > 0.05). Additionally, the asthma patients in the SLIT+PT group had a significant gradual reduction in annual ICS exposure during the 36 months (P = 0.001), which was not seen for the asthma patients in the PT group (P = 0.54).

Zieglmayer et al conducted post hoc analyses on participants who underwent environmental exposure chamber (EEC) challenges (Vienna Challenge Chamber) as part of another RCT trial by Nolte et al.^17,18 Additionally, they analyzed a subset of the original trial patients who underwent an ECC challenge conducted 1 year after trial's completion as part of the Vienna Challenge Chamber's annual diagnosis update of allergic individuals. However, this follow-up challenge visit was not a planned part of the original EEC trial and therefore optional. The primary objective was to investigate the potential long-term effect of SLIT treatment on symptoms of asthma and cough by conducting an EEC challenge approximately 1 year after trial completion with discontinuation of SLIT treatment. Briefly, a total of 106 participants with HDM allergic rhinitis with or without conjunctivitis and with or without asthma completed the trial by Nolte et al.¹⁸ The participants were in a 1:1:1 ratio randomly allocated to receive daily doses of 12 SQ-HDM (n = 36), 6 SQ-HDM (n = 36), or placebo (n = 34) for 24 weeks. At week 24 exposure challenge, Zieglmayer et al observed in the original trial a 65% improvement in the mean total asthma symptom score (TASS) in the 12 SQ-HDM group and a 53% improvement in the 6 SQ-HDM group compared with baseline screening challenge. This score included the sum of cough, wheeze, and dyspnea. Cough individually compared with baseline and at week 24 showed a 63% improvement in the 12 SQ-HDM group, a 55% improvement in the 6 SQ-HDM group, and a 6% worsening in the placebo group. At the 1-year follow-up EEC challenge after discontinuation of SLIT treatment, cough was the only measured asthma symptom. The subset of the original trial (n = 51) participating showed a 57% improvement in the 12 SQ-HDM group, while the 6 SQ-HDM group and placebo group showed a worsening of 10% and 60%, respectively. Lastly, there were no significant changes detected between treatment groups in FEV₁, FVC, and PEF from baseline to the end of the 24-week trial or at the 1-year follow-up.

In an observational, retrospective study, Marogna et al assessed if SLIT is effective in patients with either rhinitis or asthma with a primary focus on potential differences between younger and elderly patients.¹⁹ The study included 167 patients with persistent rhinitis and mild asthma who had a poor response to 1 year of standard pharmacotherapy. These patients were selected from a group of 573 patients mono-sensitized to HDM and receiving medical care between 1994 and 2006. The selected patients were given 2 options: either a 3-year SLIT treatment as add-on to standard pharmacotherapy or continuing with standard pharmacotherapy alone. Of the 167 patients, 96 chose the SLIT treatment, that consisted of a 14-week dose-increasing phase in which each dose (25, 100, 300, 1000 AU) were taken 3 times a week, followed by a maintenance phase with a maximum dose of 1000 AU taken once a week for 3 years. The remaining 71 participants preferred to continue with standard pharmacotherapy. The SLIT group (n = 96) was divided into 2 age categories: 18 to 28 years old (n = 29) and 55 to 65 years old (n = 23) and, likewise for the control group (n = 71) into 20 patients aged 18 to 28 years and 17 patients aged 55 to 65 years. Patients aged between 29 and 54 years were excluded. The SLIT groups showed significant improvements in symptom medication score (SMS), use of SABA, and use of nasal corticosteroids (P < 0.001), as recorded in clinical diaries. Additionally, the SLIT groups showed significant improvements in maximal expiratory flow at 25% of forced vital capacity (MEF25) and FEV1 (P < 0.001). The younger subgroup showed lower global symptoms (P = 0.002), defined through the symptom medication scores (SMS). This retrospective study suggests that SLIT was equally effective in both age groups.

Schmitt et al conducted a population‐based longitudinal cohort study to determine if patients who received AIT (not further specified) are less likely to experience progression of asthma severity, classified according to the 5 treatment steps recommended by the Global Initiative for Asthma (GINA), compared to those not receiving AIT, in Germany from 2005 to 2014.²⁰ Classifications of all asthma medications prescribed for the study population followed the 5 GINA steps. Allocation to low and moderate-high ICS dose was done by a pharmacist. An increase of asthma severity was defined as a step up in asthma medication according to GINA.⁶ The cohort comprised patients with allergic rhinitis and recent onset asthma, which was defined as individuals being diagnosed with asthma after year 2005 to 2006. Of the 39.167 patients included, 4.111 received AIT while 35.056 did not. AIT exposure was defined as redemption of at least 1 AIT prescription. Patients treated with AIT were, overall, less likely to experience a step-up in asthma therapy than those who did not. Furthermore, AIT treatment was associated with a significantly reduction in risk of having asthma treatment step-up from GINA step 3 to step 4 (HR 0.66: 95% CI: 0.60–0.74), and from GINA step 1 to GINA step 3 (HR 0.87: 95% CI: 0.80–0.95), indicating a beneficial effect of AIT. This effect was most pronounced in adolescents (HR 0.72: 95% CI: 0.58–0.88) and young adults (HR 0.89: 95% CI: 0.80–0.98). However, for patients aged 50 years and older, no risk reduction was observed, and, as may be expected this age group, also had a high proportion of patients with concomitant chronic obstructive pulmonary disease.

In Kashmir, Beigh et al investigated the effect of HDM SLIT and its impact on pulmonary function and ACQ score in asthma patients classified as having mild allergic asthma and a FEV_1% ≥ 80% predicted.²¹ No details are provided regarding study design but states that pharmacotherapy only was not included for ethical issues. The study enrolled 80 patients and had an intervention period of 12 months, consisting of a 6-month up-dosing of SLIT, and a 6-month maintenance phase with a dose of 100,000 U once a week. The study showed a significant increase in FEV_1%pred (82.0 ± 17.8 to 87.8 ± 12.2, P = 0.04) and FEV₁/FVC ratio (82.0 ± 17.8 to 89.0 ± 12.7, P = 0.022). There was a statistically significant reduction in mean daily ICS dose after AIT (320 ± 92.3 µg/day to 220 ± 87.2 µg/day, P = 0.001) and an improvement in ACQ scores (2.49 ± 0.21 to 1.06 ± 0.11, P = 0.001).

In 2019, Hoshino et al conducted a randomized, open, parallel-group controlled study investigating the effects of SLIT on airway inflammation and airway geometry in patients with allergic asthma (GINA treatment steps 2 and 3) and rhinitis.²² The study randomly assigned 88 patients to either the SLIT group (n = 42) receiving 10.000 JAU SLIT-tablets (6 SQ-HDM) as an add-on to pharmacotherapy or the control group (n = 46) receiving pharmacotherapy alone for 12 months. They observed a significant reduction in FeNO levels from baseline to the end of the treatment period in the SLIT group (from 3.8 ppb to −8.4 ppb, P < 0.01), but not in the control group. Furthermore, they found a significant increase in FEV1 (P < 0.01) and FVC (P < 0.01) in the SLIT group, whereas no change was seen in the control group. Additionally, SLIT treated patients had significantly better scores for symptoms and emotions in the domain analyses of AQLQ (mean standard deviation differences 0.52 ± 1.09 and 0.54 ± 0.93, respectively) (P < 0.01). No significant improvements were found in the control group.

In 2020, Hoshino et al conducted a randomized, open-label, parallel-group controlled trial to evaluate level of lung function in allergic patients with asthma before and after HDM SLIT treatment and especially to assess the association between biomarkers and FEV1.²³ The study randomly allocated 98 patients into either a SLIT group (n = 46) receiving 10.000 JAU SLIT-tablets (6 SQ-HDM) as add-on to pharmacotherapy or a control group (n = 52) receiving pharmacotherapy alone for a duration of 12 months. The study observed modest, but statistically significant, improvements in FEV₁ (P < 0.001) and FVC (P = 0.003) in the SLIT group compared to the control group, but not for the FEV₁/FVC ratio. Both asthma- and rhinitis-related quality of life questionnaires revealed significant improvements with add-on SLIT compared with pharmacotherapy alone. Domain analysis of AQLQ revealed significant differences regarding symptoms, activities, and emotions (P < 0.05, respectively).

Discussion

Overall, the studies investigating the effect of HDM SLIT-tablets in patients with HDM-triggered asthma revealed trends towards beneficial effects on asthma symptom control, asthma-related biomarkers and required daily dose of ICS, the latter not least in patients treated with moderate to high doses of ICS. ^{4,7,8,12,15,20,21}

The ACQ results of SLIT therapy pointed towards better outcomes in patients with not well-controlled asthma at baseline in terms of improving their symptom score compared to those who had better control of their asthma symptoms at baseline, as reported in all 4 published studies.^8,12,16,21 This indicates that having well-controlled asthma at baseline leaves limited room for improvement, suggesting that AIT seems to work better in patients with more severe or uncontrolled asthma. Nonetheless, most guidelines deem uncontrolled asthma as an absolute contraindication due to the risk of adverse reactions and therefore not recommended.²⁴

The major challenge in asthma management is adherence with controller medication. It is important to acknowledge that uncontrolled asthma is often due to insufficient adherence with controller medication and, therefore, in many cases do not indicate severe asthma. This is further supported by the findings reported in the present paper, as, the findings from the studies often showing substantial improvements in asthma control in the control group most likely due to increased adherence during the course of the study.

Ten studies^7,9,12,15, 16, 17^,19,21, 22, 23 reported on lung function. However, the findings were inconclusive, as 6 studies^15,16,19,21, 22, 23 reported significant improvements in groups treated with HDM SLIT-tablets, while 4^7,9,12,17 studies did not. Nonetheless, it can be argued that the latter 4 studies contribute to a greater validity and reliability of the findings. This is due to the fact that out of the 4 studies comprising a total of 2.020 participants, 3 were RCT trials with placebo-treated control groups. Conversely, out of the 6 studies revealing significant effects comprising a total of 506 participants, only 1 study¹⁵ was conducted as a RCT trial. Furthermore, 2 studies^16,21 out of the 6 studies provided no details on study design and did not have a control group, while 3 studies^19,22,23 had control groups that were not allocated to placebo. Out of these three, one was an observational retrospective study, and the other 2 were randomized, open-label, parallel-group controlled trials. Another possible explanation for the differences in findings with regard to changes in lung function may be, that most of the included patients in the studies at baseline had an FEV₁ of at least 80%pred, and by that reducing the room for improvement.

A study with no significant changes in either asthma symptoms, pulmonary function or reduction in daily mean dose of ICS was conducted by Tanaka et al. The study adhered to the Japanese guidelines, which they point out to be stricter than the GINA guidelines. This difference in assessment of asthma severity definitions impedes comparison with other studies, e.g., studies carried out in countries adhering to GINA guidelines.

In terms of quality assessment, among the 15 included studies, 5 either conducted post hoc analyses due to a lack of significant findings in the main study or were entirely post hoc sub-group analyses.8, 9, 10^,12,17 Additionally, 2 out of the 15 studies lacked control groups, which also significantly impacts the validity with regard to the effectiveness of HDM SLIT. The extraction of data therefore revealed heterogeneity, particularly regarding study design, clinical characteristics and guideline-related differences. This variation made it challenging to sufficiently compare the findings for quantitative analysis. To preserve the validity of the findings and avoid potential biases due to methodological differences, a meta-analysis was not included.

As asthma management continues to evolve, personalized therapeutic interventions are likely to play an increasingly important role in improving patient outcomes.

A study by Hoof et al suggests that the efficacy of AIT treatment may be linked to genetic and type 2 (T2) biomarkers.²⁵ They found positive results with AIT in asthma patients with HDM allergy and with genetic asthma predisposition and/or underlying T2 inflammatory biomarkers. This suggests that patients can be selected for AIT based on specific biomarkers and genetic profiles. By gaining a better understanding on the specific subgroups of asthma patients such as genetic profiles, biomarkers, and type 2-inflammatory patterns, future research and clinical guidelines can move towards a more effective and targeted approach to treatment for the benefit of the many patients with asthma triggered by exposure to house dust mite.

Conclusion

In most of the included studies, treatment with HDM SLIT was associated with improvements in asthma symptom control and a reduction in daily dose of ICS. The studies suggest that this is primarily seen in patients with less well-controlled asthma and more severe asthma, in some cases probably due suboptimal adherence with prescribed controller therapy.. On the contrary, there is limited evidence for an association between HDM SLIT treatment and changes in lung function. In spite of the beneficial effects of HDM SLIT in patients with allergic asthma, it is still highly important in the individual patient to assess the association between asthma control end exposure to house dust mites, and, likewise, to address the challenge with adherence to controller medication. Future studies will have to address these aspects to optimize the use of HDM SLUT in the management of adults with asthma.

Declaration of competing interest

PVH, ASR and AHR reports no conflicts of interests. CSU has received fee for lectures, participation in advisory boards etc. from AZ, GSK, TEVA, Sanofi, Chiesi, TFF Pharmaceuticals, BI, Takeda, Pfizer, Orion Pharma, Berlin Chemie and Hikma Pharmaceuticals outside the submitted work.