House dust mite sublingual immunotherapy in Thai allergic rhinitis

Introduction Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease, affecting ~20% of the global population and substantially impairing quality of life. The burden of AR on daily functioning is considerable and has been reported to exceed that of several chronic non-communicable diseases, including type 2 diabetes mellitus and hypertension 1,2. Management strategies include allergen avoidance, pharmacotherapy, and allergen immunotherapy (AIT). Among these, AIT represents a paradigm of personalized medicine, targeting disease-specific immune mechanisms and offering the potential to modify the natural history of allergic disease. Since its introduction in 1910, AIT has evolved significantly, with advances in allergen standardization, administration routes, and adjunctive approaches 3. House dust mites (HDM), particularly Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), are among the most common aeroallergens worldwide. Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have demonstrated efficacy in HDM-induced AR, reducing symptom severity, medication use, and improving quality of life 4. Recent network meta-analyses suggest comparable efficacy between SCIT and SLIT, with a trend favoring HDM-SLIT for symptom improvement, although differences were not statistically significant 5. Safety profile of HDM-SLIT has been shown with extremely low rates of systemic reactions and no reported fatalities 6. In Thailand, the prevalence of AR varies widely depending on the population studied and the methodology used. Overall, the prevalence has increased over time, with the highest rates exceeding 40% reported in clinic-based data among adults attending routine consultations 7,8. Unsurprisingly, HDM remains the predominant indoor allergen in Southeast Asian countries, including Thailand, with major allergen groups 1 (Der p 1, Der f 1) and 2 (Der p 2, Der f 2) being the most prevalent sensitizing components 9–12. Despite this high burden, real-world evidence on HDM-SLIT in Southeast Asia remains limited 13. This study, therefore, aimed to evaluate the early effectiveness, safety, and tolerability of SQ HDM-SLIT tablets (Acarizax, ALK-Abello´ A/S, Hørsholm, Denmark) in Thai adults with HDM-induced AR, with or without asthma, under routine clinical conditions. 2. Materials and methods This multicenter, open-label, prospective study was conducted across five tertiary hospitals in Thailand between August 2020 and March 2022. Adults aged 18–65 years with persistent moderate-to-severe AR despite pharmacotherapy and confirmed dominant HDM sensitization were enrolled. Persistent symptoms were defined as occurring on more than 4 days per week for more than 4 consecutive weeks, with a screening total nasal symptom score (TNSS) ≥6, or ≥5 with at least one severe symptom. HDM sensitization was confirmed by skin prick testing or specific IgE testing. Patients with asthma were required to have a post-treatment forced expiratory volume ≥70% predicted. After a washout period of prior pharmacotherapy (intranasal corticosteroids for ≥2 weeks; antihistamines, nasal saline irrigation and decongestants for ≥1 week), participants received once-daily 12 SQ HDM-SLIT tablets. Follow-up visits occurred at baseline, 1, 2, and 4 months. Symptom outcomes included TNSS and total symptom score (TSS). Symptoms were rated on a 0–3 scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) for four nasal symptoms (runny nose, nasal congestion, sneezing, itchy nose) and two ocular symptoms (red/itchy eyes, watery eyes). Total combined rhinitis score (TCRS) combined TNSS and medication score (MS). Medication scoring followed Demoly et al. 14 Asthma control was assessed using the asthma control test (ACT). Immunologic outcomes included serum HDM-specific IgE and IgG4. Safety assessments captured treatment-related adverse events (TRAEs). Statistical analyses were performed using repeated-measures ANOVA and paired tests, with P < 0.05 considered significant. The study was approved by the Central Research Ethics Committee, approval number CREC072/62BPm. 3. Results Of 49 enrolled participants, 42 completed the 4-month follow-up. The mean age was 31.9 ± 8.0 years, and 59.5% were female. Eight participants (19%) had comorbid asthma. Most of these patients had mild asthma. All participants were sensitized to Dp, and 95.2% were co-sensitized to Df. Significant improvements in rhinitis symptoms were observed at 4 months compared with baseline. TNSS decreased from 7.55 ± 1.79 to 2.30 ± 1.89 (69.5% improvement), TSS from 9.26 ± 2.60 to 2.63 ± 2.38 (71.6% improvement), and TCRS from 8.79 ± 3.52 to 3.49 ± 3.15 (60.3% improvement) (all P < 0.05) (Table 1, Fig. 1). Individual nasal and ocular symptoms also improved significantly (Fig. 2). Post-hoc analyses demonstrated that symptom improvement was evident as early as 1 month and continued through 4 months. MS showed a non-significant downward trend. ACT scores did not change significantly during the study period (Table 1). Follow-up skin prick testing demonstrated a significant reduction in wheal size to Dp from 11.73 ± 6.47 to 9.77 ± 5.86 mm (P < 0.05), while changes for Df did not reach statistical significance. Immunologically, serum HDM-specific IgE levels increased significantly at 4 months, consistent with early AIT responses. Specific IgG4 levels showed an increasing trend but did not reach statistical significance (Figs. 3 and 4). No correlation was observed between immunologic changes and clinical symptom improvement. TRAEs were reported by 83.3% of participants and were exclusively local reactions, most commonly oral or sublingual itching and swelling. Symptoms were generally mild and transient, resolving within 2 months in most cases. One participant discontinued treatment due to intolerance. No systemic reactions or serious adverse events were observed. Table 1. - Symptom score Symptoms score Baseline 1 month 2 month 4 month P value TNSS 7.55 ± 1.79 4.00 ± 2.26 2.83 ± 2.04 2.30 ± 1.89 <0.05* TSS 9.26 ± 2.60 4.76 ± 2.66 3.47 ± 2.78 2.63 ± 2.38 <0.05* MS 1.23 ± 3.32 2.38 ± 3.93 1.85 ± 3.42 1.16 ± 2.43 0.08 TCRS 8.79 ± 3.52 6.43 ± 4.86 4.68 ± 4.39 3.49 ± 3.15 <0.05* ACT 22.14 ± 3.13 19.43 ± 8.81 19.43 ± 9.18 22.80 ± 3.35 0.19 Individual symptom Runny nose 1.67 ± 0.77 0.97 ± 0.83 0.62 ± 0.79 0.56 ± 0.66 <0.05* Nasal congestion 2.16 ± 0.64 1.16 ± 0.84 0.93 ± 0.75 0.86 ± 0.77 <0.05* Sneezing 1.60 ± 0.69 0.90 ± 0.75 0.59 ± 0.61 0.45 ± 0.47 <0.05* Itchy nose 1.67 ± 0.71 0.78 ± 0.65 0.54 ± 0.57 0.38 ± 0.53 <0.05* Red/itchy eye 1.15 ± 0.84 0.62 ± 0.66 0.51 ± 0.68 0.24 ± 0.48 <0.05* Watery eye 0.56 ± 0.76 0.14 ± 0.38 0.13 ± 0.43 0.10 ± 0.28 <0.05* ACT, asthma control test; Df, Dermatophagoides farinae; Dp, Dermatophagoides pteronyssinus; MS, medication score; SPT, skin prick test; TCRS, total combine rhinitis score; TNSS, total nasal symptom score; TSS, total symptom score. Figure 1.: Change in clinical symptom score and medication score. ACT, asthma control test; MS, medication score; TCRS, total combine rhinitis score; TNSS, total nasal symptom score; TSS, total symptom score.Figure 2.: Change in individual symptom score.Figure 3.: serum specific IgE before and after SQ HDM-SLIT. Dp, Dermatophagoides pteronyssinus; Df, Dermatophagoides farina.Figure 4.: serum specific IgG4 before and after SQ HDM-SLIT. Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae.4. Discussion Despite the short study duration, this multicenter, real-world study demonstrates that 12 SQ HDM-SLIT provides early and clinically meaningful symptom improvement in Thai adults with HDM-induced AR. The magnitude of symptom reduction was significant across composite scores, representing one of the highest reductions reported. Although this was a single-arm study, the degree of improvement appears to exceed the expected placebo effect 15. Early onset of benefit, observed within 1 to 2 months, is particularly relevant in real-world practice and aligns with findings from other observational studies 16,17. The safety profile was consistent with existing literature, with a high frequency of local but tolerable adverse reactions and no systemic events. Although the TRAE rate was higher than that reported in some trials, all reactions were mild and self-limiting, supporting the overall safety of SLIT in routine care. The observed immunologic changes were consistent with early AIT responses, with increases in specific IgE and emerging IgG4 responses. However, the short study duration limited the ability to detect longer-term immunologic shifts, such as reductions in the IgE/IgG4 ratio. 5. Limitations and conclusion The main limitations include the non-randomized study design, the short study duration, and the modest sample size. Further studies are needed to elucidate the long-term efficacy of HDM-SLIT over an extended follow-up period. Nonetheless, the study demonstrates robust early effectiveness and safety signals. In conclusion, SQ HDM-SLIT tablets provide early, substantial symptom relief with an acceptable safety profile in Thai adults with HDM-induced AR. These findings support the effectiveness of HDM-SLIT as a real-world treatment option for patients with AR. Acknowledgements The authors would like to thank all co-authors from the participating centers for their valuable contributions across all stages of the study, which were essential to its successful completion. Conflicts of interest This study was funded by Abbott Laboratories. DK has received honoraria for scientific lectures from Abbott, GSK, and Viatris. MS has received honoraria for scientific lectures from A. Menarini, AstraZeneca, GSK, Takeda, and Viatris. TT has received honoraria for scientific lectures from A. Menarini, AstraZeneca, GSK, Novartis, P research support from Abbott and Sanofi; and has served on the advisory board for AstraZeneca, Sanofi, and Viatris. OP has received honoraria for scientific lectures from A. Menarini, AstraZeneca, GSK, Mead Johnson, Organon, and Viatris. TR has received honoraria for scientific lectures from A. Menarini, MSD, and Mylan. SC has received honoraria for scientific lectures from GSK, Abbott, A. Menarini, Viatris, DKSH, Siam Pharma, and ALK. CW has received honoraria for scientific lectures from A. Menarini, AstraZeneca, GSK, Novartis, Sanofi, and Takeda; and research support from Abbott, AstraZeneca, and Sanofi. WM has received honoraria for scientific lectures from Abbott, A. Menarini, AstraZeneca, GlaxoSmithKline, Novartis, Organon, Sanofi, Takeda, and Viatris. SN has received honoraria for scientific lectures from ALK. TS has received honoraria for scientific lectures from Organon, GSK, and Viatris. JK has received honoraria for scientific lectures from GSK, Organon, Menarini, Viatris, Siam pharma, Sandoz, Reckitt Benckiser, Inova, Abbott, Stada, and TMAN. PT has received honoraria for scientific lectures from ALK, Abbott, GSK, Menarini, and Viatris. NL, AS, and TB have no financial conflicts of interest. ALK was involved in supplying product samples. Abbott Laboratories and ALK had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors retained full control over the research and manuscript content.