Schuster Antje, Caimmi Davide, Nolte Hendrik, Novakova Silviya, Mikler Jan, Foss-Skiftesvik Majken Hougaard, Østerdal Anne Sofie, Emeryk Andrzej, Gagnon Remi, Pfaar Oliver
Center for Paediatric and Adolescent Medicine, University Medical Center, Düsseldorf, Germany.
Allergy Unit, CHU de Montpellier, Université de Montpellier, Montpellier 34295, France.
Lancet Reg Health Eur. 2024 Nov 26;48:101136. doi: 10.1016/j.lanepe.2024.101136. eCollection 2025 Jan.
Allergic rhinitis/rhinoconjunctivitis (AR/C) induced by house dust mites (HDM) often begins in childhood and negatively impacts a child's quality of life. The daily burden can be further compounded by comorbid asthma. Allergen immunotherapy is the only available treatment targeting the underlying cause of allergic disease. Efficacy and safety of the SQ HDM sublingual immunotherapy (SLIT)-tablet has been demonstrated in adults and adolescents with HDM AR/C with or without asthma, but data are lacking for younger children.
Phase III, randomised, double-blind, placebo-controlled trial in younger children (5-11 years) with HDM AR/C with or without asthma. Eligible subjects were randomised 1:1 to SQ HDM SLIT-tablet or placebo for ∼1 year and had free access to AR/C symptom-relieving medications. The primary outcome was the total combined rhinitis score (TCRS) during the final 8 weeks of the treatment period (∼1 year). Secondary outcomes included the rhinitis daily symptom score (DSS) and medication score (DMS), the rhinoconjunctivitis total combined score (TCS), and the Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) score. Efficacy analyses were conducted on the full analysis set (observed cases). Asthma-related outcomes were also explored. The trial was registered on ClinicalTrials.gov: NCT04145219 and EudraCT: 2019-000560-22.
A total of 1460 subjects were randomised to SQ HDM SLIT-tablet (n = 729) or placebo (n = 731). The primary outcome, TCRS, was statistically significantly different for SQ HDM SLIT-tablet (n = 693) versus placebo (n = 706), with an absolute difference of 1.0 (95% CI: 0.5, 1.4; p < 0.0001) corresponding to a relative reduction of 22.0% (95% CI: 12.0, 31.1). Key secondary outcomes (DSS, DMS, TCS, PRQLQ) showed statistically significant reductions in symptoms and medication use, and improved disease-related quality of life for SQ HDM SLIT-tablet versus placebo. Improvements in asthma symptoms and reduced asthma medication use indicated an additional effect of SQ HDM-SLIT tablet versus placebo. The SQ HDM SLIT-tablet showed a higher event rate for treatment-related adverse events (AEs) than placebo. Most events were of mild or moderate severity and few subjects discontinued due to AEs (2.5%).
The trial confirmed the efficacy and safety of the SQ HDM SLIT-tablet for treating HDM AR/C in younger children (5-11 years) with or without asthma. The safety profile supports daily self-administration of the SQ HDM SLIT-tablet in children.
ALK-Abellό, Hørsholm, Denmark.
屋尘螨（HDM）诱发的变应性鼻炎/鼻结膜炎（AR/C）通常始于儿童期，对儿童的生活质量产生负面影响。合并哮喘会使日常负担进一步加重。变应原免疫疗法是唯一针对变应性疾病根本病因的可用治疗方法。SQ HDM舌下免疫疗法（SLIT）片剂在患有或未患有哮喘的成人和青少年HDM AR/C患者中已证明其有效性和安全性，但年幼儿童的数据尚缺。
针对患有或未患有哮喘的年幼儿童（5 - 11岁）HDM AR/C患者进行的III期随机、双盲、安慰剂对照试验。符合条件的受试者按1:1随机分配至SQ HDM SLIT片剂组或安慰剂组，为期约1年，且可自由使用缓解AR/C症状的药物。主要结局是治疗期（约1年）最后8周的鼻炎总综合评分（TCRS）。次要结局包括鼻炎每日症状评分（DSS）和药物评分（DMS）、鼻结膜炎总综合评分（TCS）以及儿童鼻结膜炎生活质量问卷（PRQLQ）评分。在全分析集（观察病例）上进行疗效分析。还探讨了与哮喘相关的结局。该试验已在ClinicalTrials.gov注册：NCT04145219，在欧盟临床试验数据库（EudraCT）注册：2019 - 000560 - 22。
共有1460名受试者被随机分配至SQ HDM SLIT片剂组（n = 729）或安慰剂组（n = 731）。主要结局TCRS在SQ HDM SLIT片剂组（n = 693）与安慰剂组（n = 706）之间存在统计学显著差异，绝对差异为1.0（95%CI：0.5，1.4；p < 0.0001），相当于相对降低22.0%（95%CI：12.0，31.1）。关键次要结局（DSS、DMS、TCS、PRQLQ）显示，与安慰剂相比，SQ HDM SLIT片剂在症状和药物使用方面有统计学显著降低，且疾病相关生活质量得到改善。哮喘症状的改善和哮喘药物使用的减少表明SQ HDM SLIT片剂相对于安慰剂有额外效果。SQ HDM SLIT片剂的治疗相关不良事件（AE）发生率高于安慰剂。大多数事件为轻度或中度严重程度，很少有受试者因AE停药（2.5%）。
该试验证实了SQ HDM SLIT片剂治疗患有或未患有哮喘的年幼儿童（5 - 11岁）HDM AR/C的有效性和安全性。安全性概况支持儿童每日自行使用SQ HDM SLIT片剂。
丹麦霍斯霍尔姆的ALK - Abellό公司。
