Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet (12 SQ-HDM) in children with allergic rhinitis/rhinoconjunctivitis with or without asthma (MT-12): a randomised, double-blind, placebo-controlled, phase III trial

IF 13.6 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Europe Pub Date : 2024-11-26 DOI:10.1016/j.lanepe.2024.101136

Antje Schuster , Davide Caimmi , Hendrik Nolte , Silviya Novakova , Jan Mikler , Majken Hougaard Foss-Skiftesvik , Anne Sofie Østerdal , Andrzej Emeryk , Remi Gagnon , Oliver Pfaar

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引用次数: 0

Abstract

Background

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.

Methods

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.

Findings

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%).

Interpretation

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.

Funding

ALK-Abellό, Hørsholm, Denmark.

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SQ屋尘螨舌下免疫疗法片剂（12 SQ-HDM）对伴有或不伴有哮喘（MT-12）的过敏性鼻炎/鼻结膜炎患儿的疗效和安全性：随机、双盲、安慰剂对照 III 期试验

背景由屋内尘螨（HDM）诱发的过敏性鼻炎/鼻结膜炎（AR/C）通常始于儿童时期，并对儿童的生活质量造成负面影响。合并哮喘会进一步加重日常负担。过敏原免疫疗法是目前唯一针对过敏性疾病根本原因的治疗方法。SQ HDM 舌下免疫疗法（SLIT）片剂的疗效和安全性已在患有或未患有哮喘的 HDM AR/C 的成人和青少年中得到证实，但缺乏针对幼儿的数据。符合条件的受试者按 1:1 随机分配到 SQ HDM SLIT 片剂或安慰剂中，为期 1 年，并可免费获得缓解 AR/C 症状的药物。主要结果是治疗期最后 8 周（1 年）的鼻炎综合评分（TCRS）。次要结果包括鼻炎日常症状评分（DSS）和用药评分（DMS）、鼻结膜炎综合评分（TCS）和儿童鼻结膜炎生活质量问卷（PRQLQ）评分。疗效分析在完整的分析集（观察病例）上进行。还对哮喘相关结果进行了探讨。该试验已在 ClinicalTrials.gov 上注册：NCT04145219和EudraCT：2019-000560-22.研究结果共有1460名受试者被随机分配到SQ HDM SLIT片剂（n = 729）或安慰剂（n = 731）中。SQ HDM SLIT 片剂（n = 693）与安慰剂（n = 706）的主要结果 TCRS 有显著统计学差异，绝对差异为 1.0（95% CI：0.5，1.4；p < 0.0001），相对减少 22.0%（95% CI：12.0，31.1）。主要次要结果（DSS、DMS、TCS、PRQLQ）显示，与安慰剂相比，SQ HDM SLIT 片剂的症状和用药量明显减少，与疾病相关的生活质量也有所提高。哮喘症状的改善和哮喘药物用量的减少表明，SQ HDM-SLIT片剂与安慰剂相比具有额外效果。与安慰剂相比，SQ HDM SLIT 片剂的治疗相关不良事件（AEs）发生率较高。该试验证实了SQ HDM SLIT片剂治疗患有或未患有哮喘的幼儿（5-11岁）HDM AR/C的有效性和安全性。该试验证实了SQ HDM SLIT片剂对患有或未患有哮喘的年幼儿童（5-11岁）治疗HDM AR/C的有效性和安全性，其安全性也支持儿童每天自行服用SQ HDM SLIT片剂。

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.