Michelle Rosenzwajg, Alina Gherasim, Franck Dietsch, Marine Beck, Nathalie Domis, Roberta Lorenzon, Yannick Chantran, Bertrand Bellier, E Vicaut, Angele Soria, Frederic De Blay, David Klatzmann
{"title":"治疗桦树花粉过敏的低剂量白细胞介素-2：第二阶段随机双盲安慰剂对照试验。","authors":"Michelle Rosenzwajg, Alina Gherasim, Franck Dietsch, Marine Beck, Nathalie Domis, Roberta Lorenzon, Yannick Chantran, Bertrand Bellier, E Vicaut, Angele Soria, Frederic De Blay, David Klatzmann","doi":"10.1016/j.jaci.2024.10.033","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2<sub>LD</sub>) activates Tregs.</p><p><strong>Objective: </strong>To assess IL-2<sub>LD</sub> efficacy for controlling clinical responses to allergen exposures.</p><p><strong>Methods: </strong>RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/day of IL-2 (n=12) or Placebo (n=12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC).</p><p><strong>Results: </strong>IL-2<sub>LD</sub> treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2<sub>LD</sub> group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV<sub>1P</sub>) and the forced mid-expiratory flow (FEF<sub>25-75%</sub>) showed improvement in the IL-2<sub>LD</sub> vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events.</p><p><strong>Conclusion: </strong>IL-2<sub>LD</sub> is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4000,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial.\",\"authors\":\"Michelle Rosenzwajg, Alina Gherasim, Franck Dietsch, Marine Beck, Nathalie Domis, Roberta Lorenzon, Yannick Chantran, Bertrand Bellier, E Vicaut, Angele Soria, Frederic De Blay, David Klatzmann\",\"doi\":\"10.1016/j.jaci.2024.10.033\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2<sub>LD</sub>) activates Tregs.</p><p><strong>Objective: </strong>To assess IL-2<sub>LD</sub> efficacy for controlling clinical responses to allergen exposures.</p><p><strong>Methods: </strong>RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/day of IL-2 (n=12) or Placebo (n=12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC).</p><p><strong>Results: </strong>IL-2<sub>LD</sub> treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2<sub>LD</sub> group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV<sub>1P</sub>) and the forced mid-expiratory flow (FEF<sub>25-75%</sub>) showed improvement in the IL-2<sub>LD</sub> vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events.</p><p><strong>Conclusion: </strong>IL-2<sub>LD</sub> is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.</p>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2024-11-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jaci.2024.10.033\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2024.10.033","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
Low-dose interleukin-2 in birch pollen allergy: a phase-2 randomized double-blind placebo-controlled trial.
Background: Regulatory T cells (Tregs) are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2LD) activates Tregs.
Objective: To assess IL-2LD efficacy for controlling clinical responses to allergen exposures.
Methods: RHINIL-2 was a phase-2a, randomised, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included, 66% having concomitant asthma. All had a total nasal symptom score (TNSS) ≥5 following nasal exposure to BP in an environmental-exposure-chamber (EEC). Patients received 1 MUI/day of IL-2 (n=12) or Placebo (n=12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the EEC were evaluated using TNSS, the rhinitis visual analogue scale (VAS) and spirometry. The primary efficacy endpoint was the difference in TNSS area under the curve between inclusion and day 40 (TNSSΔAUC).
Results: IL-2LD treatment induced a significant expansion of Tregs. The TNSSΔAUC in the IL-2 and Placebo groups was non significantly different. TNSS and VAS AUCs were significantly reduced from baseline to day 40 in the IL-2LD group only (p=0.04 and p=0.01, respectively). The ratio of forced expiratory volume in 1 second/forced vital capacity (FEV1P) and the forced mid-expiratory flow (FEF25-75%) showed improvement in the IL-2LD vs Placebo groups at day 40 (p=0.04 and 0.04, respectively). However, the short treatment duration used in this study cannot have effects on specific IgE or IgG4 levels given their half-life. There was no severe treatment-related adverse events.
Conclusion: IL-2LD is well-tolerated in allergic patients, even with asthma, clearing the path for further therapeutic development. Our work suggests that Treg can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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