Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis A Randomized Clinical Trial
Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis A Randomized Clinical Trial
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DOI：
10.1001/jama.2015.19330
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发表时间：
2016-02-02
影响因子：
120.7
通讯作者：
Sutherland, E. Rand
中科院分区：
文献类型：
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作者：
Bachert, Claus;Mannent, Leda;Sutherland, E. Rand
重要性Dupilumab已经证明对哮喘和特应性皮炎患者有效，这两种疾病都是2型辅助T细胞介导的疾病。目的评估Dupilumab对慢性鼻窦炎和鼻息肉病患者白细胞介素4和13的抑制作用。安慰剂对照平行-2013年8月至2014年8月在美国和欧洲的13个研究中心进行的一项分组研究，纳入了60例鼻内给药难治性慢性鼻窦炎和鼻息肉病成人患者干预：皮下注射dupilumab（600 mg负荷剂量，然后每周300 mg; n = 30）或安慰剂（n = 30）加糠酸莫米松鼻喷雾剂，持续16周。主要结果和指标：16周时内窥镜鼻息肉评分的变化（范围，0-8;评分越高表示状态越差）（主要终点）。次要终点包括Lund-Mackay计算机断层扫描（CT）评分（范围：0-24;评分越高表示状态越差），22项鼻鼻窦结局检查评分（范围：0-110;评分越高表明生活质量越差;最小临床重要差异>= 8.90），使用宾夕法尼亚大学嗅觉识别测试（UPSIT）评分评估嗅觉结果在60名随机分组的患者中（平均[SD]年龄48.4岁[9.4岁]; 34名男性[56.7%]; 35名患有哮喘共病），51名完成了研究。安慰剂组鼻息肉评分的最小二乘（LS）平均变化为-0.3（95%CI，-1.0至0.4），dupilumab组为-1.9（95%CI，-2.5至-1.2）（LS平均差异，-1.6（95%CI，-2.4至-0.7）; P <0.001）。两组Lund-Mackay CT总分的LS均值差异为-8.8（95%CI，-11.1至-6.6; P < .001）。dupilumab组的22项鼻腔鼻窦结局测试（组间LS均值差，-18.1 [95%CI，-25.6至-10.6]; P < .001）和UPSIT评估的嗅觉（LS均值差，14.8 [95%CI，10.9至18.7]; P < .001）也观察到显著改善。最常见的不良事件是鼻咽炎（安慰剂组33% vs dupilumab组47%），注射部位反应（分别为7%和40%）和头痛结论和相关性在鼻内皮质类固醇难治的有症状慢性鼻窦炎和鼻息肉病的成人中，16周后，与莫米松单独给药相比，在糠酸莫米松鼻喷雾剂中加入dupilumab皮下给药可降低内镜鼻息肉负荷。需要进一步的研究来评估更长的治疗时间，更大的样本，并与其他药物进行直接比较。
IMPORTANCE Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.OBJECTIVE To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis.DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.INTERVENTIONS Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.MAIN OUTCOMES AND MEASURES Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference >= 8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.RESULTS Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).CONCLUSIONS AND RELEVANCE Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.