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abrocitinib、安慰剂或度普利尤单抗治疗特应性皮炎的比较
Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis


Thomas Bieber ... 其他 • 2021.03.25
相关阅读
• 特应性皮炎 • nemolizumab并用外用药治疗特应性皮炎伴瘙痒的试验

摘要


背景

口服Janus激酶1(JAK1)抑制剂abrocitinib可减少白介素4和白介素13信号传导,目前正被研究用于治疗特应性皮炎。比较JAK1抑制剂和阻断白介素4受体的单克隆抗体(如度普利尤单抗)的试验数据有限。

 

方法

在一项3期、双盲试验中,我们(以2∶2∶2∶1的比例)将对外用药无应答或需要全身治疗的特应性皮炎患者随机分组,四组分别接受200 mg或100 mg abrocitinib每日一次口服给药、300 mg度普利尤单抗每2周一次皮下给药(给予600 mg负荷剂量后)或安慰剂治疗;所有患者均接受了外用药治疗。主要终点是第12周时的研究者总体评估(Investigator's Global Assessment,IGA)应答(定义为IGA[评分范围为0~4分]评分为0分[无]或1分[几乎无],并且相对于基线改善≥2分)以及湿疹面积和严重程度指数-75(Eczema Area and Severity Index-75,EASI-75)应答(定义为EASI[评分范围为0~72分]评分相对于基线改善≥75%)。关键次要终点包括第2周时的瘙痒应答(定义为峰值瘙痒数字评定量表[Peak Pruritus Numerical Rating Scale,评分范围为0~10分]评分改善≥4分),以及第16周时的IGA和EASI-75应答。

 

结果

共计838例患者接受了随机分组,226例患者被分配至200 mg abrocitinib组,238例被分配至100 mg abrocitinib组,243例被分配至度普利尤单抗组,131例被分配至安慰剂组。在200 mg abrocitinib组、100 mg abrocitinib组、度普利尤单抗组和安慰剂组中,在第12周时观察到IGA应答的患者百分比分别为48.4%、36.6%、36.5%和14.0%(两种abrocitinib剂量vs.安慰剂的P<0.001);在第12周时观察到EASI-75应答的患者百分比分别为70.3%、58.7%、58.1%和27.1%(两种abrocitinib剂量vs.安慰剂的P<0.001)。在第2周时的瘙痒应答方面,200 mg剂量abrocitinib优于度普利尤单抗(但100 mg剂量并未优于度普利尤单抗)。对于第16周时的大多数其他关键次要终点比较,两种剂量abrocitinib与度普利尤单抗均无显著差异。200 mg abrocitinib组11.1%的患者和100 abrocitinib组4.2%的患者出现了恶心,两组分别有6.6%和2.9%的患者出现了痤疮。

 

结论

在本试验中,第12和16周时,与安慰剂相比,200 mg或100 mg abrocitinib每日一次给药均使中度至重度特应性皮炎患者的症状和体征有显著较大幅减轻。在第2周时的瘙痒应答方面,200 mg剂量abrocitinib优于度普利尤单抗(但100 mg剂量并未优于度普利尤单抗)。对于第16周时的大多数其他关键次要终点比较,两种剂量abrocitinib与度普利尤单抗均无显著差异(由辉瑞资助,JADE COMPARE在ClinicalTrials.gov注册号为NCT03720470)。





作者信息

Thomas Bieber, M.D., Ph.D., Eric L. Simpson, M.D., Jonathan I. Silverberg, M.D., Ph.D., M.P.H., Diamant Thaçi, M.D., Carle Paul, M.D., Ph.D., Andrew E. Pink, Ph.D., Yoko Kataoka, M.D., Chia-Yu Chu, M.D., Ph.D., Marco DiBonaventura, Ph.D., Ricardo Rojo, M.D., Jeremias Antinew, M.D., Ileana Ionita, Ph.D., Rodney Sinclair, M.D., Seth Forman, M.D., Jacek Zdybski, M.D., Pinaki Biswas, Ph.D., Bimal Malhotra, Ph.D., Fan Zhang, Ph.D., and Hernan Valdez, M.D. for the JADE COMPARE Investigators*
From the University Hospital of Bonn, Bonn (T.B.), and University of Lübeck, Lübeck (D.T.) — both in Germany; Oregon Health and Science University, Portland (E.L.S.); George Washington University School of Medicine and Health Sciences, Washington, DC (J.I.S.); Toulouse University and Centre Hospitalier Universitaire, Toulouse, France (C.P.); St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London (A.E.P.); Osaka Habikino Medical Center, Osaka, Japan (Y.K.); the Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei (C.-Y.C.); Pfizer, New York (M.D., P.B., B.M., H.V.); Pfizer, Groton, CT (R.R., J.A., I.I., F.Z.); Sinclair Dermatology, East Melbourne, VIC, Australia (R.S.); ForCare Clinical Research, Tampa, FL (S.F.); and Dermedic Jacek Zdybski, Ostrowiec Świętokrzyski, Poland (J.Z.). Address reprint requests to Dr. Valdez at Pfizer, 235 E. 42nd St., New York, NY 10017, or at hernan.valdez@pfizer.com. *A complete list of the investigators in the JADE COMPARE trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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