NEJM：磷酸二酯酶4B抑制剂治疗特发性肺纤维化的临床试验( 二 )

图2.在全部患者中，随着时间推移FVC的变化（MMRM分析）

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原文摘要
BACKGROUND
Phosphodiesterase4(PDE4)inhibitionisassociatedwithantiinflammatoryandantifibroticeffectsthatmaybebeneficialinpatientswithidiopathicpulmonaryfibrosis.
METHODS
Inthisphase2,double-blind,placebo-controlledtrial,weinvestigatedtheefficacyandsafetyofBI1015550,anoralpreferentialinhibitorofthePDE4Bsubtype,inpatientswithidiopathicpulmonaryfibrosis.Patientswererandomlyassignedina2:1ratiotoreceiveBI1015550atadoseof18mgtwicedailyorplacebo.Theprimaryendpointwasthechangefrombaselineintheforcedvitalcapacity(FVC)at12weeks,whichweanalyzedwithaBayesianapproachseparatelyaccordingtobackgroundnonuseoruseofanantifibroticagent.
RESULTS
Atotalof147patientswererandomlyassignedtoreceiveBI1015550orplacebo.Amongpatientswithoutbackgroundantifibroticuse,themedianchangeintheFVCwas5.7ml(95%credibleinterval,–39.1to50.5)intheBI1015550groupand–81.7ml(95%credibleinterval,–133.5to–44.8)intheplacebogroup(mediandifference,88.4ml;95%credibleinterval,29.5to154.2;probabilitythatBI1015550wassuperiortoplacebo,0.998).Amongpatientswithbackgroundantifibroticuse,themedianchangeintheFVCwas2.7ml(95%credibleinterval,–32.8to38.2)intheBI1015550groupand–59.2ml(95%credibleinterval,–111.8to–17.9)intheplacebogroup(mediandifference,62.4ml;95%credibleinterval,6.3to125.5;probabilitythatBI1015550wassuperiortoplacebo,0.986).AmixedmodelwithrepeatedmeasuresanalysisprovidedresultsthatwereconsistentwiththoseoftheBayesiananalysis.Themostfrequentadverseeventwasdiarrhea.Atotalof13patientsdiscontinuedBI1015550treatmentowingtoadverseevents.Thepercentagesofpatientswithseriousadverseeventsorsevereadverseeventsweresimilarinthetwotrialgroups.
CONCLUSIONS
Inthisplacebo-controlledtrial,treatmentwithBI1015550,eitheraloneorwithbackgrounduseofanantifibroticagent,preventedadecreaseinlungfunctioninpatientswithidiopathicpulmonaryfibrosis.(FundedbyBoehringerIngelheim;1305-0013ClinicalTrials.govnumber,NCT04419506)
译者

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程重生
北京协和医院2020级内科学博士，师从徐凯峰教授，参与间质性肺疾病的临床与机制研究，以及呼吸系统罕见病、遗传病等多项研究。
审核

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汪劭婷
主治医师，北京协和医院呼吸与危重症医学科。 2011年毕业于北京协和医学院，获八年制临床医学博士学位。在国内核心期刊或SCI杂志共发表论文十余篇，参编专著三部，参与科室所承担的973、十三五等课题。
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