重组人干扰素α2b口咽部喷雾治疗疱疹性咽峡炎的有效性和安全性多中心随机对照研究

目的评估重组人干扰素α2b(rhIFNα2b)口咽部喷雾治疗小儿疱疹性咽峡炎的有效性和安全性。方法本研究采用前瞻性、随机、开放、对照、多中心研究方法,2018年8月至2019年3月参加本研究的安徽省内11家三甲医院共收集了疱疹性咽峡炎患儿180例,按住院的时间顺序随机分为干扰素治疗组和利巴韦林对照组。在清热解毒和抗感染治疗基础上,治疗组患儿咽部喷洒rhIFNα2b 9 g/L盐水溶液100万IU/mL,10万IU/(0.1 mL·揿)],对照组患儿咽部喷洒利巴韦林喷剂(0.5 mg/揿,150揿),2组治疗方法相同,均为每次3揿,每日4次,连续给药5 d,提前痊愈者不再给药治疗。所有患儿观察至临床痊愈,比较2组患儿的疗效、症状和体征消失时间,并评估口咽局部喷洒rhIFNα2b的安全性。结果180例患儿均完成研究,其中治疗组90例,对照组90例,2组性别、年龄、体质量和就诊前病程等方面比较差异均无统计学意义(均P>0.05),具有临床可比性。治疗组显效率63.3%(57/90例)]显著高于对照组38.9%(35/90例)],差异有统计学意义(χ^2=10.934,P=0.004);治疗组总有效率为96.7%(87/90例),与对照组92.2%(83/90例)]比较差异无统计学意义(χ^2=2.924,P=0.169)。治疗组发热(32.59±20.73)h比(45.72±26.96)h]、充血(76.48±23.12)h比(92.44±24.31)h]、疱疹(72.99±25.77)h比(85.09±26.62)h]、流涎(45.44±24.96)h比(54.42±31.20)h]和畏食(62.70±23.99)h比(78.71±30.54)h]等症状和体征持续时间均短于对照组,差异均有统计学意义(均P<0.05)。用药前2组血清肿瘤坏死因子α(TNF-α)(13.02±4.41)ng/L比(13.57±9.27)ng/L]、白细胞介素-6(IL-6)(26.48±11.31)ng/L比(30.15±15.55)ng/L]和C反应蛋白(CRP)(19.34±14.11)mg/L比(19.83±14.57)mg/L]比较差异均无统计学意义(均P>0.05);治疗后,治疗组血清TNF-α和IL-6水平分别为(7.26±1.99)ng/L和(2.42±0.73)ng/L,均低于对照组(12.09±6.39)ng/L和(7.32±11.51)ng/L],差异均有统计学意义(均P<0.05),但2组患儿血清CRP水平(2.21±3.34)mg/L比(2.99±4.81)mg/L]比较差异无统计学意义(P>0.05)。治疗组患儿咽拭子治疗前后病毒阳性率分别为65.3%(32/49例)和40.6%(13/32例),与对照组66.7%(36/54例)和41.0%(16/39例)]比较,差异均无统计学意义(均P>0.05)。治疗期间2组均未见严重不良反应事件,治疗组不良反应发生率为1.1%(1/90例),对照组不良反应发生率为5.6%(5/90例);对照组治疗后的血红蛋白水平显著低于治疗前和治疗组,差异均有统计学意义(均P<0.05)。结论rhIFNα2b口咽部喷雾治疗疱疹性咽峡炎相对利巴韦林可明显提高临床显效率,加快临床症状和体征消失,缩短总病程且安全性良好,值得临床应用。

A prospective multicenter randomized controlled study on the efficacy and safety of pharyngeal spraying recombinant human interferon alpha 2b in the treatment of children with herpangina

Objective To evaluate the efficacy and safety of pharyngeal spraying recombinant human interfe-ron alpha 2b(rhIFNα2b)in the treatment of herpangina in children.Method s A prospective,multicenter,rando-mized,opened and controlled study was carried out in 11 hospitals in Anhui province from August 2018 to March 2019.According to the time of admission,180 patients diagnosed as herpangina were prospectively and randomly divided into rhIFNα2b treatment group and Ribavirin control group.On the basis of giving both groups the heat-clearing,detoxifying and anti-infection treatment,the patients in treatment group received pharyngeal spraying rhIFNα2b 9 g/L saline solution1 million IU/mL,0.1 million IU/(0.1 mL·press)],and the patients in control group were treated by pharyngeal spraying Ribavirin(0.5 mg RBV/press,150 press),3 presses per time,4 times per day,continuous administration for 5 days for both groups.Those who recovered in advance were no longer given medication.All patients were observed to fully recover.The clinical efficacy and the disappearing time of symptoms and signs between two groups were compared,and the safety of pharyngeal spraying rhIFNα2b for patients was evaluated.Result s All of the 180 patients completed the study,including 90 cases in the treatment group and 90 cases in the control group.There was no statistically significant difference in terms of gender,age,weight and course of illness before treatment between the two groups(all P>0.05),which had clinical comparability.The apparent efficiency of the treatment group63.3%(57/90 cases)]was significantly higher than that in the control group38.9%(35/90 cases)]and the difference was statistically significant(χ^2=10.934,P=0.004);no significant difference in the total efficiency between the treatment group96.7%(87/90 cases)]and the control group92.2%(83/90 cases)]was observed(χ^2=2.924,P=0.169).The duration of fever(32.59±20.73)h vs.(45.72±26.96)h],hyperemia(76.48±23.12)h vs.(92.44±24.31)h],herpes(72.99±25.77)h vs.(85.09±26.62)h],salivation(45.44±24.96)h vs.(54.42±31.20)h]and anorexia(62.70±23.99)h vs.(78.71±30.54)h]in the treatment group were significantly shorter than those in the control group,and the differences were statistically significant(all P<0.05).Before treatment,the serum levels of tumor necrosis factorα(TNF-α)(13.02±4.41)ng/L vs.(13.57±9.27)ng/L],interleukin-6(IL-6)(26.48±11.31)ng/L vs.(30.15±15.55)ng/L]and C-reactive protein(CRP)(19.34±14.11)mg/L vs.(19.83±14.57)mg/L]were not significantly different between the two groups(all P>0.05).After treatment,the serum levels of TNF-αand IL-6 were(7.26±1.99)ng/L and(2.42±0.73)ng/L in the treatment group,which were significantly lower than those in the control group(12.09±6.39)ng/L and(7.32±11.51)ng/L](all P<0.05),but no significant difference in serum levels of CRP between the two groups was observed(P>0.05).The comparison on positive rate of virus in pharyngeal swab between the treatment group65.3%(32/49 cases)and 40.6%(13/32 cases)respectively]and the control group66.7%(36/54 cases)and 41.0%(16/39 cases),respectively]before and after therapy showed no significant difference(all P>0.05).During the treatment,no serious adverse reactions were observed in the two groups.The incidence of adverse reactions was 1.1%(1/90 cases)in the treatment group and 5.6%(5/90 cases)in the control group.In addition,the serum hemoglobin level of children in the control group after treatment was significantly lower than that before treatment and that in the treatment group(all P<0.05).Conclusions Compared with pharyngeal spraying ribavirin,pharyngeal spraying rhIFNα2b can greatly improve the clinical efficiency,accelerate the disappearance of clinical symptoms and signs,and shorten the total course of disease,and is more safe and worthy of clinical application.