培塞利珠单抗治疗育龄期女性炎性关节疾病的研究  

A study on certolizumab pegol in the treatment of inflammatory joint diseases of women of childbearing age

作　　者：唐果 郦源 吕文涵 杨扬 张乐[1] 吕良敬[1] Tang Guo;Li Yuan;Lyu Wenhan;Yang Yang;Zhang Le;Lv Liangjing(Department of Rheumatology and Clinical Immunology,Shanghai Jiaotong University Renji Hospital,Shanghai,200001,China)

机构地区：[1]上海交通大学医学院附属仁济医院风湿病科,上海200001

出　　处：《中华风湿病学杂志》2022年第6期361-366,共6页Chinese Journal of Rheumatology

基　　金：国家重点研发计划(2017YFC0909000);国家自然科学基金(81974251,71804109);上海市"医苑新星"青年医学人才培养资助计划(沪卫人事〔2021〕99)。

摘　　要：目的评价分析培塞利珠单抗(CZP)治疗中国育龄期女性炎性关节疾病患者的有效性,以及宫内暴露对婴儿疫苗接种与继发感染风险的影响。方法本研究为回顾性观察研究,纳入2019年11月至2020年10月门诊使用CZP治疗的育龄期女性炎性关节疾病患者,随访24周,观察记录临床各项指标,以DAS28-CRP、临床疾病活动指数(CDAI)和简化疾病活动指数(SDAI)评判RA患者疾病活动度;以BASDAI、强直性脊柱炎疾病活动评分(ASDAS-ESR)评价AS及SpA患者的疾病活动度;计算患者低疾病活动度(LDA)、糖皮质激素(GC)用量以及ACR20与ASAS20的达标率以评价CZP药物有效性;并记录患者胎儿疫苗接种及继发感染情况评估宫内暴露对婴儿的影响。统计学处理采用配对t检验或Mann WhitneyU检验。结果研究纳入20例患者,失访5例,共分析15例患者,其中8例RA患者,6例AS患者,1例SpA患者,平均年龄(30±5)岁,中位病程5.0(3.0,6.5)年。RA患者入组时DAS28-CRP、CDAI及SDAI分别为3.4±1.2、15.5(9.5,21.0)与18±12;用药后DAS28-CRP、CDAI及SDAI为2.5±0.9(t=2.48,P=0.042)、4.5(3.5,10.8)(U=12.50,P=0.040)与9±6(t=2.76,P=0.028);初次随访ACR 20达标率50%,研究结束时LDA达标率为75%(6/8),3例(37.5%)患者实现GC减量。7例AS/SpA患者中,入组时BASDAI为19.0(14.5,26.0),ASDAS-ESR为(2.4±1.0);用药后两者分别为9.0(1.0,10.5)(U=11.50,P=0.100)、1.4±0.5(t=3.44,P=0.014);初次随访ASAS 20达标率71.4%(5/7),研究结束时达标率为85.7%(6/7)。4例患者出现不良事件,其中1例停用CZP。3例入组时已孕,中位数孕程12周,3例入组后妊娠,共活产6名婴儿均按计划接种减毒活疫苗及灭活疫苗,未报告疫苗接种相关不良事件,但其中1名出现肛周脓肿,1名出现感冒症状,治疗后好转。结论CZP能有效控制炎性关节疾病患者孕期的病情,在研究期间宫内暴露婴儿疫苗接种的安全性可接受。Objective To evaluate the efficacy of certolizumab pegol(CZP)in the treatment of Chinese women of childbearing age with inflammatory joint diseases and the effect of intrauterine exposure on infant vaccination and risk of infection.Methods This study is a retrospective observation study,including female patients of childbearing age who were treated with CZP in the outpatient clinic from November 2019 to October 2020.The patients were followed up for 24 weeks,and the related data was collected.We adopted disease activity score-28 for rheumatoid arthritis with CRP(DAS28-CRP),clinical disease activity index(CDAI)and simplified disease activity index(SDAI)to evaluate disease activity.Bath ankylosing spon-dylitis disease activity index(BASDAI)and ankylosing spondylitis disease activity score(ASDAS-ESR)were used to assess the disease activity of patients with ankylosing spondylitis or spondyloarthritis(AS/SpA).Low disease activity(LDA),the dosage of glucocorticoid(GC)and the qualified rates of ACR20 and ASAS20 were calculated to validate the efficacy of CZP.The data of infants vaccination and infection was recorded to estimate the effect of intrauterine exposure on infants.Correlation analysis were performed using paired t test or Mann Whitney test.All statistical tests were bilateral,with a significance of P<0.05.Results Twenty women entered the study and fifteen completed,including eight patients with RA,six patients with AS and 1 patient with SpA.The average age was(30±5)years and the median symptom duration was 5.0(3.0,6.5)years.When these RA patients were enrolled into the study,DAS28-CRP,CDAI and SDAI were(3.4±1.2),15.5(9.5,21.0)and(18±12)respectively;and after the use of CZP,the DAS28-CRP,CDAI and SDAI changed to(2.5±0.9)(t=2.48,P=0.042),4.5(3.5,10.8)(U=12.50,P=0.040)and(9±6)(t=2.76,P=0.028).At the first follow-up,the ACR20 rate was 50%.and at the end of the study,the LDA rate was 75%(6/8),three(37.5%)women reduced the dosage of GC.Among the AS/SpA patients,BASDAI was 19.0(14.5,26.0)and ASDAS-ESR was(2.4±1

关 键 词：生物因子 关节疾病 妊娠 培塞利珠单抗 疫苗 宫内暴露 

分 类 号：R684[医药卫生—骨科学]