枸橼酸托法替布治疗强直性脊柱炎的疗效和安全性分析  

Efficacy and Safety of Tofacitinib in the Treatment of Ankylosing Spondylitis

作　　者：明斌 廖霞 简桂林 张全波[1] 谢泓源 李秀 青玉凤[1] Ming Bin;Liao Xia;Jian Guilin(Department of Geriatrics,Department of Rheumatology,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China)

机构地区：[1]川北医学院附属医院老年科,风湿免疫科,四川南充637000

出　　处：《四川医学》2024年第12期1297-1302,共6页Sichuan Medical Journal

基　　金：国家自然科学基金面上项目(编号:81974250);四川省南充市科技项目(编号:20SXQT0308,20SXCXTD0002)。

摘　　要：目的了解真实世界中强直性脊柱炎(AS)患者服用枸橼酸托法替布治疗6个月的疗效及安全性,检测并分析托法替布治疗前后Janus蛋白酪氨酸激酶(JAK)信号通路中相关分子的表达与变化。方法搜集并分析2020年1月至2021年1月在我院就诊并服用托法替布治疗6个月的AS患者治疗前后的临床及实验室资料。qRT-PCR与Western-Blot分别检测并比较标本合格的20例AS患者治疗前后外周血单个核细胞(PBMCs)中JAK3、STAT5a、STAT5b基因与蛋白表达水平。结果(1)30例AS患者被纳入研究,男22例,女8例,平均年龄(35.73±9.41)岁,平均病程(10.98±8.46)年。(2)与治疗前相比,患者BASDAI、BASFI、ASDAS、ESR和hsCRP均明显降低(P均<0.05);WBC、GR、GR%、PLT、ALP水平均下降(P均<0.05),LY%、ALB DBIL水平则显著升高(P均<0.05)。(3)与治疗前相比,PBMCs中STAT5a、STAT5b mRNA表达水平和P-JAK3/JAK3、P-STAT5a/STAT5a、P-STAT5b/STAT5b蛋白比值均显著降低(P均<0.05)。结论托法替布对中重度疾病活动的AS患者有效、安全;治疗后JAK3/STAT5基因及蛋白磷酸化水平明显降低,提示托法替布可能通过抑制JAK3/STAT5磷酸化水平发挥作用。Objective To observe the clinical efficacy and safety of Tofacitinib in the treatment of ankylosing spondylitis(AS)patients through real-world study,detect and analyze the expression and changes of related molecules in Janus protein tyrosine kinase signalling pathway before and after Tofacitinib treatment.Methods To collect and analyze the clinical and laboratory data of AS patients who were hospitalized in our hospital from January 2020 to January 2021 and treated with Tofacitinib for 6 months.The mRNA and the protein expression levels of JAK3、STAT5a、STAT5b were detected by qRT-PCR and Western-Blot.Results①30 AS cases were included in the study,22 were male and 8 were female,with an average age of(35.73±9.41)years and an average course of disease of(10.98±8.46)years.②After treatment,BASDAI,BASFI,ASDAS,ESR and hsCRP in patients with AS were significantly lower than those before treatment(P<0.05).The levels of WBC,GR,GR%,PLT and ALP in AS patients decreased(P<0.05),while the levels of LY%,ALB and DBIL increased(P<0.05);③After treatment,the mRNA expression levels of STAT5a and STAT5b in PBMCs and the protein expression levels of P-JAK3/JAK3,P-STAT5a/STAT5a,P-STAT5b/STAT5b were significantly lower than those before treatment(P<0.05).Conclusion Tofacitinib is effective and safe for patients with AS with moderate to severe disease activity.After treatment,the expression mRNA and the protein expression levels of JAK3/STAT5 decrease significantly,indicating that Tofacitinib may play a role by inhibiting the JAK3/STAT5 pathway.

关 键 词：枸橼酸托法替布 强直性脊柱炎 真实世界研究 Janus激酶3 信号转导和转录激活因子5 

分 类 号：R593.23[医药卫生—内科学]