不同剂量托法替布联合甲氨蝶呤治疗类风湿关节炎疗效安全性分析及对血清因子水平的影响

Effect of different doses of tofacitinib combined with methotrexate on patients with rheumatoid arthritis and its effect on the levels of serum factors

目的探讨分析不同剂量托法替布联合甲氨蝶呤对类风湿性关节炎患者(rheumatoid arthritis,RA)的疗效和血清因子水平的影响。方法选取2019年7月至2021年4月在哈励逊国际和平医院诊治的90例RA患者作为研究对象,应用随机数表的方法按1∶1比例将患者分为低剂量联合组(n=45)和高剂量联合组(n=45)。两组患者均固定给予甲氨蝶呤治疗(10 mg,每周1次),低剂量联合组患者额外给予低剂量托法替布治疗(5 mg,每天1次),高剂量联合组患者额外给予高剂量托法替布治疗(5 mg,每天2次)。两组持续治疗3个月,比较两组患者治疗前后的疼痛评分指标VAS、疾病活动性指标DAS28、C反应蛋白(C-reactive protein,CRP)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、血清因子(IL-35、IL-17、IL-6和IFN-γ)和不良反应发生情况。结果两组患者治疗后的VAS评分、DAS28评分、CRP和ESR水平均低于治疗前(P<0.05),且高剂量联合组上述各项指标均明显低于低剂量联合组。两组患者治疗后的IL-17、IL-6和IFN-γ水平均低于治疗前(P<0.05),而IL-35水平高于治疗前(P<0.05)。高剂量联合组除IL-35外,其他血清因子(IL-17、IL-6和IFN-γ)水平均明显低于低剂量联合组。两组患者主要不良反应为恶心呕吐、腹泻和白细胞减少等,组间差异无统计学意义(P>0.05)。结论高剂量托法替布联合甲氨蝶呤相比较低剂量托法替布联合甲氨蝶呤能更有效的改善RA患者临床症状,降低CRP和ESR水平,上调IL-35水平而下调IL-17、IL-6和IFN-γ水平,且不增加不良反应。

Objective The study aimed to explore and analyze the effects of different doses of tofacitinib combined with methotrexate on patients with rheumatoid arthritis(RA)and its effect on the levels of serum factors.Methods A total of 90 RA patients who were diagnosed and treated in Harrison International Peace Hospital from July 2019 to April 2021 were randomly assigned at a 1:1 ratio into two groups:low-dose combination group(n=45)and high-dose combination group(n=45).Patients in both groups were treated with methotrexate(10 mg,once per week).Patients in low-dose combination group were given additional low-dose tofacitinib treatment(5 mg,once per day),and patients in high-dose combination group were given additional high-dose tofacitinib treatment(5 mg,twice per day).Both groups were treated with continuous treatment and observation for 3 months.The mean visual analogue score(VAS),disease activity score(DAS28),the levels of C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),serum factors(IL-35,IL-17,IL-6 and IFN-γ)and adverse drug reaction were compared between two groups before and after treatment.Results After treatment,the VAS scores,DAS28scores,levels of CRP and ESR of the two groups after treatment were lower than those before treatment(P<0.05),and these above-mentioned indexes in the high-dose combination group were significantly lower than those in the low-dose combination group.The levels of IL-17,IL-6 and IFN-γin both groups after treatment were lower than those before treatment,while the level of IL-35 was higher than that before treatment(P<0.05).In addition to IL-35,the levels of other serum factors(IL-17,IL-6 and IFN-γ)in the high-dose combination group were significantly lower than those in the low-dose combination group.The commonly adverse drug reactions of the two groups were vomiting,nausea,diarrhea and leukopenia,etc.There was no significant difference in the adverse drug reactions between the two groups(P>0.05).Conclusion Compared with low-dose tofacitinib combined with methotrexate,high-dose tofacitinib combined with methotrexate could effectively improve the clinical symptoms of RA patients,reduce the levels of CRP and ESR,upregulate the level of IL-35 whereas downregulate the levels of IL-17,IL-6 and IFN-γ,and it does not increase the occurrence of adverse reactions.