利妥昔单抗联合来氟米特治疗系统性红斑狼疮患者的临床研究

Clinical trial of rituximab and leflunomide in the treatment of patients with systemic lupus erythematosus

目的观察利妥昔单抗注射液联合来氟米特片治疗系统性红斑狼疮(SLE)患者的临床疗效及安全性。方法将SLE患者按队列法分成对照组和试验组。对照组给予来氟米特治疗,开始治疗的前3 d餐后口服50 mg·d^(-1),之后调整为20 mg·d^(-1)。试验组在对照组治疗的基础上,联合利妥昔单抗治疗,开始治疗前3次每2周静脉滴注375 mg·m^(-2),从第4次调整为每4周给药1次。2组患者均治疗24周。比较2组患者的临床疗效、系统性红斑狼疮疾病活动指数(SLEDAI)评分、血清学指标、24 h尿蛋白,以及药物不良反应的发生情况。结果试验组入组74例,对照组入组72例。治疗后,试验组和对照组的总有效率分别为91.89%(68例/74例)和79.17%(57例/72例),在统计学上差异有统计学意义(P<0.05)。治疗后,试验组和对照组的SLEDAI评分分别为(7.21±1.67)和(9.03±1.35)分,史密斯/核糖核蛋白抗体分别为(81.43±18.25)和(59.38±14.61)U·mL^(-1),免疫球蛋白G分别为(12.04±2.15)和(17.28±2.64)g·L^(-1),白细胞介素-10分别为(33.39±7.13)和(39.87±9.02)pg·mL^(-1),24 h尿蛋白定量分别为(1.46±0.32)和(2.67±0.54)g·24 h^(-1),在统计学上差异均有统计学意义(均P<0.05)。2组患者的药物不良反应均以肝肾功能损伤、消化道反应等为主。试验组和对照组的总药物不良反应发生率分别为13.51%和5.56%,在统计学上差异无统计学意义(P>0.05)。结论利妥昔单抗注射液联合来氟米特片治疗SLE患者的临床疗效确切,其能显著地降低患者的病情活动度,改善免疫功能,减轻炎症反应,且不增加药物不良反应的发生率。

Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d^(-1)after meal in the first 3 days of treatment and was adjusted to 20 mg·d^(-1)thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m^(-2)was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were91.89%(68 cases/74 cases)and 79.17%(57 cases/72 cases)with significant difference(P<0.05).Aftertreatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;thelevels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL^(-1);the levelsof immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L^(-1);the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL^(-1);24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h^(-1);all the differences were statistically significant(allP<0.05).The drug adverse reactionsof two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adversereactions in the treatment and control groups were 13.51%and 5.56%without significant difference(P>0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment ofSLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.