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阿达木单抗治疗难治性幼年特发性关节炎患儿的临床研究
Clinical trial of adalimumab in the treatment of children with refractory juvenile idiopathic arthritis
【摘要】 目的 观察阿达木单抗治疗难治性幼年特发性关节炎(JIA)患儿疗效及对血清白细胞介素(IL)-17、IL-8、IL-4、γ干扰素(IFN-γ)水平的影响。方法 将难治性JIA患儿根据随机数字表法分为对照组(给予甲氨蝶呤片治疗,每周10 mg·m-2)和试验组(给予阿达木单抗治疗,体质量<30 kg,每次20 mg;体质量≥30 kg,每次40 mg,每2周注射一次)。2组均治疗24周。比较2组治疗前、治疗24周后临床症状的变化,治疗前、治疗24周后的28处关节疾病活动度评分(DAS28)和幼年关节炎活动性系统评分(JADAS)、白细胞计数、血小板计数、血红蛋白、红细胞沉降率(ESR)、C反应蛋白(CRP)、血清IL-17、IL-8、IL-4、IFN-γ水平,以及治疗期间的药物不良反应发生率。结果 试验组和对照组各25例。治疗24周后,试验组和对照组关节炎发生率分别为4.00%和20.00%,淋巴结肿大发生率分别为0和16.00%,DAS28得分分别为(1.98±0.44)和(2.69±0.67)分,JADAS得分分别为(0.96±0.24)和(1.24±0.34)分,白细胞计数分别为(6.34±0.93)×109·L-1和(8.96±1.37)×109·L-1,血小板计数分别为(287.61±45.49)×109·L-1和(321.64±46.21)×109·L-1,血红蛋白水平分别为(132.91±16.55)和(118.16±12.70)g·L-1,ESR水平分别为(17.25±2.32)和(23.15±3.35)mm·h-1,CRP水平分别为(9.34±1.77)和(16.42±1.88)mg·L-1,IL-17水平分别为(10.05±1.29)和(11.47±1.47)ng·L-1,IL-8水平分别为(9.06±1.42)和(11.18±1.47)pg·mL-1,IL-4水平分别为(3.02±0.32)和(2.51±0.30)pg·mL-1,IFN-γ水平分别为(5.21±0.70)和(4.79±0.52)pg·mL-1,差异均有统计学意义(P<0.05)。治疗期间,试验组与对照组药物不良反应发生率分别为24.00%和12.00%,差异无统计学意义(P>0.05)。结论 阿达木单抗治疗难治性JIA患儿的效果显著,能够改善其临床症状,缓解病情活动度,控制病情发展,其可能的作用机制与调节血清炎性细胞因子水平,改善免疫状态有关。
【Abstract】 Objective To explore the clinical effect of adalimumab and its influences on levels of serum interleukin(IL)-17, IL-8, IL-4 and interferon-γ(IFN-γ) in children with refractory juvenile idiopathic arthritis(JIA). Methods According to random number table method, children with refractory JIA were divided into control group(methotrexate tablets, 10 mg·m-2 a week) and treatment group (adalimumab, 20 mg once for weight < 30 kg while 40 mg once for weight ≥30 kg, once every 2 weeks). All were treated for 24 weeks. The changes of clinical symptoms before treatment and after 24 weeks of treatment, disease activity score in 28 joints(DAS28), juvenile arthritis disease activity score(JADAS), white blood cell count, platelet count, hemoglobin, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), serum IL-17, IL-8, IL-4 and IFN-γ levels before treatment and after 24 weeks of treatment, and the incidence of adverse drug reactions during treatment were compared between the two groups.Results There were 25 cases in treatment group and 25cases in control group. After 24 weeks of treatment, incidence of arthritis in treatment group and control group were4. 00% and 20. 00%; incidence of lymph node enlargement were 0 and 16. 00%, DAS28 were(1. 98 ± 0. 44) and(2. 69 ± 0. 67) points; JADAS were(0. 96 ± 0. 24) and(1. 24 ± 0. 34) points; levels of white blood cell count were(6. 34 ± 0. 93) and(8. 96 ± 1. 37) × 109·L-1; platelet count levels were(287. 61 ± 45. 49) and(321. 64 ± 46. 21)× 109·L-1; hemoglobin levels were(132. 91 ±16. 55) and(118. 16 ±12. 70) g·L-1; ESR levels were(17. 25 ±2. 32)and(23. 15 ± 3. 35) mm·h-1; CRP levels were(9. 34 ± 1. 77) and(16. 42 ± 1. 88) mg·L-1; IL-17 levels were(10. 05 ± 1. 29) and(11. 47 ± 1. 47) ng·L-1; IL-8 levels were(9. 06 ± 1. 42) and(11. 18 ± 1. 47) pg·mL-1;IL-4 levels were(3. 02 ± 0. 32) and(2. 51 ± 0. 30) pg · mL-1; IFN-γ levels were(5. 21 ± 0. 70) and(4. 79 ± 0. 52) pg · mL-1, the differences were statistically significant( allP< 0. 05). During treatment, the difference in incidence of adverse drug reactions between treatment group and control group was not statistically significant(24. 00%vs12. 00%,P> 0. 05).Conclusion Clinical effect of adalimumab is significant on children with refractory JIA, which can improve clinical symptoms, relieve disease activity and control disease progression. The possible mechanism of action is related to regulating serum inflammatory cytokines and improving immune status.
【Key words】 refractory juvenile idiopathic arthritis; methotrexate; adalimumab; interleukin-17; interleukin-8; interleukin-4; interferon-γ;
- 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2023年21期
- 【分类号】R725.9
- 【下载频次】22