Dynamics of clinical manifestations and cytokine concentrations in patients with rheumatoid arthritis on olokizumab therapy

N. Lapkina, A. A. Baranov, N. Levshin, A. Kolinko, L. Mineeva, A. Artyuhov, E. Nasonov
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Abstract

The aim of the study was to investigate the dynamics of clinical and laboratory parameters of inflammatory disease activity and cytokines in patients with rheumatoid arthritis (RA) against the background of olokizumab (OKZ) treatment.Materials and methods. Ten patients with a reliable diagnosis of RA were examined: patients’ age was 46.00 (30.00; 60.00) years, duration of disease was 9.0 (3.0; 12,0) years. All patients had moderate to high disease activity: DAS28-ESR (Disease Activity Score 28 with Erythrocyte Sedimentation Rate) – 513 (4.34; 5,80); CDAI (Clinical Disease Activity Index) – 30.00 (24.00; 35.00); SDAI (Simplified Disease Activity Index) – 31.86 (24.36; 38.59). All patients were treated with OKZ at a dose of 64 mg subcutaneously every 4 weeks on the background of therapy with methotrexate, leflunomide, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin (IL) 1β, IL-4, IL-6, tumor necrosis factor α (TNF-α), interferon (INF) γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L, – were examined using multiplex xMAR technology.Results. After 3 and 6 months of OKZ therapy, there was a significant decrease in DAS28-ESR of 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10); CDAI – 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0); SDAI – 10.0 (5.0; 15.0) and 10.17 (7.02; 15.02); C-reactive protein (CRP) concentrations (initial – 14.30 (7.00; 24.70) mg/l, after 3 months – 0.70 (0.40; 0.90) mg/l and after 6 months – 0.65 (0.20; 3.00) mg/l). After 3 months of treatment we found an increase in IL-6 concentration (initial – 1.89 (1.61; 2.33) pg/ml and 89.98 (35.09; 165.84) pg/ml; p<0.01), after 6 months – its level decreased to 44.88 (5.25; 80.90) pg/ml without reaching, however, the initial values (p<0.05). Against the background of OCZ, after 3 months of treatment there was an increase in IL-25 concentration (p<0.01), and after 6 months of therapy – TNF-α (p<0.05).Conclusion. The use of OKZ leads to an increase in the concentration of total IL-6 in the blood serum of RA patients, while the clinical and laboratory activity of the disease decreases.
类风湿关节炎患者在olokizumab治疗下的临床表现和细胞因子浓度的动态变化
该研究的目的是在olokizumab (OKZ)治疗的背景下,研究类风湿关节炎(RA)患者炎症疾病活动性和细胞因子的临床和实验室参数的动态。材料和方法。对10例可靠诊断为RA的患者进行了检查:患者年龄为46.00岁(30.00岁;60.00)年,病程9.0 (3.0;12,0)年。所有患者均有中度至高度疾病活动性:DAS28-ESR(疾病活动性评分28伴红细胞沉降率)- 513 (4.34;5, 80);CDAI(临床疾病活动指数)30.00 (24.00;35.00);SDAI(简化疾病活动指数)- 31.86 (24.36;38.59)。所有患者在接受甲氨蝶呤、来氟米特、非甾体抗炎药和糖皮质激素治疗的基础上,每4周皮下注射64mg OKZ。分别于治疗前、治疗后3、6个月进行观察。采用多重xMAR技术检测血清15种细胞因子:白细胞介素(IL) 1β、IL-4、IL-6、肿瘤坏死因子α (TNF-α)、干扰素(INF) γ、IL-10、IL- 17a、IL- 17f、IL-21、IL-22、IL-23、IL-25、IL-31、IL-33、sCD40L、-的水平。OKZ治疗3个月和6个月后,DAS28-ESR显著下降,分别为3.53 (2.83;4.26)和3.48 (2.8;4.10);Cdai - 11.00 (6.0;16.00)和10.0 (5.0;15.0);Sdai - 10.0 (5.0;15.0)和10.17 (7.02;15.02);c反应蛋白(CRP)浓度(初始值- 14.30 (7.00;24.70) mg/l, 3个月后- 0.70 (0.40;0.90) mg/l, 6个月后- 0.65 (0.20;3.00 mg / l)。治疗3个月后,我们发现IL-6浓度升高(初始- 1.89 (1.61;2.33) pg/ml和89.98 (35.09;165.84) pg / ml;P <0.01), 6个月后降至44.88 (5.25;80.90) pg/ml,但未达到初始值(p<0.05)。在OCZ背景下,治疗3个月后IL-25浓度升高(p<0.01),治疗6个月后TNF-α浓度升高(p<0.05)。OKZ的使用导致RA患者血清中总IL-6浓度升高,而疾病的临床和实验室活动降低。
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