Abstract:

Objective　To investigate the effect of low-dose leflumide combined with methotrexate for elderly patients with first-episode rheumatoid arthritis (RA). Methods　One hundred and twenty elderly patients with first-episode RA admitted to Xi'an Fifth Hospital from February 2020 to February 2023 were selected for the randomized controlled trial. They were divided into a combination group and a reference group by the random number table method, with 60 cases in each group. There were 37 males and 23 females in the combination group; they were (70.22±5.29) years old; their body mass index (BMI) was (22.87±1.55) kg/m²; their disease course was (4.76±0.85) years. There were 38 males and 22 females in the reference group; they were (70.31±5.34) years old; their BMI was (22.94±1.58); their disease course was (4.82±0.87) years. The reference group were treated with methotrexate, and the combination group with low-dose leflunomide and methotrexate, for 90 d. The clinical efficacies, improvement of clinical symptoms, levels of bone metabolism indicators and serum levels of chitinase 3-like protein1 (CHI3L1), soluble suppression of tumorigenicity 2 (sST2), and interleukin-32 (IL-32) before and after the treatment, and adverse reactions were compared between the two groups. χ² and t tests were applied. Results　The total effective rate of the combination group was higher than that of the reference group [96.67% (58/60) vs. 83.33% (50/60); χ²=5.926, P=0.015]. The joint number with tenderness, joint number with swelling, duration of morning stiffness, and grip strength of both hands in the combination group were better than those in the control group [(5.23±1.05) vs. (7.45±1.36), (4.18±0.66) vs. (6.39±0.82), (34.58±4.68) min vs. (50.40±8.21) min, and (14.03±2.55) kPa vs. (11.28±2.09) kPa; t=10.008, 16.263, 12.967, and 6.461; P<0.001]. After the treatment, the levels of bone gla protein (BGP), osteoprotectin (OPG), and total type Ⅰ collagen amino terminal extension peptide (T-PⅠNP) in the combination group were higher than those in the reference group [(27.48±5.02) ng/L vs. (24.16±4.19) ng/L, (5.02±0.74) ng/L vs. (4.45±0.66) ng/L, and (43.17±8.59) μg/L vs. (36.92±7.33) μg/L; t=3.933, 4.453, and 4.287; all P<0.001]. After the treatment, the serum levels of CHI3L1, sST2, and IL-32 in the combination group were lower than those in the reference group [(50.82±6.12) μg/L vs. (78.45±8.39) μg/L, (28.45±4.11) μg/L vs. (33.05±5.24) μg/L, and (14.32±2.01) ng/L vs. (16.85±2.77) ng/L; t=20.609, 5.350, 5.726; all P<0.001]. There was no statistical difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion　Low-dose leflunomide combined with methotrexate for elderly patients with first-episode RA is effective, and can significantly improve their bone metabolism indicators and serum levels of CHI3L1, sST2, and IL-32.

Key words:

Rheumatoid arthritis, Leflunomide, Methotrexate, Chitinase 3-like protein 1, Soluble matrix lysin 2, Interleukin-32

摘要：

目的　探讨小剂量来氟米特配合甲氨蝶呤治疗老年首发类风湿关节炎（rheumatoid arthritis，RA）患者的效果。方法　选取2020年2月至2023年2月西安市第五医院收治的120例老年首发RA患者进行随机对照试验。采用随机数字表法将其分为配合组及参考组，各60例。配合组男37例，女23例，年龄（70.22±5.29）岁，体质量指数（body mass index，BMI）（22.87±1.55）kg/m²，病程（4.76±0.85）年。参考组男38例，女22例，年龄（70.31±5.34）岁，BMI（22.94±1.58）kg/m²，病程（4.82±0.87）年。参考组采用甲氨蝶呤治疗，配合组则于参考组的基础上采用小剂量来氟米特治疗。两组均治疗90 d。对比两组临床疗效，临床症状改善情况，治疗前后骨代谢指标水平和血清壳多糖酶3样蛋白1（chitinase 3-like protein1，CHI3L1）、可溶性基质裂解素2（soluble suppression of tumorigenicity 2，sST2）、白细胞介素-32（interleukin-32，IL-32）水平，不良反应。采用χ²检验和t检验。结果　配合组总有效率高于参考组［96.67%（58/60）比83.33%（50/60）］（χ²=5.926，P=0.015）。配合组关节压痛数目、关节肿胀数目分别为（5.23±1.05）个、（4.18±0.66）个，均少于参考组的（7.45±1.36）个、（6.39±0.82）个，晨僵时长为（34.58±4.68）min，短于参考组的（50.40±8.21）min，双手握力为（14.03±2.55）kPa，高于参考组的（11.28±2.09）kPa（t=10.008、16.263、12.967、6.461，均P<0.001）。治疗后，配合组骨钙素（bone gla protein，BGP）、骨保护素（osteoprotectin，OPG）及总Ⅰ型胶原氨基端延长肽（total type I collagen amino terminal extension peptide，T-PⅠNP）水平分别为（27.48±5.02）ng/L、（5.02±0.74）ng/L、（43.17±8.59）μg/L，均高于参考组的（24.16±4.19）ng/L、（4.45±0.66）ng/L、（36.92±7.33）μg/L（t=3.933、4.453、4.287，均P<0.001）。治疗后，配合组血清CHI3L1、sST2、IL-32水平分别为（50.82±6.12）μg/L、（28.45±4.11）μg/L、（14.32±2.01）ng/L，均低于参考组的（78.45±8.39）μg/L、（33.05±5.24）μg/L、（16.85±2.77）ng/L（t=20.609、5.350、5.726，均P<0.001）。两组不良反应发生率对比，差异无统计学意义（P>0.05）。结论　小剂量来氟米特配合甲氨蝶呤应用于老年首发RA患者中的效果较佳，可改善患者骨代谢指标及血清CHI3L1、sST2、IL-32水平。

关键词:

类风湿关节炎, 来氟米特, 甲氨蝶呤, 壳多糖酶3样蛋白1, 可溶性基质裂解素2, 白细胞介素-32