Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis

Xiangxian LIU; Yi LIN; Jinzhu GUO

doi:10.19723/j.issn.1671-167X.2025.05.018

Journal of Peking University(Health Sciences) >

2025 , Vol. 57 >Issue 5: 934 - 940

DOI: https://doi.org/10.19723/j.issn.1671-167X.2025.05.018

Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis

Xiangxian LIU ¹^,² ,
Yi LIN ¹^,² ,
Jinzhu GUO ^,¹^,*

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1. Department of Dermatology, Peking University Third Hospital, Beijing 100191, China
2. Peking University Health Science Center, Beijing 100191, China

GUO Jinzhu, e-mail, guojinzhu_826@163.com

Received date: 2024-11-12

Online published: 2025-08-28

Supported by

the National Key Research and Development Program of China(2023YFC2508106)

the Beijing Health Promotion Association Medical Science Research Fund(Z2022023058008)

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Abstract

Objective: To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients. Methods: The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies. Results: A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (P>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=－2.100, P=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L, t=5.215, P < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (P> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=－2.082, P=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (P>0.05). Conclusion: Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients may result in elevated uric acid levels, particularly in patients with normal uric acid levels before treatment. The long-term use of IL-17 inhibitors, IL-23 inhibitors or IL-12/23 inhibitors might reduce LDL-C levels.

Key words： Psoriasis; Biologics; Metabolic; Retrospective study

Cite this article

Xiangxian LIU , Yi LIN , Jinzhu GUO . Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis[J]. Journal of Peking University(Health Sciences), 2025 , 57(5) : 934 -940 . DOI: 10.19723/j.issn.1671-167X.2025.05.018

银屑病是一种与遗传、免疫、环境因素有关的慢性、复发性、炎症性、系统性疾病^[1]。在中重度银屑病的治疗中，生物制剂因治疗效果显著优于传统药物，在临床中的应用越来越广^[2]。此外，银屑病的复发率极高(达到90%)^[3]，特别是中重度患者，大多数需要长期接受生物制剂进行治疗^[4]。

银屑病不仅累及皮肤、关节，还累及多个器官和系统，被称为银屑病共病，其中包括多种代谢性疾病，如代谢综合征(肥胖、高血压、胰岛素抵抗/糖尿病、血脂异常等)、非酒精性脂肪肝、心血管疾病等^[5]。既往研究发现，银屑病共病(如肥胖)会影响生物制剂的治疗效果，应用生物制剂治疗中重度斑块型银屑病，体重正常组患者的治疗效果显著优于超重组、肥胖组^[6-8]。然而，生物制剂的长期应用是否影响中重度斑块型银屑病患者的代谢性生化指标尚无定论，国外相关研究具有争议，国内关于在银屑病患者中应用生物制剂对于代谢性生化指标影响的研究非常少见^[9]。因此，本研究旨在观察生物制剂的长期应用对于我国中重度斑块型银屑病患者代谢性生化指标的影响。

1 资料与方法

1.1 数据来源和研究人群

选择2015年11月至2024年1月在北京大学第三医院皮肤科门诊和住院的中重度斑块型银屑病患者的病例资料进行回顾性分析。病例纳入标准：(1)18岁及以上的中重度斑块型银屑病患者；(2)长期(至少24周)使用同一种生物制剂进行治疗，并具备治疗前30 d内及治疗至少24周以后生化指标化验结果的患者。排除标准：(1)用药期间改变锻炼频率者；(2)调查期间受到饮食限制，或新使用可能影响血糖、血脂、尿酸等的药物者；(3)处于怀孕或哺乳期的女性患者; (4)慢性肾病、艾滋病、肿瘤等慢性消耗性疾病患者。

因使用生物制剂不同将患者分为白介素(interleukin，IL)-17抑制剂组(应用司库奇尤单抗和依奇珠单抗)、IL-23和IL-12/23抑制剂组(应用古塞奇尤单抗和乌司奴单抗)与肿瘤坏死因子-α (tumor necrosis factor-α，TNF-α)抑制剂组(应用英夫利西单抗和阿达木单抗)三组。本研究开始前已经北京大学第三医院医学科学研究伦理委员会审查批准(批准号：2024医伦审第053-02号)。

1.2 观察指标

收集患者信息包括：(1)人口学特征(年龄、性别)；(2)银屑病病程；(3)生物制剂用药情况；(4)其他疾病情况；(5)应用生物制剂治疗前30 d内及治疗至少24周以后的身高、体重、丙氨酸氨基转移酶(alanine aminotransferase，ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase，AST)、空腹血糖(fasting glucose，GLU)、总胆固醇(total cholesterol，TC)、甘油三酯(triglycerides，TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol，HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cho-lesterol，LDL-C)、尿酸(uric acid，UA)等检查结果。患者在接受同一生物制剂治疗期间，可能会产生多个符合纳入和排除标准的代谢性生化指标数据，鉴于持续用药时间的增长更能反映长期用药对指标的影响，本研究选择患者用药时间最长的时段数据进行分析。对三组患者治疗前及治疗至少24周以后的体重、体重指数(body mass index，BMI)、ALT、AST、GLU、TC、TG、HDL-C、LDL-C、UA进行比较。

1.3 统计学分析

应用SPSS 26.0软件，分类变量以n(%)表示，使用卡方检验进行统计学分析。符合正态分布的计量资料采用$\bar x \pm s$表示，不符合正态分布的计量资料采用M(P₂₅, P₇₅)表示。符合正态分布的计量资料使用单因素方差分析来比较组间差异，不符合正态分布的计量资料使用Kruskal-Wallis H检验比较组间差异；治疗前后均符合正态分布的计量资料采用配对t检验分析治疗前后计量资料的变化情况，否则采用非参数检验分析前后计量资料的变化情况；采用Spearman相关分析进行IL-17抑制剂组尿酸水平差异与各因素之间的相关性分析。统计检验均为双侧，P＜0.05认为差异有统计学意义。

2 结果

2.1 基本情况

研究共纳入应用生物制剂长期治疗的中重度斑块型银屑病患者共174例，包括男性127人(73.00%)，女性47人(27.00%)，年龄中位数为38.00(31.50, 49.00)岁。银屑病病程中位数为12.00(10.00, 20.00)年。既往合并高血压24例(13.80%)，合并糖尿病11例(6.32%)，合并高脂血症22例(12.64%)，合并高尿酸血症11例(6.32%)。应用生物制剂治疗时间为26~301周，均大于24周，中位数为61.00(49.00, 96.25)周。IL-17抑制剂组为101例，IL-23和IL-12/23抑制剂组为38例，TNF-α抑制剂组为35例。比较IL-17抑制剂、IL-23和IL-12/23抑制剂以及TNF-α抑制剂，各药物组之间性别、年龄、病程、用药前的各项代谢性生化指标差异均无统计学意义(P>0.05，表 1)。

表1 IL-17抑制剂组、IL-23和IL-12/23抑制剂组、TNF-α抑制剂组基线情况比较

Table 1 Comparison among IL-17 inhibitors group, IL-23 & IL-12/23 inhibitors group, and TNF-α inhibitors group at baseline

Items	IL-17 (n=101)	IL-23 & IL-12/23 (n=38)	TNF-α (n=35)	F/H/χ²	P
Psoriasis duration/years	12.00 (8.50, 20.50)	12.50 (9.75, 18.50)	12.50 (10.00, 20.00)	0.721^b	0.697
Duration of treatment/weeks	64.00 (90.00, 91.50)	58.00 (49.00, 95.00)	55.00 (40.00, 105.00)	0.309^b	0.857
Age/years	38.00 (31.50, 51.00)	37.00 (31.00, 45.50)	39.00 (32.00，51.00)	1.281^b	0.527
Male	72 (71.3)	26 (68.4)	29 (82.9)	1.135^c	0.324
Weight at baseline/kg	74.07±15.15	70.87±15.06	73.05±14.73	0.881^a	0.417
BMI at baseline/(kg/m²)	25.11±4.08	24.45±3.86	24.70±4.26	2.855^a	0.063
ALT at baseline/(U/L)	22.00 (13.00, 37.25)	19.00 (13.50, 31.50)	26.00 (13.00, 36.00)	0.425^b	0.809
ALT elevated cases	21 (21.9)	6 (17.1)	7 (20.0)	0.359^c	0.836
AST at baseline/(U/L)	21.00 (18.00, 29.00)	21.00 (17.50, 25.50)	24.54±7.36	1.241^b	0.538
AST elevated cases	5 (5.2)	2 (5.7)	2 (5.7)	0.020^c	0.990
GLU at baseline/(mmol/L)	5.40 (4.90, 5.70)	5.40 (5.05, 5.80)	5.48±0.78	0.754^b	0.686
GLU elevated cases	14 (14.9)	7 (20.6)	4 (14.3)	0.678^c	0.712
TC at baseline/(mmol/L)	4.74±0.95	4.94±0.88	4.76±0.94	0.502^a	0.606
TC elevated cases	29 (30.5)	15 (40.5)	9 (29.0)	1.429^c	0.490
TG at baseline/(mmol/L)	1.38 (0.91, 2.19)	1.22 (0.77, 2.10)	1.40 (0.94, 1.85)	0.461^b	0.794
TG elevated cases	33 (34.4)	17 (45.9)	12 (38.7)	1.534^c	0.464
HDL-C at baseline/(mmol/L)	1.11 (0.98, 1.32)	1.15 (1.02, 1.40)	1.19±0.26	1.479^b	0.477
HDL-C lowered cases	37 (38.5)	10 (27.0)	8 (25.8)	2.613^c	0.271
LDL-C at baseline/(mmol/L)	3.05±0.79	3.12±0.68	3.30 (2.56, 3.68)	0.947^b	0.623
LDL-C elevated cases	22 (23.2)	9 (24.3)	9 (29.0)	0.437^c	0.804
UA at baseline/(μmol/L)	364.94±91.11	367.78±101.13	406.34±110.71	1.805^a	0.168
UA elevated cases	24 (25.3)	12 (33.3)	12 (41.3)	2.994^c	0.224

Data are $\bar x \pm s$, M(P₂₅, P₇₅) or n(%). BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate transaminase; GLU, fasting glucose; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid. a, F value, one-way ANOVA; b, H value, Kruskal-Wallis test; c, χ² value, Pearson’s chi-squared test.

2.2 各组用药前后代谢性生化指标变化情况

IL-17抑制剂组患者治疗后，体重、BMI、ALT、AST、GLU、TC、TG、HDL-C较治疗前差异均无统计学意义(P>0.05), LDL-C较治疗前显著降低[(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=－2.100, P=0.038]，UA较治疗前显著升高[(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L，t=5.215, P＜0.001，表 2]；IL-23和IL-12/23抑制剂组患者治疗后，体重、BMI、ALT、AST、GLU、TC、TG、HDL-C、UA较治疗前差异均无统计学意义(P>0.05)，LDL-C较治疗前显著降低[(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=－2.082, P=0.045，表 3]；TNF-α抑制剂组患者治疗后，体重、BMI、ALT、AST、GLU、TC、TG、HDL-C、LDL-C、UA较治疗前差异均无统计学意义(P>0.05，表 4)。

表2 IL-17抑制剂组患者用药前后代谢性生化指标变化

Table 2 Changes in metabolic biomarkers before and after IL-17 inhibitor therapy

Items	n	At baseline	After treatment	t/Z	P
Weight/kg	78	74.07±15.15	74.79±14.55	1.260^a	0.211
BMI/(kg/m²)	78	25.11±4.08	25.38±4.02	1.452^a	0.151
ALT/(U/L)	96	22.00(13.00, 37.25)	23.00(15.75, 42.25)	-1.901^b	0.057
AST/(U/L)	96	21.00(18.00, 29.00)	23.00(18.00, 30.25)	-1.730^b	0.084
GLU/(mmol/L)	94	5.40(4.90, 5.70)	5.30(5.00, 5.75)	-0.410^b	0.682
TC/(mmol/L)	95	4.74±0.95	4.64±0.97	-1.052^a	0.295
TG/(mmol/L)	96	1.38(0.91, 2.19)	1.35(1.01, 1.87)	-0.226^b	0.821
HDL-C/(mmol/L)	96	1.11(0.98, 1.32)	1.11(0.94, 1.29)	-1.128^b	0.259
LDL-C/(mmol/L)	95	3.05±0.79	2.90±0.75	-2.100^a	0.038
UA/(μmol/L)	95	364.94±91.11	401.13±99.13	5.215^a	＜0.001

Data are $\bar x \pm s$ or M(P₂₅, P₇₅). BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate transaminase; GLU, fasting glucose; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid. a, t value, Student’s t test; b，Z value, Wilcoxon signed rank test.

表3 IL-23和IL-12/23抑制剂组患者用药前后代谢性生化指标变化

Table 3 Changes in metabolic biomarkers before and after IL-23 & IL-12/23 inhibitor therapy

Items	n	At baseline	After treatment	t/Z	P
Weight/kg	26	70.87±15.06	71.37±14.40	0.953^a	0.350
BMI/(kg/m²)	26	24.45±3.86	24.65±3.71	1.119^a	0.274
ALT/(U/L)	35	19.00 (13.50, 31.50)	21.00 (16.00, 36.75)	-0.659^b	0.510
AST/(U/L)	35	21.00 (17.50, 25.50)	22.00 (19.00, 28.50)	-1.065^b	0.287
GLU/(mmol/L)	34	5.40 (5.05, 5.80)	5.40 (5.10, 5.80)	-0.236^b	0.814
TC (mmol/L)	37	4.94±0.88	4.77±0.76	-1.454^a	0.155
TG/(mmol/L)	37	1.22 (0.77, 2.10)	1.23 (0.84, 2.04)	-0.158^b	0.874
HDL-C/(mmol/L)	37	1.15 (1.02, 1.40)	1.19 (1.00, 1.34)	-0.883^b	0.377
LDL-C/(mmol/L)	37	3.12±0.68	2.85±0.74	-2.082^a	0.045
UA/(μmol/L)	36	367.78±101.13	371.00±91.79	0.287^a	0.768

Data are $\bar x \pm s$ or M (P₂₅, P₇₅). BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate transaminase; GLU, fasting glucose; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid. a, t value, Student’s t test; b, Z value, Wilcoxon signed rank test.

表4 TNF-α抑制剂组患者用药前后代谢性生化指标变化

Table 4 Changes in metabolic biomarkers before and after TNF-α inhibitor therapy

Items	n	At baseline	After treatment	t/Z	P
Weight/kg	31	73.05±14.73	73.77±14.73	1.160^a	0.255
BMI/(kg/m²)	31	24.70±4.26	24.96±4.31	1.252^a	0.220
ALT/(U/L)	35	26.00(13.00, 36.00)	25.00(18.00, 31.00)	-0.094^b	0.925
AST/(U/L)	35	24.54±7.36	22.00(18.00, 29.00)	-0.322^b	0.747
GLU/(mmol/L)	28	5.48±0.78	5.40(5.00, 6.10)	-0.013^b	0.990
TC/(mmol/L)	31	4.76±0.94	4.72±0.88	-0.282^a	0.780
TG/(mmol/L)	31	1.40(0.94, 1.85)	1.70±0.86	0.075^a	0.940
HDL-C/(mmol/L)	31	1.19±0.26	1.13(1.01, 1.26)	-1.358^b	0.174
LDL-C/(mmol/L)	31	3.30(2.56, 3.68)	3.08±0.81	-0.392^b	0.695
UA/(μmol/L)	29	406.34±110.71	378.14±77.45	-1.572^a	0.127

2.3 IL-17抑制剂组尿酸水平差异

在应用IL-17抑制剂长期治疗后，UA较治疗前显著升高，参照高尿酸血症专家共识，设定420 μmol/L为尿酸水平的分界值^[10]，将治疗前尿酸正常组和治疗前尿酸升高组分别进行治疗前后UA水平的比较，发现治疗前尿酸正常亚组患者在长期应用IL-17抑制剂后较治疗前UA水平显著升高[(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P＜0.001]，并且在治疗前尿酸正常亚组中，男性和女性的UA水平均显著升高，而治疗前尿酸升高组在长期应用IL-17抑制剂后较治疗前尿酸水平差异无统计学意义(表 5)。

表5 IL-17抑制剂组患者用药前后尿酸水平差异

Table 5 Changes in uric acid levels before and after IL-17 inhibitors therapy

Items	n	At baseline	After treatment	t	P
Normal uric acid group/(μmol/L)	71	324.66±64.50	370.69±89.59	5.856	＜0.001
Male in normal uric acid group/(μmol/L)	46	353.35±51.08	406.74±81.34	4.930	＜0.001
Female in normal uric acid group/(μmol/L)	25	271.88±52.66	304.36±62.69	3.329	0.003
High uric acid group/(μmol/L)	24	489.08±38.01	491.17±66.44	0.538	0.596

Data are $\bar x \pm s$.

2.4 IL-17抑制剂组尿酸水平差异与其他指标的相关性

在IL-17抑制剂治疗后，尿酸水平差异与年龄、性别和治疗周数均无明显相关性(P>0.05, 表 6)。

表6 IL-17抑制剂组患者用药前后尿酸水平差异的影响因素分析

Table 6 Analysis of influencing factors of uric acid level before and after IL-17 inhibitors therapy

Items	Ixekizumab			Secukinumab
Items	n	r	P	n	r	P
Age	21	-0.185	0.423	74	-0.014	0.909
Gender	21	0.382	0.087	74	-0.003	0.977
Duration of treatment	21	0.267	0.242	74	0.027	0.819

r, Spearman’s rank correlation coefficient.

3 讨论

近年来，生物制剂在皮肤科领域，特别是在治疗中重度斑块型银屑病患者中的应用日益广泛。生物制剂能够迅速控制病情，显著提升患者的生活质量，同时，由于生物制剂需要长期应用，其安全性也备受皮肤科医生的关注。因此，本课题组针对中国中重度斑块型银屑病患者，研究了IL-17抑制剂、IL-23和IL-12/23抑制剂、TNF-α抑制剂的长期应用对患者代谢性生化指标的影响。发现在应用生物制剂治疗前后，患者的BMI、ALT、AST、空腹血糖差异均无统计学意义(P>0.05)，这与多项既往研究的结果大体上一致^[11-14]。然而，有研究表明，应用生物制剂治疗后患者的BMI会有所上升，但这些研究存在一定的局限性，如未排除混杂因素(如运动和饮食)的影响^[15]，或者样本量不足^[16]。

本研究中，在分别应用IL-17抑制剂、IL-23抑制剂和IL-12/23抑制剂长期治疗后，患者的LDL-C水平显著降低，应用TNF-α抑制剂长期治疗后，患者的LDL-C水平无显著变化，各种生物制剂对于TC、TG、HDL-C无显著影响。然而，关于IL-17抑制剂对于血脂的影响研究结果不一致。大部分研究显示，在使用IL-17抑制剂治疗银屑病前后，患者的血脂水平并未呈现统计学上的显著差异^{[14, 17-21]}。匈牙利的一项研究同样表明IL-17抑制剂能导致LDL-C水平下降^[22]，与本研究结果一致。也有研究表明可依奇珠单抗使脂代谢的失调恢复至正常水平^[23]。一项研究显示，IL-17A主要参与银屑病的发病，且在银屑病患者的体循环中水平升高，可能损害肝细胞，导致肝整体代谢功能障碍，使用抗IL-17A抗体治疗银屑病小鼠，能够减轻银屑病炎症，进而纠正肝蛋白和脂质的代谢失调^[24]。

本研究中，在分别应用IL-23抑制剂、IL-12/23抑制剂、TNF-α抑制剂长期治疗后，患者的尿酸水平无显著变化，而IL-17抑制剂组尿酸水平显著升高。既往研究发现^[17]，TNF-α抑制剂治疗银屑病后患者的尿酸水平显著降低。本研究也观察到TNF-α组尿酸水平有下降趋势，但未达到有统计学意义的显著差异。值得注意的是，既往研究关于IL-17抑制剂对患者尿酸水平的影响并不一致。多项研究表明，IL-17抑制剂对银屑病患者尿酸水平无显著影响^{[11, 17, 25]}，而也有研究发现，使用IL-17抑制剂使尿酸水平显著降低^{[9, 15, 20, 26]}。本研究在应用IL-17抑制剂后尿酸水平显著升高的结果目前尚未见文献报道。基于此，将应用IL-17抑制剂长期治疗的患者按治疗前尿酸水平正常和升高分为两个亚组，发现尿酸水平的显著升高发生在治疗前正常尿酸水平亚组，且升高后的平均值仍在正常范围内，推测此现象有可能与大部分中国患者在应用生物制剂治疗前“忌口”有关^[27]，但此推测尚缺乏有力的证据支持，需要进一步研究。

本研究为回顾性单中心研究，存在一定的局限性，首先，IL-23和IL-12/23抑制剂组、TNF-α抑制剂组的患者样本量较小，这可能影响分析结果的可靠性；其次，尽管患者应用生物制剂的时间均在24周以上，但跨度较大，这可能无法准确排除患者其他潜在的混杂因素，对研究结果产生一定的干扰。因此，本研究结论需要在更大样本量的多中心前瞻性研究及随机对照试验中进行进一步验证和确认。

综上所述，生物制剂安全性较高，对多数代谢性生化指标无显著影响。长期应用IL-17抑制剂治疗中重度斑块型银屑病患者，可能出现尿酸水平上升，尤其是用药前尿酸正常的患者，尽管升高后尿酸水平在正常范围内，但仍需注意减少高尿酸血症的发生。长期应用IL-17抑制剂、IL-23抑制剂和IL-12/23抑制剂，可能降低LDL-C水平。

利益冲突 所有作者均声明不存在利益冲突

作者贡献声明 刘相贤、林毅：收集、整理、分析数据，撰写论文；郭金竹：提出研究思路，设计研究方案，总体把关和审定论文，经费支持。

References

Publishing order | Descend order by publishing year | Descend order by cited within

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