Abstract：
OBJECTIVE: To summarize and analyze the results of published randomized controlled trials of tofacitinib for the treatment of chronic plaque psoriasis and psoriatic arthritis(PsA) and discuss its efficacy and safety.
METHODS: An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software.
RESULTS: A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician\'s Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA).
CONCLUSIONS: A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug\'s long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events, and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer\'s disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.
METHODS: An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software.
RESULTS: A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician\'s Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA).
CONCLUSIONS: A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug\'s long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events, and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer\'s disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.
摘要：
目的：总结和分析已发表的托法替尼治疗慢性斑块型银屑病和银屑病关节炎(PsA)的随机对照试验结果，探讨其疗效和安全性。
方法：包含PubMed的详尽系统搜索，科克伦,Embase,和WebofScience数据库进行到2023年7月。分析了符合纳入条件的研究，使用ReviewManager版本5.4.1(CochraneCollaboration,牛津,英国)和STATA15.0版本(StataCorp，学院站,TX,美国）软件。
结果：共六篇文章，涵盖1393名患者（844名接受托法替尼治疗，549名接受安慰剂治疗），包括在内。托法替尼组和安慰剂组的基本特征显示出相似性，除年龄和皮肤病生活质量指数（DLQI）评分外，特别是在慢性斑块型银屑病的背景下。值得注意的是，我们发现托法替尼对银屑病面积和严重程度指数75（PASI75）反应有显著影响，医师的全球评估（PGA）反应，和不良事件（AEs）的情况下，慢性斑块型银屑病。同样，托法替尼对美国风湿病学会20/50（ACR20/50）反应有重大影响，PASI75响应，以及慢性疾病治疗功能评估-疲劳(FACIT-F)评分的改变，健康评估问卷-残疾指数(HAQ-DI)评分，指炎严重程度评分(DSS),在银屑病关节炎（PsA）的背景下，和利兹端炎指数（LEI）评分。然而，托法替尼对慢性斑块型银屑病严重不良事件（SAE）无统计学意义，以及银屑病关节炎（PsA）中的不良事件（AE）和SAE。
结论：综合分析表明，托法替尼对解决皮肤和关节症状具有积极作用，以及改善慢性斑块型银屑病和银屑病关节炎（PsA）患者的生活质量。然而,该药物长期使用的安全性甚至需要进一步验证。关键点•在总共1393名患者的6项分析中，托法替尼对治疗慢性斑块型银屑病和银屑病关节炎（PsA）均具有积极作用。•尽管基于剂量的亚组分析已经证明了有效性。一些研究表明，由于比较托法替尼与安慰剂的非劣效性试验失败，5-mg剂量（每天两次）可能不会显示效果。因此,在解释其有效性时需要谨慎。另一方面,10mg剂量（BID）与不良事件和严重不良事件的增加有关，建议有心血管或葡萄膜炎危险因素的患者谨慎使用。•Tofacitinib对合并症精神疾病（抑郁症，焦虑,或阿尔茨海默病）和炎症性肠病（溃疡性结肠炎），但合并肾功能不全的患者,肝功能障碍,骨质疏松,心血管疾病,或葡萄膜炎可能需要使用托法替尼缓解或避免。
方法：包含PubMed的详尽系统搜索，科克伦,Embase,和WebofScience数据库进行到2023年7月。分析了符合纳入条件的研究，使用ReviewManager版本5.4.1(CochraneCollaboration,牛津,英国)和STATA15.0版本(StataCorp，学院站,TX,美国）软件。
结果：共六篇文章，涵盖1393名患者（844名接受托法替尼治疗，549名接受安慰剂治疗），包括在内。托法替尼组和安慰剂组的基本特征显示出相似性，除年龄和皮肤病生活质量指数（DLQI）评分外，特别是在慢性斑块型银屑病的背景下。值得注意的是，我们发现托法替尼对银屑病面积和严重程度指数75（PASI75）反应有显著影响，医师的全球评估（PGA）反应，和不良事件（AEs）的情况下，慢性斑块型银屑病。同样，托法替尼对美国风湿病学会20/50（ACR20/50）反应有重大影响，PASI75响应，以及慢性疾病治疗功能评估-疲劳(FACIT-F)评分的改变，健康评估问卷-残疾指数(HAQ-DI)评分，指炎严重程度评分(DSS),在银屑病关节炎（PsA）的背景下，和利兹端炎指数（LEI）评分。然而，托法替尼对慢性斑块型银屑病严重不良事件（SAE）无统计学意义，以及银屑病关节炎（PsA）中的不良事件（AE）和SAE。
结论：综合分析表明，托法替尼对解决皮肤和关节症状具有积极作用，以及改善慢性斑块型银屑病和银屑病关节炎（PsA）患者的生活质量。然而,该药物长期使用的安全性甚至需要进一步验证。关键点•在总共1393名患者的6项分析中，托法替尼对治疗慢性斑块型银屑病和银屑病关节炎（PsA）均具有积极作用。•尽管基于剂量的亚组分析已经证明了有效性。一些研究表明，由于比较托法替尼与安慰剂的非劣效性试验失败，5-mg剂量（每天两次）可能不会显示效果。因此,在解释其有效性时需要谨慎。另一方面,10mg剂量（BID）与不良事件和严重不良事件的增加有关，建议有心血管或葡萄膜炎危险因素的患者谨慎使用。•Tofacitinib对合并症精神疾病（抑郁症，焦虑,或阿尔茨海默病）和炎症性肠病（溃疡性结肠炎），但合并肾功能不全的患者,肝功能障碍,骨质疏松,心血管疾病,或葡萄膜炎可能需要使用托法替尼缓解或避免。
