■临床医生和医疗保健政策制定者已经被大量重叠的荟萃分析(MA)所淹没,并且迫切需要在特应性皮炎(AD)中使用Janus激酶抑制剂(JKIs)的全面和明确的证据。
■搜索了直到2023年10月发布的MA的六个数据库。主要使用MA的定性分析,和研究者的全球评估反应(IGA反应),湿疹面积和严重程度指数(EASI75)改善75%,瘙痒峰数值评分(PP-NRS),和不良反应被引用来描述JKIs的疗效和安全性。通过评估系统评价II(AMSTARII)的测量工具评估了纳入的MA的方法学质量,通过推荐的分级来评估证据的质量,评估,发展,和评估(等级)。
■本次审查汇集了16个MA,其中五项研究评估了JKIs,五个评估的系统JKIs,五篇论文仅评估了abrocitinib,和一个评估baricitinib。两项研究具有“高”方法学质量,14项MAs具有“中等”质量。11个MA整合了JKIs的结果,并报告JKIs提供了更快的IGA反应开始(RR=2.83,95%CI[2.25,3.56],高质量的证据)。同样,10MA显示JAK抑制剂在改善EASI75方面更有效(RR=2.84,95%CI[2.2,3.67],高质量的证据)。来自12个MA的结果显示JKIs在降低PP-NRS方面具有活性(SMD=-0.49,95%CI[-0.67,-0.32])。所有MA确认JKIs均未添加导致停药和严重不良事件的不良反应(P<0.05)。然而,200mg的abrocitinib具有较高的痤疮风险(RR=4.34,95%CI[1.61,11.71),带状疱疹(RR=1.64,95%CI[0.42,6.39]),头痛(RR=1.76,95%CI[1.03,3]),和恶心(RR=7.81,95%CI[3.84,15.87])。已知Upadacitinib会增加痤疮(RR=6.23,95%CI[4.08,9.49]),鼻咽炎(RR=1.36,95%CI[1.03,1.8])和血肌酸磷酸激酶(血CPK)(RR=2.41,95%CI[1.47,3.95])。2mg巴利替尼与血CPK升高相关(RR=2.25,95%CI[1.1,2.97])。
■与安慰剂或dupilumab相比,JKIs的管理可以更有效地改善IGA反应,改善EASI75,缓解瘙痒无严重不良反应,同时伴随着更多的痤疮,鼻咽炎,头痛,和消化紊乱。200mgabrocitinib的疗效显著,对胃肠功能障碍的患者应更加谨慎。带状疱疹,还有那些容易长痘痘的人.心血管事件高危人群应避免使用巴利替尼和upadacitinib。
■https://www.crd.约克。AC.uk/prospro/display_record.php?RecordID=369369,PROSPERO(CRD42022369369)。
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator\'s Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak
pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
Sixteen MAs were pooled in this
review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of \"high\" methodological quality and 14 MAs were of \"moderate\" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve
pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).