He Qingying, Xie Xin, Chen Qian, Li Wenquan, Song Zongzhou, Wang Xurui, Ma Xiao, Zeng Jinhao, Guo Jing
Dermatological Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Immunol. 2024 Feb 23;15:1342810. doi: 10.3389/fimmu.2024.1342810. eCollection 2024.
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).
临床医生和医疗保健政策制定者被大量重叠的荟萃分析所淹没，因此迫切需要关于 Janus 激酶抑制剂（JKIs）治疗特应性皮炎（AD）的全面且明确界定的证据。
检索了六个数据库，以查找截至 2023 年 10 月发表的荟萃分析。主要采用对荟萃分析的定性描述，并引用研究者整体评估反应（IGA 反应）、湿疹面积和严重程度指数改善 75%（EASI75）、瘙痒峰值数字评分（PP-NRS）以及不良反应来描述 JKIs 的疗效和安全性。通过评估系统评价的测量工具 II（AMSTAR II）评估纳入的荟萃分析的方法学质量，并通过推荐分级、评估、制定和评价（GRADE）来评估证据质量。
本综述汇总了 16 项荟萃分析，其中五项研究评估了 JKIs，五项评估了系统性 JKIs，五篇论文仅评估了阿布昔替尼，一篇评估了巴瑞替尼。两项研究的方法学质量为“高”，14 项荟萃分析的质量为“中等”。11 项荟萃分析整合了 JKIs 的结果并报告称，JKIs 能更快出现 IGA 反应（RR = 2.83，95%CI [2.25, 3.56]，高质量证据）。同样，10 项荟萃分析表明 JAK 抑制剂在改善 EASI75 方面更有效（RR = 2.84，95%CI [2.2, 3.67]，高质量证据）。12 项荟萃分析的结果显示 JKIs 在降低 PP-NRS 方面有效（SMD = -0.49，95%CI [-0.67, -0.32]）。所有荟萃分析均确认 JKIs 不会增加导致停药的不良反应和严重不良事件（P < 0.05）。然而，200mg 阿布昔替尼出现痤疮（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]）的风险更高。已知乌帕替尼会增加痤疮（RR = 6.23，95%CI [4.08, 9.49]）、鼻咽炎（RR = 1.36，95%CI [1.03, 1.8]）和血液肌酸磷酸激酶（血液 CPK）（RR = 2.41，95%CI [1.47, 3.95]）。2mg 巴瑞替尼与血液 CPK 升高有关（RR = 2.25，95%CI [1.1, 2.97]）。
与安慰剂或度普利尤单抗相比，使用 JKIs 可更有效地改善 IGA 反应，提高 EASI75，并缓解瘙痒且无严重不良反应，同时伴有更多痤疮、鼻咽炎、头痛和消化系统紊乱。200mg 阿布昔替尼疗效显著，对于胃肠功能障碍、带状疱疹患者以及易患痤疮者应更加谨慎。对于心血管事件高危人群，应避免使用巴瑞替尼和乌帕替尼。
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369，PROSPERO（CRD42022369369）。
