Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China.
Dermatology Department, National Center for Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China.
Front Immunol. 2024 Oct 14;15:1462158. doi: 10.3389/fimmu.2024.1462158. eCollection 2024.
Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening auto-inflammatory disease. Currently, there are no consensus-based guidelines or universally accepted treatments. Biologics represent a potential therapeutic option. This study systematically assessed the efficacy and safety of biologics in GPP.
Relevant studies from three databases were systematically searched until June 28, 2024. Statistical information, including the single-arm proportion rate of the outcomes and 95% confidence intervals (CIs), was analyzed to determine treatment effects. Heterogeneity was assessed using I² values, and subgroup analyses were performed based on drug targets and treatment durations. Data were quantitatively synthesized using a random-effects meta-analysis. Analyses were performed using R statistical software version 4.4.0.
A total of 329 patients from 16 studies were included. The proportion of responders treated with IL-36 inhibitors and IL-17 inhibitors is higher than those treated with TNF-α inhibitors and IL-23 inhibitors. IL-36 inhibitors appear to achieve the highest response rates between 4 and 8 weeks, while IL-17 inhibitors, TNF-alpha inhibitors, and IL-23 inhibitors show a gradual increase in response rates up to 12 weeks. IL-36 inhibitors achieve a 40% (95% CI: 27%-54%) GPPASI75 response rate and a 55% (95% CI: 41%-68%) GPPGA (0,1) response rate within 2 weeks, significantly outperforming other biologics. The recurrence rates of GPP within 52 weeks, ranked from highest to lowest, are: IL-36 inhibitors (21% [95% CI: 9%-28%]), TNF-alpha inhibitors (20% [95% CI: 2%-46%]), IL-17 inhibitors (15% [95% CI: 1%-37%]), and IL-23 inhibitors (5% [95% CI: 0%-29%]). Additionally, 6% (95% CI: 1%-11%) of patients experienced severe adverse events.
This meta-analysis highlights the efficacy and safety of biologics in patients with GPP, offering valuable evidence to guide future clinical practice. IL-36 inhibitors show a faster and more substantial clinical response in GPP compared to other biologics. Further research is necessary to assess their role in specific subpopulations and to evaluate their potential long-term effects on flare prevention.
泛发性脓疱型银屑病（GPP）是一种罕见且可能危及生命的自身炎症性疾病。目前，尚无基于共识的指南或普遍接受的治疗方法。生物制剂是一种潜在的治疗选择。本研究系统评估了生物制剂在 GPP 中的疗效和安全性。
系统检索了截至 2024 年 6 月 28 日三个数据库中的相关研究。分析了包括结局的单臂比例率和 95%置信区间（CI）在内的统计信息，以确定治疗效果。使用 I²值评估异质性，并根据药物靶点和治疗持续时间进行亚组分析。使用 R 统计软件版本 4.4.0 进行数据定量综合。
共纳入了 16 项研究中的 329 名患者。与 TNF-α 抑制剂和 IL-23 抑制剂相比，接受 IL-36 抑制剂和 IL-17 抑制剂治疗的应答者比例更高。IL-36 抑制剂似乎在 4 至 8 周时达到最高应答率，而 IL-17 抑制剂、TNF-α 抑制剂和 IL-23 抑制剂在 12 周时应答率逐渐增加。IL-36 抑制剂在 2 周内达到 40%（95%CI：27%-54%）GPPASI75 应答率和 55%（95%CI：41%-68%）GPPGA（0,1）应答率，显著优于其他生物制剂。52 周内 GPP 的复发率从高到低依次为：IL-36 抑制剂（21%[95%CI：9%-28%]）、TNF-α 抑制剂（20%[95%CI：2%-46%]）、IL-17 抑制剂（15%[95%CI：1%-37%]）和 IL-23 抑制剂（5%[95%CI：0%-29%]）。此外，6%（95%CI：1%-11%）的患者发生严重不良事件。
这项荟萃分析强调了生物制剂在 GPP 患者中的疗效和安全性，为指导未来的临床实践提供了有价值的证据。与其他生物制剂相比，IL-36 抑制剂在 GPP 中表现出更快、更显著的临床反应。需要进一步研究来评估它们在特定亚群中的作用，并评估它们在预防复发方面的潜在长期影响。
