Puig Lluís, Fujita Hideki, Thaçi Diamant, Zheng Min, Hernandez Daly Ana Cristina, Leonardi Craig, Lebwohl Mark G, Barker Jonathan
Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Nihon University, Tokyo, Japan.
Dermatol Ther (Heidelb). 2024 Sep;14(9):2331-2378. doi: 10.1007/s13555-024-01230-z. Epub 2024 Aug 1.
Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients' quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980-September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy.
泛发性脓疱型银屑病（GPP）是一种罕见的、慢性的且可能危及生命的自身炎症性皮肤病，其特征为广泛出现无菌性脓疱，可伴有或不伴有全身炎症。GPP可显著降低患者的生活质量（QoL）。文献中描述了几种治疗方法，但对于最佳治疗方案尚无共识。在本综述中，我们总结了已发表的关于使用已批准和未批准产品治疗GPP的疗效、安全性和生活质量结果的文献。检索了Embase和MEDLINE数据库（1980年至2023年9月）。根据系统评价和Meta分析的首选报告项目（PRISMA）指南设计了检索方案，并在PROSPERO数据库（CRD42021215437）上进行了注册。由独立评审人员收集并检查有关发表情况、研究人群、干预措施、疗效、安全性和生活质量的详细信息。总共纳入了118篇出版物，其中只有19%的出版物报告了临床试验结果。报告的GPP治疗方式包括非生物系统性疗法，如维甲酸、环孢素和甲氨蝶呤、局部用药、生物制剂和小分子药物等。结果高度异质性，方法学质量非常低，只有白细胞介素-36R抑制剂司库奇尤单抗报告了安慰剂对照随机试验的结果；基于此，司库奇尤单抗目前已在美国、日本、中国、欧盟和其他几个国家/地区获批用于治疗GPP。其他一些生物制剂仅在日本和中国台湾基于小样本开放标签研究而非双盲研究获批用于治疗GPP。各研究之间临床结局的非标准化仍然是就最佳治疗达成共识的主要障碍。然而，最近已经开展了使用明确的、疾病特异性终点来评估针对GPP治疗的试验，有望推动患者护理的发展。总之，本综述强调需要进行以GPP特异性终点为指标的前瞻性随机研究，以确定最佳治疗策略。
