目的:最近的文献强调了生物制剂在治疗遗传性角质化疾病方面的潜力。在这项研究中,我们对现有文献进行了系统回顾,这些文献涉及使用生物制剂治疗遗传性角化病的治疗结果.
方法:通过搜索MEDLINE电子数据库检索合格记录,Embase,PubMed和Scopus。从开始到2023年7月,对数据库进行了搜索,以查找合格的记录。采用滚雪球法搜索检索到的记录的参考,以识别潜在相关的文章。
结果:纳入了由166名遗传性角质化疾病患者组成的104项符合条件的研究。患者的中位年龄为19岁(范围:0.5至70岁)。最常见的疾病是Netherton综合征(n=63;38%),常染色体隐性先天性鱼鳞病(n=27;16%),CARD14相关的丘疹鳞状出疹(n=17;10%)和家族性毛发红疹性糠疹(PRP)(n=15;9%)。在使用生物制剂的207次中,三种最常用的生物制剂是苏金单抗(n=47;23%),dupilumab(n=44;21%)和ustekinumab(n=37;18%)。在10例(5%)中观察到完全缓解,129例部分缓解(62%),68例(32%)对生物治疗无反应或反应有限,在一个案例中,结果仍在等待中。共报告了33起不良事件。
结论:虽然生物制剂可考虑用于难以接受标准治疗的遗传性角质化疾病,纳入研究的证据水平低,方法学上存在实质性异质性,因此无法得出明确的结论.建立共识定义,和随机临床试验可能有助于确定在这种情况下生物治疗的有效性和安全性,并为每种疾病建立最佳的药物和给药方案。
OBJECTIVE: Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics.
METHODS: Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records. A snowballing method was employed to search the references of the retrieved records for the identification of potentially relevant articles.
RESULTS: One hundred and four eligible studies consisting of a total of 166 patients with an inherited disorder of keratinisation were included. Patients had a median age of 19 years (range: 0.5 to 70 years). The most common disorders were Netherton syndrome (n = 63; 38%), autosomal recessive congenital ichthyoses (n = 27; 16%), CARD14-associated papulosquamous eruptions (n = 17; 10%) and familial pityriasis rubra pilaris (PRP) (n = 15; 9%).Of the 207 times biologics were employed, the three most frequently employed biologics were secukinumab (n = 47; 23%), dupilumab (n = 44; 21%) and ustekinumab (n = 37; 18%). Complete remission was observed in 10 (5%) instances, partial remission in 129 (62%), no or limited response to biologic therapy in 68 (32%) cases, and results are still pending in one case. A total of 33 adverse events were reported.
CONCLUSIONS: Whilst biologics may be considered in cases of inherited keratinisation disorders recalcitrant to standard therapy, definitive conclusions are prohibited by the low-level of evidence and substantial heterogeneity in methodology across the included studies. Establishment of consensus definitions, and randomised clinical trials may help ascertain the efficacy and safety of biologic therapy in this context and establish the best agent and dosing protocol for each disorder.