On which evidence can we rely when prescribing off-label methotrexate in dermatological practice? – a systematic review with GRADE approach

If an authorized drug is prescribed for a use that is not described in the Summary of Product Characteristics, this is defined as ‘off-label use.’ Methotrexate is often used off-label for dermatological indications. Off-label use is permitted if physicians can justify the treatment based on scientific evidence available to them. Our objective here was therefore to summarize the evidence for the effectiveness, efficacy, and safety of the dermatological off-label use of methotrexate in a systematic review. We searched MEDLINE, EMBASE, and CENTRAL for studies for evidence on the effectiveness, efficacy, and safety of the off-label use of methotrexate in dermatological indications up to November 2019. We used the GRADE system to rate the quality of the evidence. The search retrieved 34,583 hits of which 3566 were selected after the title and abstract screening. After the full-text screening, 143 studies were included, which involved 3688 patients in total. We found low-quality evidence for the effectiveness, efficacy, and safety of the off-label use of methotrexate in 31 dermatological diseases. To optimize the quality of evidence to support off-label use, we need high-quality studies in which well-characterized patients are treated with standardized treatments regimens using well-validated outcomes relevant to patients and physicians.

若经授权的药物被用于未在产品特性概要中描述的用途，则此类使用被定义为‘超说明书使用’。甲氨蝶呤常被超说明书用于皮肤科适应症。若医生能基于其可获取的科学证据对治疗进行合理论证，则超说明书使用是被允许的。因此，我们的目标是通过对甲氨蝶呤在皮肤科超说明书使用中的有效性、疗效和安全性进行系统评价，总结相关证据。我们检索了至2019年11月为止的MEDLINE、EMBASE和CENTRAL数据库，以寻找关于甲氨蝶呤在皮肤科超说明书使用中的有效性、疗效和安全性证据的研究。我们采用GRADE系统对证据质量进行评级。搜索共检索到34,583条记录，其中3566条在标题和摘要筛选后入选。经过全文筛选，共有143项研究被纳入，总计涉及3688名患者。我们发现31种皮肤科疾病中，甲氨蝶呤超说明书使用的有效性、疗效和安全性证据质量较低。为了优化支持超说明书使用的证据质量，我们需要高质量的研究，其中应包括特征明确的病人接受标准化治疗方案，并使用经充分验证的、与患者及医生相关的结局指标。