Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Bochum, Germany.
Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg, Heidelberg, Germany.
J Eur Acad Dermatol Venereol. 2018 Oct;32(10):1710-1727. doi: 10.1111/jdv.15019. Epub 2018 May 18.
Fumaric acid esters (FAEs) are an established systemic treatment for moderate-to-severe psoriasis. However, the long-term clinical safety and effectiveness of continuous FAE monotherapy and combination therapy have not been established.
To examine the long-term safety and effectiveness of FAEs as monotherapy and in combination with phototherapy or methotrexate in patients with psoriasis treated at a single centre in Germany.
This monocentric, retrospective observational study, with a follow-up period of up to 32.5 years, included 859 patients: 626 received FAE monotherapy, 123 received FAEs with concomitant phototherapy and 110 received FAEs with methotrexate.
Approximately half of patients (49.0%) reported adverse events (566 total events), most of which involved the gastrointestinal tract. Serious adverse events were reported in 2.3% of patients, but none were deemed to have a causal relationship with any of the treatment regimens. Adverse events leading to treatment discontinuation were observed in 12.9% of patients. A median duration of 1 year was observed in all three treatment subcohorts (P = 0.70) from initiation of FAE treatment to a 50% response rate, where response was defined as achieving a cumulative static Physician's Global Assessment (PGA) score of 'light' and at least a 2-point reduction in baseline PGA. A 50% response rate for the cumulative Psoriasis Area and Severity Index 75 was achieved in the FAE monotherapy subcohort after a median of 3 years of treatment, in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001).
According to our data, FAEs as monotherapy or in combination with phototherapy or methotrexate are safe and beneficial for long-term clinical use. However, multicentre, randomized controlled trials are required to establish the clinical value of monotherapy versus combination therapy and the optimal treatment duration.
富马酸酯（FAE）是一种已被证实的中重度银屑病的系统治疗药物。然而，FAE 单药治疗和联合光疗或甲氨蝶呤治疗的长期临床安全性和有效性尚未确定。
在德国的一个单一中心，评估 FAE 单药治疗和联合光疗或甲氨蝶呤治疗银屑病患者的长期安全性和有效性。
这是一项单中心、回顾性观察研究，随访时间长达 32.5 年，共纳入 859 例患者：626 例接受 FAE 单药治疗，123 例接受 FAE 联合光疗，110 例接受 FAE 联合甲氨蝶呤治疗。
约一半的患者（49.0%）报告了不良事件（共 566 例事件），大多数涉及胃肠道。3 例患者（2.3%）报告了严重不良事件，但均认为与任何治疗方案无关。12.9%的患者因不良事件而停止治疗。在所有 3 个治疗亚组中，从开始 FAE 治疗到达到 50%反应率的中位时间为 1 年（P = 0.70），其中反应定义为累积静态医师整体评估（PGA）评分达到“轻度”，且 PGA 基线至少降低 2 分。在 FAE 单药治疗亚组中，达到累积银屑病面积和严重程度指数 75 缓解率的中位时间为 3 年，在 FAE+光疗亚组中为 6.7 年，在 FAE+甲氨蝶呤亚组中为 8.1 年（P = 0.001）。
根据我们的数据，FAE 单药治疗或联合光疗或甲氨蝶呤治疗安全且长期临床应用有益。然而，需要进行多中心、随机对照试验来确定单药治疗与联合治疗的临床价值以及最佳治疗持续时间。
