Schmitt J, Wozel G, Pfeiffer C
Department of Dermatology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307, Germany.
Br J Dermatol. 2004 Jun;150(6):1182-5. doi: 10.1111/j.0007-0963.2003.05846.x.
Based on the increasing knowledge of T-cell-mediated pathogenesis in atopic dermatitis (AD), systemic immunosuppressive drugs are increasingly applied. The chronic, relapsing course of severe AD necessitates a drug, both efficacious and safe in long-term application. Leflunomide is a pyrimidine de novo synthesis-inhibiting immunosuppressant exhibiting an extremely long in vivo half life of its active metabolite.
To evaluate the efficacy of leflunomide in long-term treatment of AD.
As a proof of principle, we treated two patients with severe AD, recalcitrant to different systemic treatment modalities, for 20 months with leflunomide (loading dose 100 mg daily during 3 days; maintenance dose 20 mg daily). At regular visits physical examination, eczema area and severity index (EASI), visual analogue scale (VAS) for itching, and laboratory findings were assessed with according adjustment of the leflunomide dose.
At the initiation of leflunomide therapy, both patients presented with almost erythrodermic AD (patient 1, EASI 40.0, VAS 10; patient 2, EASI 43.0, VAS 8). Partial remission was observed within 4 and 7 weeks, respectively, and maintained over 20 months (patient 1, median EASI 4.2, median VAS 2; patient 2, median EASI 8.4, median VAS 2) except for one episode of exacerbation in each case. In one patient, remission was stable even after cessation of drug dosing. Severe adverse events were not observed.
Leflunomide was efficient in the long-term treatment of recalcitrant AD. Controlled studies will be necessary to evaluate the subset of severe AD patients benefiting most from this drug.
基于对特应性皮炎(AD)中T细胞介导的发病机制的认识不断增加,全身免疫抑制药物的应用越来越广泛。重度AD的慢性复发性病程需要一种长期应用既有效又安全的药物。来氟米特是一种抑制嘧啶从头合成的免疫抑制剂,其活性代谢物在体内的半衰期极长。
评估来氟米特在AD长期治疗中的疗效。
作为一项原理验证,我们对两名对不同全身治疗方式均无效的重度AD患者使用来氟米特治疗20个月(负荷剂量:3天内每日100mg;维持剂量:每日20mg)。在定期随访时进行体格检查、评估湿疹面积和严重程度指数(EASI)、瘙痒视觉模拟评分(VAS),并根据来氟米特剂量的调整评估实验室检查结果。
来氟米特治疗开始时,两名患者均表现为几乎全身性的AD(患者1,EASI 40.0,VAS 10;患者2,EASI 43.0,VAS 8)。分别在4周和7周内观察到部分缓解,并维持了20个月(患者1,EASI中位数4.2,VAS中位数2;患者2,EASI中位数8.4,VAS中位数2),但每例均有一次病情加重。在一名患者中,即使停药后缓解仍保持稳定。未观察到严重不良事件。
来氟米特对难治性AD的长期治疗有效。有必要进行对照研究以评估最能从此药物中获益的重度AD患者亚组。