Leflunomide as a novel treatment option in severe atopic dermatitis

Background 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. Objectives To evaluate the efficacy of leflunomide in long-term treatment of AD. Methods 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. Results 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. Conclusions 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.