Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial.
OBJECTIVE
Current treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis.


METHODS
One hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality-of-life assessments were performed.


RESULTS
At 24 weeks, 56 of 95 leflunomide-treated patients (58.9%; 95% confidence interval [95% CI] 48.4-68.9) and 27 of 91 placebo-treated patients (29.7% [95% CI 20.6-40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality-of-life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed.


CONCLUSIONS
Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.
Kaltwasser
J Peter
JP
Abteilung Rheumatologie, Medizinische Klinik III, Zentrum der Innere Medizin, J. W. Goethe-Universität, Frankfurt am Main, Germany. kaltwasser@em.uni-frankfurt.de
Nash
Peter
P
Gladman
Dafna
D
Rosen
Cheryl F
CF
Behrens
Frank
F
Jones
Peter
P
Wollenhaupt
Jürgen
J
Falk
Franziska G
FG
Mease
Philip
P
D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007555:Isoxazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011788:Quality of Life; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D010919:Placebos; D000077339:Leflunomide