OP0081 LEFLUNOMIDE IN THE TREATMENT OF PSORIATIC ARTHRITIS AND PSORIASIS: DATA FROM A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CLINICAL TRIAL
J Kaltwasser, P Nash, D Gladman, C Rosen, F Behrens, and P Mease

In this study, the safety and efficacy of leflunomide for treatment of psoriatic arthritis is assessed in a 6 month, double-blind, placebo-controlled clinical trial (TOPAS Treatment with Leflunomide in Psoriatic Arthritis).

Methods: 188 patients with active psoriatic arthritis (diagnosed by skin and nail changes) and psoriasis (> 3% of body with plaque). Patients were randomized to receive either leflunomide (100 mg daily x 3 days, then 20 mg daily, n=95) or placebo (n=91). No concomitant DMARDs were permitted. The Psoriatic Arthritis Response Criteria (PsARC) was assessed as the primary endpoint with secondary endpoints being ACR 20, PASI, and target lesion scores.

Results: At 24 weeks, a significantly greater response was found among patients receiving leflunomide compared with patients receiving placebo in all measurements, indicated in the table below.

Diarrhea and an increase in SGPT occurred at a slightly higher rate in the leflunomide group compared to the placebo group, 24% versus 13% and 12.5% versus 5.4%, respectively. An increase in ALT (> 2x the upper limit of normal) occurred in 8.3% of the leflunomide group compared to 2.2% of the placebo group. There were no cases of acute liver failure or severe liver toxicity in either group.

Conclusion: Leflunomide is safe and efficacious for treatment of psoriatic arthritis, providing both an improvement in psoriatic skin lesions as well as a reduction in actively inflamed joints.

Editorial Comment: This study confirms that leflunomide is a modestly effective agent for psoriatic arthritis. Liver toxicity is a continuing concern as with methotrexate in psoriatic arthritis.

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OP0082 THE INFLIXIMAB MULTINATIONAL PSORIATIC ARTHRITIS CONTROLLED TRIAL (IMPACT): SUBSTANTIAL EFFICACY ON SYNOVITIS AND PSORIATIC LESIONS WITH OR WITHOUT CONCOMITANT DMARD THERAPY
C Antoni, A Kavanaugh, B Kirkham, G Burmester, B Manger, Z Tutuncu, U Schneider, W Ebner, S Wassenberg, D Furst, J Molitor, M Weisman, D Wallace, E Keystone, J Kalden, J Smolen

The purpose of this study is to assess the safety and efficacy of infliximab, with and without concomitant DMARDs, for the treatment of psoriatic arthritis. The study design consists of 2 phases, an initial double blind placebo-controlled phase followed by an open label treatment phase. The results of the 16 week blinded phase of the trial are reported here.

Methods: Patients, in addition to having psoriatic arthritis, had to meet the following criteria: rheumatoid factor negative, > 1 DMARD failure, > 5 swollen/tender joints, and > 45 min. morning stiffness. Concomitant DMARDs, NSAIDs, and steroid (< 10 mg/day) use were permitted if the dose was stable. 101 patients with a mean disease duration of 18 years were randomized to one of two arms: infliximab (5 mg/kg, n=51) or placebo (n=51). Infusions were given at week 0, 2, 6, and 14 weeks. ACR responses, dactylitis scores, and enthesitis were assessed. PASI scores were compared in patients with a baseline PASI score of >25.

Results: The percent of patients achieving ACR responses were significantly higher in the infliximab group compared to the placebo group: 69% vs. 8% for ACR20, 49% vs. 0% for ACR50, and 29% vs. 0% for ACR70, respectively. 63% of patients in the infliximab group and 74% of patients in the placebo group had concomitant DMARD therapy, which had no significant impact on ACR responses.

21 patients in the infliximab group and 38 patients in the placebo group had PASI scores >25 and were included in the assessment. At baseline, the mean PASI score was 8.43 for the infliximab group and 8.44 for the placebo group. At week 16, the mean change was +10.2 for the infliximab group and 80.7 for the placebo group. 67% of patients in the infliximab group compared to 0% of patients in the placebo group had a >75% improvement in the PASI score. Again, concomitant DMARD use did not have an impact the mean PASI scores in either group.

Both groups had 13 patients showing enthesitis at baseline. By week 16, only 7 patients in the infliximab group had enthesitis compared to an increase to 15 patients in the placebo group. Dactylitis scores were reduced from 2.33 to 0.24 in the infliximab group versus 2.0 to 1.33 in the placebo group (p= 0.0026). Swollen/tender joints and patient/physician global assessments were also improved in the infliximab group compared to no change in either measurement among patients in the placebo group.

Conclusions: Infliximab, regardless of concomitant DMARD use, is a safe and effective treatment for reducing the signs and symptoms of psoriatic arthritis.

Editorial Comment: Similar to etanercept which is already FDA approved for the treatment of psoriatic arthritis, infliximab is highly effective as well. There is information in rheumatoid arthritis and crohns disease that concomitant methotrexate use increases the durability of response. We await the open label results to see if this is true in psoriatic arthritis as well.

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