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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.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.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.Leflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies. [ABSTRACT FROM AUTHOR]

To determine whether an elevated serum total cholesterol level in a first‐available sample obtained at a systemic lupus erythematosus (SLE) clinic is associated with worse renal outcome in patients with SLE.Survival analysis methods were used on prospectively gathered data on 1,060 patients with SLE who were registered in the University of Toronto Lupus Databank. The effect of total cholesterol and 15 additional variables on the outcomes of renal deterioration, end‐stage renal disease (ESRD), and death was assessed using Cox proportional hazards methods.In 474 (45%) of the 1,060 patients, the total cholesterol level exceeded 5.2 mmoles/liter. In the entire study group, the median total cholesterol level was 5.1 mmoles/liter (range 1.6–17.1). During a mean followup period of 8.8 years, 93 patients (9%) experienced renal deterioration, 42 patients (4%) had ESRD, and 161 deaths occurred, 48 (30%) of which were associated with renal dysfunction (renal death), and 113 (70%) of which were not associated with renal dysfunction (nonrenal death). Kaplan‐Meier survival estimates for each outcome were statistically significantly different between patients with normal versus those with elevated total cholesterol levels (cutoff 5.2 mmoles/liter), with a worse outcome observed among those with an elevated total cholesterol concentration. In multivariate analyses, total cholesterol level (hazard ratio [HR] 1.17, 95 confidence interval [95% CI] 1.01–1.36), serum creatinine level (HR 1.06, 95% CI 1.04–1.07), proteinuria (HR 2.44, 95% CI 1.25–4.76), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (HR 1.44, 95% CI 1.16–1.80), and corticosteroid dose (HR 1.01, 95% CI 1.00–1.02) were associated with renal deterioration. Significant predictors of ESRD were baseline proteinuria (HR 6.24, 95% CI 1.96–19.88) and serum creatinine level (HR 1.15, 95% CI 1.08–1.22). The total cholesterol level was correlated with death (HR 1.20, 95% CI 1.11–1.29), retaining statistical significance for renal death (HR 1.33, 95% CI 1.20–1.47) but not for nonrenal death (HR 1.12, 95% CI 0.99–1.25).Those results indicate that an elevated serum total cholesterol level in a first‐available sample obtained at an SLE clinic is associated with adverse renal outcomes and mortality. [ABSTRACT FROM AUTHOR]

The interleukin‐1 (IL‐1) cytokine elicits a wide variety of biologic activities that initiate and promote an inflammatory response. The loci in the IL1 gene cluster have recently been associated with ankylosing spondylitis (AS). Since there is clinical and immunologic overlap between psoriatic arthritis (PsA) and AS, we wanted to examine the association between a panel of single‐nucleotide polymorphisms (SNPs) in the IL1 gene family cluster and chromosome 2q12–13 in a PsA cohort.Two hundred twelve PsA patients and 150 ethnically matched controls were genotyped with 11 SNPs in IL1A, 9 SNPs in IL1B, and 9 SNPs in IL1F5–10. Univariate analyses of the 29 single markers and short intragenic haplotypes identified several associated regions. Seventeen markers of interest were noted and further investigated to determine which markers or short haplotypes independently predict case–control status, using a stepwise logistic model.Two regions contributing independently to risk of disease in PsA were noted: a region spanned by markers rs3783547, rs3783543, and rs17561 in IL1A, and a region near the end of IL1B, through IL1F7, IL1F8, and into IL1F10. The best model contained markers rs3811047, rs1562304, and rs3811058, and 1 haplotype constructed from the 3 markers in region 1, with a likelihood ratio of 25.34 (4 degrees of freedom).The IL1 locus appears to be a high‐priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA).One hundred four patients with PsA in whom prior therapy with at least 1 disease‐modifying antirheumatic drug (DMARD) had failed were recruited into this investigator‐initiated, multicenter, randomized, double‐blind, placebo‐controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score.The proportion of infliximab‐treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo‐treated patients who achieved this response (10%). In addition, 46% of infliximab‐treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo‐treated patient achieved these end points. Among patients who had PASI scores of ≥2.5 at baseline, 68% of infliximab‐treated patients achieved improvement of ≥75% in the PASI score at week 16 compared with none of the placebo‐treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups.Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit‐to‐risk ratio appeared favorable in this study population. [ABSTRACT FROM AUTHOR]