Amgen Inc (THOUSAND OAKS, California) and Wyeth Pharmaceuticals (MADISON, New Jersey) announced findings from a retrospective analysis demonstrating that Enbrel® (etanercept), a fully human soluble TNF receptor, reduced C-reactive protein (CRP) in patients with moderate-to-severe plaque psoriasis following 12 weeks of treatment. Median reduction in CRP levels, a marker of inflammation, was 10 times greater in the Enbrel group compared with the placebo group.

The 24-week registrational study was originally designed to test the efficacy and safety of Enbrel therapy in patients with moderate-to-severe plaque psoriasis, the results of which have previously been reported. The primary objective of the retrospective analysis was to evaluate the drug's effectiveness compared with placebo in reducing levels of CRP in psoriasis patients with and without psoriatic arthritis from baseline to week 12. Secondary objectives were to assess CRP values at baseline, and to assess the relationship between CRP levels and patient characteristics, such as body mass index (BMI), use of statin drugs, and Psoriasis Area and Severity Index (PASI). During the double-blind portion of the analysis, patients were randomly assigned to receive either placebo or Enbrel injections (25 mg once weekly, 25 mg or 50 mg twice weekly) for 12 weeks. During the subsequent 12 weeks, patients who initially received the drug therapy continued to receive it at the same dose, whereas patients in the placebo group switched to the drug 25 mg twice weekly.

Key findings of plaque psoriasis patients without psoriatic arthritis (N = 501) demonstrated that patients had intermediate-to-high baseline CRP levels, indicating that psoriasis is a systemic inflammatory disease, and that median reduction in CRP levels from baseline was 1 mg/L in psoriasis patients receiving Enbrel versus 0.1 mg/L in those receiving placebo. The study was not designed to determine whether reducing CRP levels lowers the risk for developing conditions such as cardiovascular disease that may derive from increased systemic inflammation.

The analysis also evaluated the relationship between CRP levels and BMI in people with psoriasis but without psoriatic arthritis. Notably, obesity is common among patients with psoriasis. Findings showed that heavier patients with higher BMIs tended to have higher CRP levels, and that Enbrel decreased CRP levels in overweight and obese psoriasis patients. Specifically, among patients treated with the drug, median CRP values decreased from high or intermediate levels to intermediate or low levels after 12 weeks of treatment in all BMI groups except normal weight psoriasis patients.

CRP is a marker for a number of inflammatory conditions and is an indicator of risk for cardiovascular disease. The development of a high sensitivity CRP assay has enabled detection of low levels of CRP previously undetectable by traditional CRP evaluations. Even low levels of CRP (ie, <3 mg/L), as measured by the high sensitivity test, are associated with increased cardiovascular risk; however, it is not clear that CRP plays a causal role in the development of cardiovascular disease. The safety and efficacy of Enbrel have not been established for decreasing cardiovascular risk.

Enbrel is indicated for the treatment of adult patients (>e;18 years) with chronic moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The drug was first approved in 1998 for moderate-to-severe rheumatoid arthritis and has since been used in ~500,000 patients worldwide across indications. Amgen and Wyeth market Enbrel in North America. Wyeth markets the drug outside of North America.