Enbrel shown to significantly reduced levels of C-reactive protein

Feb 5 2008

Amgen and Wyeth Pharmaceuticals, a division of Wyeth have announced findings from a retrospective analysis, which demonstrated that ENBREL reduced C-reactive protein (CRP), a marker of inflammation, in patients with moderate to severe plaque psoriasis following 12 weeks of treatment. Median reduction in CRP levels was 10 times greater in the ENBREL treated group compared to the placebo treated group.

These results will be presented today at the American Academy of Dermatology Scientific Meeting in San Antonio, Texas.

Psoriasis is a non-contagious, chronic disease in which the immune system causes skin cells to grow at an accelerated rate. Approximately 80 percent of psoriasis patients have plaque psoriasis, which is characterized by painful and itchy, red, scaly patches.

Key findings of the analysis of moderate to severe plaque psoriasis patients without psoriatic arthritis (n=501) demonstrated:

• Patients had intermediate to high baseline CRP levels, indicating that psoriasis is a systemic inflammatory disease.
• The median reduction in CRP levels from baseline was 1.0 mg/L in psoriasis patients receiving ENBREL vs. 0.1 mg/L in those receiving placebo (P<0.001).

“The finding that patients with moderate to severe plaque psoriasis had increased inflammation, as exhibited by elevated CRP levels, reinforces that psoriasis is not only a skin disease, but in some patients may be a serious medical condition,” said Bruce Strober, M.D., Ph.D., study investigator, co-director of the Psoriasis and Psoriatic Arthritis Center of New York University Medical Center. “The results from this study are encouraging because they show that ENBREL not only improved the symptoms of patients with moderate to severe psoriasis, but reduced their levels of CRP as well. However, further research is needed to better understand 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 body mass index (BMI), an indicator of body fat, in people with psoriasis without psoriatic arthritis. Notably, obesity is common among patients with psoriasis. Findings showed:

• Heavier patients with higher BMIs tended to have higher CRP levels.
• ENBREL decreased CRP levels in overweight and obese psoriasis patients. Specifically, among patients treated with ENBREL, 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.

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 in The New England Journal of Medicine. The primary objective of this retrospective analysis was to evaluate the effectiveness of ENBREL in reducing levels of CRP in psoriasis patients with and without psoriatic arthritis from baseline to week 12 compared to placebo. Secondary objectives were to assess CRP values at baseline, and to assess the relationship between CRP levels and patient characteristics, such as 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 twice weekly or 50 mg twice weekly) for 12 weeks. During the subsequent 12 weeks, patients who initially received ENBREL continued to receive treatment with ENBREL at the same dose, while patients in the placebo group switched to ENBREL 25 mg twice weekly.

CRP is a blood protein that 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 (hs-CRP) has enabled detection of low levels of CRP previously undetectable by traditional CRP evaluations. Even low levels of CRP (i.e., less than 3 mg/L), as measured by this 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 a fully human soluble tumor necrosis factor (TNF) receptor. ENBREL was first approved in 1998 for moderate to severe rheumatoid arthritis and has since been used in nearly 500,000 patients worldwide across indications.

ENBREL indications in the U.S.:

• ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with moderate to severe rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone.

• ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more disease modifying antirheumatic drugs.

• ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse, and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone.

• ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

• ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

What important information do I need to know about taking prescription Enbrel® (etanercept)"

ENBREL is a type of protein called a tumor necrosis factor (TNF) blocker that blocks the action of a substance your body's immune system makes called TNF. People with an immune disease, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, have too much TNF in their bodies. ENBREL can reduce the amount of TNF in the body to normal levels, helping to treat your disease. But, in doing so, ENBREL can also lower the ability of your immune system to fight infections.

All medicines have side effects, including ENBREL. Possible side effects of ENBREL include:

• Serious infections
  • Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes
  • Some serious infections have been fatal
  • Rare cases of tuberculosis have occurred
• What not to do
  • Do not start ENBREL if you have an infection, such as an open sore or the flu, or are allergic to ENBREL or its components
• What to do
  • Tell your doctor if you are prone to infection or have had hepatitis B
  • Stop ENBREL if a serious infection occurs
  • Contact your doctor if you have questions about ENBREL or develop an infection
  • Tell your doctor if you have ever been treated for heart failure
  • Serious nervous system disorders, such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes
  • Tell your doctor if you have ever had any of these disorders or if you develop them after starting ENBREL
• Rare reports of serious blood disorders (some fatal)
  • Contact your doctor immediately if you develop symptoms, such as persistent fever, bruising, bleeding, or paleness
• In medical studies of all TNF blockers, including ENBREL, a higher rate of lymphoma (a type of cancer) was seen compared to the general population. The risk of lymphoma may be up to several-fold higher in rheumatoid arthritis and psoriasis patients
• The role of TNF blockers, including ENBREL, in the development of lymphoma is unknown
• ENBREL can cause injection site reaction
• In a medical study of patients with JRA, infection, headache, abdominal pain, vomiting, and nausea occurred more frequently than in adults
  • The kinds of infections reported were generally mild and similar to those usually seen in children
  • Other serious adverse reactions were reported rarely, including serious infection (2 percent) and depression/personality disorder (1 percent)