Etanercept for the Treatment of Chronic Urticaria (EtanerceptCIU)
The purpose of this study is to evaluate the safety and efficacy of etanercept for patients with chronic idiopathic urticaria unresponsive to antihistamines.
Chronic Idiopathic Urticaria
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A 6 Week Randomized, Double Blind, Placebo-controlled Study With a 6 Week Open Label Extension to Assess the Efficacy of Etanercept in the Treatment of Chronic Idiopathic Urticaria|
- To determine the efficacy of etanercept on the clinical features of CIU. A positive response to treatment (a % change from baseline of urticaria activity scores [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Study the safety of etanercept in the treatment of CIU [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||October 2012|
|Estimated Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
Active Comparator: etanercept
etanercept 50mg BIW
etanercept 50mg BIW S.Q.
Other Name: enbrel
Placebo Comparator: placebo
Chronic urticaria is a common condition which can be debilitating, difficult to treat, and sometimes life-threatening. Approximately 15-25% of the population is affected by urticaria at least once in their lifetime, and chronic urticaria develops in more than 25% of these cases. Chronic urticaria is characterized by frequent, often daily, development of pruritic wheals of 6 weeks duration or longer. The average duration of chronic urticaria is 3-5 years in adults. In the majority of cases, an underlying trigger for the urticaria is not identified and these cases are referred to as idiopathic (CIU). These considerations have led to the hypothesis that CIU may have an autoimmune etiology.
CIU is a major affliction causing serious disability to a degree equal to that experienced by sufferers from coronary artery disease. Antihistamines are the most common therapy used. However, most cases of CIU are resistant to combinations of antihistamines and other therapies. In addition, patients are often intolerant to the side effects of antihistamines including sedation and cognitive dysfunction. The treatment of CIU patients can be frustrating. For those who do not respond to typical treatments, other therapies are needed. In many patients, immunosuppressant medications are required but this can lead to adverse effects such as renal dysfunction, liver function abnormalities, and anemia. A safer and more efficacious therapy is clearly needed for CIU.
A few preclinical investigations have demonstrated an upregulation of TNF-alpha in patients with CIU. This is in contrast to acute urticaria where TNF-alpha does not appear to play as important of a role in the inflammatory response . This may explain why patients with CIU do not typically respond to usual therapies for acute urticaria. It has been suggested that CIU is an immediate hypersensitivity phenomenon appearing immediately after exposure to an antigen, but the presence of a delayed inflammatory phase is nevertheless observed in this pathology. Soluble factors play a role in this delayed inflammatory phase. Cytokines, including TNF-alpha, are important mediators the pathogenesis of this delayed response. Studies have demonstrated a similar immune profile as that found in patients with rheumatoid arthritis. In one study, cytokines were evaluated in lesional and non-lesional skin of patients with acute urticaria, CIU, delayed pressure urticaria, and cold urticaria. This study demonstrated upregulation of TNF-alpha on endothelial cells and perivascular cells in the dermis. Additionally, TNF-alpha was expressed throughout the epidermis in lesional and non-lesional skin of CIU patients, but not controls. These preclinical investigations support the use of targeted therapy of TNF-alpha in patients with CIU. Therapies directed at modulating the effects of TNF-alpha, including etanercept, may provide effective and safe long-term treatment for patients not responding to anti-histamines alone.
HYPOTHESIS: We hypothesize that the blockage of TNF with etanercept could be a useful and safe therapy for patients with CIU.
Primary Objective: To determine the efficacy of etanercept on the clinical features of CIU. A positive response to treatment (a % change from baseline of urticaria activity scores
Secondary Objective: Study the safety of etanercept in the treatment of CIU
|United States, Utah|
|University of Utah Department of Dermatology|
|Salt Lake City, Utah, United States, 84132|
|Principal Investigator:||Christopher Hull, MD||University of Utah Department of Dermatology|