Use of Etanercept in the Treatment of Moderate to Severe Lichen Planus
The purpose is to assess the response of subjects to etanercept (as compared to placebo) in treating the physical signs of mucosal and cutaneous lichen planus. The investigators also wish to assess the effect of etanercept on disease-related itching, pain, and serious adverse events in patients with lichen planus.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Randomized, Multicenter Pilot Study to Evaluate the Efficacy and Safety of Etanercept 50mg SC Twice Weekly in the Treatment of Moderate to Severe Lichen Planus|
- The Percentage of Patients Achieving a Response in Mucosal Disease (or Cutaneous Disease if no Mucosal Disease) at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]This is a physician global assessment of disease (0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease). The subject have a level >=3 at baseline. To be considered a responder, the subject must achieve a level of 0 or 1, or, at least a 2 point improvement in the scale.
- The Percentage of Patients Achieving a Response in Cutaneous or Mucosal Disease at 24 Weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The Physician Assessment of Surface Area of Disease, PSAD, (Mucosal Erosions and Cutaneous Disease) at 12 and 24 Weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The Individual and Total Cutaneous Target Lesion Scores at 12 and 24 Weeks [ Time Frame: 12 weeks and 24 weeks ] [ Designated as safety issue: No ]
- Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
- Patient Assessment of Pruritus/Itching on a Visual Analogue Scale (VAS) at 12 and 24 Weeks [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
- Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
- The Number and Percentage of Subjects Experiencing Serious Adverse Events (SAE) on Etanercept and Placebo [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: Yes ]
- The Percentage of Placebo Patients Who do Not Have a Complete Response (Defined as a Physician Global Assessment of "Clear") at 12 Weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- The Percentage of Placebo and Study-drug Patients Able to Discontinue Use of Topical Corticosteroids Through Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo injection
patients receive normal saline injection twice weekly for weeks 1-12
patients receive etanercept injection twice weekly for weeks 1-12.
etanercept 50 mg twice weekly for 12 weeks
Lichen planus affects up to 1% of the worldwide population. Recent estimates suggest approximately 0.44% of the US population suffers from this disease. Oral or genital involvement occurs in 60-70% of patients, and it may be the sole manifestation of disease in 20-30% of patients.
Lichen planus is a mucocutaneous disorder that can involve the skin, oral or genital mucosa, conjunctiva, and nails. On the skin, the disease presents as multiple papules, which can be localized or generalized, that are often extremely itchy. Mucosal disease can consist of either asymptomatic plaques or extremely painful erosive lesions. The disease course is unpredictable and typically lasts 1-2 years but can follow a chronic, relapsing course. Erosive mucosal disease is important to aggressively treat for many reasons: First, the associated pain can be debilitating for the patient. Patients with severe oral lichen planus can become malnourished due to pain associated with eating. Vulvar disease can cause dyspareunia, burning pain, and discharge; second, the disease tends to be chronic, with little chance for self-resolution; third, erosive disease is associated with an increased risk of squamous cell carcinoma in the affected areas. These cancers occur in up to 1% of patients over a 3-year period, and they can be aggressive and even-life threatening for the patient if not recognized and treated early.
Several lines of evidence suggest that TNF-alpha plays a role in the pathogenesis of lichen planus. It has been shown that there are increased levels of TNF-alpha in the serum of these patients. In addition, skin and mucosal biopsies show increased TNF-alpha produced by the infiltrating lymphocytes as well as the basal keratinocytes. It has been suggested that the expression of TNF-alpha receptor on the basal keratinocytes may contribute to apoptosis. Also, TNFR1 (a TNF-alpha receptor) is expressed by the infiltrating mononuclear cells as well as the keratinocytes. Increased levels of soluble TNF receptors are also found in the serum of patients with lichen planus. A recent report also has shown that polymorphisms in the TNF-alpha gene are associated with both oral and cutaneous lichen planus. Finally, thalidomide, which partly functions as a potent inhibitor of TNF-alpha transcription, has been shown to be effective (in small case series and reports) in selected patients for the treatment of oral and genital lichen planus. However, thalidomide is a potent teratogen and cannot be used in women of childbearing potential. In addition, thalidomide usage not uncommonly results in neurotoxicity, which can be permanent, and thus limits use of this drug. Despite the evidence for a role of TNF-alpha in LP there are no reports of any TNF inhibitors being used for this disease.
This is a double-blind, placebo-controlled pilot study to observe the safety and efficacy of etanercept in patients with lichen planus.
This study will consist of 3 periods: first, a double-blind period (weeks 0-12) in which subjects will be randomized to etanercept 50 mg twice weekly or placebo; second, an open-label period (weeks 12-24) in which subjects who were randomized to placebo treatment, who have not achieved a complete remission, will be rolled over to use etanercept at 50 mg twice weekly. Subjects who previously received etanercept during weeks 0-12, who have not achieved a complete remission, will be continued on etanercept at a lower dosage of 25 mg twice weekly for weeks 12-24; third, an 8 week follow-up period for all subjects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00285779
|United States, California|
|Stanford University Medical Center|
|Stanford, California, United States, 94305|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, Kentucky|
|University of Louisville|
|Louisville, Kentucky, United States, 40202|
|United States, Massachusetts|
|Tufts - New England Medical Center|
|Boston, Massachusetts, United States, 02111|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|David Fivenson, M.D. Dermatology, PLLC|
|Ann Arbor, Michigan, United States, 48103|
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029|
|United States, North Carolina|
|Wake Forest University School of Medicine|
|Winston Salem, North Carolina, United States, 26157|
|United States, Ohio|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|University Hospitals of Cleveland|
|Cleveland, Ohio, United States, 44106|
|Wright State University School of Medicine|
|Dayton, Ohio, United States, 45408|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||David F Fiorentino, MD, PhD||Stanford University|
|Study Director:||David F Fiorentino, MD, PhD||Stanford University|