Lichen Planus
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGEtanercept
etanercept 50 mg twice weekly for 12 weeks
DRUGPlacebo
Sponsors
Wright State University
Tufts Medical Center
University of Louisville
Wake Forest University Health Sciences
University of Michigan
Emory University
University Hospitals Cleveland Medical Center
Icahn School of Medicine at Mount Sinai
Oregon Health and Science University
The Cleveland Clinic
Fivenson, David, M.D.
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old. * Must carry a diagnosis of lichen planus as determined by biopsy * Patients must have a score of 3 or greater on the physician global assessment (PGA). * Patient must be considered appropriate for systemic therapy based upon fulfilling one of the following criteria: 1. inability to maintain weight due to pain with eating, chewing, or swallowing; 2. dyspareunia or dysuria due to genital lesions; 3. itch/pain of sufficient severity that activities of daily living are significantly affected * Must be off systemic lichen planus treatment for 4 weeks prior to starting etanercept * If using topical corticosteroid to the affected areas, the dose and frequency must be unchanged for 2 weeks prior to beginning the study agent and during the course of the study. * Must be off topical cyclosporine, tacrolimus, or pimecrolimus for 2 weeks prior to starting the study drug and for the entire duration of the study. * Must be able and willing to give written informed consent and comply with the requirements of the study protocol and must authorize release and use of protected health information. * Women of childbearing potential must have a negative pregnancy test at the time of entry into the study and must be practicing successful contraception for at least 3 months prior to the study. * Subject or designee must have the ability to self-inject investigational product. * Screening laboratory results are within the following parameters: * Hemoglobin \> 10 g/dL * White blood cells \> 3.5 x 10\^9/L * Neutrophils \> 1.5 x 10\^9/L * Platelets \> 100 x 10\^9/L * Lymphocytes \> 0.5 x 10\^9/L * Serum creatinine \< 1.5 mg/dL * Hepatitis C serology - nonreactive * AST and ALT \< 2X upper limit of normal (ULN)
Exclusion criteria
* Subject is currently enrolled in another investigational device or drug trial(s), or subject has received investigational agent(s) within 90 days of baseline visit. * Known HIV-positive status, any other immuno-suppressive disease, or inability to practice safe sex during the length of the study * Subject has been diagnosed with a malignancy within the past 5 years * Subject has signs or symptoms of a lymphoproliferative disease. * Other skin or mucosal disease that might interfere with lichen planus assessments. * Lichen planus variants including hypertrophic, atrophic, follicular (including lichen planopilaris), and bullous cutaneous forms. * Patients with lichen sclerosis et atrophicus (LS&A) * Clinical history and lesion distribution suspicious for a lichenoid drug eruption * Severe co-morbidities * History of tuberculosis (TB) or positive PPD at screening. Known history of active hepatitis B or C, or lupus, SLE, history of multiple sclerosis or prior episode of central nervous system demyelination, transverse myelitis, optic neuritis, epilepsy, psychiatric condition, or other chronic serious medical illnesses. * Subject has a diagnosis of congestive heart failure (CHF) of any severity * Use of a live vaccine 90 days prior to, or during this study. * Previous exposure and/or known sensitivity to etanercept * Concurrent use, or failure of, any TNF-inhibitor * Previous exposure to alefacept or efalizumab within 6 weeks of administration of study drug * Concurrent sulfasalazine therapy * Prior or concurrent cyclophosphamide therapy * Active severe infections, or prior infection requiring hospitalization or oral/intravenous antibiotics within 4 weeks before screening visit, or between the screening and baseline visits. * Active inflammatory bowel disease or peptic ulcer disease * Drug or alcohol abuse within 12 months of screening visit. * History of non-compliance with other therapies * Pregnant or lactating * Documented presence of any of the following: * Proteinuria \> 1+ by dipstick screening * 24 Hour protein excretion \> 0.5 g * Symptomatic liver disease with serum albumin \< 3 G/DL * PT or PTT \> ULN, or * Chronic liver disease * Documented forced vital capacity \< 50% of predicted
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Achieving a Response in Mucosal Disease (or Cutaneous Disease if no Mucosal Disease) at 12 Weeks | 12 weeks | Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. Subjects had 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Baseline; Week 12; Week 24 | The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%. |
| The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Baseline; Week 12; Week 24 | The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%. |
| The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Baseline; Week 12; Week 24 | The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%. |
| Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Week 12; Week 24 | This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse erythema. 0=clear, 1=mild/pink, 2=moderately red, 3=severely red/violaceous. |
| Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Week 12; Week 24 | This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse elevation. 0=flat, 1=barely palpable (\<0.5 mm), 2=moderate (0.5 mm-1 mm), 3=severe (\>1 mm). |
| Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Week 12; Week 24 | This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse scaling. 0=none, 1=fine/dusty scale, 2=moderate scale, 3=thick/tenacious scale. |
| Count of Patients Achieving a Response in Cutaneous or Mucosal Disease at 24 Weeks | Baseline; Week 24 | Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. Subjects had 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. |
| Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline; Week 12; Week 24 | Participants were asked to indicate their pain level by marking it on a 10 cm linear VAS scale. The number of centimeters from the left end of the line to the mark was measured in cm. Total range was 0-10. Lower scores correspond to less pain, higher scores correspond to more pain. |
| Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline; Week 12; Week 24 | Participants were asked to indicate their itching level by marking it on a 10 cm linear VAS scale. The number of centimeters from the left end of the line to the mark was measured in cm. Total range was 0-10. Lower scores correspond to less itching, higher scores correspond to more itching. |
| Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Baseline; Week 12; Week 24 | Participants were asked to indicate their rate their overall assessment of disease severity compared to where it was at their baseline visit. The scale ranges from 0-5, with lower scores correspond to more disease improvement. 0=clear/no disease, 1=much improved (\>75% improved), 2=improved (25-75%), 3=minimally improved (\<25%), 4=no change, 5=worsened disease. |
| The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24 | Baseline; Week 12; Week 24 | A serious adverse event was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
| The Count of Placebo Patients Who do Not Have a Complete Response (Defined as a Physician Global Assessment of Clear) at 12 Weeks | 12 weeks | A complete response is defined as a score of 0 (representing no disease) on the Physician Global Assessment. Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. This endpoint is the number of patients on placebo that had any score other than 0 on this measure. |
| The Percentage of Placebo and Study-drug Patients Able to Discontinue Use of Topical Corticosteroids Through Week 24 | 24 weeks | — |
| Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Week 12; Week 24 | This score sums all of the 3 elements of the target lesion score (erythema, elevation, scale) described in Outcome Measures 6-8. Assessment scores range from 0-9 on a Likert scale, with higher numbers meaning more severe disease in the target skin lesion. |
Countries
United States
Participant flow
Recruitment details
This is a randomized, multi-center interventional trial in which patients were recruited at 11 sites in the United States (10 academic and one private practice). Enrollment was between June, 2006 and December, 2008. The first subject was enrolled in August, 2006 and the last patient was enrolled in November, 2008.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Injection Placebo: Normal saline twice weekly for 12 weeks | 14 |
| Etanercept Etanercept: etanercept 50 mg twice weekly for 12 weeks | 13 |
| Total | 27 |
Baseline characteristics
| Characteristic | Etanercept | Total | Placebo Injection |
|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 16 | 53.7 years STANDARD_DEVIATION 16.5 | 50.4 years STANDARD_DEVIATION 16.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 14 | 14 / 24 |
| serious Total, serious adverse events | 0 / 14 | 1 / 24 |
Outcome results
Primary
The Percentage of Patients Achieving a Response in Mucosal Disease (or Cutaneous Disease if no Mucosal Disease) at 12 Weeks
Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. Subjects had 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.
Time frame: 12 weeks
Population: Intention to treat analysis (all participants received at least one dose of study drug). Missing data imputed using Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Injection | The Percentage of Patients Achieving a Response in Mucosal Disease (or Cutaneous Disease if no Mucosal Disease) at 12 Weeks | 28.6 percentage of participants |
| Etanercept | The Percentage of Patients Achieving a Response in Mucosal Disease (or Cutaneous Disease if no Mucosal Disease) at 12 Weeks | 0 percentage of participants |
p-value: 0.0978Fisher Exact
Secondary
Count of Patients Achieving a Response in Cutaneous or Mucosal Disease at 24 Weeks
Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. Subjects had 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.
Time frame: Baseline; Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Injection | Count of Patients Achieving a Response in Cutaneous or Mucosal Disease at 24 Weeks | 5 Participants |
| Etanercept | Count of Patients Achieving a Response in Cutaneous or Mucosal Disease at 24 Weeks | 4 Participants |
p-value: >0.9999Fisher Exact
Secondary
Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks
This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse elevation. 0=flat, 1=barely palpable (\<0.5 mm), 2=moderate (0.5 mm-1 mm), 3=severe (\>1 mm).
Time frame: Week 12; Week 24
Population: Participants with missing data were excluded from the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Baseline | 2.1 units on a scale | Standard Deviation 0.64 |
| Placebo Injection | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Week 12 | 1.5 units on a scale | Standard Deviation 1.16 |
| Placebo Injection | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Week 24 | 1.0 units on a scale | Standard Deviation 1.22 |
| Etanercept | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Baseline | 2.1 units on a scale | Standard Deviation 0.87 |
| Etanercept | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Week 12 | 1.6 units on a scale | Standard Deviation 0.7 |
| Etanercept | Cutaneous Target Lesion Scores - Elevation, at 12 and 24 Weeks | Week 24 | 0.8 units on a scale | Standard Deviation 0.83 |
Comparison: Week 12 versus baselinep-value: 0.094Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: 0.25Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.13Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.13Wilcoxon Paired
Secondary
Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks
This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse erythema. 0=clear, 1=mild/pink, 2=moderately red, 3=severely red/violaceous.
Time frame: Week 12; Week 24
Population: Participants with missing data were excluded from the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Baseline | 2.5 units on a scale | Standard Deviation 0.76 |
| Placebo Injection | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Week 12 | 1.6 units on a scale | Standard Deviation 1.3 |
| Placebo Injection | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Week 24 | 0.9 units on a scale | Standard Deviation 1.05 |
| Etanercept | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Baseline | 2.3 units on a scale | Standard Deviation 0.67 |
| Etanercept | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Week 12 | 1.8 units on a scale | Standard Deviation 0.83 |
| Etanercept | Cutaneous Target Lesion Scores - Erythema, at 12 and 24 Weeks | Week 24 | 1.8 units on a scale | Standard Deviation 0.97 |
Comparison: Week 12 versus baselinep-value: 0.063Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: 0.25Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.031Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.32Wilcoxon Paired
Secondary
Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks
This is an investigator-based assessment of a single preselected target skin lesion. Assessment scores range from 0-3 on a Likert scale, with higher scores meaning worse scaling. 0=none, 1=fine/dusty scale, 2=moderate scale, 3=thick/tenacious scale.
Time frame: Week 12; Week 24
Population: Participants with missing data were excluded from the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Baseline | 0.9 units on a scale | Standard Deviation 0.76 |
| Placebo Injection | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Week 12 | 0.8 units on a scale | Standard Deviation 0.72 |
| Placebo Injection | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Week 24 | 0.4 units on a scale | Standard Deviation 0.99 |
| Etanercept | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Baseline | 1.2 units on a scale | Standard Deviation 0.79 |
| Etanercept | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Week 12 | 0.8 units on a scale | Standard Deviation 0.66 |
| Etanercept | Cutaneous Target Lesion Scores - Scale, at 12 and 24 Weeks | Week 24 | 0.8 units on a scale | Standard Deviation 0.83 |
Comparison: Week 12 versus baselinep-value: 0.63Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: 0.38Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.38Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.5Wilcoxon Paired
Secondary
Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks
This score sums all of the 3 elements of the target lesion score (erythema, elevation, scale) described in Outcome Measures 6-8. Assessment scores range from 0-9 on a Likert scale, with higher numbers meaning more severe disease in the target skin lesion.
Time frame: Week 12; Week 24
Population: Participants with missing data were excluded from the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Baseline | 4.7 units on a scale | Standard Deviation 2.55 |
| Placebo Injection | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Week 12 | 3.1 units on a scale | Standard Deviation 3.1 |
| Placebo Injection | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Week 24 | 1.3 units on a scale | Standard Deviation 2.52 |
| Etanercept | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Baseline | 3.9 units on a scale | Standard Deviation 3.02 |
| Etanercept | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Week 12 | 2.5 units on a scale | Standard Deviation 2.5 |
| Etanercept | Cutaneous Target Lesion Scores - Total, at 12 and 24 Weeks | Week 24 | 2.4 units on a scale | Standard Deviation 2.59 |
Comparison: Week 12 versus baselinep-value: 0.031Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: 0.094Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.039Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.19Wilcoxon Paired
Secondary
Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks
Participants were asked to indicate their rate their overall assessment of disease severity compared to where it was at their baseline visit. The scale ranges from 0-5, with lower scores correspond to more disease improvement. 0=clear/no disease, 1=much improved (\>75% improved), 2=improved (25-75%), 3=minimally improved (\<25%), 4=no change, 5=worsened disease.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Baseline | 3.9 units on a scale | Standard Deviation 0.87 |
| Placebo Injection | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Week 12 | 2.3 units on a scale | Standard Deviation 1.56 |
| Placebo Injection | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Week 24 | 2.9 units on a scale | Standard Deviation 1.46 |
| Etanercept | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Baseline | 4.1 units on a scale | Standard Deviation 0.54 |
| Etanercept | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Week 12 | 3.1 units on a scale | Standard Deviation 1.23 |
| Etanercept | Patient Assessment of Overall Disease Severity (Patient Global Assessment) at 12 and 24 Weeks | Week 24 | 2.6 units on a scale | Standard Deviation 1.43 |
Comparison: Week 12 versus baselinep-value: 0.033Paired t test
Comparison: Week 12 versus baselinep-value: 0.069Paired t test
Comparison: Week 24 versus baselinep-value: 0.015Paired t test
Comparison: Week 24 versus baselinep-value: 0.026Paired t test
Secondary
Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks
Participants were asked to indicate their pain level by marking it on a 10 cm linear VAS scale. The number of centimeters from the left end of the line to the mark was measured in cm. Total range was 0-10. Lower scores correspond to less pain, higher scores correspond to more pain.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 12 | 3.4 units on a scale | Standard Deviation 3.08 |
| Placebo Injection | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline | 3.8 units on a scale | Standard Deviation 3.08 |
| Placebo Injection | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 24 | 2.4 units on a scale | Standard Deviation 2.83 |
| Etanercept | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline | 3.4 units on a scale | Standard Deviation 2.5 |
| Etanercept | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 12 | 3.0 units on a scale | Standard Deviation 2.85 |
| Etanercept | Patient Assessment of Pain on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 24 | 2.8 units on a scale | Standard Deviation 3.25 |
Comparison: Week 12 versus baselinep-value: 0.26Paired t test
Comparison: Week 12 versus baselinep-value: 0.55Paired t test
Comparison: Week 24 versus baselinep-value: 0.18Paired t test
Comparison: Week 24 versus baselinep-value: 0.13Paired t test
Secondary
Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks
Participants were asked to indicate their itching level by marking it on a 10 cm linear VAS scale. The number of centimeters from the left end of the line to the mark was measured in cm. Total range was 0-10. Lower scores correspond to less itching, higher scores correspond to more itching.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline | 3.8 units on a scale | Standard Deviation 2.84 |
| Placebo Injection | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 12 | 3.3 units on a scale | Standard Deviation 3.38 |
| Placebo Injection | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 24 | 1.5 units on a scale | Standard Deviation 1.64 |
| Etanercept | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Baseline | 3.2 units on a scale | Standard Deviation 2.55 |
| Etanercept | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 12 | 3.4 units on a scale | Standard Deviation 3.14 |
| Etanercept | Patient Assessment of Pruritus (Itching) on a Visual Analogue Scale (VAS) at 12 and 24 Weeks | Week 24 | 3.0 units on a scale | Standard Deviation 2.71 |
Comparison: Week 12 versus baselinep-value: 0.51Paired t test
Comparison: Week 24 versus baselinep-value: 0.47Paired t test
Comparison: Week 24 versus baselinep-value: 0.087Paired t test
Comparison: Week 24 versus baselinep-value: 0.86Paired t test
Secondary
The Count of Placebo Patients Who do Not Have a Complete Response (Defined as a Physician Global Assessment of Clear) at 12 Weeks
A complete response is defined as a score of 0 (representing no disease) on the Physician Global Assessment. Physician global assessment of disease scores: 0=clear; 1=minimal disease; 2=mild disease; 3=moderate disease; 4=severe disease. This endpoint is the number of patients on placebo that had any score other than 0 on this measure.
Time frame: 12 weeks
Population: Only participants in the Placebo injection group were evaluated for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Injection | The Count of Placebo Patients Who do Not Have a Complete Response (Defined as a Physician Global Assessment of Clear) at 12 Weeks | 13 Participants |
Secondary
The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24
A serious adverse event was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: Baseline; Week 12; Week 24
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Injection | The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24 | SAE by week 12 | 0 Participants |
| Placebo Injection | The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24 | SAE by week 24 | 0 Participants |
| Etanercept | The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24 | SAE by week 12 | 0 Participants |
| Etanercept | The Count of Subjects Experiencing Serious Adverse Events (SAEs) by Week 12 and Week 24 | SAE by week 24 | 1 Participants |
Secondary
The Percentage of Placebo and Study-drug Patients Able to Discontinue Use of Topical Corticosteroids Through Week 24
Time frame: 24 weeks
Population: Data were not collected for this outcome measure
Secondary
The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks
The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Baseline | 0.3 units on a scale | Standard Deviation 0.82 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Week 12 | 0.5 units on a scale | Standard Deviation 0.96 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Week 24 | 0.7 units on a scale | Standard Deviation 1.05 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Baseline | 0.4 units on a scale | Standard Deviation 1.33 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Week 12 | 0.4 units on a scale | Standard Deviation 1.38 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Genital Disease at 12 and 24 Weeks | Week 24 | 0.5 units on a scale | Standard Deviation 1.5 |
Comparison: Week 12 versus baselinep-value: >0.9999Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: >0.9999Wilcoxon Paired
Secondary
The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks
The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Week 12 | 0.8 units on a scale | Standard Deviation 1.03 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Baseline | 1.2 units on a scale | Standard Deviation 1.31 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Week 24 | 1.1 units on a scale | Standard Deviation 1.1 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Week 12 | 1.5 units on a scale | Standard Deviation 1.44 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Baseline | 1.6 units on a scale | Standard Deviation 1.73 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Oral Disease at 12 and 24 Weeks | Week 24 | 1.5 units on a scale | Standard Deviation 1.2 |
Comparison: Week 12 versus baselinep-value: 0.031Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: 0.34Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.13Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.22Wilcoxon Paired
Secondary
The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks
The percentage of surface area involved with disease is reported as assessed by the physician using a Likert scale. Assessment scores range from 0-5, with lower scores corresponding lower percentage of surface area with disease. 0=clear, 1=\<2%, 2=2-9%, 3=10-29%, 4=30-50%, 5=\>50%.
Time frame: Baseline; Week 12; Week 24
Population: Participants with missing data were excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Baseline | 2.8 units on a scale | Standard Deviation 1.56 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Week 12 | 2.2 units on a scale | Standard Deviation 1.77 |
| Placebo Injection | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Week 24 | 1.0 units on a scale | Standard Deviation 0.94 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Baseline | 1.8 units on a scale | Standard Deviation 1.61 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Week 12 | 1.7 units on a scale | Standard Deviation 1.43 |
| Etanercept | The Physician Assessment of Surface Area of Disease (PSAD) for Skin Disease at 12 and 24 Weeks | Week 24 | 1.6 units on a scale | Standard Deviation 1.36 |
Comparison: Week 12 versus baselinep-value: 0.25Wilcoxon Paired
Comparison: Week 12 versus baselinep-value: >0.9999Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: 0.063Wilcoxon Paired
Comparison: Week 24 versus baselinep-value: >0.9999Wilcoxon Paired