Psoriasis
Conditions
Keywords
Psoriasis
Brief summary
The purpose of this study is to evaluate the use of etanercept as a replacement therapy for ciclosporin in patients with plaque psoriasis.
Detailed description
The purpose of this study is to evaluate the efficacy and safety of etanercept as a replacement therapy for ciclosporin in patients with moderate to severe plaque psoriasis who have achieved an adequate response with ciclosporin.
Interventions
DRUGEtanercept
Etanercept 50 mg QW initiated during taper of ciclosporin
OTHERPlacebo
Randomized to placebo during taper of ciclosporin
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Between age 18 and 70 years * Active and stable plaque psoriasis with a BSA≥10 or PASI≥10.
Exclusion criteria
* Evidence of skin conditions other than psoriasis * Psoralen plus psoralen + ultraviolet A (PUVA), ciclosporin, acitretin, alefacept, anakinra, or any other systemic anti-psoriasis therapy or disease-modifying antirheumatic drugs (DMARD) with 28 days of screening * ultraviolet B (UVB) therapy, topical steroids, topical Vitamin A or D analog preparations, or anthralin * Prior exposure to any TNF-inhibitor. Prior exposure to efalizumab * Corticosteroid dose of prednisone \>10 mg/day * Serious infection * Receipt of any live vaccine * Abnormal hematology or chemistry * Body mass index (BMI) \> 38 * Pregnancy or Breastfeeding * Significant concurrent medical conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomization in PASI Score to Week 24 (Week 18 of Etanercept Monotherapy/Placebo) | Randomization to Week 24. | PASI score: range: 0 (none) to 72 (maximum). Body was divided into head, upper extremities, trunk and lower extremities; each area score was combined for final PASI. For each section, percent area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: (erythema, induration, and desquamation); scale: 0 (none) to 4 (maximum). Final PASI= sum of severity parameters for each section times area score times weight of section (head: 0.1, upper extremities: 0.2, trunk: 0.3, lower extremities: 0.4). Change = PASI at Week 24 - PASI at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Randomization in PGA Score to Week 24 | Randomization to Week 24. | PGA score is based on dermatologist's assessment of disease averaged over all lesions. Overall lesions were graded for individual scores of induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Change = PGA at Week 24 - PGA at baseline. |
| Relapse (Loss of 50% Improvement in PASI) During the 24 Weeks After Randomization | Randomization to Week 24. | Relapse was defined as the loss of 50% improvement in PASI. |
| Probability of Being Relapse Free During the 24 Weeks After Randomization | Randomization to Week 24. | Relapse was defined as loss of 50% improvement in PASI. The time to relapse was estimated using a Kaplan-Meier analysis. |
| PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Randomization to Week 24. | PASI AUC = Area under the curve from randomization (Week 6) to Week 24. |
| Change From Randomization in DLQI to Week 24 | Randomization to Week 24. | DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire has a score range of 0 to 30 with higher scores indicating poor quality of life. An estimate of the minimal clinically important difference of the DLQI total score is a 5 point improvement. Total score range: 0 (best) to 30 (worst). |
| DLQI at Each Visit From Baseline | Baseline to Week 24. | DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10 item questionnaire has a score range of 0 to 30 with higher scores indicating poor quality of life. An estimate of the minimal clinically important difference of the DLQI total score is a 5 point improvement. Total score range: 0 (best) to 30 (worst). |
| Percentage of Rebound Effects | Baseline to Week 24. | Rebound effects was defined as worsening of psoriasis to 125% of the baseline PASI or appearance of psoriasis variants such as erythrodermic or pustular psoriasis within 12 weeks of discontinuation of therapy. |
| Percent (%) Change of PASI Score From Randomization to Week 24 | Randomization to Week 24. | Percent improvement in PASI score was calculated from Week 6 to Week 24. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were administered placebo subcutaneously once a week after an initial course of ciclosporin. | 62 |
| Etanercept Participants were administered a 50 mg dose of etanercept subcutaneously once a week after an initial course of ciclosporin. | 58 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Other reasons | 16 | 4 |
| Overall Study | Physician Decision | 3 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 9 |
Baseline characteristics
| Characteristic | Placebo | Etanercept | Total |
|---|---|---|---|
| Age Continuous | 41.50 years STANDARD_DEVIATION 12.97 | 41.78 years STANDARD_DEVIATION 9.86 | 41.63 years STANDARD_DEVIATION 11.52 |
| DLQI score | 11.26 units on scale STANDARD_DEVIATION 6.3 | 11.20 units on scale STANDARD_DEVIATION 7.22 | 11.23 units on scale STANDARD_DEVIATION 6.72 |
| PASI score | 19.35 units on scale STANDARD_DEVIATION 6.98 | 20.19 units on scale STANDARD_DEVIATION 7.76 | 19.74 units on scale STANDARD_DEVIATION 7.26 |
| PGA | 4.07 units on scale STANDARD_DEVIATION 0.73 | 4.25 units on scale STANDARD_DEVIATION 0.85 | 4.15 units on scale STANDARD_DEVIATION 0.78 |
| Sex: Female, Male Female | 17 Participants | 20 Participants | 37 Participants |
| Sex: Female, Male Male | 45 Participants | 38 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 62 | 43 / 58 |
| serious Total, serious adverse events | 1 / 62 | 2 / 58 |
Outcome results
Primary
Change From Randomization in PASI Score to Week 24 (Week 18 of Etanercept Monotherapy/Placebo)
PASI score: range: 0 (none) to 72 (maximum). Body was divided into head, upper extremities, trunk and lower extremities; each area score was combined for final PASI. For each section, percent area of skin involved was estimated: 0 (0%) to 6 (90 - 100%), and severity was estimated by clinical signs: (erythema, induration, and desquamation); scale: 0 (none) to 4 (maximum). Final PASI= sum of severity parameters for each section times area score times weight of section (head: 0.1, upper extremities: 0.2, trunk: 0.3, lower extremities: 0.4). Change = PASI at Week 24 - PASI at baseline.
Time frame: Randomization to Week 24.
Population: Intent-To-Treat (ITT) population: included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Randomization in PASI Score to Week 24 (Week 18 of Etanercept Monotherapy/Placebo) | 2.9 scores on a scale |
| Etanercept | Change From Randomization in PASI Score to Week 24 (Week 18 of Etanercept Monotherapy/Placebo) | -1.8 scores on a scale |
Comparison: Analysis from randomization to Week 24.p-value: <0.00195% CI: [2.1, 7.3]mixed model of ANCOVA
Secondary
Change From Randomization in DLQI to Week 24
DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10-item questionnaire has a score range of 0 to 30 with higher scores indicating poor quality of life. An estimate of the minimal clinically important difference of the DLQI total score is a 5 point improvement. Total score range: 0 (best) to 30 (worst).
Time frame: Randomization to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Randomization in DLQI to Week 24 | 2.0 scores on a scale |
| Etanercept | Change From Randomization in DLQI to Week 24 | -0.4 scores on a scale |
Comparison: Analysis from randomization to Week 24.p-value: 0.13995% CI: [-0.8, 5.5]mixed model of ANCOVA
Secondary
Change From Randomization in PGA Score to Week 24
PGA score is based on dermatologist's assessment of disease averaged over all lesions. Overall lesions were graded for individual scores of induration, erythema, and scaling; range: 0 (no evidence) to 5 (severe). The sum of the 3 scores was divided by 3 to obtain a final PGA score. Higher scores indicate greater severity of disease. Change = PGA at Week 24 - PGA at baseline.
Time frame: Randomization to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Randomization in PGA Score to Week 24 | 0.9 scores on a scale |
| Etanercept | Change From Randomization in PGA Score to Week 24 | 0.2 scores on a scale |
Comparison: Analysis from randomization to Week 24.p-value: 0.04995% CI: [0, 1.2]mixed model of ANCOVA
Secondary
DLQI at Each Visit From Baseline
DLQI is the dermatology-specific quality of life measure used for psoriatic population. The 10 item questionnaire has a score range of 0 to 30 with higher scores indicating poor quality of life. An estimate of the minimal clinically important difference of the DLQI total score is a 5 point improvement. Total score range: 0 (best) to 30 (worst).
Time frame: Baseline to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | DLQI at Each Visit From Baseline | Week 24 (n= 20, 40) | 6.1 scores on a scale | Standard Error 10.9 |
| Placebo | DLQI at Each Visit From Baseline | Week 2 (n= 28, 30) | 4.1 scores on a scale | Standard Error 0.9 |
| Placebo | DLQI at Each Visit From Baseline | Week 4 (n= 25, 22) | 3.0 scores on a scale | Standard Error 0.9 |
| Placebo | DLQI at Each Visit From Baseline | Week 6 (n= 8, 3) | 1.5 scores on a scale | Standard Error 1.2 |
| Placebo | DLQI at Each Visit From Baseline | Week 8 (n= 58, 55) | 1.6 scores on a scale | Standard Error 0.6 |
| Placebo | DLQI at Each Visit From Baseline | Week 10 (n= 56, 54) | 1.7 scores on a scale | Standard Error 0.6 |
| Placebo | DLQI at Each Visit From Baseline | Week 12 (n= 52, 54) | 2.0 scores on a scale | Standard Error 0.7 |
| Placebo | DLQI at Each Visit From Baseline | Week 16 (n= 44, 48) | 5.5 scores on a scale | Standard Error 0.7 |
| Placebo | DLQI at Each Visit From Baseline | Week 20 (n= 29, 44) | 6.2 scores on a scale | Standard Error 0.8 |
| Etanercept | DLQI at Each Visit From Baseline | Week 16 (n= 44, 48) | 2.8 scores on a scale | Standard Error 0.7 |
| Etanercept | DLQI at Each Visit From Baseline | Week 10 (n= 56, 54) | 1.0 scores on a scale | Standard Error 0.7 |
| Etanercept | DLQI at Each Visit From Baseline | Week 2 (n= 28, 30) | 4.0 scores on a scale | Standard Error 0.9 |
| Etanercept | DLQI at Each Visit From Baseline | Week 24 (n= 20, 40) | 3.6 scores on a scale | Standard Error 0.7 |
| Etanercept | DLQI at Each Visit From Baseline | Week 4 (n= 25, 22) | 4.0 scores on a scale | Standard Error 0.9 |
| Etanercept | DLQI at Each Visit From Baseline | Week 12 (n= 52, 54) | 1.0 scores on a scale | Standard Error 0.7 |
| Etanercept | DLQI at Each Visit From Baseline | Week 6 (n= 8, 3) | 1.9 scores on a scale | Standard Error 1.9 |
| Etanercept | DLQI at Each Visit From Baseline | Week 20 (n= 29, 44) | 3.3 scores on a scale | Standard Error 0.7 |
| Etanercept | DLQI at Each Visit From Baseline | Week 8 (n= 58, 55) | 1.6 scores on a scale | Standard Error 0.7 |
Comparison: Analysis from baseline to Week 2.p-value: 0.95695% CI: [-2.3, 2.5]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 4.p-value: 0.4195% CI: [-3.6, 1.5]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 6.p-value: 0.84495% CI: [-4.8, 3.9]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 8.p-value: 0.96895% CI: [-1.8, 1.8]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 10.p-value: 0.44195% CI: [-1.1, 2.5]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 12.p-value: 0.395% CI: [-0.9, 2.8]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 16.p-value: 0.00895% CI: [0.7, 4.5]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 20.p-value: 0.00595% CI: [0.9, 5]mixed model of ANCOVA
Comparison: Analysis from baseline to Week 24.p-value: 0.03195% CI: [0.2, 4.6]mixed model of ANCOVA
Secondary
PASI Area Under the Curve (AUC) Between Randomization and Week 24
PASI AUC = Area under the curve from randomization (Week 6) to Week 24.
Time frame: Randomization to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 8 (n= 59, 56) | 20.7 scores on a scale * weeks | Standard Error 5.2 |
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 10 (n= 55, 55) | 7.0 scores on a scale * weeks | Standard Error 5.3 |
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 12 (n= 52, 55) | 6.7 scores on a scale * weeks | Standard Error 5.3 |
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 16 (n= 45, 49) | 17.5 scores on a scale * weeks | Standard Error 5.4 |
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 20 (n= 29, 45) | 33.6 scores on a scale * weeks | Standard Error 5.6 |
| Placebo | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 24 (n= 21,40) | 54.8 scores on a scale * weeks | Standard Error 5.8 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 20 (n= 29, 45) | 17.5 scores on a scale * weeks | Standard Error 5.5 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 8 (n= 59, 56) | 20.7 scores on a scale * weeks | Standard Error 5.4 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 16 (n= 45, 49) | 10.8 scores on a scale * weeks | Standard Error 5.4 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 10 (n= 55, 55) | 5.0 scores on a scale * weeks | Standard Error 5.4 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 24 (n= 21,40) | 24.3 scores on a scale * weeks | Standard Error 5.5 |
| Etanercept | PASI Area Under the Curve (AUC) Between Randomization and Week 24 | Week 12 (n= 52, 55) | 4.4 scores on a scale * weeks | Standard Error 5.4 |
Comparison: Analysis at randomization to Week 8.p-value: 0.99995% CI: [-14.7, 14.7]mixed model of ANCOVA
Comparison: Analysis at randomization to Week 10.p-value: 0.79595% CI: [-12.8, 16.7]mixed model of ANCOVA
Comparison: Analysis at randomization to Week 12.p-value: 0.75895% CI: [-12.5, 17.1]mixed model of ANCOVA
Comparison: Analysis at randomization to Week 16.p-value: 0.38195% CI: [-8.3, 21.6]mixed model of ANCOVA
Comparison: Analysis at randomization to Week 20.p-value: 0.04195% CI: [0.8, 31.4]mixed model of ANCOVA
Comparison: Analysis at randomization to Week 24.p-value: <0.00195% CI: [14.8, 46.3]mixed model of ANCOVA
Secondary
Percentage of Rebound Effects
Rebound effects was defined as worsening of psoriasis to 125% of the baseline PASI or appearance of psoriasis variants such as erythrodermic or pustular psoriasis within 12 weeks of discontinuation of therapy.
Time frame: Baseline to Week 24.
Population: ITT population: included all randomized participants.n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Rebound Effects | 26.67 percentage of participants |
| Etanercept | Percentage of Rebound Effects | 0.00 percentage of participants |
Comparison: Analysis from baseline to Week 24.p-value: 0.1196Pearson chi-square or Fisher exact test
Secondary
Percent (%) Change of PASI Score From Randomization to Week 24
Percent improvement in PASI score was calculated from Week 6 to Week 24.
Time frame: Randomization to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Percent (%) Change of PASI Score From Randomization to Week 24 | 121.9 percent change |
| Etanercept | Percent (%) Change of PASI Score From Randomization to Week 24 | -13.3 percent change |
Comparison: Analysis from randomization to Week 24.p-value: 0.00195% CI: [52.3, 218.1]mixed model of ANCOVA
Secondary
Probability of Being Relapse Free During the 24 Weeks After Randomization
Relapse was defined as loss of 50% improvement in PASI. The time to relapse was estimated using a Kaplan-Meier analysis.
Time frame: Randomization to Week 24.
Population: ITT population: included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 8 | 0.84 probability of relapse free |
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 4 | 0.93 probability of relapse free |
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 20 | 0.22 probability of relapse free |
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 12 | 0.44 probability of relapse free |
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 24 | 0.17 probability of relapse free |
| Placebo | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 16 | 0.34 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 24 | 0.58 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 4 | 0.91 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 8 | 0.84 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 12 | 0.69 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 16 | 0.60 probability of relapse free |
| Etanercept | Probability of Being Relapse Free During the 24 Weeks After Randomization | Week 20 | 0.58 probability of relapse free |
p-value: 0.0003Log Rank
Secondary
Relapse (Loss of 50% Improvement in PASI) During the 24 Weeks After Randomization
Relapse was defined as the loss of 50% improvement in PASI.
Time frame: Randomization to Week 24.
Population: ITT population: that included all randomized participants. n equals number of participants with evaluable data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Relapse (Loss of 50% Improvement in PASI) During the 24 Weeks After Randomization | 63.77 Percentage of participants |
| Etanercept | Relapse (Loss of 50% Improvement in PASI) During the 24 Weeks After Randomization | 36.23 Percentage of participants |
Comparison: Analysis from randomization to Week 24.p-value: 0.002Pearson chi-square