Plaque Psoriasis
Conditions
Keywords
plaque psoriasis, tofacitinib, biopsy, Janus Kinase, randomized placebo controlled clinical trial, psoriasis vulgaris
Brief summary
There are cells in the skin and blood of humans with chronic moderate to severe plaque psoriasis with specific activities that may determine the effectiveness of treatment. These activities may be described by obtaining samples of skin and blood and analyzing them using a variety of tests.
Detailed description
The final subject in Cohort 1 completed the study on 19-Nov-2013 (LSLV date). Because the study analyses were novel and exploratory, they required extensive analyses by study team and external experts. As a result of this analysis it was determined on 21-July-2014 that the data from Cohort 1 were sufficiently definitive and that enrollment of Cohort 2 would not be justified. Since this decision resulted in the LSLV for Cohort 1 becoming the LSLV for the study, the full data analysis and reporting is not projected to be complete within 12 Months of LSLV. The final analysis and final reporting is planned to be completed on 18-Feb-2015. Results for this data are anticipated to be released in April 2015.
Interventions
DRUG(CP-6890,550) Tofacitinib
2 x 5 mg oral capsules taken twice daily (every 12 hours) for 12 consecutive weeks
DRUGPlacebo
2 matching oral capsules taken twice daily (every 12 hours) for 12 consecutive weeks
DRUG(CP-690,550) Tofacitinib
2 x 5 mg oral capsules taken twice daily (every 12 hours) for 12 weeks
Sponsors
Pfizer
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
* Adults over 18 years of age with a diagnosis of chronic moderate to severe plaque psoriasis for at least 12 months; in generally good health; on stable dose of non-prohibited medications; able to stop current psoriasis therapy (systemic or topical) for several weeks prior to and during study participation.
Exclusion criteria
* Serious underlying disease including viral disorders such as hepatitis or HIV or skin condition that would interfere with skin biopsies or evaluation of psoriasis; conditions that could interfere with drug absorption after oral administration; history of malignancy or auto-immune disease. * Use of oral or injected corticosteroids (steroids).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a 75% Reduction in the Psoriasis Area and Severity Index (PASI75) at Week 12 | Week 12 | Combined assessment of lesion severity and area affected into single score; range equals (=) 0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section\*area score\*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections. |
| Percentage of Participants Achieving a Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 12 | Week 12 | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). ‘Clear’ and “Almost clear’ includes all participants who were scored as a 0 or 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in PASI by Visit | Weeks 1, 2, 4, and 12 | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0= 0% to 6= 90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. |
| Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Weeks 1, 2, and 4 | Combined assessment of lesion severity and area affected into single score; range=0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section\*area score\*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections. |
| Change From Baseline in PGA Score by Visit | Weeks 1, 2, 4, and 12 | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score. |
| Percentage of Participants in Each PGA Category at Various Timepoints by Baseline Category | Baseline and Weeks 1, 2, 4, and 12 | — |
| Percentage of Participants by PGA Response Category and Timepoint | Baseline and Weeks 1, 2, 4, and 12 | PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). Response category scores: 0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe. The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score. |
| Body Surface Area (BSA) | Baseline and Weeks 1, 2, 4, and 12 | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. |
| Psoriasis Area and Severity Index (PASI) Score by Visit | Baseline and Weeks 1, 2, 4, and 12 | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. |
| Percent Change From Baseline in BSA | Weeks 1, 2, 4, and 12 | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. |
| Itch Severity Item (ISI) Score by Visit | Baseline and Weeks 1, 2, 4, and 12 | The severity of itch (pruritus) due to psoriasis was assessed using the ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. the baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15. |
| Change From Baseline in ISI by Visit | Weeks 1, 2, 4 and 12 | ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. The baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/Day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15. A negative value indicates an improvement. |
| Target Plaque Severity Score (TPSS) by Visit | Baseline and Weeks 1, 2, 4, and 12 | Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12. |
| Percent Change From Baseline in TPSS by Visit | Weeks 1, 2, 4, and 12 | Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12. A negative value indicated improvment. |
| Change From Baseline in BSA | Weeks 1, 2, 4, and 12 | Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. |
| Change From Baseline in PASI by Visit | Weeks 1, 2, 4 and 12 | Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tofacitinib 10 mg BID Participants received tofacitinib tablets, 10 mg, orally, BID for 12 weeks. | 9 |
| Placebo Participants received matching placebo tablets, orally, BID for 12 weeks. | 3 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Tofacitinib 10 mg BID | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.2 Years STANDARD_DEVIATION 11.3 | 46.7 Years STANDARD_DEVIATION 21.5 | 45.6 Years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 1 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 9 | 1 / 3 |
| serious Total, serious adverse events | 0 / 9 | 1 / 3 |
Outcome results
Primary
Percentage of Participants Achieving a 75% Reduction in the Psoriasis Area and Severity Index (PASI75) at Week 12
Combined assessment of lesion severity and area affected into single score; range equals (=) 0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section\*area score\*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections.
Time frame: Week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a 75% Reduction in the Psoriasis Area and Severity Index (PASI75) at Week 12 | 62.50 percentage of participants |
| Placebo | Percentage of Participants Achieving a 75% Reduction in the Psoriasis Area and Severity Index (PASI75) at Week 12 | 33.33 percentage of participants |
Primary
Percentage of Participants Achieving a Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 12
PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). ‘Clear’ and “Almost clear’ includes all participants who were scored as a 0 or 1.
Time frame: Week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 12 | 50.00 percentage of participants |
| Placebo | Percentage of Participants Achieving a Physician's Global Assessment (PGA) Response of Clear or Almost Clear at Week 12 | 33.33 percentage of participants |
Secondary
Body Surface Area (BSA)
Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs.
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Body Surface Area (BSA) | Week 1 (n=9,3) | 31.20 % BSA | Standard Error 7.35 |
| Tofacitinib 10 mg BID | Body Surface Area (BSA) | Week 4 (n=9,3) | 19.03 % BSA | Standard Error 4.7 |
| Tofacitinib 10 mg BID | Body Surface Area (BSA) | Week 2 (n=9,3) | 24.20 % BSA | Standard Error 5.38 |
| Tofacitinib 10 mg BID | Body Surface Area (BSA) | Week 12 (n=8,3) | 7.35 % BSA | Standard Error 3.1 |
| Tofacitinib 10 mg BID | Body Surface Area (BSA) | Baseline (n=9,3) | 34.16 % BSA | Standard Error 8.12 |
| Placebo | Body Surface Area (BSA) | Week 12 (n=8,3) | 23.03 % BSA | Standard Error 10.5 |
| Placebo | Body Surface Area (BSA) | Baseline (n=9,3) | 30.50 % BSA | Standard Error 10.87 |
| Placebo | Body Surface Area (BSA) | Week 1 (n=9,3) | 24.83 % BSA | Standard Error 10.43 |
| Placebo | Body Surface Area (BSA) | Week 2 (n=9,3) | 24.67 % BSA | Standard Error 10.59 |
| Placebo | Body Surface Area (BSA) | Week 4 (n=9,3) | 23.33 % BSA | Standard Error 10.43 |
Secondary
Change From Baseline in BSA
Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs.
Time frame: Weeks 1, 2, 4, and 12
Population: Because Cohort 2 of the study was not conducted and Cohort 1 had a limited number of participants, the analyses were simplified and this analysis was not performed.
Secondary
Change From Baseline in ISI by Visit
ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. The baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/Day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15. A negative value indicates an improvement.
Time frame: Weeks 1, 2, 4 and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Change From Baseline in ISI by Visit | Week 1 (n=9,3) | -2.55 units on a scale | Standard Error 0.59 |
| Tofacitinib 10 mg BID | Change From Baseline in ISI by Visit | Week 2 (n=9,3) | -3.90 units on a scale | Standard Error 0.67 |
| Tofacitinib 10 mg BID | Change From Baseline in ISI by Visit | Week 4 (n=9,3) | -5.13 units on a scale | Standard Error 0.77 |
| Tofacitinib 10 mg BID | Change From Baseline in ISI by Visit | Week 12 (n=8,3) | -5.96 units on a scale | Standard Error 0.99 |
| Placebo | Change From Baseline in ISI by Visit | Week 12 (n=8,3) | 2.54 units on a scale | Standard Error 2.61 |
| Placebo | Change From Baseline in ISI by Visit | Week 1 (n=9,3) | 0.45 units on a scale | Standard Error 0.52 |
| Placebo | Change From Baseline in ISI by Visit | Week 4 (n=9,3) | -0.79 units on a scale | Standard Error 2.35 |
| Placebo | Change From Baseline in ISI by Visit | Week 2 (n=9,3) | -1.47 units on a scale | Standard Error 1.31 |
Secondary
Change From Baseline in PASI by Visit
Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease.
Time frame: Weeks 1, 2, 4 and 12
Population: Because Cohort 2 of the study was not conducted and Cohort 1 had a limited number of participants, the analyses were simplified and this analysis was not performed.
Secondary
Change From Baseline in PGA Score by Visit
PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score.
Time frame: Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Change From Baseline in PGA Score by Visit | Week 1 (n=9,3) | -0.6 units on a scale | Standard Error 0.2 |
| Tofacitinib 10 mg BID | Change From Baseline in PGA Score by Visit | Week 2 (n=9,3) | -0.8 units on a scale | Standard Error 0.2 |
| Tofacitinib 10 mg BID | Change From Baseline in PGA Score by Visit | Week 4 (n=9,3) | -1.2 units on a scale | Standard Error 0.3 |
| Tofacitinib 10 mg BID | Change From Baseline in PGA Score by Visit | Week 12 (n=8,3) | -1.5 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in PGA Score by Visit | Week 12 (n=8,3) | -1.0 units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in PGA Score by Visit | Week 1 (n=9,3) | -0.7 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in PGA Score by Visit | Week 4 (n=9,3) | -1.0 units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in PGA Score by Visit | Week 2 (n=9,3) | -1.0 units on a scale | Standard Error 0.6 |
Secondary
Itch Severity Item (ISI) Score by Visit
The severity of itch (pruritus) due to psoriasis was assessed using the ISI, a single-item, horizontal numeric rating scale. Participants were asked to rate your worst itching due to psoriasis over the past 24 hours on a numeric rating scale anchored by the terms No itching (0) and Worst possible itching (10) at the ends. the baseline is defined as the average of all available diary entries before Baseline/Day 1 and the in-clinic measurement on Baseline/day 1. Week 1 is the mean of daily values of study days 2 to 8 and Week 2 is the mean of daily values of study days 9 to 15.
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Itch Severity Item (ISI) Score by Visit | Week 1 (n=9,3) | 3.81 units on a scale | Standard Error 0.97 |
| Tofacitinib 10 mg BID | Itch Severity Item (ISI) Score by Visit | Week 4 (n=9,3) | 1.22 units on a scale | Standard Error 0.57 |
| Tofacitinib 10 mg BID | Itch Severity Item (ISI) Score by Visit | Week 2 (n=9,3) | 2.45 units on a scale | Standard Error 0.91 |
| Tofacitinib 10 mg BID | Itch Severity Item (ISI) Score by Visit | Week 12 (n=8,3) | 0.75 units on a scale | Standard Error 0.62 |
| Tofacitinib 10 mg BID | Itch Severity Item (ISI) Score by Visit | Baseline (n=9,3) | 6.35 units on a scale | Standard Error 0.89 |
| Placebo | Itch Severity Item (ISI) Score by Visit | Week 12 (n=8,3) | 6.00 units on a scale | Standard Error 1.53 |
| Placebo | Itch Severity Item (ISI) Score by Visit | Baseline (n=9,3) | 3.46 units on a scale | Standard Error 1.94 |
| Placebo | Itch Severity Item (ISI) Score by Visit | Week 1 (n=9,3) | 3.90 units on a scale | Standard Error 1.73 |
| Placebo | Itch Severity Item (ISI) Score by Visit | Week 2 (n=9,3) | 1.99 units on a scale | Standard Error 0.73 |
| Placebo | Itch Severity Item (ISI) Score by Visit | Week 4 (n=9,3) | 2.67 units on a scale | Standard Error 1.2 |
Secondary
Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4
Combined assessment of lesion severity and area affected into single score; range=0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section\*area score\*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) summed over all sections.
Time frame: Weeks 1, 2, and 4
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 1 | 0.00 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 2 | 0.00 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 4 | 22.22 percentage of participants |
| Placebo | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 1 | 0.00 percentage of participants |
| Placebo | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 2 | 33.33 percentage of participants |
| Placebo | Percentage of Participants Achieving a PASI75 Response at Weeks 1, 2, and 4 | Week 4 | 33.33 percentage of participants |
Secondary
Percentage of Participants by PGA Response Category and Timepoint
PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). Response category scores: 0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe. The severity scores of 3 components (erythema, induration, and scaling) are averaged and rounded to the nearest whole number to determine the PGA score.
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Moderate (n=9,3) | 44.4 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 1, Moderate (n=9,3) | 55.6 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Almost clear (n=9,3) | 44.4 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Baseline, Moderate (n=9,3) | 88.9 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Mild (n=9,3) | 22.2 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Almost clear (n=9,3) | 11.1 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Moderate (n=9,3) | 33.3 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 1, Mild (n=9,3) | 44.4 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Almost clear (n=8,3) | 50.0 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Mild (n=9,3) | 44.4 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Mild (n=8,3) | 37.5 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Moderate (n=8,3) | 12.5 percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants by PGA Response Category and Timepoint | Baseline, Severe (n=9,3) | 11.1 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Moderate (n=8,3) | 66.7 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Baseline, Moderate (n=9,3) | 66.7 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Baseline, Severe (n=9,3) | 33.3 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 1, Mild (n=9,3) | 33.3 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 1, Moderate (n=9,3) | 66.7 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Almost clear (n=9,3) | 33.3 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Mild (n=9,3) | 0 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 2, Moderate (n=9,3) | 66.7 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Almost clear (n=9,3) | 33.3 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Mild (n=9,3) | 0 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 4, Moderate (n=9,3) | 66.7 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Almost clear (n=8,3) | 33.3 percentage of participants |
| Placebo | Percentage of Participants by PGA Response Category and Timepoint | Week 12, Mild (n=8,3) | 0 percentage of participants |
Secondary
Percentage of Participants in Each PGA Category at Various Timepoints by Baseline Category
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: Because Cohort 2 of the study was not conducted and Cohort 1 had a limited number of participants, the analyses were simplified and this analysis was not performed.
Secondary
Percent Change From Baseline in BSA
Assessment of BSA with psoriasis was performed separately for 4 body regions: head and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including buttocks). The percent surface area with psoriasis was estimated by means of the handprint method, where the full palmar hand of the participant (ie, the participant's fully extended palm, fingers and thumb together) represents approximately 1% of the total BSA. The number of handprints of psoriatic skin in a body region can be used to determine the extent (%) to which a body regions is involved with psoriasis. In each body region, the percent body region surface area with psoriasis is multiplied by the Body Region Weighting (head and neck=10%, upper limbs=5%, trunk \[including axillae and groin\]=3.33% and lower limbs \[including buttocks\]=2.5%). BSA (%)=0.1Sh + 0.2Sh+0.3St+0.4Sl, where S=body region suface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs.
Time frame: Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Percent Change From Baseline in BSA | Week 1 (n=9,3) | -6.87 percent change from baseline | Standard Error 4.97 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in BSA | Week 2 (n=9,3) | -22.51 percent change from baseline | Standard Error 7.14 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in BSA | Week 4 (n=9,3) | -35.13 percent change from baseline | Standard Error 10.45 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in BSA | Week 12 (n=8,3) | -77.40 percent change from baseline | Standard Error 11.98 |
| Placebo | Percent Change From Baseline in BSA | Week 12 (n=8,3) | -37.26 percent change from baseline | Standard Error 21.53 |
| Placebo | Percent Change From Baseline in BSA | Week 1 (n=9,3) | -27.80 percent change from baseline | Standard Error 17.46 |
| Placebo | Percent Change From Baseline in BSA | Week 4 (n=9,3) | -34.93 percent change from baseline | Standard Error 21.8 |
| Placebo | Percent Change From Baseline in BSA | Week 2 (n=9,3) | -29.47 percent change from baseline | Standard Error 19.01 |
Secondary
Percent Change From Baseline in PASI by Visit
Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0= 0% to 6= 90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease.
Time frame: Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Percent Change From Baseline in PASI by Visit | Week 1 (n=9,3) | -18.38 percent change from baseline | Standard Error 7.52 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in PASI by Visit | Week 2 (n=9,3) | -36.95 percent change from baseline | Standard Error 8.28 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in PASI by Visit | Week 4 (n=9,3) | -47.39 percent change from baseline | Standard Error 11.95 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in PASI by Visit | Week 12 (n=8,3) | -71.78 percent change from baseline | Standard Error 9.63 |
| Placebo | Percent Change From Baseline in PASI by Visit | Week 12 (n=8,3) | -49.13 percent change from baseline | Standard Error 19.67 |
| Placebo | Percent Change From Baseline in PASI by Visit | Week 1 (n=9,3) | -39.61 percent change from baseline | Standard Error 19.97 |
| Placebo | Percent Change From Baseline in PASI by Visit | Week 4 (n=9,3) | -49.66 percent change from baseline | Standard Error 19.41 |
| Placebo | Percent Change From Baseline in PASI by Visit | Week 2 (n=9,3) | -48.66 percent change from baseline | Standard Error 20.28 |
Secondary
Percent Change From Baseline in TPSS by Visit
Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12. A negative value indicated improvment.
Time frame: Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Percent Change From Baseline in TPSS by Visit | Week 1 (n=9,3) | -16.69 percent change from baseline | Standard Error 7.72 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in TPSS by Visit | Week 2 (n=9,3) | -29.78 percent change from baseline | Standard Error 8.39 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in TPSS by Visit | Week 4 (n=9,3) | -47.55 percent change from baseline | Standard Error 12.4 |
| Tofacitinib 10 mg BID | Percent Change From Baseline in TPSS by Visit | Week 12 (n=8,3) | -67.28 percent change from baseline | Standard Error 15.17 |
| Placebo | Percent Change From Baseline in TPSS by Visit | Week 12 (n=8,3) | -29.17 percent change from baseline | Standard Error 18.16 |
| Placebo | Percent Change From Baseline in TPSS by Visit | Week 1 (n=9,3) | -16.67 percent change from baseline | Standard Error 11.02 |
| Placebo | Percent Change From Baseline in TPSS by Visit | Week 4 (n=9,3) | -20.83 percent change from baseline | Standard Error 20.83 |
| Placebo | Percent Change From Baseline in TPSS by Visit | Week 2 (n=9,3) | -20.83 percent change from baseline | Standard Error 11.02 |
Secondary
Psoriasis Area and Severity Index (PASI) Score by Visit
Combined assessment of lesion severity and area affected into single score. Body was divided into 4 sections: head, arms, trunk, legs. For each section, percent area of skin involved was estimated: 0=0% to 6=90â€100%. Severity was estimated by clinical signs: erythema, induration, desquamation; scale: 0= none to 4= maximum. Final PASI = sum of severity parameters for each section\*area score\*weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4) summed over all sections; total possible score range: 0= no disease to 72= maximal disease.
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: FAS; n (number) =number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 1 (n=9,3) | 17.81 units on a scale | Standard Error 3.1 |
| Tofacitinib 10 mg BID | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 4 (n=9,3) | 11.72 units on a scale | Standard Error 3.51 |
| Tofacitinib 10 mg BID | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 2 (n=9,3) | 13.84 units on a scale | Standard Error 2.71 |
| Tofacitinib 10 mg BID | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 12 (n=8,3) | 5.80 units on a scale | Standard Error 1.8 |
| Tofacitinib 10 mg BID | Psoriasis Area and Severity Index (PASI) Score by Visit | Baseline (n=9,3) | 21.91 units on a scale | Standard Error 2.86 |
| Placebo | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 12 (n=8,3) | 13.40 units on a scale | Standard Error 6.12 |
| Placebo | Psoriasis Area and Severity Index (PASI) Score by Visit | Baseline (n=9,3) | 23.33 units on a scale | Standard Error 5.67 |
| Placebo | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 1 (n=9,3) | 15.53 units on a scale | Standard Error 6.6 |
| Placebo | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 2 (n=9,3) | 13.13 units on a scale | Standard Error 6.27 |
| Placebo | Psoriasis Area and Severity Index (PASI) Score by Visit | Week 4 (n=9,3) | 13.37 units on a scale | Standard Error 6.05 |
Secondary
Target Plaque Severity Score (TPSS) by Visit
Target lesions were selected at baseline and followed for the duration of the study. Each target lesion was scored by the investigator on severity of erythema, induration, and scaling according to a 5-point (0 to 4) severity scale with a maximum sum score for a plaque of 12. The TPSS was calculated as the sum of the scores for erythema, induration, and scaling; the score can vary in increments of 1 unit from 0 to 12.
Time frame: Baseline and Weeks 1, 2, 4, and 12
Population: FAS; n=number of participants with nonmissing observations at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tofacitinib 10 mg BID | Target Plaque Severity Score (TPSS) by Visit | Week 12 (n=8,3) | 2.8 score on a scale | Standard Error 1.3 |
| Tofacitinib 10 mg BID | Target Plaque Severity Score (TPSS) by Visit | Baseline (n=9,3) | 8.7 score on a scale | Standard Error 0.6 |
| Tofacitinib 10 mg BID | Target Plaque Severity Score (TPSS) by Visit | Week 1 (n=9,3) | 7.1 score on a scale | Standard Error 0.7 |
| Tofacitinib 10 mg BID | Target Plaque Severity Score (TPSS) by Visit | Week 2 (n=9,3) | 6.0 score on a scale | Standard Error 0.7 |
| Tofacitinib 10 mg BID | Target Plaque Severity Score (TPSS) by Visit | Week 4 (n=9,3) | 4.6 score on a scale | Standard Error 1.1 |
| Placebo | Target Plaque Severity Score (TPSS) by Visit | Week 4 (n=9,3) | 6.7 score on a scale | Standard Error 1.9 |
| Placebo | Target Plaque Severity Score (TPSS) by Visit | Week 2 (n=9,3) | 6.7 score on a scale | Standard Error 1.2 |
| Placebo | Target Plaque Severity Score (TPSS) by Visit | Baseline (n=9,3) | 8.3 score on a scale | Standard Error 0.3 |
| Placebo | Target Plaque Severity Score (TPSS) by Visit | Week 12 (n=8,3) | 6.0 score on a scale | Standard Error 1.7 |
| Placebo | Target Plaque Severity Score (TPSS) by Visit | Week 1 (n=9,3) | 7.0 score on a scale | Standard Error 1.2 |