Plaque Psoriasis
Conditions
Keywords
Randomized, Double-blind, Chronic plaque psoriasis, Pediatric
Brief summary
This study will compare how well adalimumab works versus methotrexate (MTX) in children with moderate to severe psoriasis in the short term. It will also study how safe and how well adalimumab works in the long term and how long disease response can be maintained after stopping therapy.
Detailed description
The study had a 30-day screening period and a multi-period study design, as described below: Period A - Primary Treatment Phase: Participants were randomized to receive adalimumab 0.8 mg/kg, adalimumab 0.4 mg/kg, or MTX in 1:1:1 ratio for 16 weeks. Period B - Treatment Withdrawal Phase: Responders were withdrawn from active treatment and monitored for loss of disease control for up to 36 weeks. Period C - Re-Treatment Phase: Participants who had experienced loss of disease control in Period B were re-treated with adalimumab for 16 weeks. Period D - Long-Term Follow-Up Phase: Participants received adalimumab or were observed off-treatment (if disease remained under control) for 52 weeks.
Interventions
BIOLOGICALAdalimumab
Adalimumab by subcutaneous injection every other week (eow)
DRUGMethotrexate
Methotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally.
BIOLOGICALPlacebo to Adalimumab
A single subcutaneous loading dose at Week 0 followed by eow dosing beginning at Week 1.
Orally once a week
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is ≥ 4 years and \< 18 years of age; 2. Subject weighs ≥ 13 kg; 3. Subject must have failed to respond to topical therapy; 4. Subject must need systemic treatment to control his/her disease and meet one of the following: * Physician's Global Assessment (PGA) ≥ 4 * Body surface area (BSA) involved \> 20% * Very thick lesions with BSA \> 10% * Psoriasis Area and Severity Index (PASI) \> 20 * PASI \> 10 and at least one of the following: * Active psoriatic arthritis unresponsive to non-steroid anti-inflammatory drugs (NSAIDs) * Clinically relevant facial involvement * Clinically relevant genital involvement * Clinically relevant hand and/or foot involvement * Children's Dermatology Life Quality Index (CDLQI) \> 10 5. If subject is \< 12 years of age and resides in a geographic region where heliotherapy is practical, subject must have failed to respond, be intolerant, or have a contraindication to heliotherapy, or is not a suitable candidate for heliotherapy; 6. If ≥ 12 years of age, subject must have failed to respond, be intolerant, or have a contraindication to phototherapy, or is not a suitable candidate for phototherapy; 7. Subject must have a clinical diagnosis of psoriasis for at least 6 months as determined by the subject's medical history and confirmation of diagnosis through physical examination by the Investigator; 8. Subject must have stable plaque psoriasis for at least 2 months prior to Baseline
Exclusion criteria
1. Prior biologic use other than prior treatment with etanercept; 2. Treatment with etanercept therapy within 4 weeks prior to the Baseline visit; 3. Methotrexate (MTX) use within the past year or prior MTX use at any time where the subject did not respond, or did not tolerate MTX; 4\. Contraindication for treatment with MTX during the study; 5. Erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication exacerbated psoriasis or new onset guttate psoriasis; 6. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit; 7. Treatment of psoriasis with topical therapies such as corticosteroids, vitamin D analogs, or retinoids within 7 days prior to the Baseline visit; 8. Treatment of psoriasis with ultraviolet (UV)B phototherapy, excessive sun exposure, or the use of tanning beds within 7 days prior to the Baseline visit; 9. Treatment of psoriasis with ultraviolet A with psoralen (PUVA) phototherapy, non-biologic systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis within 14 days prior to the Baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | Baseline and Week 16 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in PASI score at Week 16. |
| Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared (0) or Minimal (1) at Week 16 | Week 16 | The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: * 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; * 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; * 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; * 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; * 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; * 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16 | Baseline and Week 16 | The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. |
| Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16 | Baseline and Week 16 | The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). |
| Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Upon Re-Treatment in Period C | Period C, Week 16 | The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \< 5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. |
| Time to Loss of Disease Control for Participants Who Entered Period B | Period B (36 weeks) and Period D (52 weeks) | Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation). Participants who did not lose disease control in period B continued off drug into period D and were observed off-drug until they finally lost disease control or until the end of the 52 weeks of period D. |
| Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. |
| Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) is reported. |
| Percentage of Participants Who Achieved a PASI 50 Response Over Time | Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 50 response is at least a 50% reduction (improvement) from Baseline in PASI score. |
| Percentage of Participants Who Achieved a PASI 75 Response Over Time | Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is at least a 75% reduction (improvement) from Baseline in PASI score. |
| Percentage of Participants Who Achieved a PASI 90 Response at Week 16 | Baseline and Week 16 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score at Week 16. |
| Percentage of Participants Who Achieved a PASI 100 Response Over Time | Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score. |
| Percent Change From Baseline in PASI Score Over Time | Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). |
| Change From Baseline in CDLQI Over Time | Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52 | The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. |
| Percentage of Participants With CDLQI = 0 Over Time | Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52 | The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life. |
| Time to PASI 50/75/90/100 Response in Period A | Period A, 16 weeks | Participants who did not have a response during Period A were censored. |
| Change From Baseline in PedsQL Over Time | Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52 | The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). |
| Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Baseline, Period A, Weeks 4, 8, and 16 | The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms. |
| Percentage of Participants Who Achieved a PASI 90 Response Over Time | Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score. |
| Percentage of Participants Who Achieved a PASI 100 Response at Week 16 | Baseline and Week 16 | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score at Week 16. |
Participant flow
Recruitment details
Participants were enrolled at 38 sites in Belgium, Canada, Chile, Czech Republic, Germany, Hungary, Italy, Mexico, Netherlands, Poland, Spain, Switzerland, and Turkey.
Pre-assignment details
Participants were randomized to receive adalimumab 0.8 mg/kg, adalimumab 0.4 mg/kg, or methotrexate (MTX) in a 1:1:1 ratio and were stratified according to prior history of etanercept treatment.
Participants by arm
| Arm | Count |
|---|---|
| Methotrexate Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Participants who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow. | 37 |
| Adalimumab 0.4 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow. | 39 |
| Adalimumab 0.8 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow. | 38 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Clearing of Psoriatic Lesions | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 9 | 4 |
| Overall Study | Loss of Disease Control | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Adalimumab 0.4 mg/kg | Total | Methotrexate | Adalimumab 0.8 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 12.6 years STANDARD_DEVIATION 4.43 | 13.0 years STANDARD_DEVIATION 3.76 | 13.4 years STANDARD_DEVIATION 3.49 | 13.0 years STANDARD_DEVIATION 3.29 |
| Physician's Global Assessment of Psoriasis Cleared | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician's Global Assessment of Psoriasis Marked | 15 Participants | 49 Participants | 17 Participants | 17 Participants |
| Physician's Global Assessment of Psoriasis Mild | 3 Participants | 7 Participants | 1 Participants | 3 Participants |
| Physician's Global Assessment of Psoriasis Minimal | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Physician's Global Assessment of Psoriasis Moderate | 18 Participants | 54 Participants | 19 Participants | 17 Participants |
| Physician's Global Assessment of Psoriasis Severe | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Psoriasis Area and Severity Index (PASI) | 16.9 units on a scale STANDARD_DEVIATION 5.76 | 18.3 units on a scale STANDARD_DEVIATION 8.78 | 19.2 units on a scale STANDARD_DEVIATION 10.02 | 18.9 units on a scale STANDARD_DEVIATION 10.03 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mutli Race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 103 Participants | 34 Participants | 35 Participants |
| Sex: Female, Male Female | 18 Participants | 65 Participants | 26 Participants | 21 Participants |
| Sex: Female, Male Male | 21 Participants | 49 Participants | 11 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 37 | 27 / 39 | 23 / 38 | 6 / 13 | 6 / 18 | 6 / 23 | 5 / 11 | 16 / 27 | 8 / 13 | 64 / 87 |
| serious Total, serious adverse events | 0 / 37 | 3 / 39 | 0 / 38 | 0 / 13 | 0 / 18 | 1 / 23 | 0 / 11 | 0 / 27 | 0 / 13 | 5 / 87 |
Outcome results
Primary
Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared (0) or Minimal (1) at Week 16
The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: * 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; * 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; * 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; * 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; * 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; * 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.
Time frame: Week 16
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate | Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared (0) or Minimal (1) at Week 16 | 40.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared (0) or Minimal (1) at Week 16 | 41.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared (0) or Minimal (1) at Week 16 | 60.5 percentage of participants |
Comparison: The a priori defined order of the statistical hypotheses was as follows:~1. Superiority of adalimumab 0.8 mg/kg versus MTX for the percentage of participants achieving a ≥ PASI 75 response at Week 16.~2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the percentage of participants achieving a PGA cleared or minimal at Week 16.~This order was adhered to for confirmatory testing, all statistical tests were at a level of significance of 5% and the overall type I error was preserved.p-value: 0.08395% CI: [-42.2, 2.2]Chi-squared
Primary
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in PASI score at Week 16.
Time frame: Baseline and Week 16
Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | 32.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | 43.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 | 57.9 percentage of participants |
Comparison: The a priori defined order of the statistical hypotheses was as follows:~1. Superiority of adalimumab 0.8 mg/kg versus MTX for the percentage of participants achieving a ≥ PASI 75 response at Week 16.~2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the percentage of participants achieving a PGA cleared or minimal at Week 16.~This order was adhered to for confirmatory testing, all statistical tests were at a level of significance of 5% and the overall type I error was preserved.p-value: 0.02795% CI: [-47.2, -3.7]Chi-squared
Secondary
Change From Baseline in CDLQI Over Time
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Time frame: Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methotrexate | Change From Baseline in CDLQI Over Time | Period A, Week 4 | -2.9 units on a scale | Standard Deviation 5.24 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period A, Week 8 | -4.0 units on a scale | Standard Deviation 6.44 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period C, Week 0 | -6.1 units on a scale | Standard Deviation 4.55 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period C, Week 4 | -9.8 units on a scale | Standard Deviation 3.92 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period D, Week 0 | -5.6 units on a scale | Standard Deviation 7.55 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period D, Week 11 | -8.5 units on a scale | Standard Deviation 5.37 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period D, Week 28 | -8.3 units on a scale | Standard Deviation 5.93 |
| Methotrexate | Change From Baseline in CDLQI Over Time | Period D, Week 52 | -8.4 units on a scale | Standard Deviation 6.08 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period C, Week 0 | -4.7 units on a scale | Standard Deviation 9.08 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 28 | -6.8 units on a scale | Standard Deviation 7.91 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period C, Week 4 | -5.5 units on a scale | Standard Deviation 7.24 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 0 | -5.5 units on a scale | Standard Deviation 5.95 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 11 | -6.8 units on a scale | Standard Deviation 7.07 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period A, Week 4 | -3.9 units on a scale | Standard Deviation 5.22 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period A, Week 8 | -4.1 units on a scale | Standard Deviation 6.29 |
| Adalimumab 0.4 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 52 | -6.6 units on a scale | Standard Deviation 8.12 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period C, Week 0 | -6.1 units on a scale | Standard Deviation 6.92 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period A, Week 8 | -5.5 units on a scale | Standard Deviation 5.66 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period A, Week 4 | -4.9 units on a scale | Standard Deviation 5.8 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period C, Week 4 | -7.0 units on a scale | Standard Deviation 6.63 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 28 | -8.4 units on a scale | Standard Deviation 6.72 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 11 | -7.4 units on a scale | Standard Deviation 6.21 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 0 | -6.8 units on a scale | Standard Deviation 6.7 |
| Adalimumab 0.8 mg/kg | Change From Baseline in CDLQI Over Time | Period D, Week 52 | -8.2 units on a scale | Standard Deviation 6.75 |
Secondary
Change From Baseline in PedsQL Over Time
The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).
Time frame: Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methotrexate | Change From Baseline in PedsQL Over Time | Period D, Week 0 | 2.3 units on a scale | Standard Deviation 10.93 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period C, Week 0 | 3.0 units on a scale | Standard Deviation 10.45 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period D, Week 52 | 8.6 units on a scale | Standard Deviation 13.93 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period C, Week 4 | 5.2 units on a scale | Standard Deviation 11.08 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period A, Week 4 | -0.8 units on a scale | Standard Deviation 11.75 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period D, Week 28 | 8.0 units on a scale | Standard Deviation 13.4 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period A, Week 8 | 0.5 units on a scale | Standard Deviation 10.18 |
| Methotrexate | Change From Baseline in PedsQL Over Time | Period D, Week 11 | 5.4 units on a scale | Standard Deviation 10.36 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 52 | 14.0 units on a scale | Standard Deviation 20.4 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period A, Week 8 | 7.0 units on a scale | Standard Deviation 13.16 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period A, Week 4 | 4.9 units on a scale | Standard Deviation 13.8 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period C, Week 0 | 8.9 units on a scale | Standard Deviation 25.35 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period C, Week 4 | 11.6 units on a scale | Standard Deviation 25.19 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 0 | 9.4 units on a scale | Standard Deviation 16.9 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 11 | 12.8 units on a scale | Standard Deviation 19.03 |
| Adalimumab 0.4 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 28 | 14.5 units on a scale | Standard Deviation 20.19 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 0 | 10.5 units on a scale | Standard Deviation 15.86 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period A, Week 4 | 8.1 units on a scale | Standard Deviation 11.95 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 52 | 13.8 units on a scale | Standard Deviation 15.36 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 11 | 12.0 units on a scale | Standard Deviation 16.13 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period C, Week 0 | 14.2 units on a scale | Standard Deviation 20.25 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period C, Week 4 | 16.3 units on a scale | Standard Deviation 17.35 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period A, Week 8 | 8.8 units on a scale | Standard Deviation 15.45 |
| Adalimumab 0.8 mg/kg | Change From Baseline in PedsQL Over Time | Period D, Week 28 | 13.1 units on a scale | Standard Deviation 16.23 |
Secondary
Change From Baseline in the Children's Depression Inventory: Short (CDI:S)
The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms.
Time frame: Baseline, Period A, Weeks 4, 8, and 16
Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methotrexate | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 16 | -2.0 units on a scale | Standard Deviation 5.88 |
| Methotrexate | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 8 | 0.2 units on a scale | Standard Deviation 5.26 |
| Methotrexate | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 4 | 0.6 units on a scale | Standard Deviation 8.85 |
| Adalimumab 0.4 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 16 | -3.3 units on a scale | Standard Deviation 8.12 |
| Adalimumab 0.4 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 4 | -1.0 units on a scale | Standard Deviation 6.64 |
| Adalimumab 0.4 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 8 | -1.5 units on a scale | Standard Deviation 7.52 |
| Adalimumab 0.8 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 8 | -1.6 units on a scale | Standard Deviation 5.52 |
| Adalimumab 0.8 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 4 | -3.6 units on a scale | Standard Deviation 5.86 |
| Adalimumab 0.8 mg/kg | Change From Baseline in the Children's Depression Inventory: Short (CDI:S) | Period A, Week 16 | -2.3 units on a scale | Standard Deviation 6.29 |
Secondary
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Time frame: Baseline and Week 16
Population: Last observation carried forward (LOCF) imputation was used, the analysis was conducted in the intent-to-treat (ITT) population; only participants with Baseline and at least one post-baseline value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methotrexate | Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16 | -5.0 units on a scale | Standard Deviation 7.11 |
| Adalimumab 0.4 mg/kg | Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16 | -4.9 units on a scale | Standard Deviation 6.16 |
| Adalimumab 0.8 mg/kg | Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16 | -6.6 units on a scale | Standard Deviation 6.22 |
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (p-value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.30495% CI: [-1.48, 4.7]ANOVA
Secondary
Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16
The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).
Time frame: Baseline and Week 16
Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population; only participants with Baseline and at least one post-baseline value are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methotrexate | Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16 | 1.9 units on a scale | Standard Deviation 10.41 |
| Adalimumab 0.4 mg/kg | Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16 | 9.5 units on a scale | Standard Deviation 12.25 |
| Adalimumab 0.8 mg/kg | Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16 | 10.8 units on a scale | Standard Deviation 15.38 |
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (p-value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.00595% CI: [-14.94, -2.82]ANOVA
Secondary
Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time
The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.
Time frame: Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 11 | 18.9 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 52 | 75.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 16 | 77.8 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 16 | 62.5 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 8 | 8.1 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 0 | 30.6 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 40 | 69.4 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 28 | 69.4 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 4 | 8.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 16 | 38.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 28 | 50.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 40 | 50.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 11 | 30.8 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 52 | 50.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 16 | 27.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 4 | 20.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 0 | 19.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 8 | 35.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 52 | 55.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 4 | 28.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 8 | 44.7 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period A, Week 11 | 47.4 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period C, Week 16 | 52.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 0 | 38.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 16 | 50.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 28 | 63.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Over Time | Period D, Week 40 | 61.1 percentage of participants |
Secondary
Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Upon Re-Treatment in Period C
The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \< 5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.
Time frame: Period C, Week 16
Population: Non-responder imputation was used, the analysis was conducted in the ITT population who entered Period C.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Upon Re-Treatment in Period C | 62.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Upon Re-Treatment in Period C | 27.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) or Minimal (1) Upon Re-Treatment in Period C | 52.6 percentage of participants |
Comparison: The difference between the combined adalimumab 0.8 mg/kg + MTX groups versus the adalimumab 0.4 mg/kg group.~Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.11395% CI: [-60.6, 4]Chi-squared
Secondary
Percentage of Participants Achieving a PGA of Cleared (0) Over Time
The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) is reported.
Time frame: Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 8 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 0 | 8.3 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 28 | 33.3 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 4 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 11 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 16 | 8.1 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 16 | 25.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 16 | 25.0 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 40 | 33.3 percentage of participants |
| Methotrexate | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 52 | 41.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 28 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 11 | 10.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 52 | 25.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 16 | 12.8 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 40 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 16 | 9.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 0 | 5.6 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 16 | 11.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 4 | 2.6 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 8 | 12.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 8 | 5.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 11 | 10.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 52 | 25.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 0 | 11.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 16 | 18.4 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period A, Week 4 | 2.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 28 | 22.2 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 40 | 27.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period D, Week 16 | 25.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Achieving a PGA of Cleared (0) Over Time | Period C, Week 16 | 15.8 percentage of participants |
Secondary
Percentage of Participants Who Achieved a PASI 100 Response at Week 16
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score at Week 16.
Time frame: Baseline and Week 16
Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response at Week 16 | 2.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response at Week 16 | 10.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response at Week 16 | 18.4 percentage of participants |
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (p-value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.05695% CI: [-29.1, -2.3]Fisher Exact
Secondary
Percentage of Participants Who Achieved a PASI 100 Response Over Time
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score.
Time frame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 52 | 41.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 16 | 13.9 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 8 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 0 | 8.3 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 16 | 25.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 40 | 30.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 11 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 4 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 28 | 27.8 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 4 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 8 | 5.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 11 | 5.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 16 | 9.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 0 | 5.6 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 16 | 11.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 28 | 13.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 40 | 13.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 52 | 25.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 16 | 25.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 11 | 10.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 4 | 2.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 28 | 19.4 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period A, Week 8 | 5.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 16 | 15.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 52 | 22.2 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 0 | 11.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 100 Response Over Time | Period D, Week 40 | 22.2 percentage of participants |
Secondary
Percentage of Participants Who Achieved a PASI 50 Response Over Time
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 50 response is at least a 50% reduction (improvement) from Baseline in PASI score.
Time frame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 16 | 91.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 16 | 54.1 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 40 | 91.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 0 | 52.8 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 0 | 62.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 16 | 87.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 8 | 40.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 4 | 16.2 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 28 | 88.9 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 11 | 51.4 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 52 | 91.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 0 | 90.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 52 | 66.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 4 | 41.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 8 | 56.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 11 | 61.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 16 | 66.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 16 | 90.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 0 | 63.9 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 16 | 69.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 28 | 72.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 40 | 63.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 4 | 52.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 0 | 75.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 11 | 71.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 52 | 77.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 16 | 88.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 8 | 65.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 0 | 52.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 40 | 83.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period C, Week 16 | 89.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period D, Week 28 | 86.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 50 Response Over Time | Period A, Week 16 | 78.9 percentage of participants |
Secondary
Percentage of Participants Who Achieved a PASI 75 Response Over Time
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is at least a 75% reduction (improvement) from Baseline in PASI score.
Time frame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 16 | 86.1 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 0 | 37.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 40 | 77.8 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 0 | 30.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 16 | 75.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 8 | 13.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 4 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 28 | 80.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 11 | 21.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 52 | 86.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 16 | 54.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 4 | 15.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 8 | 38.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 11 | 43.6 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 0 | 18.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 52 | 47.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 0 | 27.8 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 16 | 50.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 28 | 58.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 40 | 52.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 11 | 60.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 52 | 72.2 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 16 | 61.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 8 | 47.4 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 40 | 75.0 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 28 | 77.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 16 | 78.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period C, Week 0 | 21.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period A, Week 4 | 23.7 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 75 Response Over Time | Period D, Week 0 | 50.0 percentage of participants |
Secondary
Percentage of Participants Who Achieved a PASI 90 Response at Week 16
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score at Week 16.
Time frame: Baseline and Week 16
Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response at Week 16 | 21.6 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response at Week 16 | 30.8 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response at Week 16 | 28.9 percentage of participants |
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (p-value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.46695% CI: [-26.9, 12.3]Chi-squared
Secondary
Percentage of Participants Who Achieved a PASI 90 Response Over Time
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score.
Time frame: Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: Non-responder imputation was used, the analysis was conducted in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 28 | 55.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 8 | 2.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 16 | 62.5 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 11 | 2.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 52 | 66.7 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 0 | 25.0 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 40 | 55.6 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 16 | 63.9 percentage of participants |
| Methotrexate | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 4 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 16 | 36.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 28 | 33.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 40 | 36.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 11 | 28.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 52 | 33.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 16 | 27.3 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 8 | 20.5 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 0 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 4 | 5.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 52 | 44.4 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 4 | 5.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 8 | 23.7 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period A, Week 11 | 28.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 0 | 10.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period C, Week 16 | 57.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 16 | 38.9 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 28 | 41.7 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 40 | 47.2 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants Who Achieved a PASI 90 Response Over Time | Period D, Week 0 | 36.1 percentage of participants |
Secondary
Percentage of Participants With CDLQI = 0 Over Time
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life.
Time frame: Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Population: Non-responder imputation was used, the analysis was conducted in the intent to-treat (ITT) population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 11 | 25.0 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 28 | 30.6 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 16 | 10.8 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 52 | 41.7 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 4 | 5.4 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 0 | 0.0 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 8 | 10.8 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 4 | 12.5 percentage of participants |
| Methotrexate | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 0 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 0 | 22.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 11 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 4 | 5.1 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 4 | 36.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 28 | 22.2 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 0 | 36.4 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 8 | 12.8 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 52 | 16.7 percentage of participants |
| Adalimumab 0.4 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 16 | 20.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 52 | 33.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 4 | 10.5 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 8 | 5.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period A, Week 16 | 23.7 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 0 | 21.1 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period C, Week 4 | 31.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 11 | 33.3 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 28 | 30.6 percentage of participants |
| Adalimumab 0.8 mg/kg | Percentage of Participants With CDLQI = 0 Over Time | Period D, Week 0 | 27.8 percentage of participants |
Secondary
Percent Change From Baseline in PASI Score Over Time
PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).
Time frame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period A, Week 8 | -30.6 percent change | Standard Deviation 45.89 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period D, Week 16 | -82.3 percent change | Standard Deviation 31.38 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period C, Week 0 | -59.0 percent change | Standard Deviation 20.61 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period A, Week 4 | -14.0 percent change | Standard Deviation 36.71 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period D, Week 0 | -41.8 percent change | Standard Deviation 54.99 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period C, Week 16 | -87.1 percent change | Standard Deviation 16.47 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period D, Week 40 | -83.0 percent change | Standard Deviation 31.94 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period A, Week 11 | -36.6 percent change | Standard Deviation 51.69 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period D, Week 52 | -86.3 percent change | Standard Deviation 28.92 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period D, Week 28 | -81.0 percent change | Standard Deviation 35.86 |
| Methotrexate | Percent Change From Baseline in PASI Score Over Time | Period A, Week 16 | -42.8 percent change | Standard Deviation 54.24 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 28 | -65.8 percent change | Standard Deviation 36.99 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 4 | -36.9 percent change | Standard Deviation 38.62 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 8 | -48.8 percent change | Standard Deviation 44.74 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 11 | -51.4 percent change | Standard Deviation 50.19 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 16 | -52.4 percent change | Standard Deviation 51.79 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period C, Week 0 | -65.3 percent change | Standard Deviation 12.16 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period C, Week 16 | -74.5 percent change | Standard Deviation 17.79 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 0 | -46.8 percent change | Standard Deviation 49.27 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 16 | -66.9 percent change | Standard Deviation 33.51 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 40 | -64.6 percent change | Standard Deviation 37.46 |
| Adalimumab 0.4 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 52 | -58.7 percent change | Standard Deviation 53.21 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 16 | -65.6 percent change | Standard Deviation 39.44 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 4 | -48.3 percent change | Standard Deviation 33.96 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 16 | -74.5 percent change | Standard Deviation 37.44 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 11 | -62.8 percent change | Standard Deviation 38.02 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 28 | -81.5 percent change | Standard Deviation 22.06 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period A, Week 8 | -60.3 percent change | Standard Deviation 35.98 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 52 | -80.1 percent change | Standard Deviation 24.17 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period C, Week 16 | -69.3 percent change | Standard Deviation 69.79 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period C, Week 0 | -45.8 percent change | Standard Deviation 39.64 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 40 | -82.1 percent change | Standard Deviation 23.99 |
| Adalimumab 0.8 mg/kg | Percent Change From Baseline in PASI Score Over Time | Period D, Week 0 | -61.5 percent change | Standard Deviation 42.96 |
Secondary
Time to Loss of Disease Control for Participants Who Entered Period B
Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation). Participants who did not lose disease control in period B continued off drug into period D and were observed off-drug until they finally lost disease control or until the end of the 52 weeks of period D.
Time frame: Period B (36 weeks) and Period D (52 weeks)
Population: This analysis was conducted in the ITT population who entered period B, no imputation was used.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Methotrexate | Time to Loss of Disease Control for Participants Who Entered Period B | 184 days |
| Adalimumab 0.4 mg/kg | Time to Loss of Disease Control for Participants Who Entered Period B | 217 days |
| Adalimumab 0.8 mg/kg | Time to Loss of Disease Control for Participants Who Entered Period B | 118 days |
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.34395% CI: [0.66, 3.17]Log Rank
Comparison: Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.p-value: 0.27695% CI: [0.71, 3.21]Log Rank
Secondary
Time to PASI 50/75/90/100 Response in Period A
Participants who did not have a response during Period A were censored.
Time frame: Period A, 16 weeks
Population: Analysis was conducted in the intent to-treat (ITT) population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Methotrexate | Time to PASI 50/75/90/100 Response in Period A | PASI 50 | 76 days |
| Methotrexate | Time to PASI 50/75/90/100 Response in Period A | PASI 75 | 116 days |
| Methotrexate | Time to PASI 50/75/90/100 Response in Period A | PASI 90 | NA days |
| Methotrexate | Time to PASI 50/75/90/100 Response in Period A | PASI 100 | NA days |
| Adalimumab 0.4 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 100 | NA days |
| Adalimumab 0.4 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 50 | 55 days |
| Adalimumab 0.4 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 90 | NA days |
| Adalimumab 0.4 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 75 | 107 days |
| Adalimumab 0.8 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 100 | NA days |
| Adalimumab 0.8 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 75 | 59 days |
| Adalimumab 0.8 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 90 | NA days |
| Adalimumab 0.8 mg/kg | Time to PASI 50/75/90/100 Response in Period A | PASI 50 | 30 days |