Psoriasis
Conditions
Keywords
psoriasis vulgaris, ustekinumab, abatacept
Brief summary
The purpose of this study is to determine if the use of ustekinumab, followed by abatacept, will prevent relapse in people with moderate to severe plaque psoriasis.
Detailed description
Psoriasis is a chronic immune disease of the skin and joints that affects about 2% of the population. The most common form of psoriasis is plaque psoriasis, also called psoriasis vulgaris. A variety of drugs, including biologics, are available for treatment of moderate to severe psoriasis. When biologic agents are stopped, psoriasis can return (relapse) and often requires the biologic to be restarted and continued. No treatment program has been identified to prevent relapse of psoriasis. The study design has a lead-in period of weight-based ustekinumab treatment, with all participants receiving either 45 mg ustekinumab (\<= 100 kg) or 90 mg ustekinumab (\> 100 kg) administered subcutaneously at weeks 0 and 4. At week 12, participants will be assessed for a Psoriasis Area and Severity Index (PASI) 75 response to ustekinumab. Participants who do not achieve a PASI 75 score will be discontinued from the investigation and permitted to seek standard therapy.
Interventions
BIOLOGICALUstekinumab
Ustekinumab interferes with the actions of proteins, interleukin 12 (IL12) and interleukin 23 (IL23), which reduces inflammation (swelling) in the skin. Stelara™ is the trade name for ustekinumab and is approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis. Dose: Participants who weigh \<= 100 kg at study entry will receive 45 mg of ustekinumab. Participants who weigh \> 100 kg at study entry will receive 90 mg of ustekinumab.
BIOLOGICALAbatacept
Abatacept (one form of the protein called CTLA4-Ig) interacts with the immune system, reducing the activity of T-cells and may prevent relapse. Orencia™ is the trade name for abatacept, and it is approved by the FDA to treat rheumatoid arthritis in adults. Dose: 125 mg sub-cutaneous injection
DRUGUST Placebo
The abatacept treatment group will also receive subcutaneous placebo for ustekinumab (sterile normal saline) at week 16 and week 28, corresponding to the ustekinumab dosing regimen.
DRUGABA Placebo
The ustekinumab treatment group will also receive weekly subcutaneous injections of placebo for abatacept from week 12 to week 39, corresponding to the abatacept dosing regimen.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of plaque psoriasis for at least 6 months * Baseline Psoriasis Area and Severity Index (PASI) score \>= 12 * \>=10% body surface area psoriasis involvement * Willingness to forgo other available psoriasis therapies, live vaccines, and pregnancy during the trial * Ability and willingness to provide informed consent and comply with study requirements
Exclusion criteria
* Non-plaque forms of psoriasis * Grade 2 or 3 moderate to severe psoriatic arthritis not adequately managed with non-steroidal anti-inflammatory drugs (NSAIDs) * Myocardial infarction, unstable angina, cerebrovascular accident, or other significant cardiovascular event within the previous one year * Chronic obstructive pulmonary disease (COPD) * Comorbid condition that requires regular systemic corticosteroid treatment * History of malignancy, except treated basal cell skin carcinoma * Treated basal cell skin carcinoma within the previous 5 years * Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, or any other medical condition that, in the investigator's opinion, places the participant at risk by participating in this study * History of recent or ongoing uncontrolled bacterial, viral, fungal, or other opportunistic infections * Evidence of infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) * Positive QuantiFERON-TB Gold test. Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON-TB Gold test. * Severe reaction or anaphylaxis to any human monoclonal antibody * Any previous treatment with agents targeting Interleukin (IL)-12 or IL-23, including ustekinumab * Any previous treatment with abatacept * Treatment with biologic agents within previous 3 months, including adalimumab, etanercept, and infliximab * Treatment with immunosuppressive medications, including methotrexate, cyclosporine, oral retinoids, prednisone, or phototherapy within previous 4 weeks * Topical psoriasis treatment within previous 2 weeks, including topical corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic acid, and coal tar * Investigational study medication within previous 6 months * Liver function test (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], or alkaline phosphatase) results that are \>/= 2x the upper limit of normal (ULN). * Serum creatinine \>= 2x the ULN. * Any of the following hematologic abnormalities, confirmed by repeat test at least 1 week apart: 1. White blood count \<3,000/μL or \>14,000/μL; 2. Lymphocyte count \<1,000/μL; 3. Neutrophil count \<1,500/μL; 4. Platelet count \<150,000 /μL; or 5. Hemoglobin \<10 g/dL. * Females who are pregnant, lactating, planning on pregnancy during the study period, or unwilling to use FDA-approved method of birth control * Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) in the 6 weeks before enrollment * BCG (Bacillus Calmette-Guérin) vaccine one year prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Post-randomization (Week 12 to 88) | The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Post-randomization (Week 12 to 88) | The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early due to reasons other than psoriasis relapse or worsening psoriasis were considered to have a missing relapse status at time of drop-out and were excluded from the analyses. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis). |
| Time to Psoriasis Relapse (Treating Drop-Outs as Relapse) | Post-randomization (Week 12 to 88) | Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis). |
| Time to Psoriasis Relapse (Treating Drop-Outs as Censored) | Post-randomization (Week 12 to 88) | Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were censored at the time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis). |
| Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA) | Week 40, Week 88 | Percentage of participants who were classified as cleared or minimal in the Physician's Global Assessment (PGA) average score at the specified post-randomization time point. The PGA assesses the severity of the psoriasis in 3 components: induration, erythema and scaling. Each component is given a score ranging from 0 to 5 based on the majority of the participant's psoriasis lesions, with higher scores indicating worse disease. A PGA average score \< 1.5 was classified as cleared or minimal. |
| Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Post-randomization (Week 12 to 88) | The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were considered to have not experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis). |
| Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Lead-In Phase (Week 0 to 12) | Number of participants who experienced adverse events (AEs) during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. |
| Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Lead-In Phase (Week 0 to 12) | Number of adverse events (AEs) that occurred during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. |
| Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | From randomization (Week 12) to last safety follow-up visit (up to Week 100) | Number of participants who experienced adverse events (AEs) during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period. |
| Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | From randomization (Week 12) to last safety follow-up visit (up to Week 100) | Number of adverse events (AEs) that occurred during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period. |
| Change in Dermatology Life Quality Index (DLQI) | Week 40, Week 88 | Change in the Dermatology Life Quality Index (DLQI) score from Week 12 to the specified post-randomization time point. DLQI is a 10-question, participant-reported questionnaire that assesses quality of life with respect to skin conditions in the areas of symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Each question measures the level of effect that the skin condition has on quality of life, and responses range from 'Not at all' (score = 0) to 'Very much' (score = 3). The overall score is the sum of the scores for all 10 questions and ranges from 0-30, with higher scores indicating worse quality of life. |
Countries
Canada, United States
Participant flow
Recruitment details
148 participants were screened and 108 of those participants were enrolled at 8 sites in the US and 2 sites in Canada between March 2014 and April 2016
Pre-assignment details
Enrolled participants received open-label ustekinumab in the lead-in phase (Week 0 to 12). Participants with at least 75% reduction in Psoriasis Area Severity Index (PASI) score at Week 12 compared to Week 0 were eligible for the blinded treatment phase (Week 12 to 40).
Participants by arm
| Arm | Count |
|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo Participants received 2 subcutaneous injections of open-label ustekinumab (45 mg for participants weighing \<=100 kg at study entry or 90 mg for those weighing \>100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and received blinded treatment of abatacept (125 mg) subcutaneous injections weekly from Week 12 to 39, in addition to ustekinumab placebo subcutaneous injections at Weeks 16 and 28. | 45 |
| Ustekinumab, Ustekinumab + Abatacept Placebo Participants received 2 subcutaneous injections of open-label ustekinumab (45 mg for participants weighing \<=100 kg at study entry or 90 mg for those weighing \>100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and received blinded treatment of ustekinumab (45 mg if \<=100 kg or 90 mg if \>100 kg at study entry) subcutaneous injections at Weeks 16 and 28, in addition to abatacept placebo subcutaneous injections weekly from Week 12 to 39. | 46 |
| Ustekinumab, Not Randomized Participants received 2 subcutaneous injections of open-label ustekinumab (45 mg for participants weighing \<=100 kg at study entry or 90 mg for those weighing \>100 kg at study entry), at Weeks 0 and 4 during the lead-in phase but were not randomized to a blinded treatment group. | 17 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Blinded Observation Phase (Week 40 - 88) | Adverse Event | 0 | 1 | 0 |
| Blinded Observation Phase (Week 40 - 88) | Lost to Follow-up | 0 | 1 | 0 |
| Blinded Observation Phase (Week 40 - 88) | Met psoriasis relapse criterion | 10 | 19 | 0 |
| Blinded Observation Phase (Week 40 - 88) | Terminated early from study in error | 0 | 2 | 0 |
| Blinded Observation Phase (Week 40 - 88) | Withdrawal by Subject | 1 | 2 | 0 |
| Blinded Observation Phase (Week 40 - 88) | Worsening psoriasis | 12 | 4 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Adverse Event | 1 | 1 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Lost to Follow-up | 3 | 4 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Met psoriasis relapse criterion | 8 | 1 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Met study drug Discontinuation Criteria | 1 | 2 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Pregnancy | 0 | 1 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Transportation issues | 1 | 0 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Withdrawal by Subject | 0 | 2 | 0 |
| Blinded Treatment Phase (Week 12 - 40) | Worsening psoriasis | 4 | 0 | 0 |
| Lead-in Phase (Week 0 - 12) | Lost to Follow-up | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | Ustekinumab, Abatacept + Ustekinumab Placebo | Ustekinumab, Ustekinumab + Abatacept Placebo | Ustekinumab, Not Randomized | Total |
|---|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 10.5 | 44.1 years STANDARD_DEVIATION 11.8 | 42.8 years STANDARD_DEVIATION 15 | 46.1 years STANDARD_DEVIATION 12.1 |
| Dermatology Life Quality Index (DLQI) Score | 14.2 units on a scale STANDARD_DEVIATION 8.1 | 13.5 units on a scale STANDARD_DEVIATION 7 | 13.5 units on a scale STANDARD_DEVIATION 8.8 | 13.8 units on a scale STANDARD_DEVIATION 7.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 39 Participants | 15 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician's Global Assessment (PGA) Score | 3.5 units on a scale STANDARD_DEVIATION 0.7 | 3.3 units on a scale STANDARD_DEVIATION 0.5 | 3.5 units on a scale STANDARD_DEVIATION 0.6 | 3.4 units on a scale STANDARD_DEVIATION 0.6 |
| Physician's Global Assessment (PGA) Score (Categorical) Cleared or Minimal (PGA <1.5) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Physician's Global Assessment (PGA) Score (Categorical) Worse than Minimal (PGA ≥ 1.5) | 45 Participants | 46 Participants | 17 Participants | 108 Participants |
| Psoriasis Area Severity Index (PASI) (Randomization Strata) High (>20) | 14 Participants | 14 Participants | 9 Participants | 37 Participants |
| Psoriasis Area Severity Index (PASI) (Randomization Strata) Low (12 - 20) | 31 Participants | 32 Participants | 8 Participants | 71 Participants |
| Psoriasis Area Severity Index (PASI) Score | 19.2 units on a scale STANDARD_DEVIATION 8.1 | 20.0 units on a scale STANDARD_DEVIATION 8.2 | 21.2 units on a scale STANDARD_DEVIATION 7.7 | 19.9 units on a scale STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 42 Participants | 17 Participants | 95 Participants |
| Region of Enrollment Canada | 15 participants | 14 participants | 6 participants | 35 participants |
| Region of Enrollment United States | 30 participants | 32 participants | 11 participants | 73 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 3 Participants | 35 Participants |
| Sex: Female, Male Male | 27 Participants | 32 Participants | 14 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 108 | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 4 / 108 | 6 / 45 | 6 / 46 |
| serious Total, serious adverse events | 2 / 108 | 2 / 45 | 5 / 46 |
Outcome results
Primary
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
Time frame: Post-randomization (Week 12 to 88)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 12-88 | 91.1 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 12-40 | 55.6 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 28-88 | 88.9 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 40-88 | 84.6 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 40-88 | 83.3 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 12-88 | 87.0 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 28-88 | 84.2 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse) | Week 12-40 | 30.4 percentage of participants |
Comparison: Week 12 to 88. This interval corresponds to the time from randomization until the end of the study. This analysis is the primary analysis of the primary endpoint.p-value: 0.41Regression, Logistic
Comparison: Week 12 to 40. This interval corresponds to the time from randomization until the end of the blinded treatment phase.p-value: 0.013Regression, Logistic
Comparison: Week 28 to 88. This interval corresponds to the time from the last scheduled dose of ustekinumab or ustekinumab placebo until the end of the study.p-value: 0.5Regression, Logistic
Comparison: Week 40 to 88. This interval corresponds to the time from the beginning of the blinded observation phase until the end of the study.p-value: 0.67Regression, Logistic
Secondary
Change in Dermatology Life Quality Index (DLQI)
Change in the Dermatology Life Quality Index (DLQI) score from Week 12 to the specified post-randomization time point. DLQI is a 10-question, participant-reported questionnaire that assesses quality of life with respect to skin conditions in the areas of symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Each question measures the level of effect that the skin condition has on quality of life, and responses range from 'Not at all' (score = 0) to 'Very much' (score = 3). The overall score is the sum of the scores for all 10 questions and ranges from 0-30, with higher scores indicating worse quality of life.
Time frame: Week 40, Week 88
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Change in Dermatology Life Quality Index (DLQI) | Week 40 | 2.2 Units on a Scale | Standard Deviation 5.3 |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Change in Dermatology Life Quality Index (DLQI) | Week 88 | -4.3 Units on a Scale | Standard Deviation 3.7 |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Change in Dermatology Life Quality Index (DLQI) | Week 40 | 0.6 Units on a Scale | Standard Deviation 3.9 |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Change in Dermatology Life Quality Index (DLQI) | Week 88 | 0.0 Units on a Scale | Standard Deviation 2.1 |
Comparison: Week 12 to 40p-value: 0.18ANCOVA
Comparison: Week 12 to 88p-value: 0.045ANCOVA
Secondary
Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)
Number of adverse events (AEs) that occurred during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
Time frame: Lead-In Phase (Week 0 to 12)
Population: The safety population includes all participants who received at least one dose of treatment after enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 4 AEs | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | All AEs | 51 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | AEs indicated as serious | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | AEs with an outcome of death | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | AEs of special interest | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 2 AEs | 47 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 3 AEs | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 1 Psoriatic Arthritis AEs | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 2 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | Grade 3 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | AEs that lead to study drug discontinuation | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase) | AEs related to open label Ustekinumab | 20 Number of Events |
Secondary
Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)
Number of adverse events (AEs) that occurred during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
Time frame: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | All AEs | 59 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs indicated as serious | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs with an outcome of death | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs of special interest | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 2 AEs (CTCAE) | 53 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 3 AEs (CTCAE) | 4 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 4 AEs (CTCAE) | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 1 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 2 Psoriatic Arthritis AEs | 2 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 3 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs that lead to study drug discontinuation | 1 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to open-label Ustekinumab | 5 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to Ustekinumab/Ustekinumab Placebo | 9 Number of Events |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to Abatacept/Abatacept Placebo | 15 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs that lead to study drug discontinuation | 3 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | All AEs | 59 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 1 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs indicated as serious | 9 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to Ustekinumab/Ustekinumab Placebo | 17 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs with an outcome of death | 0 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 2 Psoriatic Arthritis AEs | 1 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs of special interest | 1 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to open-label Ustekinumab | 11 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 2 AEs (CTCAE) | 47 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 3 Psoriatic Arthritis AEs | 0 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 3 AEs (CTCAE) | 7 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | AEs related to Abatacept/Abatacept Placebo | 20 Number of Events |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization) | Grade 4 AEs (CTCAE) | 4 Number of Events |
Secondary
Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)
Number of participants who experienced adverse events (AEs) during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
Time frame: Lead-In Phase (Week 0 to 12)
Population: The safety population includes all participants who received at least one dose of treatment after enrollment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | All AEs | 30 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | AEs indicated as serious | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | AEs with an outcome of death | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | AEs of special interest | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 2 AEs | 28 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 3 AEs | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 4 AEs | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 1 Psoriatic Arthritis AEs | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 2 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | Grade 3 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | AEs that lead to study drug discontinuation | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase) | AEs related to open label Ustekinumab | 11 Number of participants |
Secondary
Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)
Number of participants who experienced adverse events (AEs) during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
Time frame: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | All AEs | 28 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs indicated as serious | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs with an outcome of death | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs of special interest | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 2 AEs (CTCAE) | 27 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 3 AEs (CTCAE) | 4 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 4 AEs (CTCAE) | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 1 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 2 Psoriatic Arthritis AEs | 2 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 3 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs that lead to study drug discontinuation | 1 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to open-label Ustekinumab | 5 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to Ustekinumab/Ustekinumab Placebo | 7 Number of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to Abatacept/Abatacept Placebo | 11 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs that lead to study drug discontinuation | 2 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | All AEs | 22 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 1 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs indicated as serious | 5 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to Ustekinumab/Ustekinumab Placebo | 9 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs with an outcome of death | 0 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 2 Psoriatic Arthritis AEs | 1 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs of special interest | 1 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to open-label Ustekinumab | 8 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 2 AEs (CTCAE) | 20 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 3 Psoriatic Arthritis AEs | 0 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 3 AEs (CTCAE) | 7 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | AEs related to Abatacept/Abatacept Placebo | 11 Number of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization) | Grade 4 AEs (CTCAE) | 2 Number of participants |
Secondary
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)
The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early due to reasons other than psoriasis relapse or worsening psoriasis were considered to have a missing relapse status at time of drop-out and were excluded from the analyses. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
Time frame: Post-randomization (Week 12 to 88)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 12-88 | 89.5 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 12-40 | 48.7 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 28-88 | 88.2 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 40-88 | 84.0 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 40-88 | 79.3 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 12-88 | 80.0 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 28-88 | 79.3 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status) | Week 12-40 | 13.5 percentage of participants |
Comparison: Week 12 to 88. This interval corresponds to the time from randomization until the end of the study.p-value: 0.16Regression, Logistic
Comparison: Week 12 to 40. This interval corresponds to the time from randomization until the end of the blinded treatment phase.p-value: 0.002Regression, Logistic
Comparison: Week 28 to 88. This interval corresponds to the time from the last scheduled dose of ustekinumab or ustekinumab placebo until the end of the study.p-value: 0.23Regression, Logistic
Comparison: Week 40 to 88. This interval corresponds to the time from the beginning of the blinded observation phase until the end of the study.p-value: 0.43Regression, Logistic
Secondary
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)
The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were considered to have not experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
Time frame: Post-randomization (Week 12 to 88)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 12-88 | 75.6 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 12-40 | 42.2 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 28-88 | 83.3 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 40-88 | 80.8 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 40-88 | 63.9 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 12-88 | 52.2 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 28-88 | 60.5 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse) | Week 12-40 | 10.9 percentage of participants |
Comparison: Week 12 to 88. This interval corresponds to the time from randomization until the end of the study.p-value: 0.019Regression, Logistic
Comparison: Week 12 to 40. This interval corresponds to the time from randomization until the end of the blinded treatment phase.p-value: 0.001Regression, Logistic
Comparison: Week 28 to 88. This interval corresponds to the time from the last scheduled dose of ustekinumab or ustekinumab placebo until the end of the study.p-value: 0.018Regression, Logistic
Comparison: Week 40 to 88. This interval corresponds to the time from the beginning of the blinded observation phase until the end of the study.p-value: 0.07Regression, Logistic
Secondary
Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)
Percentage of participants who were classified as cleared or minimal in the Physician's Global Assessment (PGA) average score at the specified post-randomization time point. The PGA assesses the severity of the psoriasis in 3 components: induration, erythema and scaling. Each component is given a score ranging from 0 to 5 based on the majority of the participant's psoriasis lesions, with higher scores indicating worse disease. A PGA average score \< 1.5 was classified as cleared or minimal.
Time frame: Week 40, Week 88
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA) | Week 40 | 26.9 percentage of participants |
| Ustekinumab, Abatacept + Ustekinumab Placebo | Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA) | Week 88 | 75.0 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA) | Week 40 | 58.8 percentage of participants |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA) | Week 88 | 50.0 percentage of participants |
Comparison: Week 40p-value: 0.013Regression, Logistic
Comparison: Week 88p-value: 0.95Regression, Logistic
Secondary
Time to Psoriasis Relapse (Treating Drop-Outs as Censored)
Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were censored at the time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
Time frame: Post-randomization (Week 12 to 88)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Time to Psoriasis Relapse (Treating Drop-Outs as Censored) | 28 weeks |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Time to Psoriasis Relapse (Treating Drop-Outs as Censored) | 48 weeks |
Comparison: Week 12 to 88. This interval corresponds to the time from randomization until the end of the study.p-value: 0.005Grouped survival analysis
Comparison: Week 12 to 40. This interval corresponds to the time from randomization until the end of the blinded treatment phase.p-value: 0.001Grouped survival analysis
Secondary
Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)
Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
Time frame: Post-randomization (Week 12 to 88)
Population: The intent-to-treat population includes all participants who were found to be eligible after the 12-week lead-in period and underwent random assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ustekinumab, Abatacept + Ustekinumab Placebo | Time to Psoriasis Relapse (Treating Drop-Outs as Relapse) | 28 weeks |
| Ustekinumab, Ustekinumab + Abatacept Placebo | Time to Psoriasis Relapse (Treating Drop-Outs as Relapse) | 40 weeks |
Comparison: Week 12 to 88. This interval corresponds to the time from randomization until the end of the study.p-value: 0.06Grouped survival analysis
Comparison: Week 12 to 40. This interval corresponds to the time from randomization until the end of the blinded treatment phase.p-value: 0.008Grouped survival analysis