Psoriasis
Conditions
Brief summary
This study will assess the safety and efficacy of ixekizumab (LY2439821), compared to etanercept and placebo in participants with moderate to severe chronic plaque psoriasis.
Interventions
Sponsors
Eli Lilly and Company
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Presents with chronic plaque psoriasis based on a confirmed diagnosis of chronic psoriasis for at least 6 months prior to randomization * At least 10% Body Surface Area (BSA) of Psoriasis at screening and at randomization * Static Physician Global Assessment (sPGA) score of at least 3 and Psoriasis Area and Severity Index (PASI) score of at least 12 at screening and at randomization * Candidate for phototherapy and/or systemic therapy * Men must agree to use a reliable method of birth control or remain abstinent during the study * Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
Exclusion criteria
* Pustular, erythrodermic, and/or guttate forms of psoriasis * History of drug-induced psoriasis * Prior use of etanercept * Clinically significant flare of psoriasis during the 12 weeks prior to randomization * Concurrent or recent use of any biologic agent * Received non-biologic systemic psoriasis therapy or phototherapy (including psoralens and ultraviolet A \[PUVA\], ultraviolet B \[UVB\]) within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to randomization * Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks prior to randomization and during the study * Have participated in any study with interleukin 17 (IL-17) antagonists, including ixekizumab * Serious disorder or illness other than plaque psoriasis * Serious infection within the last 3 months * Breastfeeding or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | Week 12 | The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1. |
| Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | Week 12 | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 was defined as having an improvement of at least 75% in the PASI scores compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | Week 12 | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 100 were defined as having an improvement of at least 100% in the PASI scores compared to baseline. |
| Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | Week 12 | The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Participants indicate their overall severity of itching from Psoriasis by circling the number that best describes the worst level of itching in the past 24 hours. |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | Baseline, Week 12 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. |
| Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | Baseline, Week 12 | The NAPSI is a numeric, reproducible, objective tool used to evaluate the severity of fingernail bed psoriasis and fingernail matrix psoriasis by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed psoriasis: 0 (none) to 4 (psoriasis in 4 quadrants of the nail) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, and the sum of all the fingernails is the total NAPSI score (range, 0 to 80). LS Means in NAPSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. |
| Percent of Body Surface Area (BSA) Involvement of Psoriasis | Week 12 | Percentage involvement of psoriasis on each participants body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including palm, fingers and thumb). LS Means in BSA were calculated using MMRM with baseline BSA as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. |
| Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | Baseline, Week 12 | PSSI is a composite score ranging from 0 (best) to 72 (worst), derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. LS Means in PSSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. |
| Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | Baseline, Week 12 | The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance \[initial, middle and late insomnia or hypersomnia\], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. LS Means in total QIDS-SR16 score were calculated using the analysis of covariance (ANCOVA) model with treatment, pooled center and baseline QIDS total score. |
| Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | Week 12 | The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0) response was defined as a post-baseline sPGA score of 0. |
| Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | Baseline, Week 12 | The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS Means in SF-36 score were calculated using the ANCOVA model with treatment, pooled center and baseline SF-36 score. |
| Change From Baseline in Patient's Global Assessment of Disease Severity | Baseline, Week 12 | The Patient's Global Assessment of Disease Severity is a single-item participant-reported outcome measure on which participants are asked to rate the severity of their psoriasis today from 0 (Clear) = no psoriasis, to 5 (Severe) = the worst their psoriasis has ever been. LS Means in Patient's Global Assessment of Disease Severity score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. |
| Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement | Week 12 | Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 50 were defined as having an improvement of at least 50% in the PPASI scores compared to baseline. |
| Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement | Week 12 | Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 75 were defined as having an improvement of at least 75% in the PPASI scores compared to baseline. |
| Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement | Week 12 | Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 100 were defined as having an improvement of 100% in the PPASI scores compared to baseline. |
| Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies | Week 12 | The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at any time post-baseline were summarized by treatment group. Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies were calculated as: number of participants with an evaluable baseline sample and ≥1 evaluable post-baseline sample/number of participants in the analysis population \* 100. |
| Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Baseline, Week 12 | The WPAI-PSO is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days. It has four domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score \* 100 and ranged from 0 to 100. Higher scores indicate greater impairment in productivity. LS Means in each WPAI-PSO score were calculated using the ANCOVA model with treatment, pooled center and baseline WPAI-PSO score. |
| Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | Week 12 | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 90 were defined as having an improvement of at least 90% in the PASI scores compared to baseline. |
Countries
Argentina, Bulgaria, Canada, Chile, Germany, Hungary, Mexico, Poland, Russia, United States
Participant flow
Pre-assignment details
This study has 4 periods: Period 1 - Screening; Period 2 - Blinded Induction Dosing Period (Weeks 0 to 12); Period 3 - Long-Term Extension Period (Weeks 12 to 264); Period 4 - Post-Treatment Follow-Up Period (Minimum of 12 Weeks)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for ixekizumab (Week 0) given as 2 SC injections followed by placebo for ixekizumab Q2W (Weeks 2, 4, 6, 8, and 10). Placebo for etanercept (1 SC injection) given twice weekly (every 3-4 days) starting at Week 0 up to Week 12. | 193 |
| 50 mg Etanercept Etanercept 50 mg (1 SC injection) given twice weekly (every 3-4 days) starting at Week 0 and up to Week 12. Placebo for ixekizumab given as 2 SC injections (Week 0) followed by placebo for ixekizumab Q2W given as 1 SC injection (Weeks 2, 4, 6, 8, and 10). | 382 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q4W (Weeks 4 and 8). Placebo for ixekizumab given as 1 SC injection at Weeks 2, 6, and 10.
Placebo for etanercept (1 SC injection) given twice weekly starting at Week 0 up to Week 12. | 386 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) A starting dose of 160 mg (Week 0) given as 2 SC injections followed by 80 mg given as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10). Placebo for etanercept (1 SC injection) given twice weekly starting at Week 0 up to Week 12. | 385 |
| Total | 1,346 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blinded Induction Dosing (Week 0-12) | Adverse Event | 2 | 4 | 9 | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blinded Induction Dosing (Week 0-12) | Lack of Efficacy | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blinded Induction Dosing (Week 0-12) | Lost to Follow-up | 3 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blinded Induction Dosing (Week 0-12) | Physician Decision | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blinded Induction Dosing (Week 0-12) | Protocol Violation | 1 | 3 | 8 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blinded Induction Dosing (Week 0-12) | Withdrawal by Subject | 3 | 2 | 4 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Follow-Up Period (Minimum of 12 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 13 | 28 | 34 | 30 |
| Follow-Up Period (Minimum of 12 Weeks) | Clinical Relapse | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 |
| Follow-Up Period (Minimum of 12 Weeks) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Follow-Up Period (Minimum of 12 Weeks) | Entry Criteria Not Met | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Follow-Up Period (Minimum of 12 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 9 | 8 | 9 |
| Follow-Up Period (Minimum of 12 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 8 | 9 | 9 |
| Follow-Up Period (Minimum of 12 Weeks) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 3 |
| Follow-Up Period (Minimum of 12 Weeks) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 6 | 4 | 7 |
| Follow-Up Period (Minimum of 12 Weeks) | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Follow-Up Period (Minimum of 12 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 21 | 19 | 19 |
| Long-Term Extension Period (Week 12-264) | Adverse Event | 0 | 0 | 0 | 0 | 16 | 34 | 43 | 30 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Clinical Relapse | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 4 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Death | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 3 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Lack of Efficacy | 0 | 0 | 0 | 0 | 6 | 14 | 10 | 11 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Lost to Follow-up | 0 | 0 | 0 | 0 | 6 | 17 | 23 | 18 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Missing Disposition Form | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 1 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Parent/Caregiver Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Physician Decision | 0 | 0 | 0 | 0 | 3 | 5 | 5 | 5 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 4 | 0 | 5 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Sponsor Decision | 0 | 0 | 0 | 0 | 3 | 2 | 2 | 2 | 0 | 0 | 0 | 0 |
| Long-Term Extension Period (Week 12-264) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 11 | 30 | 29 | 27 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 50 mg Etanercept | 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Placebo | 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 28 Participants | 13 Participants | 34 Participants | 108 Participants |
| Age, Categorical Between 18 and 65 years | 349 Participants | 358 Participants | 180 Participants | 351 Participants | 1238 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 50 Participants | 25 Participants | 57 Participants | 184 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 263 Participants | 269 Participants | 133 Participants | 259 Participants | 924 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 67 Participants | 67 Participants | 35 Participants | 69 Participants | 238 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 4 Participants | 1 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 11 Participants | 7 Participants | 12 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 9 Participants | 8 Participants | 5 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 351 Participants | 360 Participants | 176 Participants | 361 Participants | 1248 Participants |
| Region of Enrollment Argentina | 7 Participants | 6 Participants | 2 Participants | 6 Participants | 21 Participants |
| Region of Enrollment Bulgaria | 12 Participants | 14 Participants | 9 Participants | 13 Participants | 48 Participants |
| Region of Enrollment Canada | 44 Participants | 44 Participants | 22 Participants | 42 Participants | 152 Participants |
| Region of Enrollment Chile | 21 Participants | 22 Participants | 11 Participants | 22 Participants | 76 Participants |
| Region of Enrollment Germany | 87 Participants | 90 Participants | 45 Participants | 90 Participants | 312 Participants |
| Region of Enrollment Hungary | 31 Participants | 31 Participants | 18 Participants | 33 Participants | 113 Participants |
| Region of Enrollment Mexico | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Poland | 10 Participants | 11 Participants | 5 Participants | 13 Participants | 39 Participants |
| Region of Enrollment Russia | 22 Participants | 20 Participants | 11 Participants | 24 Participants | 77 Participants |
| Region of Enrollment United States | 146 Participants | 147 Participants | 69 Participants | 141 Participants | 503 Participants |
| Sex: Female, Male Female | 113 Participants | 128 Participants | 56 Participants | 131 Participants | 428 Participants |
| Sex: Female, Male Male | 269 Participants | 258 Participants | 137 Participants | 254 Participants | 918 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 | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 40 / 193 | 90 / 382 | 115 / 382 | 123 / 384 | 117 / 183 | 240 / 369 | 236 / 360 | 249 / 362 | 9 / 157 | 23 / 309 | 14 / 305 | 15 / 313 |
| serious Total, serious adverse events | 5 / 193 | 8 / 382 | 6 / 382 | 9 / 384 | 45 / 183 | 71 / 369 | 82 / 360 | 55 / 362 | 5 / 157 | 5 / 309 | 2 / 305 | 6 / 313 |
Outcome results
Primary
Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA)
The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 13 Participants |
| 50 mg Etanercept | Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 159 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 291 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 310 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Primary
Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI)
The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 75 was defined as having an improvement of at least 75% in the PASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 14 Participants |
| 50 mg Etanercept | Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 204 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 325 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving Psoriasis Area and Severity Index ≥75% (PASI 75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 336 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)
The WPAI-PSO is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days. It has four domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as: each score \* 100 and ranged from 0 to 100. Higher scores indicate greater impairment in productivity. LS Means in each WPAI-PSO score were calculated using the ANCOVA model with treatment, pooled center and baseline WPAI-PSO score.
Time frame: Baseline, Week 12
Population: All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol, and had at least one post-dose measurement of WPAI-PSO. Participants with missing WPAI-PSO data were imputed by Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Absenteeism Score | 0.0 Units on a Scale | Standard Error 0.82 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Activity Impairment Score | -2.5 Units on a Scale | Standard Error 1.3 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Presenteeism Score | -0.8 Units on a Scale | Standard Error 1.37 |
| Placebo | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Work Productively Loss Score | 0.6 Units on a Scale | Standard Error 1.59 |
| 50 mg Etanercept | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Activity Impairment Score | -21.1 Units on a Scale | Standard Error 0.91 |
| 50 mg Etanercept | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Presenteeism Score | -16.4 Units on a Scale | Standard Error 1.04 |
| 50 mg Etanercept | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Work Productively Loss Score | -17.4 Units on a Scale | Standard Error 1.2 |
| 50 mg Etanercept | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Absenteeism Score | -2.8 Units on a Scale | Standard Error 0.62 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Presenteeism Score | -16.0 Units on a Scale | Standard Error 1.01 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Activity Impairment Score | -23.3 Units on a Scale | Standard Error 0.92 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Work Productively Loss Score | -16.7 Units on a Scale | Standard Error 1.16 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Absenteeism Score | -2.0 Units on a Scale | Standard Error 0.6 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Work Productively Loss Score | -19.3 Units on a Scale | Standard Error 1.19 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Activity Impairment Score | -24.5 Units on a Scale | Standard Error 0.92 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Absenteeism Score | -2.5 Units on a Scale | Standard Error 0.61 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) | Presenteeism Score | -18.1 Units on a Scale | Standard Error 1.04 |
Comparison: Includes analysis only from Absenteeism Score.p-value: 0.006ANCOVA
Comparison: Includes analysis only from Absenteeism Score.p-value: 0.045ANCOVA
Comparison: Includes analysis only from Absenteeism Score.p-value: 0.012ANCOVA
Comparison: Includes analysis only from Activity Impairment Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Activity Impairment Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Activity Impairment Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Presenteeism Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Presenteeism Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Presenteeism Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Work Productively Loss Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Work Productively Loss Score.p-value: <0.001ANCOVA
Comparison: Includes analysis only from Work Productively Loss Score.p-value: <0.001ANCOVA
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score
The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time frame: Baseline, Week 12
Population: All randomized participants and had at least one post-dose measurement of DLQI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | -1.7 Units on a Scale | Standard Error 0.32 |
| 50 mg Etanercept | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | -8.0 Units on a Scale | Standard Error 0.23 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | -9.6 Units on a Scale | Standard Error 0.23 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score | -10.2 Units on a Scale | Standard Error 0.23 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS Means in SF-36 score were calculated using the ANCOVA model with treatment, pooled center and baseline SF-36 score.
Time frame: Baseline, Week 12
Population: All randomized participants and had at least one post-dose measurement of SF-36. Participants with missing SF-36 data were imputed by Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | -0.1993 Units on a Scale | Standard Error 0.5077 |
| Placebo | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 1.1305 Units on a Scale | Standard Error 0.5768 |
| 50 mg Etanercept | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 2.6486 Units on a Scale | Standard Error 0.4047 |
| 50 mg Etanercept | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 3.1176 Units on a Scale | Standard Error 0.3568 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 4.1143 Units on a Scale | Standard Error 0.3587 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 3.7961 Units on a Scale | Standard Error 0.4074 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | PCS | 3.9620 Units on a Scale | Standard Error 0.3604 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey, Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores | MCS | 4.2772 Units on a Scale | Standard Error 0.4093 |
Comparison: Includes analysis only from PCS.p-value: <0.001ANCOVA
Comparison: Includes analysis only from PCS.p-value: <0.001ANCOVA
Comparison: Includes analysis only from PCS.p-value: <0.001ANCOVA
Comparison: Includes analysis only from MCS.p-value: 0.031ANCOVA
Comparison: Includes analysis only from MCS.p-value: <0.001ANCOVA
Comparison: Includes analysis only from MCS.p-value: <0.001ANCOVA
Secondary
Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score
The NAPSI is a numeric, reproducible, objective tool used to evaluate the severity of fingernail bed psoriasis and fingernail matrix psoriasis by area of involvement in the fingernail unit. The fingernail is divided with imaginary horizontal and longitudinal lines into quadrants. Each fingernail is given a score for fingernail bed psoriasis: 0 (none) to 4 (psoriasis in 4 quadrants of the nail) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis in each quadrant. The NAPSI score of a fingernail is the sum of scores in fingernail bed and fingernail matrix from each quadrant (maximum of 8). Each fingernail is evaluated, and the sum of all the fingernails is the total NAPSI score (range, 0 to 80). LS Means in NAPSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time frame: Baseline, Week 12
Population: All randomized participants and had fingernail involvement at baseline and had at least one post-dose measurement of NAPSI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | 1.6362 Units on a Scale | Standard Error 1.0991 |
| 50 mg Etanercept | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -6.4015 Units on a Scale | Standard Error 0.7716 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -9.9793 Units on a Scale | Standard Error 0.7838 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score | -10.4145 Units on a Scale | Standard Error 0.782 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Patient's Global Assessment of Disease Severity
The Patient's Global Assessment of Disease Severity is a single-item participant-reported outcome measure on which participants are asked to rate the severity of their psoriasis today from 0 (Clear) = no psoriasis, to 5 (Severe) = the worst their psoriasis has ever been. LS Means in Patient's Global Assessment of Disease Severity score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time frame: Baseline, Week 12
Population: All randomized participants and had at least one post-dose measurement of Patient's Global Assessment of Disease Severity.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient's Global Assessment of Disease Severity | -0.5 Units on a Scale | Standard Error 0.08 |
| 50 mg Etanercept | Change From Baseline in Patient's Global Assessment of Disease Severity | -2.3 Units on a Scale | Standard Error 0.06 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Patient's Global Assessment of Disease Severity | -3.1 Units on a Scale | Standard Error 0.06 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Patient's Global Assessment of Disease Severity | -3.1 Units on a Scale | Standard Error 0.06 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score
PSSI is a composite score ranging from 0 (best) to 72 (worst), derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of scalp area involved. LS Means in PSSI score were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time frame: Baseline, Week 12
Population: All randomized participants and had scalp psoriasis at baseline and had at least one post-dose measurement of PSSI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -5.0 Units on a Scale | Standard Error 0.53 |
| 50 mg Etanercept | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -15.9 Units on a Scale | Standard Error 0.38 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -18.2 Units on a Scale | Standard Error 0.38 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Psoriasis Scalp Severity Index (PSSI) Score | -18.8 Units on a Scale | Standard Error 0.38 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]
The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance \[initial, middle and late insomnia or hypersomnia\], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. LS Means in total QIDS-SR16 score were calculated using the analysis of covariance (ANCOVA) model with treatment, pooled center and baseline QIDS total score.
Time frame: Baseline, Week 12
Population: All randomized participants and had at least one post-dose measurement of QIDS-SR16. Participants with missing QIDS-SR16 data were imputed by Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | -0.3 Units on a Scale | Standard Error 0.2 |
| 50 mg Etanercept | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | -0.5 Units on a Scale | Standard Error 0.14 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | -0.9 Units on a Scale | Standard Error 0.14 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | -1.3 Units on a Scale | Standard Error 0.14 |
p-value: 0.473ANCOVA
p-value: 0.015ANCOVA
p-value: <0.001ANCOVA
Secondary
Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI)
The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 100 were defined as having an improvement of at least 100% in the PASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 0 Participants |
| 50 mg Etanercept | Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 28 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 135 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving 100% (PASI 100) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 145 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI)
The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. Participants achieving PASI 90 were defined as having an improvement of at least 90% in the PASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 6 Participants |
| 50 mg Etanercept | Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 98 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 252 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving ≥90% (PASI 90) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: PASI) | 262 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)]
The Itch NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Participants indicate their overall severity of itching from Psoriasis by circling the number that best describes the worst level of itching in the past 24 hours.
Time frame: Week 12
Population: All randomized participants and had an Itch NRS score \>=4 at baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | 33 Participants |
| 50 mg Etanercept | Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | 200 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | 250 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving an Itch Numeric Rating Scale (NRS) ≥4 Point Reduction [Quality of Life and Outcome Assessments. Measures: Patient Reported Outcomes (PRO)] | 264 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA)
The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0) response was defined as a post-baseline sPGA score of 0.
Time frame: Week 12
Population: All randomized participants. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the Non-Responder Imputation (NRI) analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 0 Participants |
| 50 mg Etanercept | Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 33 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 139 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: sPGA) | 155 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement
Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 100 were defined as having an improvement of 100% in the PPASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement | 15 Participants |
| 50 mg Etanercept | Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement | 57 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement | 54 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving Palmoplantar PASI of 100% (PPASI 100) Improvement | 61 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement
Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 50 were defined as having an improvement of at least 50% in the PPASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement | 26 Participants |
| 50 mg Etanercept | Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement | 77 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement | 75 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving Palmoplantar PASI of ≥50% (PPASI 50) Improvement | 78 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement
Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. Participants achieving PPASI 75 were defined as having an improvement of at least 75% in the PPASI scores compared to baseline.
Time frame: Week 12
Population: All randomized participants and had a diagnosis of palmoplantar psoriasis at baseline. Participants who did not meet clinical response criteria or have missing data at Week 12 will be considered non-responders for the NRI analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement | 19 Participants |
| 50 mg Etanercept | Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement | 63 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement | 69 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants Achieving Palmoplantar PASI of ≥75% (PPASI 75) Improvement | 72 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies
The percentage of participants with treatment-emergent positive anti-ixekizumab antibodies at any time post-baseline were summarized by treatment group. Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies were calculated as: number of participants with an evaluable baseline sample and ≥1 evaluable post-baseline sample/number of participants in the analysis population \* 100.
Time frame: Week 12
Population: All randomized participants who received at least one dose of study treatment and had evaluable data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies | 2 Participants |
| 50 mg Etanercept | Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies | 8 Participants |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies | 52 Participants |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Number of Participants With Treatment-Emergent Anti-Ixekizumab Antibodies | 23 Participants |
Secondary
Percent of Body Surface Area (BSA) Involvement of Psoriasis
Percentage involvement of psoriasis on each participants body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand (including palm, fingers and thumb). LS Means in BSA were calculated using MMRM with baseline BSA as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time frame: Week 12
Population: All randomized participants and had at least one post-dose measurement of BSA.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent of Body Surface Area (BSA) Involvement of Psoriasis | -0.7 Percent | Standard Error 1.03 |
| 50 mg Etanercept | Percent of Body Surface Area (BSA) Involvement of Psoriasis | -16.4 Percent | Standard Error 0.73 |
| 80 mg Ixekizumab Dosing Regimen 2 (Q4W) | Percent of Body Surface Area (BSA) Involvement of Psoriasis | -23.2 Percent | Standard Error 0.73 |
| 80 mg Ixekizumab Dosing Regimen 1 (Q2W) | Percent of Body Surface Area (BSA) Involvement of Psoriasis | -23.2 Percent | Standard Error 0.73 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis