Atopic Dermatitis
Conditions
Keywords
ABT-494, Atopic Dermatitis
Brief summary
The objective of this study was to evaluate the safety and efficacy of multiple doses of upadacitinib monotherapy versus placebo in the treatment of adults with moderate to severe atopic dermatitis (AD).
Detailed description
The study was to include a 16-week double-blind treatment period (Period 1) and a 72-week double-blind treatment period (Period 2) for a total of 88 weeks of treatment. Participants who met eligibility criteria were to be randomized in a 1:1:1:1 ratio to one of the four treatment groups. Participants who completed Period 1 were re-randomized at Week 16 into a 72-week double-blind, placebo-controlled treatment period (Period 2) in a 1:1 ratio: * Group 1: Upadacitinib 7.5 mg once daily (QD) (Day 1 to Week 16) → upadacitinib 7.5 mg QD or placebo (Week 16 - and thereafter) * Group 2: Upadacitinib 15 mg QD (Day 1 to Week 16) → upadacitinib 15 mg QD or placebo (Week 16 and thereafter) * Group 3: Upadacitinib 30 mg QD (Day 1 to Week 16) → upadacitinib 30 mg QD or placebo (Week 16 - and thereafter) * Group 4: Matching placebo (Day 1 to Week 16) → upadacitinib 30 mg QD or placebo (Week 16 and thereafter) In Period 1, discontinuation from study drug was mandatory for any participant with an Eczema Area and Severity Index (EASI) score worsening of 25% or more compared with their Baseline EASI score at any 2 consecutive scheduled study visits from Week 4 to Week 12. In Period 2, blinded rescue therapy with upadacitinib 30 mg QD was provided after the first instance of a \< EASI 50 response starting at the Week 20 visit (4 weeks after re-randomization into Period 2) for the remainder of the study.
Interventions
DRUGUpadacitinib
Tablet for oral use
DRUGPlacebo
Tablet
Sponsors
AbbVie
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Atopic dermatitis with a diagnosis confirmed by a dermatologist (according to the Hanifin and Rajka criteria) and onset of symptoms at least 1 year prior to Baseline. * Moderate to severe atopic dermatitis defined by an Eczema Area and Severity Index (EASI) ≥ 16, body surface area (BSA) ≥ 10% and an Investigators Global Assessment (IGA) score ≥ 3 at the Baseline visit. * Documented history (within 1 year prior to the screening visit) of inadequate response to treatment with topical corticosteroids (TCS), or topical calcineurin inhibitors (TCI), or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks). * Twice daily use of an additive-free, bland emollient for at least 7 days prior to Baseline.
Exclusion criteria
* Prior exposure to any systemic or topical Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, ruxolitinib, and filgotinib). * Treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin within 10 days prior to the Baseline visit. * Prior exposure to dupilumab or exposure to systemic therapies for AD including corticosteroids, methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4)-inhibitors and mycophenolate mofetil within 4 weeks prior to Baseline. * Prior exposure to any investigational systemic treatment within 30 days or 5 half-lives (whichever is longer) of the Baseline visit or is currently enrolled in another clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | Baseline and Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 | Baseline and Week 16 | EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16 | Week 16 | The Investigator's Global Assessment for Atopic Dermatitis (IGA) was scored on the following scale: * 0: Clear (No inflammatory signs of atopic dermatitis) * 1: Almost Clear (Just perceptible erythema and just perceptible papulation/infiltration) * 2: Mild (Mild erythema and mild papulation/infiltration) * 3: Moderate (Moderate erythema and moderate papulation/infiltration) * 4: Severe (Severe erythema and severe papulation/infiltration with or without oozing/crusting) The percentage of participants with a score of 0 or 1 at Week 16 is reported. |
| Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Baseline and Weeks 2, 8, and 16 | Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percent change from Baseline at each week was calculated from a rolling weekly average. |
| Percent Change From Baseline in EASI Score at Week 8 | Baseline and Week 8 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1)\] moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement. |
| Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement. |
| Percentage of Participants Who Achieved an EASI 75 Response at Week 8 | Baseline and Week 8 | EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 8 were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 50 response is defined as participants with at least a 50% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 90 response is defined as participants with at least a 90% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 50 response is defined as participants with at least a 50% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 75 response is defined as participants with at least a 75% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation). |
| Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 90 response is defined as participants with at least a 90% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation). |
| Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement. |
| Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | From re-randomization at Week 16 until Week 88 | Time to loss of EASI 50 response in Period 2 relative to Baseline among those who were re-randomized as EASI 75 responders at Week 16. Time to loss of EASI 50 response was measured from Week 16 to the date of the first assessment in Period 2 where a participant's EASI score was higher than 50% of their Baseline score. Participants with no loss of response were censored at their last treatment visit or the start of rescue treatment, whichever occurred first. |
| Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Weeks 20, 24, 32, 40, 52, 64, 76, and 88 | EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value, and was analyzed in participants who were re-randomized at Week 16 and were EASI 75 non-responders at Week 16. |
| Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of 0 or 1 at Weeks 8 and 16 | Weeks 8 and 16 | The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A score of 0 or 1 means that the disease has no effect at all. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes. |
| Change From Baseline in DLQI at Weeks 8 and 16 | Baseline and Weeks 8 and 16 | The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes. |
| Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 | Baseline and Week 16 | Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA. Last observation carried forward imputation was used. |
| Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 | Baseline and Week 16 | Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percentage of participants with reduction of ≥ 4 points from Baseline in pruritus NRS was assessed in participants with a baseline pruritus NRS of ≥ 4. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation). |
Countries
Australia, Canada, Finland, Germany, Japan, Netherlands, Spain, United States
Participant flow
Recruitment details
Participants were enrolled at 36 sites in 8 countries (Australia, Canada, Finland, Germany, Japan, Netherlands, Spain, and the United States \[US\]). The study included a 16-week double-blind treatment period (Period 1) followed by a a 72-week double-blind treatment period (Period 2) for a total of 88 weeks of treatment.
Pre-assignment details
Participants were randomized in a 1:1:1:1 ratio, stratified by geographic region (US and Canada; European Union and Australia; and Japan). Participants who completed Period 1 were re-randomized at Week 16 in a 1:1 ratio within their original treatment group assignments to either upadacitinib or placebo. Rescue therapy was provided from Week 20.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to receive placebo once daily (QD) for 16 weeks in Period 1. | 41 |
| Upadacitinib 7.5 mg Participants randomized to receive upadacitinib 7.5 mg QD for 16 weeks in Period 1. | 42 |
| Upadacitinib 15 mg Participants randomized to receive upadacitinib 15 mg QD for 16 weeks in Period 1. | 42 |
| Upadacitinib 30 mg Participants randomized to receive upadacitinib 30 mg QD for 16 weeks in Period 1. | 42 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (Weeks 0 - 16) | Adverse Event | 1 | 3 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 - 16) | Lost to Follow-up | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 - 16) | Other | 5 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 1 (Weeks 0 - 16) | Withdrawal by Subject | 10 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 (Weeks 16 - 88) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 3 | 2 |
| Period 2 (Weeks 16 - 88) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 1 |
| Period 2 (Weeks 16 - 88) | Other | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 3 | 4 | 3 | 0 |
| Period 2 (Weeks 16 - 88) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 3 | 2 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 17.52 | 41.5 years STANDARD_DEVIATION 15.36 | 38.5 years STANDARD_DEVIATION 15.24 | 39.9 years STANDARD_DEVIATION 15.3 | 39.9 years STANDARD_DEVIATION 15.77 |
| Age, Customized 40 - 64 years | 11 Participants | 16 Participants | 14 Participants | 17 Participants | 58 Participants |
| Age, Customized < 40 years | 25 Participants | 22 Participants | 25 Participants | 22 Participants | 94 Participants |
| Age, Customized ≥ 65 years | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 15 Participants |
| Duration of Atopic Dermatitis Diagnosis | 26.84 years STANDARD_DEVIATION 18.76 | 30.44 years STANDARD_DEVIATION 18.07 | 22.59 years STANDARD_DEVIATION 15.78 | 24.24 years STANDARD_DEVIATION 13.58 | 26.02 years STANDARD_DEVIATION 16.76 |
| Eczema Area and Severity Index (EASI) | 32.62 units on a scale STANDARD_DEVIATION 14.49 | 31.42 units on a scale STANDARD_DEVIATION 15.76 | 31.40 units on a scale STANDARD_DEVIATION 12.26 | 28.15 units on a scale STANDARD_DEVIATION 11.62 | 30.89 units on a scale STANDARD_DEVIATION 13.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 40 Participants | 40 Participants | 41 Participants | 162 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region EU/Australia | 10 Participants | 11 Participants | 10 Participants | 10 Participants | 41 Participants |
| Geographic Region Japan | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants |
| Geographic Region US/Canada | 29 Participants | 29 Participants | 29 Participants | 29 Participants | 116 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 9 Participants | 9 Participants | 13 Participants | 38 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 7 Participants | 10 Participants | 6 Participants | 29 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 24 Participants | 21 Participants | 23 Participants | 96 Participants |
| Sex: Female, Male Female | 17 Participants | 14 Participants | 12 Participants | 20 Participants | 63 Participants |
| Sex: Female, Male Male | 24 Participants | 28 Participants | 30 Participants | 22 Participants | 104 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 42 | 0 / 42 | 0 / 42 | 0 / 42 | 0 / 42 | 2 / 114 | 0 / 93 |
| other Total, other adverse events | 15 / 40 | 21 / 42 | 17 / 42 | 21 / 42 | 23 / 42 | 22 / 42 | 68 / 114 | 19 / 93 |
| serious Total, serious adverse events | 1 / 40 | 2 / 42 | 1 / 42 | 0 / 42 | 2 / 42 | 1 / 42 | 7 / 114 | 1 / 93 |
Outcome results
Primary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16
EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from baseline indicates improvement.
Time frame: Baseline and Week 16
Population: Randomized participants with at least one post-baseline EASI assessment; last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | -23.0 percent change | Standard Error 6.42 |
| Upadacitinib 7.5 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | -39.4 percent change | Standard Error 6.24 |
| Upadacitinib 15 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | -61.7 percent change | Standard Error 6.12 |
| Upadacitinib 30 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16 | -74.4 percent change | Standard Error 6.13 |
p-value: <0.00195% CI: [-66.5, -36.3]ANCOVA
p-value: <0.00195% CI: [-53.7, -23.6]ANCOVA
p-value: 0.03295% CI: [-31.4, -1.4]ANCOVA
Secondary
Change From Baseline in DLQI at Weeks 8 and 16
The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.
Time frame: Baseline and Weeks 8 and 16
Population: Due to an error in the electronic device used to administer the questionnaire data were not available for any participants.
Secondary
Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16
Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA. Last observation carried forward imputation was used.
Time frame: Baseline and Week 16
Population: Randomized participants with at least one post-baseline measurement; Last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 | -4.1 percentage of body surface area | Standard Error 3.58 |
| Upadacitinib 7.5 mg | Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 | -11.7 percentage of body surface area | Standard Error 3.48 |
| Upadacitinib 15 mg | Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 | -27.1 percentage of body surface area | Standard Error 3.43 |
| Upadacitinib 30 mg | Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 | -30.7 percentage of body surface area | Standard Error 3.43 |
p-value: <0.00195% CI: [-34.9, -18.1]ANCOVA
p-value: <0.00195% CI: [-31.4, -14.6]ANCOVA
p-value: 0.07595% CI: [-16, 0.8]ANCOVA
Secondary
Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16
The Investigator's Global Assessment for Atopic Dermatitis (IGA) was scored on the following scale: * 0: Clear (No inflammatory signs of atopic dermatitis) * 1: Almost Clear (Just perceptible erythema and just perceptible papulation/infiltration) * 2: Mild (Mild erythema and mild papulation/infiltration) * 3: Moderate (Moderate erythema and moderate papulation/infiltration) * 4: Severe (Severe erythema and severe papulation/infiltration with or without oozing/crusting) The percentage of participants with a score of 0 or 1 at Week 16 is reported.
Time frame: Week 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16 | 2.4 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16 | 14.3 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16 | 31.0 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Achieving an Investigator Global Assessment (IGA) of 0 or 1 at Week 16 | 50.0 percentage of participants |
p-value: <0.00195% CI: [31.1, 62.7]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [13.8, 43.4]Cochran-Mantel-Haenszel
p-value: 0.04495% CI: [0.3, 23.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Week 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 | 9.8 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 | 28.6 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 | 52.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 | 69.0 percentage of participants |
p-value: <0.00195% CI: [42.5, 74.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [25.5, 59.6]Cochran-Mantel-Haenszel
p-value: 0.02295% CI: [2.7, 34.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of 0 or 1 at Weeks 8 and 16
The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A score of 0 or 1 means that the disease has no effect at all. Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.
Time frame: Weeks 8 and 16
Population: Due to an error in the electronic device used to administer the questionnaire data were not available for any participants
Secondary
Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 50 response is defined as participants with at least a 50% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Weeks 8 and 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 8 | 22.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 16 | 22.0 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 16 | 50.0 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 8 | 54.8 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 8 | 71.4 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 16 | 71.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 8 | 92.9 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 | Week 16 | 83.3 percentage of participants |
Comparison: Analysis of EASI 50 Response at Week 8p-value: <0.00195% CI: [56.2, 85.2]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 50 Response at Week 8p-value: <0.00195% CI: [30.8, 67.3]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 50 Response at Week 8p-value: <0.00195% CI: [13.4, 52.2]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 50 Response at Week 16p-value: <0.00195% CI: [45.3, 75.9]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 50 Response at Week 16p-value: <0.00195% CI: [31.3, 65.9]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 50 Response at Week 16p-value: 0.00395% CI: [9.8, 46.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved an EASI 75 Response at Week 8
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at Week 8 were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Week 8
Population: All randomized participants; Non-responder imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved an EASI 75 Response at Week 8 | 7.3 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved an EASI 75 Response at Week 8 | 31.0 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved an EASI 75 Response at Week 8 | 52.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved an EASI 75 Response at Week 8 | 81.0 percentage of participants |
p-value: <0.00195% CI: [58.3, 87.1]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [27.9, 61.9]Cochran-Mantel-Haenszel
p-value: 0.00495% CI: [7.5, 39.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 90 response is defined as participants with at least a 90% reduction (improvement) in EASI score relative to the Baseline value. Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Weeks 8 and 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 8 | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 16 | 2.4 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 16 | 14.3 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 8 | 9.5 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 8 | 26.2 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 16 | 26.2 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 8 | 45.2 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 | Week 16 | 50.0 percentage of participants |
Comparison: Analysis of EASI 90 Response at Week 8p-value: <0.00195% CI: [29.1, 58.5]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 90 Response at Week 8p-value: <0.00195% CI: [12.6, 39.6]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 90 Response at Week 8p-value: 0.05195% CI: [0, 18.8]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 90 Response at Week 16p-value: <0.00195% CI: [31.3, 62.4]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 90 Response at Week 16p-value: 0.00195% CI: [9.6, 38.1]Cochran-Mantel-Haenszel
Comparison: Analysis of EASI 90 Response at Week 16p-value: 0.04995% CI: [0.1, 23.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 50 response is defined as participants with at least a 50% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Weeks 8 and 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 8 | 7.3 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 16 | 7.3 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 16 | 28.6 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 8 | 33.3 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 8 | 42.9 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 16 | 42.9 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 8 | 76.2 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 | Week 16 | 61.9 percentage of participants |
Comparison: Analysis of SCORAD 50 Response at Week 8p-value: <0.00195% CI: [54, 82.8]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 50 Response at Week 8p-value: <0.00195% CI: [18.5, 52.2]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 50 Response at Week 8p-value: 0.00295% CI: [9.6, 41.7]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 50 Response at Week 16p-value: <0.00195% CI: [39, 69.9]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 50 Response at Week 16p-value: <0.00195% CI: [19.1, 52.5]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 50 Response at Week 16p-value: 0.00895% CI: [5.7, 36.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 75 response is defined as participants with at least a 75% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Weeks 8 and 16
Population: All randomized participants; Non-responder imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 8 | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 16 | 2.4 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 16 | 4.8 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 8 | 9.5 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 8 | 9.5 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 16 | 21.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 8 | 31.0 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 | Week 16 | 40.5 percentage of participants |
Comparison: Analysis of SCORAD 75 Response at Week 8p-value: <0.00195% CI: [16.2, 44.6]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 75 Response at Week 8p-value: 0.05295% CI: [-0.1, 18.9]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 75 Response at Week 8p-value: 0.04895% CI: [0.1, 18.5]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 75 Response at Week 16p-value: <0.00195% CI: [22.2, 53.3]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 75 Response at Week 16p-value: 0.00695% CI: [5.6, 32.5]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 75 Response at Week 16p-value: 0.58195% CI: [-6, 10.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A SCORAD 90 response is defined as participants with at least a 90% reduction (improvement) in SCORAD score relative to the Baseline value. Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Weeks 8 and 16
Population: All randomized participants; non-responder imputation was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 8 | 0.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 16 | 0.0 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 16 | 2.4 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 8 | 4.8 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 8 | 2.4 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 16 | 9.5 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 8 | 14.3 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 | Week 16 | 23.8 percentage of participants |
Comparison: Analysis of SCORAD 90 Response at Week 8p-value: 0.01295% CI: [3.2, 25.2]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 90 Response at Week 8p-value: 0.42895% CI: [-3.4, 8]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 90 Response at Week 8p-value: 0.20695% CI: [-2.5, 11.8]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 90 Response at Week 16p-value: <0.00195% CI: [10.4, 36.2]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 90 Response at Week 16p-value: 0.04895% CI: [0.1, 18.8]Cochran-Mantel-Haenszel
Comparison: Analysis of SCORAD 90 Response at Week 16p-value: 0.42695% CI: [-3.4, 8.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease. An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value, and was analyzed in participants who were re-randomized at Week 16 and were EASI 75 non-responders at Week 16.
Time frame: Weeks 20, 24, 32, 40, 52, 64, 76, and 88
Population: Participants who were re-randomized at Week 16 and were EASI 75 non-responders at Week 16, and with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 52 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 64 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 88 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 11.1 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 100 percentage of participants |
| Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 76 | 100 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 66.7 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 52 | 66.7 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 76 | 100 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 85.7 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 88 | 100 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 100 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 12.5 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 64 | 80.0 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 0 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 33.3 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 0 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 9.1 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 64 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 76 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 52 | 0 percentage of participants |
| Upadacitinib 15 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 88 | 0 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 76 | 100 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 12.5 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 0 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 50.0 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 100 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 52 | 100 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 64 | 100 percentage of participants |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 88 | 100 percentage of participants |
| Upadacitinib 30 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 0 percentage of participants |
| Upadacitinib 30 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 20.0 percentage of participants |
| Upadacitinib 30 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 50.0 percentage of participants |
| Upadacitinib 30 mg / Placebo | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 33.3 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 76 | 100 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 20 | 25.0 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 52 | 50.0 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 88 | 100 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 40 | 50.0 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 64 | 100 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 32 | 50.0 percentage of participants |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16 | Week 24 | 33.3 percentage of participants |
Secondary
Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16
Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percentage of participants with reduction of ≥ 4 points from Baseline in pruritus NRS was assessed in participants with a baseline pruritus NRS of ≥ 4. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).
Time frame: Baseline and Week 16
Population: Randomized participants with Baseline pruritus NRS of ≥ 4; non-responder imputation was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 | 5.7 percentage of participants |
| Upadacitinib 7.5 mg | Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 | 24.3 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 | 59.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 | 52.8 percentage of participants |
p-value: <0.00195% CI: [29.6, 65.2]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [35.5, 71.3]Cochran-Mantel-Haenszel
p-value: 0.02195% CI: [2.8, 34.3]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in EASI Score at Week 8
EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1)\] moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.
Time frame: Baseline and Week 8
Population: Randomized participants with at least one post-baseline measurement; Last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EASI Score at Week 8 | -17.5 percent change | Standard Error 6.27 |
| Upadacitinib 7.5 mg | Percent Change From Baseline in EASI Score at Week 8 | -43.7 percent change | Standard Error 6.09 |
| Upadacitinib 15 mg | Percent Change From Baseline in EASI Score at Week 8 | -65.4 percent change | Standard Error 5.97 |
| Upadacitinib 30 mg | Percent Change From Baseline in EASI Score at Week 8 | -82.8 percent change | Standard Error 5.98 |
p-value: <0.00195% CI: [-80, -50.5]ANCOVA
p-value: <0.00195% CI: [-62.6, -33.3]ANCOVA
p-value: <0.00195% CI: [-40.8, -11.5]ANCOVA
Secondary
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement.
Time frame: Baseline and Weeks 8 and 16
Population: Randomized participants with Baseline and at least one post-baseline measurement; Last observation carried forward imputation was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 8 | -7.0 percent change | Standard Error 5.84 |
| Placebo | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 16 | -12.4 percent change | Standard Error 5.97 |
| Upadacitinib 7.5 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 16 | -32.5 percent change | Standard Error 5.66 |
| Upadacitinib 7.5 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 8 | -35.4 percent change | Standard Error 5.53 |
| Upadacitinib 15 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 8 | -44.1 percent change | Standard Error 5.69 |
| Upadacitinib 15 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 16 | -46.9 percent change | Standard Error 5.82 |
| Upadacitinib 30 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 8 | -65.3 percent change | Standard Error 5.52 |
| Upadacitinib 30 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 | Week 16 | -60.4 percent change | Standard Error 5.65 |
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 8p-value: <0.00195% CI: [-71.7, -44.9]ANCOVA
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 8p-value: <0.00195% CI: [-50.8, -23.4]ANCOVA
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 8p-value: <0.00195% CI: [-41.9, -15]ANCOVA
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 16p-value: <0.00195% CI: [-61.7, -34.3]ANCOVA
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 16p-value: <0.00195% CI: [-48.5, -20.5]ANCOVA
Comparison: Analysis of Percent Change from Baseline in SCORAD at Week 16p-value: 0.00495% CI: [-33.9, -6.4]ANCOVA
Secondary
Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)
Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percent change from Baseline at each week was calculated from a rolling weekly average.
Time frame: Baseline and Weeks 2, 8, and 16
Population: Randomized participants with a Baseline and at least one post-baseline measurement; last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 2 | 1.7 percent change | Standard Error 5.59 |
| Placebo | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 16 | -9.7 percent change | Standard Error 8.3 |
| Placebo | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 8 | -6.7 percent change | Standard Error 7.51 |
| Upadacitinib 7.5 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 2 | -29.3 percent change | Standard Error 5.45 |
| Upadacitinib 7.5 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 16 | -39.6 percent change | Standard Error 8.04 |
| Upadacitinib 7.5 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 8 | -35.5 percent change | Standard Error 7.28 |
| Upadacitinib 15 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 8 | -45.1 percent change | Standard Error 7.32 |
| Upadacitinib 15 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 2 | -46.0 percent change | Standard Error 5.44 |
| Upadacitinib 15 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 16 | -48.0 percent change | Standard Error 8.08 |
| Upadacitinib 30 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 2 | -57.6 percent change | Standard Error 5.24 |
| Upadacitinib 30 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 16 | -68.9 percent change | Standard Error 7.79 |
| Upadacitinib 30 mg | Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) | Week 8 | -73.1 percent change | Standard Error 7.05 |
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 2p-value: <0.00195% CI: [-72.3, -46.3]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 2p-value: <0.00195% CI: [-61.1, -34.3]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 2p-value: <0.00195% CI: [-44.3, -17.8]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 8p-value: <0.00195% CI: [-83.9, -48.9]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 8p-value: <0.00195% CI: [-56.4, -20.4]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 8p-value: 0.00295% CI: [-46.6, -11.2]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 16p-value: <0.00195% CI: [-78.6, -39.9]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 16p-value: <0.00195% CI: [-58.3, -18.4]ANCOVA
Comparison: Analysis of Percent Change from Baseline in Pruritus NRS at Week 16p-value: 0.00395% CI: [-49.4, -10.3]ANCOVA
Secondary
Percent Change From Re-randomization (Week 16) in EASI Score in Period 2
EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement.
Time frame: Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88
Population: Participants who were re-randomized at the entry of Period 2 (Week 16) with at least one post-Week 16 assessment; Last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | -2.3 percent change | Standard Error 15.15 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 13.5 percent change | Standard Error 17.13 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 50.7 percent change | Standard Error 33.5 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | -31.2 percent change | Standard Error 18.16 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | -29.8 percent change | Standard Error 17.74 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | -35.8 percent change | Standard Error 17.34 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | -37.3 percent change | Standard Error 19.09 |
| Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | -37.7 percent change | Standard Error 19.18 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | -90.1 percent change | Standard Error 16.2 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | -83.1 percent change | Standard Error 13.83 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | -91.4 percent change | Standard Error 15.83 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | -90.3 percent change | Standard Error 17.43 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 11.8 percent change | Standard Error 30.59 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | -92.0 percent change | Standard Error 16.58 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | -67.5 percent change | Standard Error 15.64 |
| Upadacitinib 7.5 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | -84.6 percent change | Standard Error 17.51 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 201.4 percent change | Standard Error 41.89 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | 189.1 percent change | Standard Error 43.65 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 170.7 percent change | Standard Error 46.87 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | 181.5 percent change | Standard Error 44.74 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 179.9 percent change | Standard Error 44.91 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 200.9 percent change | Standard Error 41.58 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 186.0 percent change | Standard Error 46.53 |
| Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 189.6 percent change | Standard Error 44.17 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 69.1 percent change | Standard Error 48.78 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 59.0 percent change | Standard Error 45.97 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 79.1 percent change | Standard Error 48.42 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 77.6 percent change | Standard Error 43.27 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | 63.5 percent change | Standard Error 46.56 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | 74.4 percent change | Standard Error 45.42 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 71.8 percent change | Standard Error 46.74 |
| Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 77.7 percent change | Standard Error 43.6 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 608.8 percent change | Standard Error 169.95 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 614.0 percent change | Standard Error 168.03 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | 613.3 percent change | Standard Error 169.63 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 582.3 percent change | Standard Error 172.19 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 617.5 percent change | Standard Error 165.84 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | 613.8 percent change | Standard Error 166.85 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 614.6 percent change | Standard Error 166.57 |
| Upadacitinib 15 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 607.3 percent change | Standard Error 169.49 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 99.3 percent change | Standard Error 163.06 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 72.6 percent change | Standard Error 175.44 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | 151.7 percent change | Standard Error 175.59 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 65.7 percent change | Standard Error 178.24 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 130.2 percent change | Standard Error 169.29 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 104.1 percent change | Standard Error 163.78 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | 104.1 percent change | Standard Error 164.05 |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 154.1 percent change | Standard Error 175.92 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | 771.5 percent change | Standard Error 252.9 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | 898.5 percent change | Standard Error 248.78 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 778.9 percent change | Standard Error 344.45 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | 799.5 percent change | Standard Error 254.3 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 802.1 percent change | Standard Error 278.76 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 769.7 percent change | Standard Error 265.64 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 787.8 percent change | Standard Error 262.89 |
| Upadacitinib 30 mg / Placebo | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | 791.5 percent change | Standard Error 262.34 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 88 | 39.0 percent change | Standard Error 226.1 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 64 | 63.6 percent change | Standard Error 237.26 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 52 | -13.3 percent change | Standard Error 216.44 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 40 | 140.6 percent change | Standard Error 293.17 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 32 | -28.8 percent change | Standard Error 210.78 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 24 | -69.6 percent change | Standard Error 200.01 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 20 | -73.8 percent change | Standard Error 215.54 |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 | Week 76 | 24.4 percent change | Standard Error 219.11 |
Secondary
Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16
Time to loss of EASI 50 response in Period 2 relative to Baseline among those who were re-randomized as EASI 75 responders at Week 16. Time to loss of EASI 50 response was measured from Week 16 to the date of the first assessment in Period 2 where a participant's EASI score was higher than 50% of their Baseline score. Participants with no loss of response were censored at their last treatment visit or the start of rescue treatment, whichever occurred first.
Time frame: From re-randomization at Week 16 until Week 88
Population: Participants who were re-randomized as EASI 75 responders at Week 16.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | NA days |
| Upadacitinib 7.5 mg | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | NA days |
| Upadacitinib 15 mg | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | 29 days |
| Upadacitinib 30 mg | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | NA days |
| Upadacitinib 15 mg / Placebo | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | 30 days |
| Upadacitinib 15 mg / Upadacitinib 15 mg | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | 114 days |
| Upadacitinib 30 mg / Placebo | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | 28 days |
| Upadacitinib 30 mg / Upadacitinib 30 mg | Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 | NA days |