Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, AD, Level-Up, Upadacitinib, Dupilumab, RINVOQ
Brief summary
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. Therapies spread over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study compares upadacitinib to dupilumab in adolescent and adult participants with moderate to severe AD who have inadequate response to systemic therapies. Adverse events and change in the disease activity will be assessed. Upadacitinib and dupilumab are approved drugs for the treatment of moderate to severe atopic dermatitis (AD). The study is comprised of a 35-day Screening Period, a 16-week treatment Period 1 and a 16-week treatment Period 2. Participants are randomly assigned to 1 of 2 groups called treatment arms to receive upadacitinib Dose A or dupilumab in Period 1. There is a 30-day or 12-week follow-up visit for those on upadacitinib or dupilumab respectively, who will not enter Period 2. In Period 2, participants will receive upadacitinib Dose A or Dose B for 16 weeks, followed by a 30-day follow-up visit. Approximately 880 adolescent and adult participants ages 12 to 64 with moderate to severe AD who are candidates for systemic therapy will be enrolled at up to 330 sites worldwide. There may be higher treatment burden for participants in this trial compared to their standard of care . Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGDupilumab
Dupilumab is administered as a subcutaneous (SC) injection.
DRUGUpadacitinib
Extended-release tablet
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to baseline and participant meets Hanifin and Rajka criteria. * Eczema area and severity index (EASI) score ≥ 16;validated Investigator´s Global Assessment for AD (vIGA-AD) score ≥ 3 and ≥ 10% Body Surface Area Involvement of Atopic Dermatitis (BSA of AD) involvement at the Baseline Visit. * Baseline weekly average of daily Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4. * Documented history of inadequate response to previous systemic treatment defined as documented history of previous inadequate response to at least one prior systemic treatment for AD OR for whom other systemic treatments are otherwise medically inadvisable.
Exclusion criteria
* History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months. * History of an organ transplant which requires continued immunosuppression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 | Baseline and Week 16 | The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 Among Participants With Baseline WP-NRS > 1 | Baseline and Week 16 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
| Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4 at Week 16 Among Those With Baseline WP-NRS ≥ 4 | Baseline and Week 16 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
| Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 4 Among Participants With Baseline WP-NRS > 1 | Baseline and Week 4 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
| Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 16 | Baseline and Week 16 | The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). |
| Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 4 | Baseline and Week 4 | The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). |
| Percentage of Participants Achieving a ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 2 | Baseline and Week 2 | The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). |
| Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 16 | Baseline and Week 16 | The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). |
| Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 2 Among Participants With Baseline WP-NRS > 1 | Baseline and Week 2 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
Countries
Australia, Belgium, Bulgaria, Canada, China, Croatia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Romania, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were randomized at 214 sites located in 28 countries (Australia, Belgium, Bulgaria, Canada, China, Croatia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Mexico, Netherlands, Poland, Portugal, Romania, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, and the United States/Puerto Rico).
Pre-assignment details
Participants who met eligibility criteria were randomized in a 1:1 ratio to receive either upadacitinib 15 mg QD or dupilumab as per its label in Period 1. At Week 16, participants from both Period 1 arms with a \< EASI 75 response entered Period 2; those from the dupilumab arm were offered the option to receive upadacitinib 15 mg QD while those from the upadacitinib arm either continued (if already receiving 30 mg) or escalated to upadacitinib 30 mg QD (if receiving 15 mg QD) until Week 32.
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab (Period 1) Adult participants received a loading dose of 600 mg dupilumab by subcutaneous (SC) injection at the Baseline visit followed by 300 mg dupilumab SC every other week (EOW) until Week 16.
Adolescents (12 to 17 years of age and weighing at least 40 kg) received treatment according to their body weight. Participants weighing 40 to \< 60 kg received a loading dose of 400 mg dupilumab SC at the Baseline visit followed by 200 mg SC EOW until Week 16. Those weighing 60 kg or more received a loading dose of 600 mg dupilumab SC at the Baseline visit followed by 300 mg dupilumab SC EOW until Week 16. | 462 |
| Upadacitinib (Period 1) Participants received 15 mg upadacitinib orally once a day (QD) up to Week 16. Starting at Week 4, participants had their dose increased to 30 mg QD if they had a \< 50% reduction from Baseline in Eczema Area and Severity Index (EASI 50) response or a \< 4-point improvement from Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS; weekly average). Starting at Week 8, participants had their dose increased to 30 mg QD if they had a \< EASI 75 response. | 458 |
| Total | 920 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 (Baseline - Week 16) | Lost to Follow-up | 2 | 0 | 0 | 0 |
| Period 1 (Baseline - Week 16) | Other, not specified | 16 | 16 | 0 | 0 |
| Period 1 (Baseline - Week 16) | Withdrawal by Subject | 21 | 24 | 0 | 0 |
| Period 2 (Week 16 - Week 32) | Lost to Follow-up | 0 | 0 | 3 | 1 |
| Period 2 (Week 16 - Week 32) | Other, not specified | 0 | 0 | 4 | 11 |
| Period 2 (Week 16 - Week 32) | Withdrawal by Subject | 0 | 0 | 3 | 4 |
Baseline characteristics
| Characteristic | Upadacitinib (Period 1) | Total | Dupilumab (Period 1) |
|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 12.71 | 31.0 years STANDARD_DEVIATION 12.74 | 30.9 years STANDARD_DEVIATION 12.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 85 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 414 Participants | 835 Participants | 421 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 122 Participants | 259 Participants | 137 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants | 39 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 303 Participants | 599 Participants | 296 Participants |
| Sex: Female, Male Female | 195 Participants | 412 Participants | 217 Participants |
| Sex: Female, Male Male | 263 Participants | 508 Participants | 245 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 462 | 0 / 458 | 0 / 208 | 0 / 147 |
| other Total, other adverse events | 87 / 462 | 156 / 458 | 57 / 208 | 30 / 147 |
| serious Total, serious adverse events | 5 / 462 | 4 / 458 | 0 / 208 | 4 / 147 |
Outcome results
Primary
Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16
The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 | 8.9 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 | 19.9 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [6.6, 15.5]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 16
The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 16 | 5.6 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 16 | 14.8 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [5.4, 13.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 2
The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).
Time frame: Baseline and Week 2
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 2 | 8.2 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 2 | 26.7 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [13.9, 23.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 16
The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 16 | 22.5 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 16 | 40.8 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [12.5, 24.2]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 4
The EASI is a composite index with scores ranging from 0 to 72. Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) assessed for severity on a scale of 0 (absent) through 3 (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).
Time frame: Baseline and Week 4
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 4 | 9.7 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 4 | 23.8 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [9.4, 18.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4 at Week 16 Among Those With Baseline WP-NRS ≥ 4
The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4 at Week 16 Among Those With Baseline WP-NRS ≥ 4 | 38.1 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4 at Week 16 Among Those With Baseline WP-NRS ≥ 4 | 54.7 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [10.2, 23]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 Among Participants With Baseline WP-NRS > 1
The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time frame: Baseline and Week 16
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 Among Participants With Baseline WP-NRS > 1 | 15.5 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 16 Among Participants With Baseline WP-NRS > 1 | 30.2 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [9.4, 20]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 2 Among Participants With Baseline WP-NRS > 1
The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time frame: Baseline and Week 2
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 2 Among Participants With Baseline WP-NRS > 1 | 1.3 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 2 Among Participants With Baseline WP-NRS > 1 | 7.7 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [3.8, 9.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 4 Among Participants With Baseline WP-NRS > 1
The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Time frame: Baseline and Week 4
Population: Intent-to-Treat (ITT) Population of Period 1 (ITT\_1 Population): all participants who were randomized at Baseline; non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 or any other missing data that can be reasonably assumed to be Missing at Random (NRI-MI) was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 4 Among Participants With Baseline WP-NRS > 1 | 2.8 percentage of participants |
| Upadacitinib (Period 1) | Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 4 Among Participants With Baseline WP-NRS > 1 | 16.1 percentage of participants |
Comparison: Upadacitinib (Period 1) vs Dupilumab (Period 1)p-value: <0.000195% CI: [9.6, 16.9]Cochran-Mantel-Haenszel