Atopic Dermatitis
Conditions
Keywords
eczema, atopic eczema
Brief summary
The purpose of this study is to evaluate the efficacy and safety of baricitinib in adult participants with moderate to severe atopic dermatitis.
Interventions
DRUGPlacebo
Administered orally
DRUGBaricitinib
Administered orally
Sponsors
Incyte Corporation
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of atopic dermatitis (AD) at least 12 months before screening. * Have moderate to severe AD, including all of the following: * EASI score ≥16 * IGA score of ≥3 * ≥10% of BSA involvement * Have had inadequate response or intolerance to existing topical (applied to the skin) medications within 6 months preceding screening. * Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period). * Agree to use emollients daily.
Exclusion criteria
* Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections. * A history of eczema herpeticum within 12 months, and/or a history of 2 or more episode of eczema herpeticum in the past. * Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics. * Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma). * Have been treated with the following therapies: * monoclonal antibody for less than 5 half-lives before randomization * received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks before randomization * received any parenteral corticosteroid administered by intramuscular or intravenous injection within 6 weeks of planned randomization or are anticipated to require parenteral injection of corticosteroids during the study * have had an intra-articular corticosteroid injection within 6 weeks of planned randomization * probenecid at the time of randomization that cannot be discontinued for the duration of the study * Have high blood pressure characterized by a repeated systolic blood pressure \>160 millimeters of mercury (mm Hg) or diastolic blood pressure \>100 mm Hg. * Have had major surgery within the past eight weeks or are planning major surgery during the study. * Have experienced any of the following within 12 weeks of screening: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure. * Have a history of venous thromboembolic event (VTE), or are considered at high risk for VTE. * Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness. * Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, tuberculosis. * Have specific laboratory abnormalities. * Have received certain treatments that are contraindicated. * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib) | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving EASI75 (1 mg Baricitinib) | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score. |
| Percentage of Participants Achieving EASI90 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score. |
| Percent Change From Baseline in EASI Score | Baseline, Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Squares (LS) Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score. |
| Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS) | 16 Weeks | The Itch NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. |
| Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | Baseline, Week 16 | Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. Item 2, frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep last night. Each item is scored individually. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects. |
| Change From Baseline in Skin Pain NRS | Baseline, Week 16 | Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no pain and 10 representing worst pain imaginable. Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Percentage of of Participants Achieving EASI50 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score. |
| Percentage of Participants Achieving IGA of 0 | Week 16 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Change From Baseline in SCORAD | Baseline, Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit and treatment-by-visit interaction as fixed categorial effects and baseline and baseline-by-visit interaction as fixed continuous effects. |
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | Week 16 | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. |
| Change From Baseline in Body Surface Area (BSA) Affected | Baseline, Week 16 | Body surface area affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1\*BSAhead and neck + 0.3\*BSAtrunk + 0.2\* BSAupper limbs + 0.4\*BSAlower limbs. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects. |
| Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | Week 16 | Percentage of participants developing skin infections requiring antibiotic treatment. |
| Percent Change From Baseline in Itch NRS | Baseline, Week 16 | The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),and treatment-by-visit-interaction as fixed categorical effects and baseline, and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | Baseline, Week 16 | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | Baseline, Week 16 | The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are (0) no symptoms, (1) very mild, (2) mild (3) moderate, and (4) severe. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Baseline, Week 16 | The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline on the Dermatology Life Quality Index (DLQI) | Baseline, Week 16 | The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last week. Response categories include not at all, a little, a lot, and very much, with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or not relevant responses scored as 0. Scores range from 0 to 30 (no impact on participant's life to extremely large effect on participant's life), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),visit, and treatment-by-visit-interaction as fixed categorical and baseline, and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Baseline, Week 16 | The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LS Mean were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects. |
| Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Baseline, Week 16 | The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the UK algorithm, with scores ranging from -0.594 to 1, and the US algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects. |
| Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | Baseline, Week 16 | EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranges from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects. |
| Percentage of Participants Achieving SCORAD90 | Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score. |
Countries
Canada, Puerto Rico, United States
Participant flow
Pre-assignment details
Participants who did not meet IGA 0 or 1 at Week 16 and completed at least 16 Weeks in JAIW were discontinued and if eligible had the option to roll over into the Open-Label Extension study JAIX (NCT03559720).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered orally every day. | 147 |
| 1 mg Baricitinib 1 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind. | 147 |
| 2 mg Baricitinib 2 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind. | 146 |
| Total | 440 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Week 0 to Week 16 | Adverse Event | 2 | 2 | 2 |
| Week 0 to Week 16 | Inadequate Response | 0 | 1 | 0 |
| Week 0 to Week 16 | Lack of Efficacy | 6 | 5 | 0 |
| Week 0 to Week 16 | Lost to Follow-up | 3 | 1 | 4 |
| Week 0 to Week 16 | Non-compliance | 1 | 0 | 2 |
| Week 0 to Week 16 | Pregnancy | 1 | 0 | 0 |
| Week 0 to Week 16 | Withdrawal by Subject | 8 | 7 | 10 |
| Week 0 to Week 16 | Withdrawal Due to Caregiver Circumstance | 0 | 0 | 1 |
| Week 16 to Week 104 | Adverse Event | 1 | 0 | 2 |
| Week 16 to Week 104 | Lack of Efficacy | 2 | 11 | 10 |
| Week 16 to Week 104 | Lost to Follow-up | 0 | 1 | 4 |
| Week 16 to Week 104 | Non--Compliance | 0 | 0 | 1 |
| Week 16 to Week 104 | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | 1 mg Baricitinib | 2 mg Baricitinib | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 13 Participants | 9 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 134 Participants | 134 Participants | 137 Participants | 405 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 26 Participants | 22 Participants | 81 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 26 Participants | 30 Participants | 80 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 6 Participants | 5 Participants | 18 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 80 Participants | 86 Participants | 85 Participants | 251 Participants |
| Region of Enrollment Canada | 42 Participants | 40 Participants | 37 Participants | 119 Participants |
| Region of Enrollment United States | 105 Participants | 107 Participants | 109 Participants | 321 Participants |
| Sex: Female, Male Female | 67 Participants | 72 Participants | 77 Participants | 216 Participants |
| Sex: Female, Male Male | 80 Participants | 75 Participants | 69 Participants | 224 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 146 | 0 / 147 | 0 / 145 | 0 / 8 | 0 / 19 | 0 / 35 |
| other Total, other adverse events | 34 / 146 | 24 / 147 | 36 / 145 | 1 / 8 | 10 / 19 | 11 / 35 |
| serious Total, serious adverse events | 3 / 146 | 1 / 147 | 2 / 145 | 0 / 8 | 0 / 19 | 0 / 35 |
Outcome results
Primary
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib)
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Time frame: Week 16
Population: All participants randomized to placebo or 2 mg of study drug. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib) | 8.2 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib) | 29.5 percentage of participants |
p-value: <0.00195% CI: [2.31, 9.15]Regression, Logistic
Secondary
Change From Baseline in Body Surface Area (BSA) Affected
Body surface area affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1\*BSAhead and neck + 0.3\*BSAtrunk + 0.2\* BSAupper limbs + 0.4\*BSAlower limbs. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 BSA data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Surface Area (BSA) Affected | -9.67 percentage of BSA | Standard Error 2.352 |
| 2 mg Baricitinib | Change From Baseline in Body Surface Area (BSA) Affected | -15.69 percentage of BSA | Standard Error 1.885 |
| 2 mg Baricitinib | Change From Baseline in Body Surface Area (BSA) Affected | -17.39 percentage of BSA | Standard Error 1.746 |
p-value: 0.04695% CI: [-11.93, -0.12]Mixed Models Analysis
p-value: 0.00995% CI: [-13.46, -1.98]Mixed Models Analysis
Secondary
Change From Baseline in SCORAD
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit and treatment-by-visit interaction as fixed categorial effects and baseline and baseline-by-visit interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 SCORAD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SCORAD | -14.37 units on a scale | Standard Error 3.058 |
| 2 mg Baricitinib | Change From Baseline in SCORAD | -18.31 units on a scale | Standard Error 2.445 |
| 2 mg Baricitinib | Change From Baseline in SCORAD | -26.18 units on a scale | Standard Error 2.22 |
p-value: 0.31695% CI: [-11.67, 3.79]Mixed Models Analysis
p-value: 0.00295% CI: [-19.23, -4.4]Mixed Models Analysis
Secondary
Change From Baseline in Skin Pain NRS
Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no pain and 10 representing worst pain imaginable. Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 Skin Pain NRS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Skin Pain NRS | -1.03 units on a scale | Standard Error 0.342 |
| 2 mg Baricitinib | Change From Baseline in Skin Pain NRS | -2.16 units on a scale | Standard Error 0.279 |
| 2 mg Baricitinib | Change From Baseline in Skin Pain NRS | -2.40 units on a scale | Standard Error 0.266 |
p-value: 0.01295% CI: [-1.99, -0.25]Mixed Models Analysis
p-value: 0.00295% CI: [-2.22, -0.51]Mixed Models Analysis
Secondary
Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score
The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are (0) no symptoms, (1) very mild, (2) mild (3) moderate, and (4) severe. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 PGI-S-AD data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.46 units on a scale | Standard Error 0.139 |
| 2 mg Baricitinib | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.71 units on a scale | Standard Error 0.111 |
| 2 mg Baricitinib | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.88 units on a scale | Standard Error 0.105 |
p-value: 0.15595% CI: [-0.6, 0.1]Mixed Models Analysis
p-value: 0.01795% CI: [-0.76, -0.07]Mixed Models Analysis
Secondary
Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)
Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. Item 2, frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep last night. Each item is scored individually. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 ADSS Item 2 (frequency of waking) data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -0.40 units on a scale | Standard Error 0.207 |
| 2 mg Baricitinib | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -0.62 units on a scale | Standard Error 0.177 |
| 2 mg Baricitinib | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -0.99 units on a scale | Standard Error 0.171 |
p-value: 0.43395% CI: [-0.75, 0.32]Mixed Models Analysis
p-value: 0.02995% CI: [-1.12, -0.06]Mixed Models Analysis
Secondary
Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM)
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 POEM data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -2.67 units on a scale | Standard Error 1.216 |
| 2 mg Baricitinib | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -4.57 units on a scale | Standard Error 0.937 |
| 2 mg Baricitinib | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -7.44 units on a scale | Standard Error 0.848 |
p-value: 0.21795% CI: [-4.93, 1.12]Mixed Models Analysis
p-value: 0.00295% CI: [-7.7, -1.84]Mixed Models Analysis
Secondary
Change From Baseline on the Dermatology Life Quality Index (DLQI)
The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last week. Response categories include not at all, a little, a lot, and very much, with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or not relevant responses scored as 0. Scores range from 0 to 30 (no impact on participant's life to extremely large effect on participant's life), and a 4-point change from baseline is considered as the minimal clinically important difference threshold. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),visit, and treatment-by-visit-interaction as fixed categorical and baseline, and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 DLQI data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the Dermatology Life Quality Index (DLQI) | -3.97 units on a scale | Standard Error 0.959 |
| 2 mg Baricitinib | Change From Baseline on the Dermatology Life Quality Index (DLQI) | -5.47 units on a scale | Standard Error 0.776 |
| 2 mg Baricitinib | Change From Baseline on the Dermatology Life Quality Index (DLQI) | -7.46 units on a scale | Standard Error 0.695 |
p-value: 0.22495% CI: [-3.92, 0.92]Mixed Models Analysis
p-value: 0.00495% CI: [-5.83, -1.16]Mixed Models Analysis
Secondary
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm
The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the UK algorithm, with scores ranging from -0.594 to 1, and the US algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 EQ-5D-5L Index Score US and UK Algorithm
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (US Algorithm) | 0.04 units on a scale | Standard Error 0.021 |
| Placebo | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (UK Algorithm) | 0.07 units on a scale | Standard Error 0.029 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (US Algorithm) | 0.06 units on a scale | Standard Error 0.016 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (UK Algorithm) | 0.09 units on a scale | Standard Error 0.023 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (US Algorithm) | 0.10 units on a scale | Standard Error 0.015 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm | Health State Index (UK Algorithm) | 0.14 units on a scale | Standard Error 0.02 |
Comparison: Health State Index Score (US algorithm)p-value: 0.48295% CI: [-0.03, 0.07]Mixed Models Analysis
Comparison: Health State Index Score (US algorithm)p-value: 0.04395% CI: [0, 0.1]Mixed Models Analysis
Comparison: Health State Index Score (UK algorithm)p-value: 0.65695% CI: [-0.06, 0.09]Mixed Models Analysis
Comparison: Health State Index Score (UK algorithm)p-value: 0.05795% CI: [0, 0.14]Mixed Models Analysis
Secondary
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS)
EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranges from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 EQ-5D-5L VAS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 4.67 millimeters | Standard Error 2.022 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 3.34 millimeters | Standard Error 1.631 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 8.14 millimeters | Standard Error 1.497 |
p-value: 0.60995% CI: [-6.45, 3.79]Mixed Models Analysis
p-value: 0.16695% CI: [-1.46, 8.41]Mixed Models Analysis
Secondary
Change From Baseline on the Hospital Anxiety Depression Scale (HADS)
The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 HADS data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Anxiety | -2.03 units on a scale | Standard Error 0.441 |
| Placebo | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Depression | -1.31 units on a scale | Standard Error 0.362 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Anxiety | -1.50 units on a scale | Standard Error 0.356 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Depression | -0.87 units on a scale | Standard Error 0.294 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Anxiety | -2.55 units on a scale | Standard Error 0.321 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety Depression Scale (HADS) | Depression | -1.73 units on a scale | Standard Error 0.263 |
Comparison: Anxietyp-value: 0.34595% CI: [-0.58, 1.65]Mixed Models Analysis
Comparison: Anxietyp-value: 0.33695% CI: [-1.59, 0.55]Mixed Models Analysis
Comparison: Depressionp-value: 0.35395% CI: [-0.48, 1.35]Mixed Models Analysis
Comparison: Depressionp-value: 0.3495% CI: [-1.31, 0.45]Mixed Models Analysis
Secondary
Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire
The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment. LS Mean were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with baseline and at least 1 post-baseline WPAI measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -9.24 units on a scale | Standard Error 3.334 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -3.44 units on a scale | Standard Error 4.037 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | 3.41 units on a scale | Standard Error 4.741 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Overall Work Impairment | -0.88 units on a scale | Standard Error 4.848 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Overall Work Impairment | -13.73 units on a scale | Standard Error 3.943 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -18.87 units on a scale | Standard Error 2.631 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | 0.05 units on a scale | Standard Error 3.642 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -15.18 units on a scale | Standard Error 3.315 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -22.53 units on a scale | Standard Error 2.401 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | 2.34 units on a scale | Standard Error 3.078 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -19.33 units on a scale | Standard Error 2.99 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Overall Work Impairment | -17.15 units on a scale | Standard Error 3.52 |
Comparison: Absenteeism Change from Baselinep-value: 0.57595% CI: [-15.3, 8.57]Mixed Models Analysis
Comparison: Absenteeism Change from Baselinep-value: 0.85195% CI: [-12.43, 10.3]Mixed Models Analysis
Comparison: Presenteeism Change from Baselinep-value: 0.02695% CI: [-22.05, -1.45]Mixed Models Analysis
Comparison: Presenteeism Change from Baselinep-value: 0.00295% CI: [-25.89, -5.91]Mixed Models Analysis
Comparison: Overall Work Impairment Change from Baselinep-value: 0.04195% CI: [-25.18, -0.51]Mixed Models Analysis
Comparison: Overall Work Impairment Change from Baselinep-value: 0.00895% CI: [-28.2, -4.34]Mixed Models Analysis
Comparison: Activity Impairment Change from Baselinep-value: 0.02395% CI: [-17.95, -1.32]Mixed Models Analysis
Comparison: Activity Impairment Change from Baselinep-value: 0.00195% CI: [-21.4, -5.17]Mixed Models Analysis
Secondary
Percentage of of Participants Achieving EASI50
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score.
Time frame: Week 16
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of of Participants Achieving EASI50 | 12.9 percentage of participants |
| 2 mg Baricitinib | Percentage of of Participants Achieving EASI50 | 19.7 percentage of participants |
| 2 mg Baricitinib | Percentage of of Participants Achieving EASI50 | 34.9 percentage of participants |
p-value: 0.10595% CI: [0.9, 3.2]Regression, Logistic
p-value: <0.00195% CI: [2.02, 6.68]Regression, Logistic
Secondary
Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS)
The Itch NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Time frame: 16 Weeks
Population: All randomized participants with a Baseline Itch NRS score \>=4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS) | 5.7 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS) | 15.9 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving a 4-Point Improvement on the Itch Numeric Rating Scale (NRS) | 25.2 percentage of participants |
p-value: 0.01295% CI: [1.29, 7.36]Regression, Logistic
p-value: <0.00195% CI: [2.31, 12.28]Regression, Logistic
Secondary
Percentage of Participants Achieving EASI75 (1 mg Baricitinib)
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Time frame: Week 16
Population: All participants randomized to placebo or 1 mg of study drug. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving EASI75 (1 mg Baricitinib) | 8.2 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving EASI75 (1 mg Baricitinib) | 12.9 percentage of participants |
p-value: 0.16795% CI: [0.8, 3.63]Regression, Logistic
Secondary
Percentage of Participants Achieving EASI90
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.
Time frame: Week 16
Population: All randomized participants. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving EASI90 | 3.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving EASI90 | 7.5 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving EASI90 | 20.5 percentage of participants |
p-value: 0.13195% CI: [0.79, 6.31]Regression, Logistic
p-value: <0.00195% CI: [2.63, 17.19]Regression, Logistic
Secondary
Percentage of Participants Achieving IGA of 0
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Week 16
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving IGA of 0 | 0.7 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving IGA of 0 | 3.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving IGA of 0 | 2.7 percentage of participants |
p-value: 0.14495% CI: [0.63, 22.85]Regression, Logistic
p-value: 0.22795% CI: [0.5, 19.4]Regression, Logistic
Secondary
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Week 16
Population: All randomized participants. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 5.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 12.9 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 24.0 percentage of participants |
p-value: 0.03395% CI: [1.08, 5.83]Regression, Logistic
p-value: <0.00195% CI: [2.4, 11.68]Regression, Logistic
Secondary
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time frame: Week 4
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 2.7 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 5.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 8.2 percentage of participants |
p-value: 0.25895% CI: [0.61, 6.26]Regression, Logistic
p-value: 0.05295% CI: [0.99, 8.97]Regression, Logistic
Secondary
Percentage of Participants Achieving SCORAD90
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.
Time frame: Week 16
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving SCORAD90 | 1.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORAD90 | 2.0 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORAD90 | 3.4 percentage of participants |
p-value: 0.68395% CI: [0.29, 6.78]Regression, Logistic
p-value: 0.27795% CI: [0.52, 9.68]Regression, Logistic
Secondary
Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75)
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Time frame: Week 16
Population: All randomized participants. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 2.7 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 3.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 14.4 percentage of participants |
p-value: 0.73395% CI: [0.36, 4.36]Regression, Logistic
p-value: 0.00295% CI: [1.93, 15.22]Regression, Logistic
Secondary
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
Percentage of participants developing skin infections requiring antibiotic treatment.
Time frame: Week 16
Population: All randomized participants who received at least 1 dose of study drug and who did not discontinue from study for reason lost to follow-up at the first post-baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 5.5 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 4.1 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 4.1 percentage of participants |
p-value: 0.598Fisher Exact
p-value: 0.785Fisher Exact
Secondary
Percent Change From Baseline in EASI Score
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Squares (LS) Means were calculated using a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 EASI data. As pre-specified in the analysis plan, outcome measures will not be reported for the Maximum Extended Enrollment (MEE) arms/groups but only for the main global study arms/groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EASI Score | -34.07 percent change | Standard Error 5.529 |
| 2 mg Baricitinib | Percent Change From Baseline in EASI Score | -46.66 percent change | Standard Error 4.469 |
| 2 mg Baricitinib | Percent Change From Baseline in EASI Score | -54.37 percent change | Standard Error 4.156 |
p-value: 0.07795% CI: [-26.54, 1.36]Mixed Models Analysis
p-value: 0.00495% CI: [-33.85, -6.75]Mixed Models Analysis
Secondary
Percent Change From Baseline in Itch NRS
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),and treatment-by-visit-interaction as fixed categorical effects and baseline, and baseline-by-visit-interaction as fixed continuous effects.
Time frame: Baseline, Week 16
Population: All randomized participants with Week 16 Itch NRS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Itch NRS | -18.01 percent change | Standard Error 5.133 |
| 2 mg Baricitinib | Percent Change From Baseline in Itch NRS | -30.28 percent change | Standard Error 4.104 |
| 2 mg Baricitinib | Percent Change From Baseline in Itch NRS | -39.87 percent change | Standard Error 3.904 |
p-value: 0.06395% CI: [-25.21, 0.66]Mixed Models Analysis
p-value: <0.00195% CI: [-34.54, -9.17]Mixed Models Analysis