Atopic Dermatitis
Conditions
Keywords
eczema, atopic eczema
Brief summary
The purpose of this study is to evaluate the efficacy and safety of baricitinib as monotherapy in participants with moderate to severe atopic dermatitis.
Interventions
DRUGBaricitinib
Administered orally.
DRUGPlacebo
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 been diagnosed with moderate to severe Atopic Dermatitis for at least 12 months. * 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 prior to randomization. * Received prior treatment with any oral Janus kinase (JAK) inhibitor. * Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study. * Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization. * 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: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure. * Have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as deemed by the investigator. * 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 Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib) | 16 Weeks | The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 16 Weeks | 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 | 16 Weeks | 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, 16 Weeks | The EASI assesses objective physician estimates of 2 dimensions of AD - 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 Square (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 effect |
| Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 16 Weeks | 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 visual analog scale (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 in Itch Numeric Rating Scale (NRS) | 16 Weeks | The Itch Numeric Rating Scale (NRS) is a participant-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 participants 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, 16 Weeks | 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 the Skin Pain Numeric Rating Scale (NRS) | Baseline, 16 Weeks | 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, 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. |
| Percentage of Participants Achieving EASI50 | 16 Weeks | 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 | 16 Weeks | 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, 16 Weeks | 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, 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. |
| Percentage of Participants Achieving SCORAD90 | 16 Weeks | 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. |
| Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib) | 16 Weeks | 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. |
| Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 16 Weeks | Percentage of participants developing skin infections requiring antibiotic treatment. |
| Percent Change From Baseline in Itch NRS | Baseline, 16 Weeks | 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, 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 the Total Score of the Patient Oriented Eczema Measure (POEM) | Baseline, 16 Weeks | 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, 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 the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | Baseline, 16 Weeks | The PGI-S-AD asked the participant to evaluate the severity of the disease at that point in time on a single-item, 5-point scale, using a daily diary. The same category labels used in the Physician's Global Assessment were used for the PGI-S-AD, i.e., (0) no symptoms, (1) very mild, (2) mild (3) moderate, and (4) severe. 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 on the Hospital Anxiety and Depression Scale (HADS) | Baseline, 16 Weeks | 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, 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 the Dermatology Life Quality Index (DLQI) | Baseline, 16 Weeks | 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 lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and at unanswered (not relevant) responses scored as 0. Scores range from 0 to 30 (less to more impairment), 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, 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 on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Baseline, 16 Weeks | 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 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 on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Baseline, 16 Weeks | 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 United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using 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 on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | Baseline, 16 Weeks | EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged 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 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. |
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 4 Weeks | 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, 16 Weeks | 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 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. |
Countries
Czechia, Denmark, France, Germany, India, Italy, Japan, Mexico, Russia, Taiwan
Participant flow
Recruitment details
Participants who completed double blind treatment phase had option to enter extension study I4V-MC-JAHN (NCT03334435).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered orally once daily. | 249 |
| 1 mg Baricitinib 1 mg Baricitinib administered orally once daily. | 127 |
| 2 mg Baricitinib 2 mg Baricitinib administered orally once daily. | 123 |
| 4 mg Baricitinib 4 mg Baricitinib administered orally once daily. | 125 |
| Placebo Maximum Extended Enrollment (MEE) Placebo administered orally once daily. | 15 |
| 1 mg Baricitinib MEE 1 mg Baricitinib administered orally once daily. . | 5 |
| 2 mg Baricitinib MEE 2 mg Baricitinib administered orally once daily. | 8 |
| 4 mg Baricitinib MEE 4 mg Baricitinib administered orally once daily. | 8 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Ineligible | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 10 | 4 | 1 | 3 | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Started New Job | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 5 | 7 | 2 | 2 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | 1 mg Baricitinib | 2 mg Baricitinib | 4 mg Baricitinib | Placebo Maximum Extended Enrollment (MEE) | 1 mg Baricitinib MEE | 2 mg Baricitinib MEE | 4 mg Baricitinib MEE | Total | Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 5 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 17 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 127 Participants | 118 Participants | 121 Participants | 15 Participants | 5 Participants | 6 Participants | 8 Participants | 642 Participants | 242 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 7 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 30 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 40 Participants | 35 Participants | 41 Participants | 15 Participants | 5 Participants | 8 Participants | 8 Participants | 225 Participants | 73 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 5 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 34 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 74 Participants | 75 Participants | 70 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 366 Participants | 147 Participants |
| Region of Enrollment Czechia | 11 Participants | 11 Participants | 18 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 76 Participants | 36 Participants |
| Region of Enrollment France | 4 Participants | 13 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 39 Participants | 15 Participants |
| Region of Enrollment Germany | 44 Participants | 37 Participants | 30 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 178 Participants | 67 Participants |
| Region of Enrollment India | 2 Participants | 1 Participants | 6 Participants | 15 Participants | 5 Participants | 8 Participants | 8 Participants | 46 Participants | 1 Participants |
| Region of Enrollment Italy | 8 Participants | 6 Participants | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 44 Participants | 17 Participants |
| Region of Enrollment Japan | 23 Participants | 21 Participants | 22 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 111 Participants | 45 Participants |
| Region of Enrollment Mexico | 15 Participants | 17 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 73 Participants | 32 Participants |
| Region of Enrollment Russia | 7 Participants | 4 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 30 Participants | 11 Participants |
| Region of Enrollment Taiwan | 13 Participants | 13 Participants | 12 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 63 Participants | 25 Participants |
| Sex: Female, Male Female | 49 Participants | 41 Participants | 42 Participants | 6 Participants | 2 Participants | 0 Participants | 2 Participants | 243 Participants | 101 Participants |
| Sex: Female, Male Male | 78 Participants | 82 Participants | 83 Participants | 9 Participants | 3 Participants | 8 Participants | 6 Participants | 417 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 249 | 0 / 127 | 0 / 123 | 0 / 125 | 0 / 15 | 0 / 5 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 55 / 249 | 37 / 127 | 34 / 123 | 29 / 125 | 3 / 15 | 1 / 5 | 2 / 8 | 3 / 8 |
| serious Total, serious adverse events | 6 / 249 | 1 / 127 | 0 / 123 | 2 / 125 | 0 / 15 | 0 / 5 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib)
The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (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: 16 Weeks
Population: All participants randomized to placebo, 2 mg, or 4 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 Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib) | 4.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib) | 11.4 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib) | 16.8 percentage of participants |
p-value: 0.0295% CI: [1.17, 5.84]Regression, Logistic
p-value: <0.00195% CI: [1.93, 8.7]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 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, 16 Weeks
Population: All randomized participants with Week 16 BSA 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 | Change From Baseline in Body Surface Area (BSA) Affected | -14.80 units on a scale | Standard Error 1.82 |
| 2 mg Baricitinib | Change From Baseline in Body Surface Area (BSA) Affected | -20.79 units on a scale | Standard Error 2.26 |
| 4 mg Baricitinib | Change From Baseline in Body Surface Area (BSA) Affected | -20.14 units on a scale | Standard Error 2.16 |
| 4 mg Baricitinib | Change From Baseline in Body Surface Area (BSA) Affected | -25.96 units on a scale | Standard Error 1.93 |
p-value: 0.03995% CI: [-11.67, -0.31]Mixed Models Analysis
p-value: 0.05895% CI: [-10.86, 0.18]Mixed Models Analysis
p-value: <0.00195% CI: [-16.33, -5.98]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, 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, 16 Weeks
Population: All randomized participants with Week 16 SCORAD 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 | Change From Baseline in SCORAD | -13.51 units on a scale | Standard Error 2 |
| 2 mg Baricitinib | Change From Baseline in SCORAD | -18.85 units on a scale | Standard Error 2.48 |
| 4 mg Baricitinib | Change From Baseline in SCORAD | -21.47 units on a scale | Standard Error 2.36 |
| 4 mg Baricitinib | Change From Baseline in SCORAD | -28.30 units on a scale | Standard Error 2.1 |
p-value: 0.09395% CI: [-11.57, 0.9]Mixed Models Analysis
p-value: 0.0195% CI: [-14.01, -1.92]Mixed Models Analysis
p-value: <0.00195% CI: [-20.46, -9.13]Mixed Models Analysis
Secondary
Change From Baseline in 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 lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and at unanswered (not relevant) responses scored as 0. Scores range from 0 to 30 (less to more impairment), 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, 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, 16 Weeks
Population: All randomized participants with Week 16 DLQI 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 | Change From Baseline in the Dermatology Life Quality Index (DLQI) | -2.46 units on a scale | Standard Error 0.57 |
| 2 mg Baricitinib | Change From Baseline in the Dermatology Life Quality Index (DLQI) | -4.64 units on a scale | Standard Error 0.7 |
| 4 mg Baricitinib | Change From Baseline in the Dermatology Life Quality Index (DLQI) | -4.30 units on a scale | Standard Error 0.68 |
| 4 mg Baricitinib | Change From Baseline in the Dermatology Life Quality Index (DLQI) | -6.76 units on a scale | Standard Error 0.6 |
p-value: 0.01595% CI: [-3.92, -0.42]Mixed Models Analysis
p-value: 0.03695% CI: [-3.56, -0.12]Mixed Models Analysis
p-value: <0.00195% CI: [-5.91, -2.69]Mixed Models Analysis
Secondary
Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score
The PGI-S-AD asked the participant to evaluate the severity of the disease at that point in time on a single-item, 5-point scale, using a daily diary. The same category labels used in the Physician's Global Assessment were used for the PGI-S-AD, i.e., (0) no symptoms, (1) very mild, (2) mild (3) moderate, and (4) severe. 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, 16 Weeks
Population: All randomized participants with Week 16 PGI-S-AD 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 | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.31 units on a scale | Standard Error 0.09 |
| 2 mg Baricitinib | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.58 units on a scale | Standard Error 0.12 |
| 4 mg Baricitinib | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.58 units on a scale | Standard Error 0.11 |
| 4 mg Baricitinib | Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score | -0.77 units on a scale | Standard Error 0.1 |
p-value: 0.06995% CI: [-0.56, 0.02]Mixed Models Analysis
p-value: 0.06695% CI: [-0.56, 0.02]Mixed Models Analysis
p-value: <0.00195% CI: [-0.73, -0.19]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, 16 Weeks
Population: All randomized participants with Week 16 ADSS Item 2 (frequency of waking) 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 | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -0.84 units on a scale | Standard Error 0.15 |
| 2 mg Baricitinib | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -1.21 units on a scale | Standard Error 0.18 |
| 4 mg Baricitinib | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -1.04 units on a scale | Standard Error 0.17 |
| 4 mg Baricitinib | Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) | -1.42 units on a scale | Standard Error 0.16 |
p-value: 0.10395% CI: [-0.82, 0.08]Mixed Models Analysis
p-value: 0.35295% CI: [-0.65, 0.23]Mixed Models Analysis
p-value: 0.00695% CI: [-1, -0.17]Mixed Models Analysis
Secondary
Change From Baseline in the Skin Pain Numeric Rating Scale (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, 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, 16 Weeks
Population: All randomized participants with Week 16 Skin Pain NRS 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 | Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) | -0.84 units on a scale | Standard Error 0.24 |
| 2 mg Baricitinib | Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) | -1.92 units on a scale | Standard Error 0.3 |
| 4 mg Baricitinib | Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) | -1.58 units on a scale | Standard Error 0.29 |
| 4 mg Baricitinib | Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) | -1.93 units on a scale | Standard Error 0.26 |
p-value: 0.00595% CI: [-1.84, -0.32]Mixed Models Analysis
p-value: 0.05195% CI: [-1.48, 0]Mixed Models Analysis
p-value: 0.00295% CI: [-1.79, -0.39]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, 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, 16 Weeks
Population: All randomized participants with Week 16 POEM 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 | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -2.68 units on a scale | Standard Error 0.76 |
| 2 mg Baricitinib | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -5.32 units on a scale | Standard Error 0.93 |
| 4 mg Baricitinib | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -6.26 units on a scale | Standard Error 0.91 |
| 4 mg Baricitinib | Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) | -7.84 units on a scale | Standard Error 0.8 |
p-value: 0.02895% CI: [-4.98, -0.29]Mixed Models Analysis
p-value: 0.00395% CI: [-5.89, -1.27]Mixed Models Analysis
p-value: <0.00195% CI: [-7.33, -2.99]Mixed Models Analysis
Secondary
Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm
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 United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Means were calculated using 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, 16 Weeks
Population: All randomized participants with Week 16 EQ-5D-5L Health State Index US and UK 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 | 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 and United Kingdom Algorithm | Health State Index Score (US Algorithm) | 0.01 units on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (UK Algorithm) | 0.01 units on a scale | Standard Error 0.02 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (UK Algorithm) | 0.07 units on a scale | Standard Error 0.02 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (US Algorithm) | 0.05 units on a scale | Standard Error 0.02 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (US Algorithm) | 0.05 units on a scale | Standard Error 0.02 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (UK Algorithm) | 0.07 units on a scale | Standard Error 0.02 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (US Algorithm) | 0.09 units on a scale | Standard Error 0.01 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm | Health State Index Score (UK Algorithm) | 0.13 units on a scale | Standard Error 0.02 |
Comparison: Health State Index Score (US algorithm)p-value: 0.06195% CI: [0, 0.08]Mixed Models Analysis
Comparison: Health State Index Score (US algorithm)p-value: 0.0695% CI: [0, 0.08]Mixed Models Analysis
Comparison: Health State Index Score (US algorithm)p-value: <0.00195% CI: [0.04, 0.12]Mixed Models Analysis
Comparison: Health State Index Score (UK Algorithm)p-value: 0.04695% CI: [0, 0.11]Mixed Models Analysis
Comparison: Health State Index Score (UK Algorithm)p-value: 0.05995% CI: [0, 0.11]Mixed Models Analysis
Comparison: Health State Index Score (UK algorithm)p-value: <0.00195% CI: [0.06, 0.16]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 ranged 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 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, 16 Weeks
Population: All randomized participants with Week 16 EQ-5D-5L VAS 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 | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 2.00 millimeters | Standard Error 2.04 |
| 2 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 4.97 millimeters | Standard Error 2.53 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 3.35 millimeters | Standard Error 2.41 |
| 4 mg Baricitinib | Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) | 9.05 millimeters | Standard Error 2.17 |
Comparison: EQ-5D-5L VAS Scorep-value: 0.35695% CI: [-3.36, 9.3]Mixed Models Analysis
Comparison: EQ-5D-5L VAS Scorep-value: 0.66895% CI: [-4.81, 7.5]Mixed Models Analysis
Comparison: EQ-5D-5L VAS Scorep-value: 0.01795% CI: [1.25, 12.86]Mixed Models Analysis
Secondary
Change From Baseline on the Hospital Anxiety and 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, 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, 16 Weeks
Population: All randomized participants with Week 16 HADS 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 | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Depression | -0.37 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Anxiety | -0.90 units on a scale | Standard Error 0.28 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Anxiety | -1.35 units on a scale | Standard Error 0.34 |
| 2 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Depression | -1.04 units on a scale | Standard Error 0.34 |
| 4 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Anxiety | -1.83 units on a scale | Standard Error 0.33 |
| 4 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Depression | -1.40 units on a scale | Standard Error 0.32 |
| 4 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Depression | -1.50 units on a scale | Standard Error 0.29 |
| 4 mg Baricitinib | Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) | Anxiety | -2.05 units on a scale | Standard Error 0.3 |
Comparison: HADS Anxietyp-value: 0.30595% CI: [-1.3, 0.41]Mixed Models Analysis
Comparison: HADS Anxietyp-value: 0.02995% CI: [-1.77, -0.1]Mixed Models Analysis
Comparison: HADS Anxietyp-value: 0.00495% CI: [-1.93, -0.36]Mixed Models Analysis
Comparison: HADS Depressionp-value: 0.11395% CI: [-1.51, 0.16]Mixed Models Analysis
Comparison: HADS Depressionp-value: 0.01495% CI: [-1.85, -0.22]Mixed Models Analysis
Comparison: HADS Depressionp-value: 0.00495% CI: [-1.91, -0.37]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 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, 16 Weeks
Population: All randomized participants with Week 16 WPAI-AD 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 | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -2.89 units on a scale | Standard Error 2.6 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | -0.49 units on a scale | Standard Error 1.68 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -5.67 units on a scale | Standard Error 2.16 |
| Placebo | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Work Productivity Loss | -2.57 units on a scale | Standard Error 2.89 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -12.98 units on a scale | Standard Error 2.63 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | -4.54 units on a scale | Standard Error 2.15 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Work Productivity Loss | -11.23 units on a scale | Standard Error 3.75 |
| 2 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -9.75 units on a scale | Standard Error 3.37 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -10.80 units on a scale | Standard Error 2.57 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | -0.84 units on a scale | Standard Error 2.23 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -11.53 units on a scale | Standard Error 3.44 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Work Productivity Loss | -9.06 units on a scale | Standard Error 3.83 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Work Productivity Loss | -13.85 units on a scale | Standard Error 3.29 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Activity Impairment | -22.20 units on a scale | Standard Error 2.3 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Absenteeism | -3.89 units on a scale | Standard Error 1.88 |
| 4 mg Baricitinib | Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire | Presenteeism | -15.17 units on a scale | Standard Error 2.95 |
Comparison: Percentage of Presenteeism (Reduced Productivity While at Work) Change from Baselinep-value: 0.04595% CI: [-17.09, -0.19]Mixed Models Analysis
Comparison: Percentage of Absenteeism Change from Baselinep-value: 0.13695% CI: [-9.39, 1.29]Mixed Models Analysis
Comparison: Percentage of Absenteeism Change from Baselinep-value: 0.89895% CI: [-5.81, 5.1]Mixed Models Analysis
Comparison: Percentage of Absenteeism Change from Baselinep-value: 0.17495% CI: [-8.32, 1.52]Mixed Models Analysis
Comparison: Percentage of Presenteeism (Reduced Productivity While at Work) Change from Baselinep-value: 0.10495% CI: [-15.13, 1.41]Mixed Models Analysis
Comparison: Percentage of Presenteeism (Reduced Productivity While at Work) Change from Baselinep-value: 0.00295% CI: [-19.97, -4.59]Mixed Models Analysis
Comparison: Work Productivity Loss (Percentage Overall Work Impairment/Absenteeism Plus Presenteeism) Change from Baselinep-value: 0.06695% CI: [-17.89, 0.57]Mixed Models Analysis
Comparison: Work Productivity Loss (Percentage Overall Work Impairment/Absenteeism Plus Presenteeism) Change from Baselinep-value: 0.17595% CI: [-15.89, 2.91]Mixed Models Analysis
Comparison: Work Productivity Loss (Percentage Overall Work Impairment/Absenteeism Plus Presenteeism) Change from Baselinep-value: 0.0195% CI: [-19.84, -2.72]Mixed Models Analysis
Comparison: Percentage of Activity Impairment Change from Baselinep-value: 0.0395% CI: [-13.93, -0.7]Mixed Models Analysis
Comparison: Percentage of Activity Impairment Change from Baselinep-value: 0.12295% CI: [-11.65, 1.39]Mixed Models Analysis
Comparison: Percentage of Activity Impairment Change from Baselinep-value: <0.00195% CI: [-22.64, -10.41]Mixed Models Analysis
Secondary
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)
The Itch Numeric Rating Scale (NRS) is a participant-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 participants 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. 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 a 4-Point Improvement in Itch Numeric Rating Scale (NRS) | 7.2 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) | 10.5 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) | 12.0 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) | 21.5 percentage of participants |
p-value: 0.24695% CI: [0.72, 3.56]Regression, Logistic
p-value: 0.16995% CI: [0.79, 3.77]Regression, Logistic
p-value: <0.00195% CI: [1.82, 7.18]Regression, Logistic
Secondary
Percentage 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: 16 Weeks
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 EASI50 | 15.3 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving EASI50 | 26.0 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving EASI50 | 30.1 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving EASI50 | 41.6 percentage of participants |
p-value: 0.01995% CI: [1.11, 3.25]Regression, Logistic
p-value: <0.00195% CI: [1.44, 4.14]Regression, Logistic
p-value: <0.00195% CI: [2.51, 6.96]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: 16 Weeks
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 | 4.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving EASI90 | 8.7 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving EASI90 | 10.6 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving EASI90 | 16.0 percentage of participants |
p-value: 0.2195% CI: [0.74, 4.05]Regression, Logistic
p-value: 0.02995% CI: [1.1, 5.7]Regression, Logistic
p-value: <0.00195% CI: [1.91, 8.91]Regression, Logistic
Secondary
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)
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: 16 Weeks
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 Eczema Area and Severity Index 75 (EASI75) | 8.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 17.3 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 18.7 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 24.8 percentage of participants |
p-value: 0.03295% CI: [1.06, 3.88]Regression, Logistic
p-value: 0.00695% CI: [1.29, 4.67]Regression, Logistic
p-value: <0.00195% CI: [2.01, 6.89]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: 16 Weeks
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 IGA of 0 | 0.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving IGA of 0 | 1.6 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving IGA of 0 | 2.4 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving IGA of 0 | 1.6 percentage of participants |
p-value: 0.42495% CI: [0.37, 10.63]Regression, Logistic
p-value: 0.18295% CI: [0.61, 13.75]Regression, Logistic
p-value: 0.44195% CI: [0.36, 10.41]Regression, Logistic
Secondary
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib)
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: 16 Weeks
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 IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib) | 4.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib) | 11.8 percentage of participants |
p-value: 0.01495% CI: [1.23, 6.01]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: 4 Weeks
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 | 2.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 3.1 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 8.9 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement | 10.4 percentage of participants |
p-value: 0.60395% CI: [0.41, 4.71]Regression, Logistic
p-value: 0.00695% CI: [1.5, 11.12]Regression, Logistic
p-value: 0.00295% CI: [1.78, 12.55]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: 16 Weeks
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 SCORAD90 | 0.8 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORAD90 | 0.8 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving SCORAD90 | 2.4 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving SCORAD90 | 2.4 percentage of participants |
p-value: 0.87495% CI: [0.17, 7.77]Regression, Logistic
p-value: 0.17695% CI: [0.62, 13.36]Regression, Logistic
p-value: 0.20195% CI: [0.59, 12.65]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 visual analog scale (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: 16 Weeks
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) | 1.2 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 5.5 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 7.3 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) | 10.4 percentage of participants |
p-value: 0.02595% CI: [1.2, 15.24]Regression, Logistic
p-value: 0.00495% CI: [1.79, 20.99]Regression, Logistic
p-value: <0.00195% CI: [2.68, 28.58]Regression, Logistic
Secondary
Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment
Percentage of participants developing skin infections requiring antibiotic treatment.
Time frame: 16 Weeks
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 Developing Skin Infections Requiring Antibiotic Treatment | 4.4 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 0.8 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 4.9 percentage of participants |
| 4 mg Baricitinib | Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment | 3.2 percentage of participants |
p-value: 0.067Fisher Exact
p-value: 0.799Fisher Exact
p-value: 0.782Fisher Exact
Secondary
Percent Change From Baseline in EASI Score
The EASI assesses objective physician estimates of 2 dimensions of AD - 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 Square (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 effect
Time frame: Baseline, 16 Weeks
Population: All randomized participants who had 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 | -34.82 percent change | Standard Error 3.64 |
| 2 mg Baricitinib | Percent Change From Baseline in EASI Score | -48.22 percent change | Standard Error 4.52 |
| 4 mg Baricitinib | Percent Change From Baseline in EASI Score | -51.89 percent change | Standard Error 4.29 |
| 4 mg Baricitinib | Percent Change From Baseline in EASI Score | -59.36 percent change | Standard Error 3.84 |
p-value: 0.02195% CI: [-24.77, -2.03]Mixed Models Analysis
p-value: 0.00295% CI: [-28.05, -6.1]Mixed Models Analysis
p-value: <0.00195% CI: [-34.84, -14.24]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, 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, 16 Weeks
Population: All randomized participants with Week 16 Itch NRS 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 Itch NRS | -12.04 Percent Change | Standard Error 4.65 |
| 2 mg Baricitinib | Percent Change From Baseline in Itch NRS | -31.30 Percent Change | Standard Error 5.7 |
| 4 mg Baricitinib | Percent Change From Baseline in Itch NRS | -29.43 Percent Change | Standard Error 5.45 |
| 4 mg Baricitinib | Percent Change From Baseline in Itch NRS | -36.55 Percent Change | Standard Error 4.88 |
p-value: 0.00995% CI: [-33.69, -4.81]Mixed Models Analysis
p-value: 0.01595% CI: [-31.43, -3.35]Mixed Models Analysis
p-value: <0.00195% CI: [-37.71, -11.3]Mixed Models Analysis