A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable

Atopic Dermatitis Clinical Trial

— BREEZE-AD4  

Official title:

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety and Efficacy of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or Are Intolerant to, or Have Contraindication to, Cyclosporine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03428100
• Other study ID #: 16841
• Secondary ID: I4V-MC-JAIN2017-
• Status: Completed
• Phase: Phase 3
• Start date: May 15, 2018
• Est. completion date: April 20, 2023

Study information

• Verified date: April 15, 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: April 20, 2023
• Est. primary completion date: November 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months.
• Have had inadequate response 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.
• Have a medical contraindication to cyclosporine, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine in the past.

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 episodes of eczema herpeticum in the past.
• Participants who are currently experiencing a skin infection that requires treatment, or are 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 less than 4 weeks prior to randomization.
• Received oral corticosteroids within 4 weeks prior to randomization or 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, gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
• Have a current or recent and/or clinically serious viral, bacterial, fungal, or parasitic infection including but not limited to herpes zoster, tuberculosis.
• Have specific laboratory abnormalities related to thyroid, renal and liver function, or blood cells.
• Have received certain treatments that are contraindicated.
• Pregnant or breastfeeding.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Baricitinib
Administered orally.
• Placebo
Administered orally.
• Topical corticosteroid
Administered as standard-of-care.

Locations

Country	Name	City	State
Austria	Universitätsklinikum Graz	Graz	Steiermark
Austria	Universitätsklinik Innsbruck	Innsbruck	Tyrol
Austria	AKH	Wien
Austria	KA Rudolfstiftung	Wien
Austria	Sozialmed. Zentrum Ost - Donauspital	Wien
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UZ Leuven - Campus Sint-Rafaël	Leuven
Brazil	Faculdade de Ciências Médicas - UNICAMP	Campinas	Sao Paulo
Brazil	Hospital Moinhos de Vento - Instituto de Educação e Pesquisa	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da FMRP	Ribeirao Preto	SP
Brazil	CCBR Brasil Centro de Analises e Pesquisas Clínicas LTDA	Rio de Janeiro	RJ
Brazil	IDERJ - Instituto de Dermatologia e Estética do Brasil	Rio de Janeiro	RJ
Brazil	Fundação Faculdade de Medicina do ABC	Santo André	Sao Paulo
Brazil	Hospital da Clinicas da Faculdade de Medicina da USP	Sao Paulo
Brazil	Cedoes Centro Diagnostico Pequisa Osteoporose E Santo Ltd	Vitoria	ES
Finland	Helsinki University Central Hospital	Helsinki
Finland	Terveystalo Tampere	Tampere	Irkanmaa
Finland	Hospital Mehiläinen Neo	Turku
France	CHU de Besancon Hopital Jean Minjoz	Besancon Cedex
France	CHU de Bordeaux Hopital Saint Andre	Bordeaux Cedex
France	Hôpital C. HURIEZ	Lille
France	Hôpital Emile Muller	Mulhouse
France	Chru De Nantes Hotel-Dieu	Nantes Cedex 1
France	CHU de Nice Hopital de L'Archet	Nice cedex 3
France	Hôpital de Pontchaillou	Rennes	Cedex 9
France	Hopital Sainte Anne (H.I.A)	Toulon Cedex 9
France	Hopital Larrey	Toulouse cedex 9
France	Centre Hospitalier de Valence	Valence
Germany	Fachklinik Bad Bentheim	Bad Bentheim	Nordrhein-Westfalen
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	St Josef-Hospital Bochum	Bochum	Nordrhein-Westfalen
Germany	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Elbe Kliniken Stade Buxtehude GmbH Klinikum Buxtehude	Buxtehude	Niedersachsen
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	Universitaetsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Klinikum der Johann Wolfgang Goethe-Universität Frankfurt	Frankfurt am Main	Hessen
Germany	Universitätsklinikum Hamburg - Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Universitätsklinikum Jena	Jena	Thüringen
Germany	Universitatsmedizin der Johannes Gutenberg-Universitat Mainz	Mainz	Rheinland-Pfalz
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
Germany	Universitätsklinikum Münster	Münster	Nordrhein-Westfalen
Germany	Klinische Forschung Osnabrück	Osnabrück	Niedersachsen
Germany	Hautarztpraxis Dr. Leitz und Kollegen	Stuttgart	Baden-Württemberg
Italy	Azienda Ospedaliera Umberto I	Ancona
Italy	Spedali Civili - Universita degli Studi	Brescia
Italy	Fondazione Universitaria degli Studi G D'Annunzio	Chieti
Italy	Fondazione IRCCS Osp.Maggiore Policlinico - Dermatologia	Milano	Milan
Italy	Azienda Ospedaliera di Perugia	Perugia
Italy	Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia	Reggio Emilia
Italy	Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza	Roma	Rome
Italy	Policlinico di Tor Vergata	Roma
Italy	Ospedale Clinicizzato San Donato	San Donato Milanese	Milan
Italy	Ospedale Policlinico Giambattista Rossi, Borgo Roma	Verona
Japan	Yanagihara dermatology clinic	Ainokawa, Ichikawa-shi	Chiba
Japan	Iidabashi Clinic	Chiyoda-ku	Tokyo
Japan	Nihonbashi Sakura Clinic	Chuo-ku	Tokyo
Japan	Sumire Dermatology Clinic	Edogawa-ku	Tokyo
Japan	Fumimori Clinic	Fukuoka-shi	Fukuoka
Japan	Noguchi Dermatology	Kashima-machi, Kamimashiki-gun	Kumamoto
Japan	Yoshioka Dermatology Clinic	Neyagawa-shi	Osaka
Japan	Kume Clinic	Nishi-ku Sakai-shi	Osaka
Japan	Queen's Square Dermatology and Allergology	Nishi-ku, Yokohama-city	Kanagawa
Japan	Sanrui Dermatology Clinic	Ohmiya-ku,Saitama-shi	Saitama
Japan	Tachikawa Dermatology Clinic	Tachikawa-shi	Tokyo
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Bravis Ziekenhuis	Bergen op Zoom
Netherlands	Amphia Ziekenhuis	Breda
Poland	NZOZ Specjalistyczna Przychodnia Dermatologiczna Specderm	Bialystok
Poland	Centrum Badan Klinicznych, PI House	Gdansk
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Barbara Rewerska DIAMOND CLINIC	Krakow
Poland	Dermed Centrum Medyczne Sp. z o.o.	Lodz
Poland	Miejski Szpital Zespolony w Olsztynie Klinika Dermatologii	Olsztyn
Poland	DermoDent, Centrum Medyczne Czajkowscy	Osielsko
Poland	LASER CLINIC Specjalistyczne Gabinety Lekarskie	Szczecin
Poland	Wojskowy Instytut Medyczny CSK MON	Warsaw
Poland	Centralny Szpital Kliniczny MSW Klinika Dermatologii	Warszawa
Russian Federation	First Moscow State Medical University n.a. Sechenov	Moscow
Russian Federation	State scientific centre for dermatovenerology and cosmetolog	Moscow
Russian Federation	LLC ArsVitae NorthWest	Saint-Petersburg
Russian Federation	LLC Medical Center "Kurator"	Saint-Petersburg
Russian Federation	SPb SBHI Skin-venerologic dispensary #10	St. Petersburg
Spain	Hospital De Basurto	Bilbao	Vizcaya
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Univ. Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital de Manises	Manises	Valencia
Spain	Hospital Universitario Quiron Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario de Torrejon	Torrejón de Ardoz	Madrid
Spain	Hospital Universitario Dr Pesset	Valencia
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	The Dudley Group NHS Foundation Trust	Dudley	West Midlands
United Kingdom	West Glasgow Ambulatory Care Hospital	Glasgow	Lanarkshire
United Kingdom	Whipps Cross University Hospital	Leytonstone	London
United Kingdom	Broadgreen Hospital	Liverpool	Merseyside
United Kingdom	Guys/St. Thomas Hospital	London	Surrey
United Kingdom	Salford Royal NHS Foundation Trust	Salford	Greater Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Incyte Corporation

Countries where clinical trial is conducted

Austria,  Belgium,  Brazil,  Finland,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (Placebo, 2 mg or 4 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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 16
Secondary	Percentage of Participants Achieving EASI75 (Placebo, 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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.; Missing values were imputed using Non-Responder Imputation (NRI), where non-responders were participants who permanently discontinue, are rescued, or are without at least 1 post-baseline observation.	Week 16
Secondary	Percentage of Participants Achieving 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.	Week 16
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 (no disease) to 72 (severe disease). The EASI90 is defined as a = 90% improvement from baseline in the EASI score.	Week 16
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 (no disease) to 72 (severe disease).; Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
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.	Week 16
Secondary	Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS)	The Itch 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 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.	Week 16
Secondary	Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS)	The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. 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 Mean were calculated using an MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
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 Mean were calculated using MMRM model includes 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.	Baseline, Week 16
Secondary	Percentage of Participants Achieving 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.	Week 24
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: (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 (no disease) to 72 (severe disease). The EASI50 is defined as a = 50% improvement from baseline in the EASI score.	Week 16
Secondary	Percentage of Participants Achieving 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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 24
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.	Week 16
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 Mean 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.	Baseline, Week 16
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 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 SCORAD90 responder is defined as a participant who achieves a = 90% improvement from baseline in the SCORAD score.	Week 16
Secondary	Change From Baseline in Body Surface Area (BSA) Affected	The BSA 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 Mean were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Secondary	Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment	Percentage of participants developing skin infections requiring antibiotic treatment.	Week 16
Secondary	Mean Number of Days Without Topical Corticosteroids (TCS) Use	The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.	Week 16
Secondary	Mean Gram Quantity of Low and Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights)	Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity, and treatment as factors in the model.	Week 16
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 MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.	Baseline, Week 16
Secondary	Percent Change From Baseline in Itch NRS at Week 24	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 MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.	Baseline, Week 24
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 Mean 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-interactions as fixed continuous effects.	Baseline, Week 16
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 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.	Baseline, Week 16
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 Mean 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.	Baseline, Week 16
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 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 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.	Baseline, Week 16
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 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.	Baseline, Week 16
Secondary	Change From Baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom 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 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.	Baseline, Week 16
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-interactions as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.	Baseline, Week 16
Secondary	Percentage of Participants Achieving 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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 52
Secondary	Percent Change From Baseline in Itch NRS at Week 52	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 MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.	Baseline, Week 52
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	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. All missing values were imputed using modified last observation carried forward (mLOCF).	Week 68
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	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. All missing values were imputed using modified last observation carried forward (mLOCF).	Week 104
Secondary	Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	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.	Week 68
Secondary	Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	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.	Week 104
Secondary	Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (All Participants Entering the Substudy)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 68
Secondary	Percentage of Participants With a Response of EASI75 From Baseline Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (All Participants Entering the Substudy)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 104
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	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. All missing values were imputed using modified last observation carried forward (mLOCF).	Week 68
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	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. All missing values were imputed using mLOCF.	Week 104
Secondary	Percentage of Participants With a Response of IGA 0 or 1 Assessed at 16 Weeks After Rerandomization (Week 68) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	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. All missing values were imputed using mLOCF.	Week 68
Secondary	Percentage of Participants With a Response of IGA 0, 1 Assessed at 16 Weeks After Rerandomization (Week 104) Randomized Downtitration (Participants Entering the Substudy With IGA 0 or 1)	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. All missing values were imputed using mLOCF.	Week 104
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 68 Participants Not Entered Into Substudy (All Participants)	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. All missing values were imputed using mLOCF.	Week 68
Secondary	Percentage of Participants With a Response of IGA 0, 1, or 2 Assessed at Week 104 Participants Not Entered Into Substudy (All Participants)	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. All missing values were imputed using mLOCF.	Week 104
Secondary	Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)	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. All missing values were imputed using mLOCF.	Week 68
Secondary	Percentage of Participants With a Response of IGA 0 or 1 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)	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. All missing values were imputed using mLOCF.	Week 104
Secondary	Percentage of Participants With A Response of EASI75 Assessed at Week 68 - Participants Not Entered Into Substudy (All Participants)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 68
Secondary	Percentage of Participants With A Response of EASI75 Assessed at Week 104 - Participants Not Entered Into Substudy (All Participants)	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 (no disease) to 72 (severe disease). The EASI75 is defined as a = 75% improvement from baseline in the EASI score.	Week 104
Secondary	Time to Retreatment (Time to IGA =3) Randomized Downtitration (All Patients Entering the Substudy)	Participants who entered the Substudy and relapsed with an IGA =3.	Week 52 Up to Week 200

External Links

•   A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis (Eczema) Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Adv