Baricitinib Versus Azathioprine in Patients With Moderate-to-Severe Atopic Dermatitis

NCT05969730 | Completed

• 1 other identifier: IR.MAZUMS.REC.1402.17653
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Atopic dermatitis, which is also known as atopic eczema, is a common inflammatory and chronic skin disease that is characterized by severe recurrent erythematous and pruritic lesions. Patients suffer from decreased quality of life and poor work productivity due to the disease complications like persistent scratching, skin pain, skin damage, sleep disturbances, and social/emotional distress. In the United States (US), the prevalence of adults with atopic dermatitis ranges from 5% to 10%. The mainstay treatment for atopic dermatitis is emollient and tropical corticosteroids which could be efficient for less severe atopic dermatitis patients but moderate to severe patients usually need additional therapies like phototherapy or systemic medications. It is revealed that Janus kinase signal transducers and activators of transcription (JAK-STAT) pathway has a prominent role in the development and progression of atopic dermatitis. JAK1/JAK2 inhibitor, baricitinib is a new-class orally available drug that is approved for systemic treatment of adult patients with moderate to severe atopic dermatitis. In the phase III clinical trial baricitinib 2-mg and 4-mg were shown efficient results as monotherapy of adult patients with moderate to severe atopic dermatitis who have an inadequate response to topical corticosteroids (TCS). Azathioprine is an immunosuppressant and antimetabolite agent interferes with the formation of lymphocytes, and suppresses prostaglandin synthesis, both of which are implicated in the inflammation associated with eczema. Azathioprine can be used (off-label) for moderate to severe atopic dermatitis patients. Multiple studies have demonstrated that azathioprine might be effective for patients with moderate-to-severe atopic dermatitis. Azathioprine is usually prescribed when cyclosporine is either contraindicated or not effective. This trial will be conducted to test the hypothesis that baricitinib 4-mg daily in combination with TCS is superior to azathioprine 1.5-2.5 mg/kg a day in combination with TCS for moderate-to-severe AD at week 12 in terms of efficacy and safety.

Conditions

Atopic Dermatitis

Keywords

Baricitinib; Azathioprine; Atopic Dermatitis; Moderate-to-Severe Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• Eczema Area and Severity Index (EASI)

  The EASI is used to measure extent of eczema in 4 body regions (head/neck, trunk, upper limbs, and lower limbs) and assesses the following 4 clinical signs: (1) Erythema/Redness, (2) Thickness/Edema/Papulation, (3) Excoriation/Scratching (4) Lichenification. The intensity of each sign in each body region is assessed as: none (0), mild (1), moderate (2) and severe (3). The EASI score is ranged from 0 to 72. The higher score indicates a worse condition.

  12 weeks

Secondary Outcomes (10)

• Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD)

  12 weeks

• SCORing Atopic Dermatitis (SCORAD)

  12 weeks

• Body surface area affected (BSA-Affected)

  12 weeks

• Dermatology Life Quality Index (DLQI)

  12 weeks

• Itch Numeric Rating Scale (Itch NRS)

  12 weeks

Study Arms (2)

A

EXPERIMENTAL

Baricitinib 4-mg daily plus fluocinolone 0.025% topical ointment and daily emollient of urea 10% topical cream

Drug: Baricitinib 4 MG

B

EXPERIMENTAL

Azathioprine 1.5-2.5 mg/kg plus fluocinolone 0.025% topical ointment and daily emollient of urea 10% topical cream

Drug: Azathioprine 1.5-2.5 mg/kg

Interventions

Baricitinib 4 MG DRUG

In visit 1 which will be scheduled after the washout period, demographic information and baseline assessment will be conducted and patients will randomize into arms, baricitinib 4-mg daily plus fluocinolone 0.025% topical ointment and daily emollient of urea 10% topical cream (Arm A). Six weeks after visit 1, Visit 2 will be set to follow up on the patient condition, particularly in terms of adverse effects, and reorder their intervention. Visit 3 will be 12 weeks after visit 1 to perform the final assessment.

A

Azathioprine 1.5-2.5 mg/kg DRUG

In visit 1 which will be scheduled after the washout period, demographic information and baseline assessment will be conducted and patients will randomize into arms, azathioprine 1.5-2.5 mg/kg plus fluocinolone 0.025% topical ointment and daily emollient of urea 10% topical cream (Arm B). Six weeks after visit 1, Visit 2 will be set to follow up on the patient condition, particularly in terms of adverse effects, and reorder their intervention. Visit 3 will be 12 weeks after visit 1 to perform the final assessment.

B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with minimum age of 18 years and maximum 75 years at the time of informed consent
• Patients who can read, understand, and provide written informed consent
• Individuals with atopic dermatitis who have had a diagnosis for at least 12 months before to screening, as defined by the American Academy of Dermatology: Guidelines of care for the management of atopic dermatitis; Section 1. Diagnosis and assessment of atopic dermatitis \[14\].
• Patients with moderate to severe atopic dermatitis which is defined as having Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and body surface area (BSA) affected ≥10%
• Individuals who have a documented history of insufficient response to topical treatments (at least a moderate potency topical corticosteroids and/or cyclosporine for at least 4 weeks or the maximum duration recommended for the product prescribed) within the 6 months before screening determined by a dermatologist.
• Patients who accept to discontinue using (1) oral systemic corticosteroids, (2) systemic immunomodulators such as methotrexate, cyclosporine, and mycophenolate mofetil, and (3) any other systemic therapy used to treat atopic dermatitis (approved or off-label use), for at least 4 weeks before randomization and throughout the study.
• Patients who accept to discontinue (1) immune modulators (e.g., tacrolimus or pimecrolimus) (2) Topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole) (3) sedating antihistamines (both old and new generations) (4) phototherapy, includes therapeutic phototherapy (psoralen plus ultraviolet A, ultraviolet B), excimer laser as well as self-treatment with tanning beds, at least 2 weeks prior to randomization.
• Patients who agree to use emollients daily for at least 14 days before randomization and who agree to continue using emollients daily during the treatment period.
• Patients undergoing chronic therapies to improve sleep should be on a stable dosage for at least 2 weeks before screening. Antihistamines with sedative effects are not approved.

You may not qualify if:

• Patients who are currently suffering from or have a history of any concurrent skin disorders that would interfere with assessments of the study medication's effect on atopic dermatitis. For example, psoriasis or lupus erythematosus or eczema herpeticum, or erythrodermic, refractory, or unstable skin disease, including, but not limited, eczema that requires hospitalizations and/or intravenous treatment for skin infections.
• Patients who have a known hypersensitivity to baricitinib or azathioprine or any component of these investigational products
• Patients with any major concomitant disease that is expected to need the administration of systemic corticosteroids, such as unstable chronic asthma, or who otherwise interfere with trial participation or require active regular monitoring.
• Patients who have been treated (1) Treatment with azathioprine in the previous 3 months (2) Having an experience of treatment with any oral JAK inhibitors including baricitinib \< 4 weeks prior to randomization (3) Fusion proteins that target inflammatory pathways or monoclonal antibodies for less than 5 half-lives before randomization (4) Any parenteral corticosteroid administered by intramuscular/intravenous/intra-articular injection within 6 weeks before randomization or is anticipated to require a parenteral injection of corticosteroids during the study (5) probenecid at the time of randomization that cannot be discontinued for the duration of the study
• Patients who have uncontrolled hypertension (repeated systolic blood Pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) in a seated position.
• Patients who have had any major surgery within 8 weeks before screening or will require major surgery during the study
• Patients who are immunocompromised and have unacceptable risk for taking part in the trial.
• Patients who have recently experienced myocardial infarction (MI) , or stroke, or venous thromboembolism (VTE) or recurrent VTE (≥2) , or unstable ischemic heart disease, or New York Heart Association Stage III/IV heart failure
• Patients who have a history of or are currently suffering from any major and/or unstable disease that might provide an unacceptable risk while taking an investigational medication or interfere with data interpretation including but not limited mentally incompetent, current active pancreatitis, cardiovascular, endocrine, respiratory, gastrointestinal, hepatic, hematological, lymphoproliferative, neurological, or neuropsychiatric disorders.
• Patients with a recent or present clinically significant viral, bacterial, fungal, or parasitic infection (including, but not limited, HIV, TB, Viral hepatitis)
• Patients who have been exposed to a live vaccine 12 weeks before randomization, or are likely to require/receive a live vaccine throughout the course of the trial
• Patients who have a history of persistent alcoholism, intravenous drug addiction, or other illicit substance usage during the last 2 years.
• Patients who have a history of organ transplantation
• Patients who have donated more than one unit of blood in the 4 weeks before screening or who intend to donate blood during the trial.
• Patients who are Pregnant/lactating or planning to become pregnant during the study period (men and women)

Sponsors & Collaborators

• Mazandaran University of Medical Sciences: lead

Study Sites (1)

Iran

Sari, Mazandaran, Iran

Location

Related Publications (14)

• Lio PA, Simpson EL, Han G, Soung J, Ball S, Sun L, Casillas M, DeLozier AM, Ding Y, Eichenfield LF. Improvement in sleep and itch and enhanced quality of life in adult patients with moderate-to-severe atopic dermatitis: results from a phase 3 trial of baricitinib therapy. J Dermatolog Treat. 2022 Jun;33(4):2057-2062. doi: 10.1080/09546634.2021.1914308. Epub 2021 Jun 28.

  PMID: 34176407 BACKGROUND

• Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, King BA, Thyssen JP, Silverberg JI, Bieber T, Kabashima K, Tsunemi Y, Costanzo A, Guttman-Yassky E, Beck LA, Janes JM, DeLozier AM, Gamalo M, Brinker DR, Cardillo T, Nunes FP, Paller AS, Wollenberg A, Reich K. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020 Aug;183(2):242-255. doi: 10.1111/bjd.18898. Epub 2020 Mar 5.

  PMID: 31995838 BACKGROUND

• Barbarot S, Auziere S, Gadkari A, Girolomoni G, Puig L, Simpson EL, Margolis DJ, de Bruin-Weller M, Eckert L. Epidemiology of atopic dermatitis in adults: Results from an international survey. Allergy. 2018 Jun;73(6):1284-1293. doi: 10.1111/all.13401. Epub 2018 Feb 13.

  PMID: 29319189 BACKGROUND

• Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis. Dermatol Ther. 2022 Sep;35(9):e15636. doi: 10.1111/dth.15636. Epub 2022 Jul 27.

  PMID: 35703351 BACKGROUND

• Wollenberg A, Nakahara T, Maari C, Peris K, Lio P, Augustin M, Silverberg JI, Rueda MJ, DeLozier AM, Pierce E, Yang FE, Sun L, Ball S, Tauber M, Paul C. Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. J Eur Acad Dermatol Venereol. 2021 Jul;35(7):1543-1552. doi: 10.1111/jdv.17278. Epub 2021 Jun 5.

  PMID: 33834521 BACKGROUND

• Bieber T, Reich K, Paul C, Tsunemi Y, Augustin M, Lacour JP, Ghislain PD, Dutronc Y, Liao R, Yang FE, Brinker D, DeLozier AM, Meskimen E, Janes JM, Eyerich K; BREEZE-AD4 study group. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol. 2022 Sep;187(3):338-352. doi: 10.1111/bjd.21630. Epub 2022 Jul 20.

  PMID: 35484697 BACKGROUND

• Bracho-Borro M, Franco-Ruiz PA, Magana M. The use of azathioprine in atopic dermatitis: A review. Dermatol Ther. 2022 Sep;35(9):e15665. doi: 10.1111/dth.15665. Epub 2022 Jul 10.

  PMID: 35751547 BACKGROUND

• Murphy LA, Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 2002 Aug;147(2):308-15. doi: 10.1046/j.1365-2133.2002.04922.x.

  PMID: 12174104 BACKGROUND

• Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006 Mar 11;367(9513):839-46. doi: 10.1016/S0140-6736(06)68340-2.

  PMID: 16530578 BACKGROUND

• Wollenberg A, Szepietowski J, Taieb A, Ring J. Corrigendum: Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2019 Jul;33(7):1436. doi: 10.1111/jdv.15719. No abstract available.

  PMID: 31259446 BACKGROUND

• Gerbens LAA, Hamann SAS, Brouwer MWD, Roekevisch E, Leeflang MMG, Spuls PI. Methotrexate and azathioprine for severe atopic dermatitis: a 5-year follow-up study of a randomized controlled trial. Br J Dermatol. 2018 Jun;178(6):1288-1296. doi: 10.1111/bjd.16240. Epub 2018 Apr 10.

  PMID: 29237228 BACKGROUND

• Silverberg JI, Lei D, Yousaf M, Janmohamed SR, Vakharia PP, Chopra R, Chavda R, Gabriel S, Patel KR, Singam V, Kantor R, Hsu DY. What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study. Br J Dermatol. 2021 May;184(5):888-895. doi: 10.1111/bjd.19457. Epub 2020 Sep 21.

  PMID: 32959390 BACKGROUND

• Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Sidbury R. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014 Feb;70(2):338-51. doi: 10.1016/j.jaad.2013.10.010. Epub 2013 Nov 27.

  PMID: 24290431 BACKGROUND

• Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Dec 1;156(12):1333-1343. doi: 10.1001/jamadermatol.2020.3260.

  PMID: 33001140 BACKGROUND

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

baricitinib; Azathioprine

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Intern

Model Details: BAAZ-AD-IR is a single-center, open-label, randomized trial which will be conducted in Iran. Patients who meet eligibility criteria will randomize (1:1) to receive baricitinib 4 mg daily or azathioprine 1.5-2.5 mg/kg for 12 weeks. All patients will receive emollient daily. Four weeks prior to randomization, patients will discontinue tropical and systemic treatments for atopic dermatitis and will not be allowed to use them during the study. The drugs will be prescribed at visit 1 (randomization day, or four weeks after screening). All demographics and baseline information will be gathered at visit 1. Six weeks after visit 1, visit 2 will be scheduled for each patient. At visit 2, patients will be followed up. Twelve weeks after visit 1, visit 3 will be scheduled, and final assessments will be done.

Study Record Dates

• First Submitted: July 23, 2023
• First Posted: August 1, 2023
• Study Start: August 15, 2023
• Primary Completion: April 30, 2025
• Study Completion: November 14, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

IR (1)