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

Prior treatment

• 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 had any major surgery within 8 weeks before screening or will require major surgery during the study
• 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 donated more than one unit of blood in the 4 weeks before screening or who intend to donate blood during the trial.

Other illness

• Patients who have uncontrolled hypertension (repeated systolic blood Pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) in a seated position.
• 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 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

Lab values

• Have any of the following specific abnormalities on screening laboratory tests:
  • AST or ALT ≥2x upper limit of normal (ULN)
  • Alkaline phosphatase (ALP) ≥2x ULN
  • Total bilirubin ≥1.5x ULN
  • Hemoglobin \<10.0 g/dL (100.0 g/L)
  • Total white blood cell count \<2500 cells/μL (\<2.50x103/μL or \<2.50 GI/L)
  • Neutropenia (absolute neutrophil count \[ANC\] \<1200 cells/μL) (\<1.20x103/μL or \<1.20 GI/L)
  • Lymphopenia (lymphocyte count \<750 cells/μL) (\<0.75x103/μL or \<0.75 GI/L)
  • Thrombocytopenia (platelets \<100,000/μL) (\<100x103/μL or \<100 GI/L) i. eGFR \<40 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration equation \[CKD-EPI\] Creatinine 2009 equation).

Other

• Patients who are immunocompromised and have unacceptable risk for taking part in the trial.
• Patients who are Pregnant/lactating or planning to become pregnant during the study period (men and women)

• 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.