A Pilot Study to Evaluate the Safety and Tolerability of Baricitinib in Patients With Job s Syndrome With Lupus-like Disease and/or Atopic Dermatitis
Background: Autosomal dominant hyper-IgE syndrome (HIES), also called Job syndrome, is a genetic disorder that affects the immune system. It can cause skin and lung infections and problems with blood vessels, connective tissues, and bones. People with HIES often have lupus-like disease or atopic dermatitis (skin rash). Researchers want to know if a drug approved to treat other immune system diseases (baricitinib) can help people with HIES.
Objective: To test baricitinib in people with HIES with lupus-like disease or skin rash.
Eligibility: People aged 12 years and older with HIES with lupus-like disease or skin rash.
Design: Participants will have 5 clinic visits, 4 remote visits, and 2 phone visits in 9 months. Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of the speed and pressure of blood flow through their body: Blood pressure cuffs will be placed on each arm and leg; electrodes will be placed on the wrists and a microphone on the chest. The study has a 3-month lead-in period. Participants will not take the study drug during this time. They will continue with their usual medical care. They will have 2 phone calls with the study team. Baricitinib is a tablet taken by mouth. Participants will take 1 or 2 tablets by mouth every day for 6 months. They will start with a low dose and may increase to a higher dose. Blood and urine tests will be repeated during each study visit. Other tests may also be repeated during some visits. A skin sample may also be taken....
∙ To be eligible to participate in this study, an individual must meet all of the following criteria:
• Must be able to understand and provide informed consent or assent.
• Aged \>=12 years.
• Documented STAT3 variant causing hyper-IgE syndrome.
• Enrollment in NIH protocol 00-I-0159, Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES).
• a. Presence of SLE and/or AD as follows: SLE patients should meet either Systemic Lupus International Collaborating Clinics (SLICC) or 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) SLE classification criteria. AD is defined as EASI tool score \>=16 and body surface area tool score of 10% at screening.
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• For individuals on glucocorticoids, the dose must be less than 10 mg daily and stable for the 30 days prior to Day 0.
• For individuals on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the dose must have been stable for 90 days prior to Day 0. The maximum allowed dose is hydroxychloroquine 400 mg/day or 6.5 mg/kg/day, whichever is greater. The maximum allowed dose for chloroquine phosphate is 500 mg daily, and for quinacrine is 100 mg daily.
• Individuals may be on lipid-lowering medications if initiated at least 90 days prior to Day 0, and the dose must be stable for 30 days prior to Day 0.
• Individuals of reproductive potential must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy while on study drug. Acceptable methods of contraception include:
‣ Intrauterine device (IUD)
⁃ Bilateral tubal ligation
⁃ Abstinence
⁃ Vasectomized partner
⁃ Hormonal contraception used in combination with barrier method: progestogen containing (oral, intravaginal, transdermal) or progestogen-only (oral, injectable, implantable) starting 30 days prior to initiation of baricitinib