Modulation of the Immune System in Down Syndrome for Improved Outcomes and Neurodevelopment - 1

Exclusion Criteria

• •1. Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment.
• •2. Current or planned use of a JAK inhibitor during the 6-month study period.
• •3. Known allergies, hypersensitivity, or intolerance to tofacitinib.
• •4. Active, uncontrolled, or life-threatening infection that at the determination of the treating physician would preclude safe use of tofacitinib.
• •5. History of gastrointestinal perforation.
• •6. Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study.
• •Note on vaccines: Participants not yet vaccinated for MMR-V should consider their timeline for MMR-V vaccination. Specifically, the study team recommends MMR-V vaccination as soon as possible and delay study start until 6 weeks after MMR-V vaccinations.
• •7. Concomitant treatment with any of the following:
• •1. Concomitant treatment with other immunosuppressants (e.g., methotrexate, azathioprine, tacrolimus, cyclosporine).
• •2. Strong CYP3A4 inhibitors (e.g., ketoconazole).
• •3. Strong CYP3A4 Inducers (e.g., rifampin).
• •4. Moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole).
• •5. Other supplements or medications that at the determination of the treating physician would preclude safe use of tofacitinib.
• •8. Evidence of severe organ dysfunction, including severe renal impairment, that at the determination of the treating physician would preclude safe administration of tofacitinib.
• •9. Any history of leukemia, lymphoma, or unresolved transient myeloproliferative disorder.
• •10. Any current, recurrent, or metastatic forms of cancer.
• •11. Any cancer treatment within five years prior to study entry.
• •12. Known personal history of thrombosis or bleeding disorder.
• •13. History of tuberculosis, disseminated herpes zoster, disseminated herpes simplex, or recurrent localized herpes zoster.
• •14. Intravenous antimicrobial therapy within 3 months of inclusion in the study.
• •15. History of organ or bone marrow transplant.
• •16. History of myocardial infarction or stroke.
• •17. Evidence of lipid disorder, including but not limited to LDL \> 190 mg/dL, per discretion of the treating physician.
• •18. Participant received blood or plasma products within 30 days of the Baseline visit.
• •19. Treatment with intravenous immunoglobulin (IVIG) within 8 weeks of the Baseline visit.
• •20. Hospitalization longer than 6 months in the last year.
• •21. History of neurological syndrome that in the opinion of the study doctors would inhibit successful participation in the study.
• •22. Less than 6 weeks post-surgery at Baseline appointment.
• •23. Total vision or hearing loss (with no corrective devices available).
• •24. Participant must be able to attempt the neurodevelopment assessment battery at Baseline and caregiver must be able to complete proxy reports for neurodevelopmental assessments.
• •25. Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements.
• •26. Participants may be excluded for other unforeseen reasons at the study doctor's discretion.
• •27. Pregnancy or breastfeeding.
• •28. Use of estrogen-containing oral contraceptives.