Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren Disease

Background: Sjogren disease is an autoimmune disease - that is, a disease that causes the body's immune system to attack its own organs and tissues. Sjogren disease can affect the kidneys, lungs, or other organs. It can also cause dry mouth and eyes, fever, joint pain, rashes, and other symptoms. Researchers want to know if a drug approved to treat rheumatoid arthritis and other autoimmune diseases can help people with Sjogren disease. Objective: To test a drug (tofacitinib) in people with Sjogren disease. Eligibility: People aged 18 to 75 years with Sjogren disease. They must be enrolled in protocol 15-D-0051. Design: * Participants will be screened. They will have a physical exam with blood and urine tests. They will give samples of saliva; a small sample of tissue will be taken from a salivary gland. They will have a test of their heart function. They will have an eye exam, including a test for dry eyes. * Tofacitinib is a tablet taken by mouth. Participants will take the drug twice a day at home. * Participants will have 9 clinic visits over 28 weeks. Each visit will take up to 5 hours. In addition to repeated tests, they will have tests of the speed and pressure of blood flow through their body. They will complete health questionnaires throughout the study. * Participants will also have 5 phone visits during the study. They will review their health and study treatments. * They will have 1 final visit after they stop taking the drug.

* INCLUSION CRITERIA: Adult SjD participants with mild-to-moderate disease activity will be eligible for this study. Enrolled participants can be naive or have failed immunosuppressive therapy beyond antimalarials and glucocorticoids, to prevent bias in the cohort of participants with more recalcitrant disease. We expect that Tofacitinib is a potential second-line therapy, in addition to antimalarials and glucocorticoids, depending on the participant's initial presentation and response. Women and members of minority groups, if eligible, will be included in accordance with the NIH Policy on Inclusion of Women and Minorities as Participants in Research Involving Human Participants. Additionally, 20-D-0131(Safety of Tofacitinib, an oral Janus Kinase Inhibitor, in primary Sjogren's syndrome Phase Ib-IIa placebo-controlled clinical trial and associated mechanistic studies) participants who, at unblinding, received a placebo will be contacted and asked to return to the study to participate in this study. To be eligible to participate in this study, an individual must meet all of the following criteria: 1. Ability of participant to understand and the willingness to sign a written informed consent document. 2. Participation and enrollment in companion protocol, 15-D-0051, Characterization of Diseases with Salivary Gland Involvement. 3. Stated willingness to comply with all study procedures and availability for the duration of the study 4. Male or female, aged between 18-75 years old 5. In good general health as evidenced by medical history 6. Meets the 2002 American European Consensus Group classification criteria for Sjogren's disease or 2016 American College of Rheumatology/European League against Rheumatism Classification Criteria (ACR-EULAR) with mild to moderate disease activity defined as ESSDAI between 0 and 13 at the screening visit and \>0 ml/min/gland stimulated saliva flow. 7. Ability to take oral medication and be willing to adhere to the study intervention regimen 8. If on glucocorticoids, the dose must be less than 10 mg daily and stable for the 4 weeks (28 days) prior to the screening visit. 9. If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the dose must have been stable for the 12 weeks (96 days) prior to screening visit. The maximum allowed dose is hydroxychloroquine up to 400 mg/day or 6.5 mg/kg/day if more than 400 mg/day. The maximum allowed dose for chloroquine phosphate is up to 500 mg daily and for quinacrine up to 100 mg daily. 10. Participants may be on lipid lowering medications if initiated at least 3 months prior to the screening visit and dose must be stable for 4 weeks (28 days) prior to study entry. 11. Males and females with potential for reproduction must agree to practice effective birth control measures. Females should be on adequate contraception if they are of child-bearing potential documented by a clinician, unless participants or spouse have previously undergone a sterilization procedure. Adequate birth control measures are: intrauterine device (IUD) alone or hormone implants, hormone patches, injectable, or oral contraceptives plus a barrier method (male condom, female condom or diaphragm), abstinence or a vasectomized partner. 12. Agreement to adhere to Lifestyle Considerations throughout study duration EXCLUSION CRITERIA: To be eligible to participate in this study, an individual must not meet any of the following criteria: 1. Current or prior treatment with rituximab, belimumab, or any other biologic agent in the 6 months prior to screening. 2. Current or prior treatment with Tofacitinib for more than 6 months in the last 2 years prior to screening. 3. Current treatment with methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or other less common immunomodulatory drugs such as those falling into the class of disease-modifying antirheumatic drugs (DMARDs), not otherwise specified herein. Participants previously on methotrexate, azathioprine, mycophenolate mofetil, cyclosporine or tacrolimus, or other DMARDs should have withdrawn drug for at least 8 weeks (56 days) at the time of screening. The use of topical or ophthalmic preparations of cyclosporine, tacrolimus, or other DMARDs is permitted and does not require an 8-week withdrawal period. 4. Treatment with cyclophosphamide, pulse methylprednisolone or IVIG within 6 months prior to screening. 5. Current treatment with potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole) or receiving one or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) that would increase serum availability of Tofacitinib. Past treatment with the agent is allowed if it was more than a week prior to the administration of the first dose of study medication. 6. History of chronic liver disease, not including well-controlled Sjogren's-related chronic liver disease or elevated LFTs: * ALT or AST \>= 2x upper limit of normal at screening * Serum unconjugated bilirubin \> 2mg/dL at screening 7. Serum creatinine \>1.5mg/dL. 8. Protein to creatinine ratio of more than 1mg/dL at screening (repeated and confirmed three times or confirmed with 24 hours urine protein of more than 1000mg). 9. Active urinary sediment (WBC, RBC or mixed cellular casts 1+ or more /hpf). 10. Hypercholesterolemia: Values after 8-12 hour fasting blood specimen: total cholesterol \>250 mg/dL or LDL \>180 mg/dL or hypertriglyceridemia (triglyceride \>300 mg/dL) within - 45 days of screening visit. 11. WBC \