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.
Ability of participant to understand and the willingness to sign a written informed consent document.
Participation and enrollment in companion protocol, 15-D-0051, Characterization of Diseases with Salivary Gland Involvement.
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged between 18-75 years old
Current or prior treatment with rituximab, belimumab, or any other biologic agent in the 6 months prior to screening.
Current or prior treatment with Tofacitinib for more than 6 months in the last 2 years prior to screening.
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on methotrexate, azathioprine, mycophenolate mofetil, cyclosporine or tacrolimus, or other DMARDs should have withdrawn drug for at least 8 weeks (56 days) at the time of screening.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.
Treatment with cyclophosphamide, pulse methylprednisolone or IVIG within 6 months prior to screening.
Single group
Tofacitinib
DrugXELJANZ(R) is the citrate salt of tofacitinib. Tofacitinib citrate is a white to off-white powder. XELJANZ(R) is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet.
Number of Adverse Events by Grade/Category
Count of adverse events by grade was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.
Participants With Adverse Events
Number participants with any adverse events by grade and severity was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activity of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.
Change in Physicians Global Assessment (PGA) Score
The Physician Global Activity (PGA) is a subjective physician reported disease activity index that uses a 10-cm Visual Analog Scale (VAS) to score a patient's disease activity. The 10-cm visual analogue scale (VAS) was scored by a physician with a vertical line on the scale marking disease activity where 0 cm indicates no evidence of disease activity, and 10 cm indicates severe disease activity, with score reported on a scale from 0-10. Higher score indicates more disease activity. Change in disease activity index was measured as the mean difference in disease activity scores between time points. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.
Change in EULAR Sjogren's Syndrome (SS) Disease Activity Index (ESSDAI) Score
The EULAR Sjogren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary SS. It includes 12 organ domains (e.g., constitutional, glandular, neurological) for disease activity, each with a 4-point scale (0 = No activity; 3=High activity). These scores are then multiplied by domain-specific weights (1-6) and summed to produce a total score ranging from 0 to 123, with higher scores indicating greater disease activity. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.
Change in Whole Unstimulated Saliva Flow
Changes in salivary flow was assessed by measuring whole unstimulated saliva flow (WUS) and glandular parotid and submandibular/sublingual unstimulated and 0.2% citric acid stimulated flow rates using ultrasonograph. Validated scoring criteria was used to assess ultrasonographic feature parameters at baseline and at the study day 168. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.
Change in Whole Stimulated Saliva Flow
Changes in salivary flow was assessed by measuring whole stimulated saliva flow and glandular parotid and submandibular/sublingual stimulated and 0.2% citric acid stimulated flow rates using ultrasonograph. Validated scoring criteria was used to assess ultrasonographic feature parameters at baseline and at the study day 168. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.
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