Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus

Summary

Background: Systemic lupus erythematosus (lupus) is an autoimmune disease that often involves many systems and organs of the body. Symptoms can include fever, joint pains, and rashes. Serious lupus can also damage organs like the kidneys, lungs, or brain. Drugs used for lupus can have serious side effects. Also, the drugs don t help some people. Researchers want to find new, more effective and safe treatments. Objective: To evaluate the safety and tolerability of the drug tofacitinib (study drug) in people with lupus. Eligibility: People ages 18 and older who have mild to moderate lupus and are not currently or haven t recently had certain lupus treatments. Design: Participants will be screened in another protocol. Participants will have 7 five-hour visits over about 3 months. They will fill out multiple questionnaires. They will have tests, including: * Physical exam * Blood and urine tests * ECG/EKG: Soft electrodes are stuck to the skin to monitor the heart. * Optional SphygmoCor: Cuffs are attached to the arm and thigh to measure blood pressure and flow speed. * Optional Endopat: A thimble-shaped cup is placed on the finger to measure blood flow. A cuff is put on the arm to measure blood pressure and flow. * Optional CAVI: ECG electrodes are placed on both wrists, a microphone placed on the chest, and a blood pressure cuff placed on each arm and leg to measure blood pressure and velocity. Participants will receive either the study drug or a placebo. They will take this twice a day by mouth for 56 days. Participants will be contacted by phone 4 times....

Timeline

Start

2015-08-28

Primary completion

2018-04-26

Completion

2018-04-26

Publications

• Background O'Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013 Jan 10;368(2):161-70. doi: 10.1056/NEJMra1202117. No abstract available.
• Background O'Shea JJ, Laurence A, McInnes IB. Back to the future: oral targeted therapy for RA and other autoimmune diseases. Nat Rev Rheumatol. 2013 Mar;9(3):173-82. doi: 10.1038/nrrheum.2013.7. Epub 2013 Feb 19.
• Background Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, Warner JD, Tanaka M, Steward-Tharp SM, Gadina M, Thomas CJ, Minnerly JC, Storer CE, LaBranche TP, Radi ZA, Dowty ME, Head RD, Meyer DM, Kishore N, O'Shea JJ. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2011 Apr 1;186(7):4234-43. doi: 10.4049/jimmunol.1003668. Epub 2011 Mar 7.
• Hasni SA, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Carlucci PM, Wang X, Naqi M, Playford MP, Goel RR, Li X, Biehl AJ, Ochoa-Navas I, Manna Z, Shi Y, Thomas D, Chen J, Biancotto A, Apps R, Cheung F, Kotliarov Y, Babyak AL, Zhou H, Shi R, Stagliano K, Tsai WL, Vian L, Gazaniga N, Giudice V, Lu S, Brooks SR, MacKay M, Gregersen P, Mehta NN, Remaley AT, Diamond B, O'Shea JJ, Gadina M, Kaplan MJ. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021 Jun 7;12(1):3391. doi: 10.1038/s41467-021-23361-z.

Drugs

Indications