XELJANZ (tofacitinib) is the new rheumatoid arthritis drug on the market and it is made by Pfizer.
– Xeljanz is a Janus Kinases inhibitor or JAKs and works by inhibiting one or more of the Janus Kinase enzymes.
– These enzymes are named JAK1, JAK2, JAK3, TYK2. Xeljanz primarily inhibits JAK3 but also has effect on other enzymes as well.
– Janus Kinase enzymes transduce Cytokine mediated signaling via JAK-STAT pathway. Cytokines use receptors who depend on Janus Kinase enzymes for signal transduction.
– By inhibiting Janus Kinase enzymes, Xeljanz in effect blocks function of Cytokines and T helper cells.
– Cytokines that are blocked here include:
– IL-2
– IL-4
– IL-15
– IL-21
– Interferon Gamma
– IL6
– The above cytokines are involved in promoting rheumatoid arthritis. Xeljanz is expected to result in improvement in signs and symptoms of rheumatoid arthritis by blocking these cytokines.
Important points about Xeljanz to remember are:
– It is a biologic therapy therefore infections can occur.
– Therapy should be stopped in case of infection.
– Patients should be screened for TB prior to start of therapy and monitored periodically afterwards.
– It should be used with caution in those with history of diverticulitis.
– No information is available for use in patients with chronic hepatitis B or hepatitis C.
– Monitoring by blood testing is needed for possible effects on blood counts specifically hemoglobin, lymphocytes, neutrophils, liver enzymes, Creatinine, and lipids.
– Xeljanz dose should be reduced to 5 mg daily in patients with moderate liver or kidney involvement and not used in severe liver disease.
– The dose should also be reduced to 5 mg daily in patients on potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole) and CYP2C19 (e.g., fluconazole).
– Use of live vaccine in patients should be avoided as has not been studied and there were reports of reactivation of herpes zoster in the clinical trials.
– No information is available in terms of multiple sclerosis
– It was recently rejected by european equivalent of FDA as they felt the risks were more than the benefits.
– Finally, as with any medication, please read safety warnings here before you proceed
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