Ruxolitinib

Ruxolitinib, formerly known as INCB018424 or INC424, is a potent and selective oral inhibitor of JAK1 and JAK2. Ruxolitinib has been approved for the treatment of myelofibrosis, which is characterized, biologically, by the activation of the JAK-STAT pathway and, clinically, by bone marrow fibrosis, splenomegaly, abnormal blood counts, and poor quality-of-life through associated symptoms. Ruxolitinib treatment results in a meaningful reduction in spleen size and symptom burden in the majority of myelofibrosis patients, and it may also have a favorable effect on survival. Treatment response apparently does not depend on the presence of a JAK2 V617F mutation. The predominant toxicities are thrombocytopenia and anemia. The metabolization of ruxolitinib through CYP3A4 needs to be considered particularly if coadministered with potent CYP3A4 inhibitors. Several further JAK inhibitors are currently studied in myelofibrosis or other immuno-inflammatory diseases.