Introduction: The hallmark discovery of hyperactivation of the janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was a sentinel moment in the history of myeloproliferative neoplasms (MPNs). This finding paved the way for the development of JAK inhibitors, which now represent the foundation of myelofibrosis therapy. With four JAK inhibitors now approved for myelofibrosis, awareness of their clinical efficacy and safety data and recognition of their unique pharmacologic attributes are of critical importance. Additionally, ruxolitinib represents an integral part of the therapeutic arsenal for polycythemia vera.
Areas covered: This review provides a broad overview of the published literature supporting JAK inhibitor therapy for MPNs. Primarily focusing on myelofibrosis, each of the four available JAK inhibitors is reviewed in detail, including pharmacology, efficacy, and safety data. Failure of JAK inhibitors and future directions in JAK inhibitor therapy are also discussed.
Expert opinion: JAK inhibitors revolutionized the treatment of MPNs and have dramatically improved patient outcomes. However, data informing selection between currently available JAK inhibitors is limited. These agents are not curative and eventually fail most patients with myelofibrosis. Combining JAK inhibitors with novel targeted agents appears to be the most promising path to further improve outcomes.
Keywords: Fedratinib; JAK inhibitors; momelotinib; myelofibrosis; myeloproliferative neoplasms; pacritinib; polycythemia vera; ruxolitinib.