Deregulated
Janus Kinase 2 (JAK2) activation is central to the pathogenesis of most myeloproliferative
neoplasms (MPNs), of which
essential thrombocythemia (ET) is the most common entity. Patients with ET are risk-stratified according to their risk of thrombo-hemorrhagic complications. High-risk patients are offered treatments to reduce their platelet count using cytoreductive
therapy. The disease course is often long and
therapy intolerance is not infrequent.
Ruxolitinib, a
Janus Kinase (JAK) 1/JAK2 inhibitor, has demonstrated efficacy in patients with both
myelofibrosis (MF) and
polycythemia vera and is well tolerated. Side effects include predictable
cytopenias and an augmented risk of
infections.
Ruxolitinib has been investigated in a small group of ET patients who were refractory/intolerant to hydroxycarbamide (HC) and demonstrated improvements in both symptoms and
splenomegaly. Of note, a proportion of treated patients (13.2%) also had a significant reduction in platelet counts. However, these results require further validation in comparison with conventional
therapy. Recently, a randomized-controlled phase 2 study (MAJIC-ET) assessed the role of
Ruxolitinib in patients refractory or intolerant to HC. This study revealed that
Ruxolitinib demonstrated some clinical efficacy but was only superior in terms of symptom control. In clinical practice, some individuals with ET do exhaust all potential treatment options and there may well be a role for
Ruxolitinib in such patients or those with a significant symptom burden. However, in the wider context the goal of
therapy with the use of
JAK inhibitor therapy in ET needs to be defined carefully and we explore this within this timely review article.