Safety evaluation of ruxolitinib for treating myelofibrosis

In 2005, the JAK2 V617F mutation was identified and found to be highly prevalent in the 'Philadephia Chromosome-negative' Myeloproliferative neoplasms (MPN). This led to new diagnostic criteria for MPN in addition to the development of the first targeted therapy for myelofibrosis (MF), ruxolitinib .

Ruxolitinib was approved within 5 years of 'first-in-man' trials; it has been assessed in two large Phase III trials, and to date, several thousand patients have been prescribed this drug. This article reviews the latest data from the Phase III trials concerning efficacy and safety in addition to post-authorisation data for this agent. Ruxolitinib is an extremely well-tolerated drug; it is associated with bruising, headaches, dizziness, anaemia and thrombocytopaenia. In addition, an augmented risk of infections has been documented.

Ruxolitinib has radically altered the therapeutic landscape for MF with demonstrated advantages over standard therapy, irrespective of JAK2 mutational status and a signal suggesting survival benefit. Other JAK inhibitors are also in late stages of development, although the furthest advanced has just been withdrawn due to cases of encephalopathy (not documented with ruxolitinib). This reminds the clinical community of the need for post-marketing surveillance of safety for these agents. Challenges ahead are identification of appropriate surrogates for survival benefit and perhaps how to best use ruxolitinib either alone or in combination with other therapies.