Introduction: Myelofibrosis (MF) is a rare chronic Ph(-) myeloproliferative neoplasm that can manifest as a primary disease or secondary to polycythaemia vera or essential thrombocythaemia. MF results from dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and the most common mutations are JAK2V617F and in the Myeloproliferative leukaemia protein (MLP) gene. For decades, the therapy has been mainly palliative (Immunomodulators, DNA methyltransferase inhibitors, colony stimulating factors) with none of them leading to complete remission. Ruxolitinib is a new generation JAK1 and JAK2 inhibitor having a remarkable impact on bone marrow fibrosis (BMF) and splenomegaly in patients with high and intermediate-risk MF. The aim of this research is a discussion of the mechanisms of actions of Ruxolitinib and its efficacy
Materials and methods: A documentary approach is used. A targeted analysis of publications, available in PubMed and ScienceDirect is presented. The keywords used to collect the data were: `ruxolitinib myelofibrosis` (5 publications); `ruxolitinib mechanisms of actions` (3 publications); `ruxolitinib trials` (4 publications).
Results: Ruxolitinib has dose-dependent efficiency on BMF, spleen size and constitutional symptoms like anaemia, fever and weight loss. Ruxolitinib`s effects are mediated by the following molecular mechanisms: a decrease in activation, proliferation and migration of Natural killer and dendritic cells, a reduction of proinflammatory cytokines like Interleukin-1, Tumor Necrosis Factor-α, Interferon-γ; an increase in plasticity and titre of Th17 cells; stabilization of the serum albumin and total cholesterol that results in weight gain. `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` I and `Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment` II are phase III trials which demonstrate how Ruxolitinib makes a reduction of 35% in spleen size and 33% in lethal exit.
Conclusion: Ruxolitinib is a good example of how targeted therapy ameliorates progression free survival and overall survival.
