Ruxolitinib

Ruxolitinib, sold under the brand names Jakafi and Jakavi, is a medication for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow, polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea, and steroid-refractory acute graft-versus-host disease. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.
Medical uses.
In the United States and the European Union, ruxolitinib is indicated for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis or post-essential thrombocythaemia myelofibrosis. It is also indicated for the treatment of adults with polycythaemia vera who are resistant to or intolerant of hydroxyurea.
In the United States, ruxolitinib is also indicated for the treatment of steroid-refractory acute graft-versus-host disease in people who are twelve years of age and older.
Mechanism of action.
Ruxolitinib is a janus kinase inhibitor ("JAK" inhibitor) with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.
Side effects.
In myelofibrosis, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), neutropenia (low levels of neutrophils), urinary tract infections (infection of the structures that carry urine), bleeding, bruising, weight gain, hypercholesterolaemia (high blood cholesterol levels), dizziness, headache and raised liver enzyme levels.
In polycythaemia vera, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), bleeding, bruising, hypercholesterolaemia (high blood cholesterol levels), hypertriglyceridemia (high blood fat levels), dizziness, raised liver enzyme levels and high blood pressure.
In acute graft-versus-host disease, the most common hematologic adverse reactions include anemia, thrombocytopenia, and neutropenia. The most common nonhematologic adverse reactions include infections and edema.
Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels.
History.
The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size and relieving debilitating symptoms.
Society and culture.
Legal status.
In November 2011, ruxolitinib was approved by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate or high-risk myelofibrosis based on results of the COMFORT-I and COMFORT-II Trials.
In 2014, it was approved in polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea, based on the RESPONSE trial.
Research.
It is also being investigated for plaque psoriasis, alopecia areata, relapsed diffuse large B-cell lymphoma, and peripheral T-cell lymphoma.
In February 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy.
Eight weeks-treatment with ruxolitinib blunted senescent cell-mediated inhibition of adipogenesis and increased insulin sensitivity in 22-month-old mice.
As of September 2019, a clinical trial was in progress to evaluate "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".