Loading
Ruxolitinib shrank the enlarged spleen by more than a third in 42% of myelofibrosis patients versus under 1% on placebo, and halved symptom scores in nearly half.
COMFORT-I was a double-blind phase 3 trial that randomised 309 patients with intermediate-2 or high-risk myelofibrosis to the JAK1/JAK2 inhibitor ruxolitinib or placebo. The primary endpoint was the proportion with at least a 35% reduction in spleen volume at 24 weeks by imaging. This was 41.9% versus 0.7%, and a 50% or greater improvement in total symptom score was seen in 45.9% versus 5.3%. Anaemia and thrombocytopenia were the main toxicities. A parallel trial, COMFORT-II, showed similar spleen responses against best available therapy. Later analyses suggested a survival advantage for ruxolitinib despite crossover. It was the first drug approved for myelofibrosis and the first approved JAK inhibitor for a malignancy.
COMFORT-I turned the 2005 discovery of the JAK2 V617F mutation into the first effective medicine for myelofibrosis, transforming symptom control for a disease with no prior standard. Ruxolitinib is still the reference first-line therapy, with fedratinib, pacritinib and momelotinib as alternatives for cytopenic patients. It does not eliminate the malignant clone or reverse fibrosis in most patients.
Shares Pacritinib, Momelotinib, JAK2, Primary myelofibrosis.
Shares Fedratinib, Pacritinib, Momelotinib, Ruxolitinib.
Shares Pacritinib, Momelotinib, JAK2, Ruxolitinib.
Shares Fedratinib, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Momelotinib, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares JAK2, Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis), New England Journal of Medicine.
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis), Novartis.