engleski

Ruxolitinib for the treatment of myelofibrosis

Ruxolitinib is an orally available, ATP-competitive inhibitor, selective for tyrosine-protein kinases JAK1 and JAK2 and is the most advanced JAK1/JAK2 inhibitor in development for the treatment of myeloproliferative neoplasms. The suggested mechanism of action of ruxolitinib is attenuation of cytokine signaling via the inhibition of JAK1 and JAK2 (wild-type or mutated forms), resulting in antiproliferative and proapoptotic effects. In the phase III COMFORT-I trial conducted in patients with myelofibrosis, ruxolitinib demonstrated durable reductions in splenomegaly. The proportion of patients that achieved spleen volume reduction ≥ 35% from baseline to 24 weeks was 41.9 % with ruxolitinib versus 0.7% with placebo (P < 0.0001), as evaluated by magnetic resonance imaging or computed tomography. In the phase III COMFORT-II trial, reductions in spleen volume ≥ 35% were observed in 31.9% of patients treated with ruxolitinib versus 0% with best available therapy at week 24, and 28.5% versus 0% at week 48 (both P < 0.0001). Low toxicity, alleviation of constitutional symptoms, weight gain and improvement in general physical condition were observed with ruxolitinib treatment which may substantially improve quality of life in patients with myelofibrosis.

ruxolitinib; myelofibrosis

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