Ruxolitinib inhibits the Janus-associated kinases (JAK) 1 and 2, which mediate the signalling of molecules involved in haematopoiesis and immune function.1 In myelofibrosis, there is typically a dysfunction of the JAK pathway.
Ruxolitinib displayed efficacy in two double-blind studies in patients with intermediate-2 or high-risk myelofibrosis. The first (COMFORT-I) compared ruxolitinib with placebo and the second (COMFORT-II) used best available therapy (BAT) as the comparator treatment.2,3
Reduced spleen volume
In COMFORT-I (n=309), 41.9% of ruxolitinib patients achieved a ≥35% reduction in spleen volume at 24 weeks compared with 0.7% of placebo patients (p<0.001). This reduction was maintained for 48 weeks or more in 67% of those who responded. Ruxolitinib was also associated with a significant survival advantage compared with placebo (13 versus 24 deaths, hazard ratio 0.5; p=0.05).2
In COMFORT-II (n=219), 28% of patients who received ruxolitinib had a ≥35% reduction in spleen volume at 48 weeks compared with 0% of patients who received BAT (p<0.001).3 In addition, there was a 56% reduction in mean palpable spleen length at 48 weeks in the ruxolitinib group compared with a 4% increase in the BAT group. The most common therapies in the BAT group were hydroxycarbamide and glucocorticoids.3
Ruxolitinib was associated with symptom improvement and was generally well tolerated, with anaemia and thrombocytopenia the most commonly reported adverse effects.2,3
1. Jakavi Summary of Product Characteristics, August 2012
2. Verstovsek S et al. N Engl J Med 2012; 366: 799-807.
3. Harrison C et al. N Engl J Med 2012; 366: 787-98.
View Jakavi drug record
Further information: Novartis
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