Efficacy
At a median follow up of 151 weeks, Kaplan-Meier estimated probabilities of maintaining a spleen response at 48 and 144 weeks were 73% and 50% respectively.r At a median follow up of 3.5 years, analysis of the accrued 70 deaths (27% {40/146} ruxolitinib and 41% {30/73} best available therapy [BAT]) suggested a significant reduction in the risk of death for ruxolitinib, hazard ratio was 0.58 (95% CI: 0.36 to 0.93), p=0.022. Estimated survival probability at 3.5 years was 71% and 54% for ruxolitinib and best available therapy respectively.r The final 5-year analysis appears to show reduction in risk of death of ruxolitinib compared to BAT, but OS analysis was not feasible due to the cross-over design of the study.r
COMFORT-I was a double-blind, multi-centre, randomised, placebo-controlled, phase III study with similar inclusion and exclusion criteria as COMFORT-II, however, patients were not suitable for BAT and other treatments had been discontinued 4 weeks prior to the first baseline visit. Patients were randomised equally to ruxolitinib (n=155, dose regimen as per COMFORT-II) or matched placebo (n=154). The study remained blinded until the last randomized patient had undergone week 24 assessment and 50% of patients had a 36 week assessment, at which point placebo patients were eligible to crossover to ruxolitinib.
Primary outcome at week 24 for a 35% or more reduction in spleen volume was significantly greater in the ruxolitinib group (42%) compared with placebo group (0.7%), p<0.001.r After a median follow up of 149 weeks, the hazard ratio was 0.69 (95% CI: 0.46 to 1.03), p=0.067. In the final 5-year analysis, median OS was not reached in the ruxolitinib-randomised group (median follow up: 268.4 weeks), compared with 108 weeks in the placebo group (median follow-up: 269 weeks). These findings suggest that earlier treatment with ruxolitinib in patients with intermediate-II and high risk MF results in better outcomes.r
Overall, the final 5-year combined COMFORT I and II analysis supports ruxolitinib as an effective long-term treatment option for patients with intermediate-2 or high-risk myelofibrosis.r
Finally, ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib of 48 patients myelofibrosis (intermediate-I, II and high-risk). Consistent with results from COMFORT studies, ROBUST demonstrated treatment success (including spleen size reduction and symptom improvement) in 50% of patients (57% in Intermediate-I).r
Finally, ruxolitinib may be beneficial in terms of splenomegaly, symptoms and survival in patients with HMR mutations, although evidence is currently conflicting and further studies are warranted.rr