Abstract: We included two trials involving 528 participants, comparing ruxolitinib with placebo or best available therapy (BAT). As the two included trials had different comparators we did not pool the data. The confidence in the results estimates of these trials was low due to the bias in their design, and their limited sample sizes that resulted in imprecise results. There is low quality evidence for the effect of ruxolitinib on survival when compared with placebo at 51 weeks of follow-up (HR 0.51, 95% CI 0.27 to 0.98) and compared with BAT at 48 weeks of follow-up (HR 0.70, 95% CI 0.20 to 2.47). Similarly there was very low quality evidence for the effect of ruxolitinib on progression free survival compared with BAT (HR 0.81, 95% CI 0.47 to 1.39). There is low quality evidence for the effect of ruxolitinib in terms of quality of life. Compared with placebo, the drug achieved a greater proportion of patients with a significant reduction of symptom scores (RR 8.82, 95% CI 4.40 to 17.69), and treated patients with ruxolitinib obtained greater MFSAF scores at the end of follow-up (MD -87.90, 95% CI -139.58 to -36.22). An additional trial showed significant differences in EORTC QLQ-C30 scores when compared ruxolitinib with best available therapy (MD 7.60, 95% CI 0.35 to 14.85). The effect of ruxolitinib on reduction in the spleen size of participants compared with placebo or BAT was uncertain (versus placebo: RR 64.58, 95% CI 9.08 to 459.56, low quality evidence; versus BAT: RR 41.78, 95% CI 2.61 to 669.75, low quality evidence). There is low quality evidence for the effect of the drug compared with placebo on anemia (RR 2.35, 95% CI 1.62 to 3.41), neutropenia (RR 3.57, 95% CI 1.02 to 12.55) and thrombocytopenia (RR 9.74, 95% CI 2.32 to 40.96). Ruxolitinib did not result in differences versus BAT in the risk of anemia (RR 1.35, 95% CI 0.91 to 1.99, low quality evidence) or thrombocytopenia (RR 1.20; 95% CI 0.44 to 3.28, low quality evidence). The risk of non-hematologic grade 3 or 4 adverse events (including fatigue, arthralgia, nausea, diarrhea, extremity pain and pyrexia) was similar when ruxolitinib was compared with placebo or BAT. The rate of neutropenia comparing ruxolitinib with standard medical treatment was not reported by the trial. Currently, there is insufficient evidence to allow any conclusions regarding the efficacy and safety of ruxolitinib for treating myelofibrosis. The findings of this Cochrane review should be interpreted with caution as they are based on trials sponsored by industry, and include a small number of patients. Unless powered randomized clinical trials provide strong evidence of a treatment effect, and the trade-off between potential benefits and harms is established, clinicians should be cautious when administering ruxolitinib for treating patients with myelofibrosis.

Plain-language summary: We identified two clinical trials that included a limited number of patients comparing ruxolitinib to placebo or standard medical treatment. Both studies were published in 2012, and were conducted in the United States of America (USA) and the United Kingdom (UK). Drug companies sponsored both trials. Although the results of the studies only showed a moderate improvement of patients treated with ruxolitinib in terms of their quality of life and a reduction in their spleen size, we could not be sure whether these effects were reliable because of the limitations of the studies and the low number of people they recruited. We also could not be sure whether the drug has an effect on overall survival compared with a placebo, or when it was compared with an active treatment. The effect of ruxolitinib in terms of progression-free survival was also uncertain. In addition, people treated with this drug showed higher rates of anemia, thrombocytopenia and neutropenia compared with patients treated with a placebo, but the rate of adverse effects was similar to those treated with a medical treatment. The confidence in the results of this review is very low. The studies have limitations in the way they were designed and executed. Moreover, the limited number of patients included in the studies led to imprecise results. Larger studies should provide more information about the effect of ruxolitinib. Researchers from Cochrane searched all available literature up to 13 November 2014.