Efficacy and Safety of Single-Agent Ruxolitinib Therapy for Myelofibrosis and Polycythemia Vera: A Meta-Analysis

Background: Ruxolitinib, a potent JAK1/JAK2 inhibitor, was approved by the FDA for the treatment of myelofibrosis (MF) and polycythemia vera (PV) in 2011 and 2014, respectively. The aim of this study was to evaluate the efficacy and safety data of single-agent ruxolitinib in patients with MF or PV through meta-analysis of reported clinical trials.

Methods: PubMed and Web of Science databases were searched for clinical trials of ruxolitinib for the treatment of MF or PV through June 30^th, 2015. Only clinical trials in which ruxolitinib was used as single-agent therapy for MF or PV were included in this meta-analysis. Pooled odds ratios (ORs) for proportion of patients with >= 35% reduction in spleen volume (primary outcome) and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were analyzed using OpenMeta[Analyst] with a random effect model. Pooled ratios of adverse events of ruxolitinib therapy were also calculated.

Results: Six clinical trials including 3 randomized controlled trials (RCTs) of 987 patients were identified and included in the analysis. Four studies were conducted in MF patients, and 2 studies in PV patients. Pooled data from the 3 RCTs (2 for MF and 1 for PV) showed that ruxolitinib, compared to placebo or standard therapy/best available therapy (BAT), significantly increased the proportion of patients with a reduction in spleen volume of 35% or more (OR = 79.55, 95% CI = 22.51-281.11, p < 0.001). Ruxolitinib improved the symptoms associated with MF or PV. Only the 2 RCTs for MF analyzed overall survival (OS), one of which showed OS benefit with ruxolitinib. Pooled data from all 6 trials showed that the most common hematologic adverse events were all grades anemia (71.8%) and thrombocytopenia (54.1%), regardless of whether or not they were deemed related to ruxolitinib therapy. Incidence of grades 3/4 anemia and thrombocytopenia was 30.2% and 15.3%, respectively, but rarely led to discontinuation of the drug. The most common non-hematologic adverse events were diarrhea (all grades = 18.1%, grades 3/4 = 1.1%), fatigue (all grades = 14.0%, grades 3/4 = 2.0%), peripheral edema (all grades = 12.0%, grades 3/4 = 0%), and dyspnea (all grades = 10.0%, grades 3/4 = 0.9%). Further analysis was conducted to evaluate the attributable risks of the adverse events using data from the 3 RCTs. Compared to placebo or standard therapy/BAT, ruxolitinib significantly increased the risk of developing all grades anemia (RR = 1.10, 95% CI = 1.03-1.17, p = 0.005), grades 3/4 anemia (RR = 1.87, 95% CI = 1.20-2.93, p = 0.006), all grades thrombocytopenia (RR = 2.04, 95% CI = 1.47-2.83, p < 0.001),  but not grades 3/4 thrombocytopenia (RR = 2.04, 95% CI = 0.72-7.98, p = 0.153), all grades diarrhea (RR = 1.45, 95% CI = 0.96-2.20, p = 0.079), fatigue (RR = 0.865, 95% CI = 0.62-1.20, p = 0.382), peripheral edema (RR = 0.85, 95% CI = 0.61-1.18, p = 0.337), and dyspnea (RR = 1.25, 95% CI = 0.63-2.49, p = 0.520).

Conclusions: Single-agent ruxolitinib therapy results in improvement of symptoms in MF or PV and significant reduction in spleen size compared to placebo or standard therapy/BAT. Anemia and thrombocytopenia were the most common hematologic adverse events, but rarely led to the discontinuation of therapy. Diarrhea, fatigue, peripheral edema and dyspnea were the most common non-hematologic adverse events, but not significant compared to placebo or standard therapy/BAT.