Ruxolitinib-associated infections: A systematic review and meta-analysis

Am J Hematol. 2018 Mar;93(3):339-347. doi: 10.1002/ajh.24976. Epub 2017 Dec 4.


Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibiotic Prophylaxis
  • Bacterial Infections / epidemiology
  • Bacterial Infections / etiology
  • Bacterial Infections / prevention & control
  • Clinical Trials, Phase III as Topic
  • Confidence Intervals
  • Disease Susceptibility
  • Herpes Zoster / epidemiology
  • Herpes Zoster / etiology
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Infections / etiology*
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 2 / antagonists & inhibitors
  • Mycoses / epidemiology
  • Mycoses / etiology
  • Nitriles
  • Odds Ratio
  • Product Surveillance, Postmarketing
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use
  • Pyrimidines
  • Randomized Controlled Trials as Topic
  • Risk


  • Immunosuppressive Agents
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2