Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review

Patients on ruxolitinib may be predisposed to mycobacterial infections. This observational, retrospective, pharmacovigilance study used the United States Food and Drug Administration adverse events reporting system to compare the number of patients that developed typical and atypical mycobacterial infections to all drugs in the system. Using the reporting odds ratio (ROR), there is an increased risk of developing tuberculosis (ROR, 9.2; 95% confidence interval, 7.5-11.4) and atypical mycobacterial infections (ROR, 8.3; 95% confidence interval, 5.5-12.6) while on treatment with ruxolitinib. Background: Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). Materials and Methods: This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. Results: There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. Conclusion: Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib. (C) 2019 Elsevier Inc. All rights reserved.