SIMPLE SUMMARY: Polycythemia vera (PV) is a chronic blood disease characterized by elevated red blood cells and splenomegaly. About 98% of all PV patients harbor the JAK2 mutation. Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, received approval as a second-line indication in PV patients who are resistant or intolerant to standard therapy hydroxyurea in both the United States (2014) and Europe (2015). In the studies relevant to approval, RUX achieved excellent PV control. Due to its mechanism of action, RUX also has immunosuppressive effects. As expected, an increased rate of infection was observed in clinical studies and in practical application. In this overview, we have compiled all previous literature references on RUX and infections in PV. However, apart from a few individual cases with special infections and an increased rate of zoster infections, there are no exceptional high infection problems. Recommendations are given on how infections in RUX treated PV patients can be avoided. ABSTRACT: Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, is approved for second-line therapy in patients with polycythemia vera (PV) who are resistant or intolerant to hydroxyurea. Due to the immunomodulatory and immunosuppressive effect of RUX, there is an increased susceptibility to infections. However, an increased risk of infection is inherent to even untreated myeloproliferative neoplasms (MPN). To obtain more information on the clinical significance of RUX-associated infections in PV, we reviewed the available literature. There is no evidence-based approach to managing infection risks. Most data on RUX-associated infections are available for MF. In all studies, the infection rates in the RUX and control groups were fairly similar, with the exception of infections with the varicella zoster virus (VZV). However, individual cases of bilateral toxoplasmosis retinitis, disseminated molluscum contagiosum, or a mycobacterium tuberculosis infection or a hepatitis B reactivation are reported. A careful assessment of the risk of infection for PV patients is required at the initial presentation and before the start of RUX. Screening for hepatitis B is recommended in all patients. The risk of RUX-associated infections is lower with PV than with MF, but compared to a normal population there is an increased risk of VZV infection. However, primary VZV prophylaxis for PV patients is not recommended, while secondary prophylaxis can be considered individually. As early treatment is most effective for VZV, patients should be properly informed and trained to seek medical advice immediately if cutaneous signs of VZV develop. Vaccination against influenza, herpes zoster, and pneumococci should be considered in all PV patients at risk of infection, especially if RUX treatment is planned. Current recommendations do not support adjusting or discontinuing JAK inhibition in MPN patients to reduce the risk of COVID-19.
Ruxolitinib-Associated Infections in Polycythemia Vera: Review of the Literature, Clinical Significance, and Recommendations