The kinase inhibitor ruxolitinib (Jakafi) is now approved to treat chronic graft-vs-host disease (GVHD) in people ages 12 years and older after one or two systemic therapies haven't been successful. Previously, ruxolitinib was approved to treat intermediate or high-risk myelofibrosis, polycythemia, and steroid-refractory acute GVHD. The starting ruxolitinib dose for chronic GVHD is 10 mg orally twice daily. Ruxolitinib inhibits Janus associated kinase, which mediates the signaling of certain cytokines and growth factors important for hematopoiesis and immune function.

The drug's efficacy was evaluated in a randomized, open-label, multicenter clinical trial of 329 patients who received ruxolitinib or best available therapy for corticosteroid-refractory chronic GVHD after allogeneic stem cell transplantation. The major efficacy outcome was overall response rate (ORR) through cycle 7, day 1 (each cycle was 28 days). The ORR was 70% for the ruxolitinib arm and 57% for the best available therapy arm. The second efficacy outcome was duration of response, calculated from first response to disease progression, death, or use of new systemic therapies for chronic GVHD. The duration of response was 4.2 months for ruxolitinib and 2.1 months for best available therapy. The median times from first response to death or use of new systemic therapies were 25 months for ruxolitinib and 5.6 months for best available therapy.

Anemia and thrombocytopenia are the most common abnormal laboratory findings in patients receiving ruxolitinib to treat chronic GVHD. They are also common in other applications of ruxolitinib and are listed in the warnings section of the product's labeling. The most common nonhematologic adverse effects were infections (the pathogen was not specified) and viral infections. The risk of infection when the drug is used for chronic GVHD is similar to the risk when it's used for acute GVHD. Bilirubin levels can also become elevated with ruxolitinib use. Other serious adverse effects of ruxolitinib that are listed as warnings on the product's labeling are symptom exacerbation following treatment interruption or discontinuation, risk of nonmelanoma skin cancer, lipid elevations, major adverse cardiovascular events, thrombosis, and secondary malignancies. The last three warnings were first identified with tofacitinib (Xeljanz) and also appear on the labeling of other Janus kinase inhibitors (see http://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requires-warnings-about-in).

Nurses caring for patients receiving ruxolitinib should determine if any coprescribed drugs are strong inhibitors of cytochrome P-450 (CYP) 3A4 and monitor closely for adverse effects, adjusting the ruxolitinib dose if necessary. Ruxolitinib should not be coadministered with doses of fluconazole 200 mg or higher because this could result in elevated ruxolitinib levels and additional adverse effects.

Nurses should confirm that laboratory values are monitored regularly. Complete blood counts, including platelet count and absolute neutrophil count, and bilirubin should be assessed prior to initiating therapy, every two to four weeks thereafter until doses are stabilized, and then as indicated. Patients should be assessed for indications of adverse effects and the patient's health care team should be consulted if adverse effects are noted.

For complete prescribing information for ruxolitinib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202192s023lbl.pdf.