Indications and Usage

Jakafi® (ruxolitinib) is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is indicated for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.

Jakafi is indicated for treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients 12 years and older.

Jakafi is indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Jakafi met the primary and secondary endpoints at week 32
  • The RESPONSE (Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care) study was a randomized, open-label, active-controlled phase 3 study comparing Jakafi with best available therapy in 222 patients with polycythemia vera1,2
  • All patients were required to demonstrate hematocrit control between 40% and 45% prior to randomization1,2
  • Best available therapy included hydroxyurea (60%), interferon/pegylated interferon (12%), anagrelide (7%), pipobroman (2%), lenalidomide/thalidomide (5%), and observation (15%)1,2
  • Patients enrolled in the study had been diagnosed with polycythemia vera for at least 24 weeks, had an inadequate response to or were intolerant of hydroxyurea, required phlebotomy for hematocrit control, and exhibited splenomegaly. After week 32, patients were able to cross over to Jakafi treatment1,2
  • The composite primary endpoint was defined as hematocrit control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by CT or MRI. To achieve the hematocrit control endpoint, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as hematocrit >45% that is ≥3 percentage points higher than baseline or hematocrit >48% (lower value)1,2
  • RESPONSE primary endpoint: A significantly larger proportion of patients in the group receiving Jakafi achieved the primary endpoint—a composite of hematocrit control and a ≥35% reduction in spleen volume at week 32—compared with best available therapy (23% vs <1%, P < 0.0001)1,2
Important information for readers regarding the RESPONSE data

Some of the information contained in this reprint is not included in the FDA-approved prescribing information for Jakafi:

  • RESPONSE was an open-label study and therefore not designed to evaluate differences in symptoms
    •  Jakafi was also studied in a randomized double-blind phase 3 study evaluating the reduction in MPN-SAF TSS-C scores in patients with polycythemia vera who were previously receiving hydroxyurea. The primary endpoint was not met, although the individual symptom scores for patients receiving Jakafi differed numerically from those for patients receiving hydroxyurea
  • The RESPONSE study was inadequate in design to evaluate rates of thrombotic events. The effect of Jakafi on thrombotic or cardiovascular outcomes has not been determined; therefore, use caution when interpreting this information
  • Reduction in allele burden was an exploratory analysis in RESPONSE. The prognostic and clinical relevance of allele burden in polycythemia vera has not been established
  • Select patient-reported outcomes from exploratory analyses using the EORTC QLQ-C30 and the Pruritus Symptom Impact Scale are presented in the supplement. Some results from these analyses are not reported in this reprint
EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; MPN-SAF TSS-C, Myeloproliferative Neoplasm-Symptoms Assessment Form Total Symptom Score-cytokine symptom cluster.
Important Safety Information
  • Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated
  • Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary
  • Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi
  • Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until recovery
  • Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines
  • Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB risk factors and test those at higher risk for latent infection. Consult a physician with expertise in the treatment of TB before starting Jakafi in patients with evidence of active or latent TB. Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit determination
  • Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate
  • Herpes zoster infection has been reported in patients receiving Jakafi. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment. Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi. Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines
  • Increases in hepatitis B viral load with or without associated elevations in alanine aminotransferase and aspartate aminotransferase have been reported in patients with chronic hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection according to clinical guidelines
  • When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within one week. After discontinuation, some patients with myelofibrosis have experienced fever, respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi without consulting their physician. When discontinuing or interrupting Jakafi for reasons other than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt discontinuation
  • Non-melanoma skin cancers (NMSC) including basal cell, squamous cell, and Merkel cell carcinoma have occurred. Perform periodic skin examinations
  • Treatment with Jakafi has been associated with increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia
  • Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke (compared to those treated with tumor TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur
  • Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In patients with myelofibrosis (MF) and polycythemia vera (PV) treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
  • Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
  • In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions (incidence ≥15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >50%) were infections (pathogen not specified) and edema. In chronic graft-versus-host disease, the most common nonhematologic adverse reactions (incidence >20%) were infections (pathogen not specified) and viral infections
  • Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be required when administering Jakafi with fluconazole doses of 200 mg or less, or with strong CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy
  • Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during treatment and for 2 weeks after the final dose

Please click here to see Full Prescribing Information for Jakafi.

Please see hcp.jakafi.com for more information and educational resources.

Financial disclosures

The RESPONSE study was sponsored by Incyte Corporation and partners.

The authors of this publication disclosed the following related to Incyte Corporation and Novartis: During the conduct of the study, Dr He, Dr Jones, and Mr Garrett were employees of Incyte Corporation, and Drs Li, Pirron, and Habr were employees of Novartis. Drs Garrett, He, Jones, Verstovsek, Durrant, Habr, Harrison, Kiladjian, Li, Pirron, and Vannucchi reported financial interests from Incyte Corporation or Novartis. Additional disclosure information is located at https://www.nejm.org/doi/suppl/10.1056/NEJMoa1409002/suppl_file/nejmoa1409002_disclosures.pdf.

The other authors declared no competing financial interests.

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References: 1. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426-435. 2. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
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  • Indications and Usage / Important Safety Information