Polycythemia Vera Pathophysiology | Mechanism of Action | Overactive JAK Pathway
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Overactive JAK pathway signaling is a key driver of PV2,3

Two Janus-associated kinases (JAK) play a role in signaling2,3:

Image that shows two Janus-associated kinases (JAK) playing a role in signaling - JAK1: Plays major role in signaling of key proinflammatory cytokines and JAK2: Mediates signals for hematopoietic growth factors
Image that shows two Janus-associated kinases (JAK) playing a role in signaling - JAK1: Plays major role in signaling of key proinflammatory cytokines and JAK2: Mediates signals for hematopoietic growth factors

JAK, Janus-associated kinase; PV, polycythemia vera; STAT, signal transducer and activator of transcription.

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IDENTIFY PATIENTS WHO MAY BE APPROPRIATE FOR JAKAFI

Jakafi targets the primary driver of PV1

Jakafi targets and inhibits JAK2 regardless of mutation status.

  • It is active against both mutant and wild-type JAK2 5*
Image that shows Jakafi binds in the JAK2 kinase domain, not at the site of the JAK2V617F mutation

JAK, Janus-associated kinase; STAT, signal transducer and activator of transcription.

*Jakafi binds in the JAK2 kinase domain, not at the site of the JAK2V617F mutation.

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What is the mechanism of action of Jakafi?

WATCH AN MPN SPECIALIST EXPLAIN TARGETED JAK INHIBITION

Video

Mechanism of Action of Jakafi® (ruxolitinib)

Hematology specialist Dr Harry Erba reviews the mechanism of action of Jakafi® (ruxolitinib), a JAK1 and JAK2 inhibitor, highlighting how Jakafi works to inhibit overactive JAK pathway signaling. Dr Erba also discusses safety data from the RESPONSE† trial, which compared Jakafi to best available therapy for patients with polycythemia vera who were either intolerant of or had an inadequate response to hydroxyurea.

WATCH NOW

†RESPONSE, Randomized study of Efficacy and Safety in POlycythemia vera with JAK iNhibitor ruxolitinib verSus bEst available care

Image of Dr. Harry Erba
Image that says What is the mechanism of action of Jakafi? – Watch an MPN Specialist Explain Targeted JAK Inhibition

What is the mechanism of action of Jakafi?

WATCH AN MPN SPECIALIST EXPLAIN TARGETED JAK INHIBITION

Image of 3 people – Identify Appropriate Patients for Jakafi

IDENTIFY PATIENTS WHO MAY BE APPROPRIATE FOR JAKAFI

References

  1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.
  2. Rampal R, Al-Shahrour F, Abdel-Wahab O, et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood. 2014;123(22):e123-e133.
  3. Keohane C, Radia DH, Harrison CN. Treatment and management of myelofibrosis in the era of JAK inhibitors. Biologics. 2013;7:189-198.
  4. Quintas-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115(15):3109-3117.
  5. Mascarenhas J, Mughal TI, Verstovsek S. Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. Curr Med Chem. 2012;19(26):4399-4413.
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Indications and Usage

Jakafi 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.

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
  • Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
  • 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 see Full Prescribing Information for Jakafi.

Jakafi and the Jakafi logo are registered trademarks of Incyte. All other trademarks are the property of their respective owners.
© 2014-2021, Incyte Corporation. MAT-JAK-02777  09/21

Jakafi and the Jakafi logo are registered trademarks of Incyte. All other trademarks are the property of their respective owners.
© 2014-2021, Incyte Corporation. MAT-JAK-02777  09/21