INCP-51133: Dosing Email

Individualized Dosing for

Dear Healthcare Professional:

Jakafi^® is a selective inhibitor of JAK1 and JAK2 for the treatment of intermediate or high-risk myelofibrosis.

Individualized dosing lets you determine the starting dose of Jakafi for each patient and helps to optimize the dosing during treatment to balance efficacy and tolerability. The information below will help you start, monitor and optimize dosing for your patients.

Indications and Usage
Jakafi is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis.

Starting doses are based on platelet counts

Proposed starting doses of Jakafi¹
5 mg twice daily	Starting dose for patients with platelet counts 50 to <100 × 10⁹/L
10 mg twice daily	For certain patients with platelet counts >100 × 10⁹/L and renal impairment, hepatic impairment or who are taking strong CYP3A4 inhibitors
15 mg twice daily	Starting dose for patients with platelet counts 100 to 200 × 10⁹/L
20 mg twice daily	Starting dose for patients with platelet counts >200 × 10⁹/L

Jakafi should be avoided in certain patients with end stage renal disease not requiring dialysis and in patients with (1) moderate or severe renal impairment, any hepatic impairment or concomitant use of strong CYP3A4 inhibitors and (2) platelet counts <100 × 10⁹/L.¹ Please refer to the Full Prescribing Information for additional details.

Monitor complete blood counts (CBCs) during treatment, beginning as early as Weeks 2 to 4¹

•	A CBC and platelet count must be performed before initiating Jakafi, every 2 to 4 weeks until doses are stabilized and then as clinically indicated
•	Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia. In patients with cytopenias, consider dose reductions, temporarily withholding Jakafi or transfusions, as clinically indicated
•	Interrupt treatment for bleeding requiring intervention

In intermediate or high-risk myelofibrosis, Jakafi demonstrated superior reductions in spleen volume and improvements in symptom scores at Week 24^1,2*^†

•	Significantly more patients receiving Jakafi vs placebo had
	–	A >35% reduction in spleen volume (41.9% vs 0.7%, respectively; P < 0.0001)^1,2*
	–	A >50% improvement in Total Symptom Score (45.9% vs 5.3%, respectively; P < 0.0001)^1,2*^†

Individualize Jakafi dosing to help optimize balance between safety and efficacy¹

•	Approximately 70% of patients in COMFORT-I required a dose adjustment in the first 12 weeks of therapy³
•	In COMFORT-I, titrating the dose to 10 mg twice daily or higher provided similar efficacy^2,3 Please see Full Prescribing Information for Jakafi for details regarding recommended dosing.

If you have any questions about Jakafi and/or how to optimize the dose for your patients, please contact your Incyte Representative or reach IncyteCARES at 1-855-452-5234 or at www.incyte.com/jakafi/patient-assistance-incytecares.

Important Safety Information

•	Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia, which are each dose-related effects, with the most frequent being thrombocytopenia and anemia. 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
•	Thrombocytopenia was generally reversible and was usually managed 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. Withhold Jakafi until recovery
•	The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache
•	Serious bacterial, mycobacterial, fungal and viral infections may occur. Active serious infections should have resolved before starting Jakafi. Observe patients receiving Jakafi for signs and symptoms of infection and initiate appropriate treatment promptly. Advise patients about early signs and symptoms of herpes zoster and to seek early treatment
•	Progressive multifocal leukoencephalopathy (PML) has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate
•	A dose modification is recommended when administering Jakafi 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 breast-feed

Please see Full Prescribing Information for Jakafi.

JAK = Janus-associated kinase; COMFORT-I = COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment (I).
*	As studied in COMFORT-I, a randomized, double-blind, placebo-controlled phase III study with 309 total patients. The primary endpoint was the proportion of subjects achieving a >35% reduction in spleen volume from baseline to Week 24. A secondary endpoint was the proportion of subjects with a >50% reduction in Total Symptom Score (TSS) from baseline to Week 24.^1,2
^†	TSS was captured by a daily patient diary (MFSAF v2.0). TSS encompasses debilitating symptoms of myelofibrosis: Abdominal discomfort, early satiety, pain under left ribs, pruritus, night sweats and bone/muscle pain. Symptom scores ranged from 0 to 10 with 0 representing symptoms “absent” and 10 representing “worst imaginable” symptoms. These scores were added to create the daily total score, which has a maximum of 60. At baseline, mean TSS was 18.0 in the Jakafi group and 16.5 in the placebo group.^1,2
References: 1. Jakafi Prescribing Information. Incyte Corporation. 2. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807. 3. Data on file. Incyte Corporation.