CASE STUDY

Apply the principles of Trend, Predict, Intervene in everyday patients: a hypothetical case study

Use lab measurements to guide the patient treatment plan

Date	Hb (g/dL)	EPOGEN^® dose (Units TIW)	Ferritin (mcg/L)	TSAT %	Reticulocyte count %	MCV (fL/cell)	TIBC (mcg/dL)	WBC (cells/mm³)	iPTH (pg/mL)	Ca (mg/dL)	P (mg/dL)	Ca x P (mg²/dL²)	Kt/V	Alburin (g/dL)	CRP (mg/dL)
3/7	11.8	7,500	250	25	2.0	95	248	5,000	270	9.0	5.5	49.5	1.8	4.0	9.0
4/4	10.4	7,500	600	19	1.7	95	245	13,000		9.0	5.0	45.0	1.6	3.5	14.0
4/18	9.6	9,400
5/16	8.5	11,800

Trend Hb over time: Hb is consistently trending down
Predict Hb response: Lab values indicate infection and inflammation^4,17-20
Ferritin, TSAT, reticulocyte count, WBC, albumin, CRP
Intervene proactively: Evaluate and address cause of infection and/or inflammation
- Physician to adjust EPOGEN^® dose by increasing approximately 25%²

The principles of Trend, Predict, Intervene in action^1,4

(+)

With frequent monitoring of Hb and dose requirements, patients can be maintained at steady state once the appropriate dose is determined by the physician^1,2,6
When an intercurrent event occurs, the steady Hb state is disrupted, homeostasis is altered, and cell production rate no longer equals cell death rate, causing Hb to decline⁴
Physician to adjust EPOGEN^® dose by increasing by approximately 25% to reestablish a steady state within the Hb range of 10 g/dL to 12 g/dL
EPOGEN^® PI dosing recommendations for downward trends, with Hb below 10 g/dL
- Increase dose by 25% if Hb is < 10 g/dL and has not increased by 1 g/dL after 4 weeks of therapy or if Hb decreases below 10 g/dL
- Increases in dose should not be made more frequently than once a month

Please see Complete Dosing Guidelines.

Continue to monitor lab values. Physician to adjust treatment accordingly

Date	Hb (g/dL)	EPOGEN^® dose (Units TIW)	Ferritin (mcg/L)	TSAT %	Reticulocyte count %	MCV (fL/cell)	TIBC (mcg/dL)	WBC (cells/mm³)	Ca (mg/dL)	P (mg/dL)	Ca x P (mg²/dL²)	Kt/V	Alburin (g/dL)	CRP (mg/dL)
5/30	9.1	11,800	620	21	1.5	97	221	7,500	9.1	4.2	38.2	1.7	3.6	11
6/27	10.3	11,800	260	26	1.9	102	245	5,500	9.2	4	36.8	1.8	3.9	8
7/11	11.1	11,800
7/25	11.9	9,400

Trend Hb over time: Hb is trending up and approaching 12 g/dL
Predict Hb response: Lab values indicate resolution of infection and inflammation^4,17-20
Ferritin, TSAT, reticulocyte count, WBC, CRP
Intervene proactively: Physician to adjust EPOGEN^® dose by reducing approximately 25%²

(+)

As the intercurrent event resolves, RBC production will exceed RBC death and Hb will increase¹
If Hb approaches 12 g/dL, the physician should decrease EPOGEN^® dose by approximately 25% to reestablish a steady state within the target Hb range²
If EPOGEN^® therapy is discontinued, RBC death rate will exceed RBC production rate due to the abrupt change in therapy¹:
- Hb steadily decreases until therapy is resumed
- Steady state is not achieved, and patients may spend more time with Hb below EPOGEN^® PI-recommended range
EPOGEN^® PI dosing recommendations for upward trends, with Hb approaching 12 g/dL:
- Reduce dose by 25% when Hb approaches 12 g/dL
- If Hb continues to increase, dose should be temporarily withheld until the Hb begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose
- Decreases in EPOGEN^® dose can be made as often as clinically appropriate

Please see Complete Dosing Guidelines.

Indication

EPOGEN^® (Epoetin alfa) is indicated for the treatment of anemia in patients with chronic renal failure (CRF) on dialysis. EPOGEN^® is indicated to elevate or maintain the red blood cell (RBC) level and to decrease the need for transfusions in these patients.

Important Safety Information, including Boxed WARNINGS

WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE

Chronic Renal Failure:

In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

Cancer:

ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense EPOGEN^® (Epoetin alfa) to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance.
Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
Discontinue following the completion of a chemotherapy course.

Perisurgery: EPOGEN^® increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

EPOGEN^® is contraindicated in patients with uncontrolled hypertension.
Patients with chronic renal failure (CRF) participating in clinical studies experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
Patients with CRF and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular events and mortality than other patients.
These events included myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis.
A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks.
Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with EPOGEN^®.
- This has been reported predominantly in patients with CRF receiving ESAs by subcutaneous administration.
- PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin.
- A sudden loss of response to EPOGEN^®, accompanied by severe anemia and low reticulocyte count, should be evaluated.
- If anti-erythropoietin antibody-associated anemia is suspected, withhold EPOGEN^® and other ESAs. EPOGEN^® should be permanently discontinued in patients with antibody-mediated anemia. Patients should not be switched to other ESAs as antibodies may cross-react.
Seizures have occurred in patients with CRF participating in EPOGEN^® clinical trials.
The most commonly reported side effects in clinical trials were hypertension, headache, arthralgias, and nausea.