Is treatment with Aranesp (darbepoetin alfa) 200 microgram/0.4 milliliter injection every 2 weeks for 12 visits/6 cycles for diagnosis D63.1 medically necessary?

Medical Necessity Assessment for Aranesp in Anemia in Chronic Disease (D63.1)

Direct Answer

Aranesp (darbepoetin alfa) 200 mcg every 2 weeks for 12 visits is NOT medically necessary for diagnosis D63.1 (anemia in chronic disease) in non-ESRD patients, as erythropoiesis-stimulating agents are contraindicated outside specific approved indications and carry significant mortality and cardiovascular risks. 1, 2

Critical Context: D63.1 Diagnosis

• D63.1 represents "anemia in chronic disease" (also called anemia of chronic inflammation), which is NOT an FDA-approved indication for darbepoetin alfa 2
• The FDA-approved indications for Aranesp are limited to: (1) anemia due to chronic kidney disease, and (2) chemotherapy-induced anemia in patients with non-myeloid malignancies receiving palliative chemotherapy 2
• Using ESAs for anemia in chronic disease without CKD or active chemotherapy represents off-label use with no supporting evidence and documented harms 1

Evidence Against ESA Use in This Population

Mortality and Cardiovascular Risks

• In patients with chronic kidney disease and anemia, targeting hemoglobin levels >11 g/dL with ESAs resulted in doubled stroke risk (both ischemic and hemorrhagic) in the TREAT study 1
• Guidelines recommend ESA therapy target hemoglobin values between 10-12 g/dL in CKD patients specifically to minimize stroke and cardiovascular risks 1
• In heart failure patients with anemia, the largest randomized trial (n=2,278) demonstrated that darbepoetin alfa provided no clinical benefit and resulted in significant increases in thromboembolic events and nonsignificant increases in fatal and nonfatal strokes 1
• The ACC/AHA/HFSA guidelines explicitly state that erythropoietin-stimulating agents should NOT be used in heart failure patients with anemia to improve morbidity and mortality 1

Cancer Population Evidence

• In cancer patients with anemia NOT receiving concurrent chemotherapy, analyses from Study 20010103 support a strong recommendation AGAINST ESA use, as ESAs increased the risk of death when administered to patients with malignancy not receiving chemotherapy 1
• The FDA added a black-box warning stating: "Use of ESAs increased the risk of death when administered to a target Hb of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy" 1
• ASCO/ASH guidelines explicitly recommend against ESA use in anemic patients with cancer who are not receiving concurrent chemotherapy 1

Required Pre-Authorization Criteria (If Considering ESA Use)

Mandatory Diagnostic Workup

Before ANY ESA consideration, the following must be documented 1, 2:

• Thorough drug exposure history to identify medication-induced anemia 1
• Peripheral blood smear review (and bone marrow examination in select cases) 1
• Iron studies: serum iron, total iron-binding capacity, transferrin saturation, and serum ferritin 3, 2
  • Iron supplementation required when ferritin <100 mcg/L or transferrin saturation <20% 2
• Assessment for vitamin B12 and folate deficiency 1
• Evaluation for occult blood loss 1
• Renal function assessment (creatinine clearance or eGFR) 1
• Reticulocyte count 1

FDA-Approved Indications Only

For CKD patients (non-dialysis) 2:

• Initiate only when hemoglobin <10 g/dL AND rate of decline indicates likelihood of requiring RBC transfusion 2
• Starting dose: 0.45 mcg/kg every 4 weeks (NOT the requested every 2 weeks schedule) 2
• If hemoglobin exceeds 10 g/dL, reduce or interrupt dose 2

For cancer patients receiving chemotherapy 1, 2:

• Use only in patients receiving palliative (not curative) chemotherapy 1
• Initiate when hemoglobin <10 g/dL 1
• Target hemoglobin should not exceed 12 g/dL 1

Monitoring Requirements (If ESA Were Appropriate)

• Weekly hemoglobin monitoring during initial weeks until stabilization 3, 2
• For every 2-week dosing, monitor hemoglobin every 2 weeks once stable 3
• Iron studies should be performed regularly throughout treatment as functional iron deficiency develops with continued ESA use 3, 2
• Discontinue if no response (<1 g/dL increase) after 8-9 weeks despite iron supplementation 3

Specific Concerns with Requested Regimen

• The 200 mcg every 2 weeks dosing is appropriate for chemotherapy-induced anemia but NOT for other indications 4, 5
• For non-dialysis CKD patients, FDA-approved dosing is 0.45 mcg/kg every 4 weeks, not every 2 weeks 2
• The requested 12 visits/6 cycles (24 weeks) duration requires documented response assessment at 4 weeks and discontinuation if non-responsive 3, 2

Alternative Management

• Address underlying chronic disease causing anemia 1
• Correct iron deficiency with oral or intravenous iron supplementation 3, 2
• RBC transfusion remains the appropriate intervention for symptomatic anemia or clinical circumstances requiring rapid correction 1
• Treat any identified nutritional deficiencies (B12, folate) 1

Denial Rationale

This request should be denied because:

1. D63.1 (anemia in chronic disease) is not an FDA-approved indication for darbepoetin alfa 2
2. ESAs have demonstrated increased mortality, stroke, and thromboembolic events when used outside approved indications 1
3. No evidence supports ESA efficacy or safety in anemia of chronic disease without concurrent CKD or chemotherapy 1
4. The requested dosing schedule (every 2 weeks) does not align with FDA-approved dosing for non-dialysis CKD patients 2