Darbepoetin Alfa improves Ribavirin-related Anemia and Allows for Maintenance of Optimal Ribavirin Dose

Use of the optimal dose of RBV may enhance sustained virologic response (SVR) in patients with chronic hepatitis C. The aim of the current study was to assess the role of darbepoetin-alfa (DA) in treating anemia associated with Ribavirin (RBV).  DA is a novel, long-acting erythropoiesis-stimulating protein.

This was an open-label study of 50 treatment-naïve CH-C patients receiving peginterferon alfa-2b (PEG-Intron/ PEG-IFN) 1.5 mcg/kg/week and RBV (800-1400 mg/day weight-based).

Patients with significant anemia [hemoglobin (Hb) £10.5 g/dL] received DA [3 mcg/kg Q2W (every- two-weeks)] titrated to target Hb 12g/dL.

Clinico-laboratory as well as health-related quality of life (HRQL) data, using Short-Form 36 (SF-36) and Chronic Liver Disease Questionnaire (CLDQ-HCV), are being assessed.

Results

Preliminary data are reported for initial 39 patients [baseline data (mean±SD or %): age 47.7±9.0, 56% male, 59% Caucasians, 64% HCV genotype 1, HCV RNA 3.57±4.89 million IU/mL (median 1.71 million IU/mL, range 1460 IU/mL to 18.9 million IU/mL), Hb 14.7±1.2 g/dL, and initial RBV dose: mean dose 1051±198 mg/d, 25%=800 mg/d, 30%=1000 mg/d, 36%=1200 mg/d and 9%=1400 mg/d].

By week 12, 58.9% (n=23) and 25.6% (n=10) experienced Hb decline to £12 g/dL and £10.5 g/dL; respectively. Of this cohort, 33% (n=13) have required DA.

Of those requiring DA, 77% (10/13) were started before treatment week 12. After 6 weeks of DA therapy, 1.27±0.73 g/dL increase in Hb was observed.

Furthermore, 83% of all patients maintained their intended RBV dose.

Early virologic response [undetectable (<50 IU/mL) or 2-log drop in HCV RNA] was seen in 83% of all patients (100% genotype 2, 3; 74% genotype 1).

HRQL data revealed that mild (Hb £12 g/dL) and severe anemia (Hb £10.5g/dL) were both associated with clinically significant HRQL impairments as measured by Activity/Energy (AC) and Systemic (SY) domains of CLDQ-HCV as well as Physical Functioning (PF), Role Physical (RP), Vitality (VT), Role Emotion (RE) scales of SF-36 (p<0.05).

The severity of this impairment was related to the severity of anemia.

After 8 weeks of DA, clinically important HRQL improvements were noted in AC domain of CLDQ-HCV and PF, RP, VT and RE scales of SF-36. To date, no significant toxicity related to DA has been noted.

In conclusion, the authors write, “DA improves anemia and HRQL, allowing for optimal RBV dose maintenance.”

05/17/04

Reference
Z M Younossi and others. Darbepoetin alfa (DA) for Ribavirin-Induced Anemia in Patients with Chronic Hepatitis C (CH-C) Treated with Pegylated Interferon and Ribavirin (peg-ifn/rbv): A Preliminary Analysis. Abstract 83. Digestive Disease Week 2004. May 15-20. New Orleans, LA.