Novel Erythropoeisis Stimulating Protein (Aranesp) Enhances Pegylated Soluble Tumor Necrosis Factor Receptor Type 1 (PEG sTNF-R1) Alleviation of Anemia of Chronic Disease (ACD) in a Rodent Model of Systemic Inflammation.

Reviewer: Walter F. Sall, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 8, 2001

Presenter: Greg Stoney
Affiliation: Amgen Inc.

Introduction

Anemia of Chronic Disease is commonly associated with several chronic inflammatory disease states. ACD has a multifactorial pathogenesis mediated by multiple inflammatory cytokines.
Aranesp is a novel erythropoetin analogue with a sustained duration of action, known to alleviate anemia.
ACD can be replicated in Lewis rats immunized with peptidoglycan-polysaccharide polymers.
TNF-alpha blockade is known to partially reverse the effects of ACD in some patients.
This study is designed to test the effects of Aranesp and the TNF-alpha blocking agent PEGsTNF-RI on this rat model of ACD

Materials and Methods

Lewis rats were immunized with PG-APS or carrier immunizations
Rats were treated for two weeks with Aranesp alone, PEG sTNF-RI alone or a combination of the two agents.
a CBC was checked twice weekly. Serum iron levels were checked once weekly.
Paw swelling volume was checked once weekly as a surrogate for systemic inflammation.

Results

Combined therapy reduced inflammation induced paw swelling. Either monotherapy did not have a significant effect.
Combined therapy alleviates ACD, with a mean increase in hgb of 4.1. Aranesp alone had no significant effect.
Combined therapy improves multiple RBC parameters including: MCV, reticulocyte count and MCH. No effect with either monotherapy was seen on these parameters.
The combination enhances total serum iron and tranferrin bound serum iron

Author's Conclusions

Aranesp alone does not alleviate ACD.
PEG sTNF-RI alone reduces inflammation but not ACD.
Combination therapy normalized hemoglobin levels, reticulocyte counts, MCH, MCV and TSI compared to controls and either monotherapy.
mechanism of synergy is enhanced erythropoietic response and increased usable transferrin bound serum iron.