NEW YORK (Reuters Health) – Anemia that develops in hepatitis C virus (HCV) patients during treatment with peginterferon-alfa and ribavirin (PEG-IFN/RBV) may be a good sign, new research hints.
In a large study, researchers found that those who developed anemia were more apt to achieve sustained virologic response (SVR) than those who did not, despite decreased RBV dosing following a decline in hemoglobin levels. In addition, the virologic relapse rate was not increased in patients who cut back on RBV dose.
These data “firmly underscore the recommendation for RBV dose reduction as the primary strategy for management of treatment-related anemia,” write Dr. Mark S. Sulkowski of Johns Hopkins University School of Medicine in Baltimore, Maryland and colleagues in the November 10 issue of Gastroenterology.
They also found that the use of erythropoiesis-stimulating agents (ESAs) minimized discontinuation of treatment in patients with early-onset anemia, leading to higher SVR rates in this subgroup.
Anemia is seen in up to 30% of treated HCV patients and often leads to fatigue and other symptoms, as well as RBV dose reduction and/or discontinuation of treatment, Dr. Sulkowski and colleagues note in their report.
However, because lower SVR rates have been reported in patients who cut back on RBV, “many clinicians and patients prefer to avoid this strategy and instead use ESAs (off-label) to improve anemia-related symptoms while maintaining RBV dose,” the investigators note.
Nonetheless, “considerable uncertainty exists regarding the role of adjuvant ESAs during HCV treatment,” they point out.
Dr. Sulkowski’s team evaluated the relationship between treatment-related anemia, ESA use, and treatment outcomes in 3,023 treatment-naive patients with HCV genotype 1. As participants in a multicenter US clinical trial, all of them were treated for up to 48 weeks with a standard PEG-IFN/RBV regimen. ESAs were allowed for patients with hemoglobin levels less than 10 g/dL after RBV dose reduction.
Anemia occurred in 28.6% of study patients. Most of these patients lowered their RBV dose and 51.9% were given an ESA.
“Unexpectedly,” the investigators say, the SVR rate was significantly higher in anemic patients than nonanemic patients (difference, +12% for anemic patients).
Moreover, SVR rates were associated with the magnitude of hemoglobin decrease. SVR rates were 43.7% in patients with an absolute hemoglobin decline greater than 3 grams per deciliter compared with 29.9% in those with a maximum decline of 3 grams per deciliter or lower.
The effect of ESAs varied by time to anemia. Patients with early-onset anemia (after 8 weeks or less of treatment) had significantly higher SVR rates with ESA use than those with late-onset anemia (after greater than 8 weeks of treatment). Rates were 45.0% versus 25.9%, respectively (P < 0.001). Those with early-onset anemia were also less apt to discontinue treatment due to adverse events (12.6% vs 30.1%; P < 0.001).
ESAs did not affect SVR or discontinuation rates among patients with late-onset anemia, suggesting that these patients are “not likely to benefit from adjuvant ESAs,” the authors note.
The finding that RBV dose reduction was not associated with lower SVR rates is important, they say.
“Taken together,” write the investigators, “these data support the use of RBV dose reduction as the primary strategy for the management of anemia related to PEG-IFN/RBV therapy; importantly, ESAs should not be used solely to avoid RBV dose reduction in anemic patients.”
“Prospective, randomized controlled trials are needed to define the optimal role of adjuvant ESAs during HCV treatment regimens that include PEG-IFN/RBV,” they conclude.
Hepatitis C Virus Treatment-Related Anemia Is Associated With Higher Sustained Virologic Response Rate