Monthly treatment with
methoxy polyethylene glycol-epoetin beta is noninferior to conventional
shorter-acting erythropoiesis-stimulating agents with regard to major
cardiovascular events and mortality when targeting hemoglobin levels of 10 to
12 g/dL in patients with renal anemia, according to a new study.
The findings, reported in
the Clinical Journal of the American
Society of Nephrology, are from the MIRCERA PASS trial (NCT00773513). In the trial, Francesco
Locatelli, MD, of Alessandro Manzoni Hospital in Lecco, Italy, and
collaborators randomly assigned 2818 patients from 27 countries to receive methoxy
polyethylene glycol-epoetin beta or a reference agent (epoetin alfa/beta or darbepoetin)
for correction or maintenance therapy to target hemoglobin levels of 10 to 12
g/dL. To show noninferiority of methoxy polyethylene glycol-epoetin beta, the
upper bound of the hazard ratio for the composite end point was set to 1.20.
Over a median of 5.1 years, 45.4% of patients in the methoxy polyethylene
glycol epoetin beta arm and 45.7% in the reference arm experienced a nonfatal
myocardial infarction or stroke or all-cause mortality, a nonsignificant
difference in cardiovascular event or mortality risk. When considering
all-cause mortality alone, investigators also found no significant difference
between treatment groups.
Similar proportions of both
groups experienced other important adverse events. Gastrointestinal bleeding
occurred in 11.7% of the methoxy polyethylene glycol-epoetin beta group versus
11.1% of the reference group. Thromboembolic events occurred in 32.8% vs 34.5%,
respectively. The team found no cases of antibody-mediated pure red cell
With respect to mortality,
conclusions from this trial differ from that of a recent observational study published
recently by Yusuke Sakaguchi, MD, and colleagues in the Journal of the American Society of
Nephrology. That study found a 13% higher rate of death among users of
long-acting vs short-acting ESAs. Dr Locatelli’s team did not directly compare
the studies due to differences in their design.
The median doses of ESAs
administered in MIRCERA PASS were 18.8 to 28.0 mg methoxy polyethylene
glycolepoetin beta, 13.3 to 23.3 mg darbepoetin alfa, and 3604 to 5345 IU
epoetin alfa/beta. Iron supplementation was used to maintain serum ferritin at
or above 100 ng/mL and transferrin saturation at or above 20%.
“In conclusion, among
patients with anemia of CKD, treatment with monthly methoxy polyethylene glycol-epoetin
beta resulted in overall rates of major cardiovascular events, all-cause
mortality, and other serious adverse events that were similar to those
associated with conventional reference ESAs administered more frequently,” Dr
Locatelli and his coauthors wrote.
The study was funded by F.
Hoffmann-La Roche Ltd, the producers of methoxy polyethylene glycolepoetin beta,
brand name Mircera.
Locatelli F, Hannedouche T, Fishbane S, et
al. Cardiovascular safety and all-cause mortality of methoxy polyethylene glycol-epoetin
beta and other erythropoiesis-stimulating agents in anemia of CKD: A randomized
noninferiority trial [published online August 16, 2019] . Clin J Am Soc Nephrol. doi:10.2215/CJN.01380219
Sakaguchi Y, Hamano T, Wada A, et al. Types of erythropoiesis-stimulating agents and mortality among patients undergoing hemodialysis. J Am Soc Nephrol. 2019;30:1037-1048. doi:10.1681/ASN.2018101007