No clarity whether different erythropoiesis-stimulating agents for anaemia treatment in CKD better or safer than each other

In an update of a Cochrane review first published in 2014, Edmund YM Chung from The Children's Hospital at Westmead, Westmead, Australia, and colleagues aimed to compare the safety and efficacy of erythropoiesis‐stimulating agents for treating anaemia in adults with CKD. ESAs investigated in the review included darbepoetin alfa, epoetin beta, methoxy polyethylene glycol‐epoetin beta, epoetin alfa, and biosimilar ESAs against each other, no treatment, or placebo.

Based on the updated Cochrane review, the team concluded that the comparative effects of different ESAs on death (any cause and cardiovascular), blood transfusions, myocardial infarction, major cardiovascular events, stroke, kidney failure, vascular access thrombosis, breathlessness, and fatigue were uncertain.

In people with chronic kidney disease, low RBC count or anaemia is common and may cause symptoms such as breathlessness or tiredness and an increase in the need for blood transfusion. Epoetin drugs are injectable medications (into the bloodstream or the skin) used for anaemia treatment in CKD patients. Owing to the unavailability of studies, it is unknown whether epoetin drugs have different harms and benefits when compared to each other. One way to compare different drugs when a clinical trial has been performed is using the network meta-analysis (NMA) technique.

In the NMA, the researchers reviewed the available studies that looked at ESAs in adults with CKD (including those needing dialysis, not requiring dialysis, and those who received a kidney transplant) to assess their potential benefits and harms versus placebo or between different forms of epoetin drugs. They looked at whether they reduced breathlessness or fatigue, prevented the need for blood transfusions, and whether they caused heart disease, death, fistula clotting, high BP (blood pressure), or kidney failure in people who have milder kidney disease.

The update included sixty‐two new studies comprising 9237 participants, so the review now consists of 117 studies having 25,237 participants. Overall, results remain comparable in this update compared to the previous review in 2014. In most methodological domains, most studies were at high or unclear risk of bias.

The study revealed the following findings:

· For preventing blood transfusion, epoetin alfa and epoetin beta may be superior to the placebo, and darbepoetin alfa was probably superior to the placebo.

· Methoxy polyethylene glycol‐epoetin beta, a biosimilar epoetin and a biosimilar darbepoetin alfa had uncertain effects on preventing blood transfusion compared to placebo.

· The comparative effects of ESAs compared with other ESA on blood transfusions prevention were uncertain, in low to very low certainty evidence.

· Effects on death (from any cause) were uncertain for epoetin alfa, epoetin beta, methoxy polyethylene glycol‐epoetin beta, a biosimilar epoetin and a biosimilar darbepoetin alfa versus placebo.

· There team noted no potential difference between darbepoetin alfa and placebo concerning odds of death (any cause).

· The comparative effects of ESAs compared with other ESA on death were uncertain in low to very low certainty evidence.

• Epoetin beta, probably when compared to the placebo, increased the odds of hypertension.
• Compared to placebo, epoetin alfa, darbepoetin alfa, and methoxy polyethylene glycol‐epoetin beta may increase the odds of hypertension. Still, a biosimilar epoetin and biosimilar darbepoetin alfa had uncertain effects on hypertension.
• The comparative effects of all ESAs compared with another ESA, placebo or no treatment on myocardial infarction, cardiovascular death, stroke, vascular access thrombosis, kidney failure, and breathlessness were uncertain.
• Due to sparse data, network analysis for fatigue was not possible.

"Based on existing studies, we cannot be confident that different epoetin drugs are better or worse than each other for chances of death, needing a blood transfusion, stroke or a heart attack, or the chances for dialysis need for people with milder kidney disease," the authors wrote in their review.

They were also unsure whether different epoetin drugs form are better at improving anaemia symptoms, such as breathlessness or tiredness, which were not reported in most available research studies.

To conclude, there is no clarity on whether different forms of epoetin drugs are better or safer than each other.

Reference:

Chung EYM, Palmer SC, Saglimbene VM, Craig JC, Tonelli M, Strippoli GFM. Erythropoiesis‐stimulating agents for anaemia in adults with chronic kidney disease: a network meta‐analysis. Cochrane Database of Systematic Reviews 2023, Issue 2. Art. No.: CD010590. DOI: 10.1002/14651858.CD010590.pub3. Accessed 16 February 2023.