Efficacy, Safety, and Tolerability of Ferric Carboxymaltose and Iron Sucrose in Iron Deficiency Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To comprehensively compare the efficacy, safety, and tolerability of two commonly used intravenous iron preparations, ferric carboxymaltose (FCM) and iron sucrose (IS), in adult patients with iron-deficiency anemia (IDA).

Methods: A systematic literature search was conducted across PubMed, Ovid Medline, Web of Science, Scopus, and the Cochrane Library up to Jan 1, 2024, to identify randomized controlled trials directly comparing FCM and IS treatments in adult patients with IDA. Primary outcome was change in hemoglobin levels during folllow-up. Meta-analyses were conducted with inverse variance random effects models.

Results: Fourteen trials were included, with a total of 4757 patients. FCM resulted in a nonsignificant increase in hemoglobin levels (mean difference [MD] = 0.45 g/dL, 95% confidence interval [CI] = 0.08 to 0.83, p=0.02) and ferritin levels (MD = 37.32 ng/mL, 95% CI = 18.98 to 55.65, p<0.01) compared to IS. FCM was associated with a higher risk of hypersensitivity reactions compared to IS (RR: 2.97, 95% CI: 1.35-6.52, p<0.01) but showed no significant difference in severe adverse events (RR: 1.03, 95% CI: 0.88-1.21, p=0.70) and had a nonsignificant increased risk of hypophosphatemia (RR: 2.84, 95% CI: 0.89-9.06, p=0.08).

Conclusions: Ten studies showed some concerns of risk of bias, and four studies had a high risk of bias for the change in hemoglobin levels during follow-up. Lack of standardized definitions for hypersensitivity reactions and variability in dosing protocols and follow-up durations across studies may affect the generalizability of our safety findings.