Efficacy and Safety of Ferric Carboxymaltose and Other Formulations in Iron-Deficient Patients: A Systematic Review and Network Meta-analysis of Randomised Controlled Trials

Carla Rognoni, Sergio Venturini, Michela Meregaglia, Melania Marmifero, Rosanna Tarricone, Carla Rognoni, Sergio Venturini, Michela Meregaglia, Melania Marmifero, Rosanna Tarricone

Abstract

Background: Iron deficiency is very common in a number of medical conditions. Ferric carboxymaltose is a new stable iron preparation that can be administered in single infusions over short periods of time. The aim of this study was to conduct a systematic review of randomised controlled trials (RCTs) regarding the efficacy and safety of the novel complex compared with other iron formulations. In addition, the feasibility of a network meta-analysis for indirect comparisons was investigated.

Methods: A systematic literature review was performed for published RCTs on the use of ferric carboxymaltose in iron deficiency between July and October 2014. Indirect comparisons were also addressed using terms referring to competing iron formulations. We further supported the qualitative results of the systematic review by a network meta-analysis that allows pooling the evidence around different intervention outcomes in the absence of trials involving a direct comparison.

Results: The initial search yielded 1027 citations, which was decreased to 21 studies eligible for inclusion in the review. Studies were heterogeneous in the number of patients randomised, iron deficiency-related conditions addressed, trial inclusion criteria, time horizon, treatment dosage and outcomes assessed. Six studies with the same time horizon (i.e. 6 weeks) were included in the network meta-analysis. Considering the differences between final and initial outcome values for each iron formulation, the mean difference of these differences (delta) was estimated for each couple of treatments involving ferric carboxymaltose. Significant improvements in serum ferritin (µg/l) were obtained with ferric carboxymaltose compared to oral iron (delta 172.8; 95 % CI 66.7-234.4) and in haemoglobin (g/dl) with respect to ferric gluconate (delta 0.6; 95 % CI 0.2-0.9), oral iron (delta 0.8; 95 % CI 0.6-0.9) and placebo (delta 2.1; 95 % CI 1.2-3.0).

Conclusions: All currently available intravenous iron preparations appear to be safe and effective, but ferric carboxymaltose seems to provide a better and quicker correction of haemoglobin and serum ferritin levels in iron-deficient patients.

Figures

Fig. 1
Fig. 1
Study selection process
Fig. 2
Fig. 2
Schematic representation of comparisons (n = 22) among different iron formulations addressed in the included studies (n = 21)
Fig. 3
Fig. 3
Risk of bias summary: judgements regarding risks of bias for each study included in the systematic review (n = 21). The symbol ‘+’ represents low risk of bias, while the symbol ‘?’ represents unclear risk of bias
Fig. 4
Fig. 4
Risk of bias graph: judgements regarding risks of bias presented as percentages across all studies included in the systematic review (n = 21). This figure illustrates, for each considered bias domain, the proportion of studies falling in each category of risk (low risk of bias, high risk of bias, unclear risk of bias)
Fig. 5
Fig. 5
Network of connected studies
Fig. 6
Fig. 6
Network meta-analysis (NMA) results on serum ferritin. Central dots represent posterior medians, triangles and crosses represent posterior means; thin lines are 95 % credible intervals, while thicker ones are 80 % credible intervals; a triangle indicates that ferric carboxymaltose is significantly superior
Fig. 7
Fig. 7
Network meta-analysis (NMA) results on haemoglobin (Hb). Central dots represent posterior medians, triangles and crosses represent posterior means; thin lines are 95 % credible intervals, while thicker ones are 80 % credible intervals; a triangle indicates that ferric carboxymaltose is significantly superior

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