Efficacy and Safety of Ferric Carboxymaltose and Other Formulations in Iron-Deficient Patients: A Systematic Review and Network Meta-analysis of Randomised Controlled Trials
Clin Drug Investig
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 0 1 2
Sergio Venturini 0 1 2
Michela Meregaglia 0 1 2
Melania Marmifero 0 1 2
Rosanna Tarricone 0 1 2
Key Points 0 1 2
0 Department of Policy Analysis and Public Management, Bocconi University , Via Roentgen 1, Milan , Italy
1 Transfusion Medicine, San Lazzaro Hospital , Alba , Italy
2 & Carla Rognoni
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.
Centre for Research on Health and Social Care Management
(CERGAS), Bocconi University, Via Roentgen 1, 20136
Ferric carboxymaltose seems to provide a better and
more rapid correction of haemoglobin and serum
ferritin levels in iron-deficient patients compared to
other iron formulations.
Iron deficiency (ID) is the most common nutritional disorder
in the world affecting most preschool children and pregnant
women in developing countries and at least 30–40 %
in industrialised countries [
]. This condition also occurs
frequently across multiple therapeutic areas and especially in
patients with chronic disease (such as inflammatory bowel
disease and chronic kidney disease). ID can result from
chronic blood loss, decreased dietary intake, reduced
intestinal absorption, or impaired use of endogenous iron due
to chronic inflammations . Common symptoms that may
result from ID are fatigue, susceptibility to stress, lack of
concentration and underperformance. ID is also associated
with increased risk of infections [
], besides representing the
most common cause of anaemia worldwide. In particular, the
WHO defines anaemia as haemoglobin (Hb) \12 g/dl in
non-pregnant women and\13 g/dl in men [
]. In developed
countries, iron deficiency anaemia (IDA) occurs in 2–5 % of
adult men and postmenopausal women and represents a
common cause of hospitalisation, morbidity and
quality-oflife impairment [
Treatment for anaemic patients should involve prompt
iron replacement plus diagnostic steps directed towards
identifying the underlying cause of IDA [
subjects with low serum ferritin concentration with
symptoms of fatigue may also benefit from iron therapies [
Oral iron supplementation is usually the first treatment
choice for iron repletion; however, intravenous iron may be
better suited to those patients who are unable to tolerate
oral iron intake due to gastrointestinal side effects or whose
chronic iron loss exceeds the replacement rate achievable
with oral therapy [
]. Parenteral iron formulations are also
prescribed when there is a need for rapid delivery of iron as
in pregnancy or following traumas [
] and in any
situations where blood transfusions should be avoided [
The first iron intravenous preparations were associated
with acute toxicity deriving from the release of free iron.
Nowadays, all parenteral therapies are formulated so that
each iron particle is surrounded by a carbohydrate
molecule which allows a slow release of iron and limits toxicity.
Current intravenous iron formulations include high or low
molecular weight iron dextran, ferric gluconate, iron
sucrose and, very recently, ferric carboxymaltose [
They all share the same structure, but differ from each
other by the size of the core and the identity and density of
the surrounding carbohydrate.
Ferric carboxymaltose is an innovative, intravenous iron
preparation surrounded by a non-dextran carbohydrate
shell—the stable ferric carboxymaltose complex, which
allows the release of iron in a controlled manner. Thanks to
this intrinsic property, ferric carboxymaltose can be
administered in a short period of time (15 min) and at large
doses (up to 750 mg in the USA and 1000 mg in EU)
ensuring the amount of iron needed to promptly relieve
patients from the debilitating effects of ID [
gluconate was approved in 2002 for use in patients
undergoing haemodialysis and rapidly replaced iron
dextran due to severe adverse events (AEs; i.e. anaphylaxis
reactions) associated with the latter formulation; its
recommended dose for adult patients is 125 mg per treatment
(from the leaflet [
]). Iron sucrose represents another
intravenous alternative to treat haemodialysis-related IDA;
iron sucrose can be safely administered as a bolus infusion
over 2 min or as a short infusion for doses up to 300 mg. A
last option, ferumoxytol, is available to treat adult patients
with IDA associated with chronic kidney disease in the
USA; however, since it may cause serious hypersensitivity
reactions (including death), from 2014 this drug is no
longer authorised in Europe.
In synthesis, current treatments with intravenous iron
either risk anaphylaxis when using iron dextran or require
multiple injections of low doses when using
non-dextrancontaining agents (i.e. ferric gluconate and iron sucrose).
Although ferric carboxymaltose appears as an attractive
option in terms of both efficacy and safety, a widespread
use of this formulation is not yet supported by a high level
of evidence. Moore and colleagues [
] examined the
available trials of intravenous ferric carboxymaltose using
details from both published and unpublished literature. The
study increased the scientific evidence supporting
recommendations for intravenous iron treatments—and for ferric
carboxymaltose in particular—versus oral iron, but also
highlighted the paucity of trial data comparing different
parenteral iron preparations [
The aim of this study was to conduct a systematic
review and perform a network meta-analysis (NMA) of
randomised controlled trials (RCTs) to combine the highest
quality evidence regarding the efficacy and safety of the
novel iron complex (ferric carboxymaltose) compared
(directly or indirectly) to other existing (intravenous and
The present review was conducted in keeping with the
current guidelines from the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) [
All reviewing activities were conducted by two
independent reviewers (CR and MM) with disagreements resolved
2.1 Literature Search
2.4 Outcome Measures
Literature searches were performed for published RCTs on
the use of intravenous ferric carboxymaltose for the
treatment of ID in any medical condition. Published studies
were identified by searching PubMed, MEDLINE,
EMBASE and The Cochrane Library using ‘‘ferric
carboxymaltose’’ OR ‘‘Ferinject’’ OR ‘‘Injectafer’’ as
keywords in the title, abstract or anywhere in a document. In
order to perform (direct or indirect) comparisons of ferric
carboxymaltose with other preparations, terms referring to
competing iron formulations (i.e. ‘‘Ferlixit’’ OR ‘‘ferric
gluconate’’; ‘‘Venofer’’ OR ‘‘iron sucrose’’; ‘‘oral iron’’ OR
‘‘ferrous sulphate’’) were included in the query. Due to
current restrictions involving the prescription of
ferumoxytol, this intravenous iron formulation was not
considered in the analysis. The search was limited to RCTs
using highly sensitive filters; electronic searches were
conducted originally between July and October 2014. No
language or journal restriction was enforced in order to
minimise the risk of publication bias.
Studies combining the administration of iron and
erythropoiesis-stimulating agents were excluded from the
analysis in order to evaluate the effect of iron treatment
alone. Moreover, trials addressing anaemia following
surgical interventions or studies not reporting the
haematopoietic response among the outcomes were not considered.
2.2 Data Extraction
The following data were extracted from each study: first
author’s last name, publication year, title, study horizon,
number of participants (per arm), ID-related medical
condition, intervention and comparator, drug dosage,
post-intervention efficacy [i.e. Hb, serum ferritin, transferring
saturation (TSAT)] and safety (i.e. number and type of
AEs) outcome values.
2.3 Quality Assessment
The evaluation of potential biases in the selected studies is
an essential element of a systematic literature review or
meta-analysis. The internal validity of the eligible studies
was assessed according to the Cochrane Collaboration’s
Risk of Bias tool in Review Manager (RevMan 5—http://
tech.cochrane.org/revman). The risk of bias assessment
was performed with reference to the following domains:
sequence generation; allocation concealment; blinding of
participants and personnel and outcome assessors; blinding
of outcome assessment; incomplete outcome data; selective
The primary efficacy endpoint to be evaluated in the
included studies was the haematopoietic response, usually
defined as the improvement in Hb levels (g/dl) achieved by
the two (or more) iron formulations compared. Secondary
outcomes were the proportion of patients achieving
correction (or avoiding a recurrence) of IDA, time to reach the
target haematopoietic response (Hb C12 g/dl), increase in
TSAT (percentage) and serum ferritin (ng/ml), and
improvement in symptoms of ID-related diseases. Safety
outcomes as the proportion of study participants reporting
serious or mild treatment-related AEs were also included.
Categorical variables were described as absolute (and
percentage) frequencies and continuous variables as mean
2.5 Network Meta-analysis
In order to quantitatively support the findings of the
systematic review, a network meta-analysis (NMA) was
conducted using data extracted from the RCTs identified
through the same literature search.
Systematic reviews of RCTs are considered the standard
basis in evidence-based medicine to inform clinical
treatment guidelines and reimbursement policies. Many
systematic reviews use meta-analysis to combine quantitative
results of comparable studies and summarise the available
]. In the absence of trials involving a direct
comparison of all the treatments of interest, an indirect
comparison can represent an effective alternative to
generate enough evidence to select the best treatment option
]. NMA is a generalization of standard pairwise
metaanalysis that allows pooling both the direct and the indirect
evidence available for a given intervention. In this way, it
is possible to obtain a more precise estimate of the relative
effect for each pair of treatments considered [
In the past few years, NMAs have been increasingly
adopted for comparing healthcare interventions [
different therapeutic areas and, subsequently, endorsed by
several health-technology assessment bodies [e.g.
Canadian Agency for Drugs and Technologies in Health,
National Institute for Health and Clinical Excellence
A Bayesian NMA implemented by using either fixed or
random effects [
] has been carried out in WinBUGS
]. The choice between the two models has been
addressed by comparing the associated information
criterion [i.e. the Deviance Information Criterion (DIC)], where
the lower the value, the better the fit of the model to the
3.1 Study Selection
The initial search from multiple databases yielded
1027 citations, decreasing to 400 after removal of
duplicates. A subsequent review of the abstracts yielded
129 articles that were evaluated in depth; eventually,
21 studies were eligible for inclusion in our systematic
review (Fig. 1).
3.2 Study Characteristics
The characteristics of the 21 studies included in the
systematic review are summarised in Table 1. All were
RCTs comparing iron treatments in anaemic (or
nonanaemic) patients requiring therapies for ID. Studies were
published between 2003 and 2014. The time horizon of
each trial spanned between 2 weeks [
] and 9 months
. The number of patients enrolled ranged between 18
] and 2584 [
], averaging at 472 subjects (±703).
The vast majority of studies (n = 16) [
8, 9, 12, 28–39
recruited adult patients (C18 years) with anaemia (i.e. Hb
\13 g/dl in men and \12 g/dl in women), although the
haematological inclusion criteria varied among studies.
Indeed, in some articles the target population included
patients with severe IDA (i.e. Hb \10.5 g/dl) only [
], while in others  these severe cases were
explicitly excluded from the analysis. Two studies
enrolled premenopausal non-anaemic women with
symptoms of fatigue and low ferritin levels (B50 ng/ml) [
], while two others [
] addressed a neurological
disorder (i.e. the restless legs syndrome) which may be
caused or worsened by ID. Finally, one study [
evaluated IDA recurrence in patients with inflammatory bowel
disease whose Hb levels where above IDA upper limits at
the time of study entry.
IDA patients across the studies were affected by a
variety of conditions including inflammatory bowel disease
(and related thrombocytosis), chronic kidney disease,
nonvariceal acute upper gastrointestinal bleeding, chronic
heart failure and post-partum uterine bleeding. Other
participants experienced bleeding owing to invasive
techniques such as apheresis and haemodialysis.
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Eight trials [
9, 12, 30, 32, 34, 36, 38, 39
intravenous ferric carboxymaltose to ferrous sulphate (oral
iron) and in one of these studies  ferric carboxymaltose
was also compared to intravenous standard of care in
patients intolerant to oral iron. Since the formulation
constituting the ‘standard of care’ was not specified in the
article, this comparison was excluded from the analysis. In
another trial [
], an additional comparison was performed
between ferric carboxymaltose and intravenous placebo. In
four articles [
8, 33, 40, 42
], ferric carboxymaltose was
compared to placebo, while in two [
] it was
compared to iron sucrose. In two RCTs [
gluconate was assessed against oral iron (ferrous sulphate) and
placebo, respectively; in four studies [
6, 26, 37, 41
sucrose was compared to placebo. Finally, one study only
directly compared ferric carboxymaltose to ferric gluconate
]. Thus, the overall number of comparisons (n = 22)
exceeded the number of studies (n = 21) due to a study
] investigating more than two formulations (Fig. 2).
3.3 Efficacy Outcomes
In ten studies comparing any iron formulation versus
6, 8, 26, 27, 30, 33, 37, 40–42
], efficacy outcomes
were always superior in the treatment group. The only
study  directly comparing ferric carboxymaltose to
ferric gluconate revealed that both iron formulations were
safe and effective (only six patients per group experienced
non-serious AEs), but the increase in haematological
parameters was more substantial and rapid in ferric
carboxymaltose. When compared to other iron formulations
9, 13, 28, 30, 31, 34, 36, 38, 39
], ferric carboxymaltose
performed better in the achievement of a rapid and
consistent Hb response with the exception of one study [
where the difference in median Hb between ferric
carboxymaltose and oral ferrous sulphate was not statistically
significant. A higher increase in serum ferritin and TSAT
Fig. 2 Schematic representation of comparisons (n = 22) among
different iron formulations addressed in the included studies (n = 21)
levels was also observed in patients receiving ferric
carboxymaltose compared to other therapies. The only study
assessing the performance of ferric gluconate versus oral
ferrous sulphate [
] revealed greater improvements in Hb,
serum ferritin and TSAT levels in ferric gluconate-treated
chronic kidney disease patients than in the oral iron group.
3.4 Safety Outcomes
Overall, ferric carboxymaltose was well tolerated and
associated with a minimal risk of AEs, even if some
8, 9, 32
] reported that AEs occurred in a larger
proportion of ferric carboxymaltose-treated patients than
those receiving oral iron or placebo; the difference seldom
reached the significance level (p \ 0.05). Moreover, some
9, 32, 34, 36, 38, 39, 42
] revealed that patients who
were administered ferric carboxymaltose experienced less
drug-related gastrointestinal disorders (e.g. constipation,
diarrhoea, nausea and vomiting) than those treated with
oral ferrous sulphate. At the same time, patients treated
with ferric carboxymaltose iron were more likely to
develop skin disorders (e.g. rash, dermatitis and pruritus)
that usually resolved within a few minutes of the infusion
9, 31, 34, 38
]. Other frequent AEs associated with ferric
carboxymaltose administration were fatigue, headache and
8, 32, 34, 39
]. No true cases of anaphylactic
reactions were reported [
9, 31, 35, 42
] and no deaths
] in patients treated with ferric
With reference to other intravenous formulations, the
safety profile of ferric gluconate seemed to be favourable
], with few AEs reported after drug injection.
Similarly, iron sucrose was well tolerated and symptoms
associated with its administration were mild and resolved
26, 28, 31, 37
3.5 Risk of Bias Assessment
The risk of bias assessment for the included studies is
presented in Figs. 3 and 4. Eight studies [
9, 13, 29, 31, 34,
36, 38, 39
] were open-label RCTs without blinding of
patients and personnel. In two cases [
] no indication
on blinding was reported while in two other cases [
blinding was performed for patients only. For the latter, in
one case the authors stated that the primary end-point (Hb
values) was unlikely to be affected by the study personnel’s
awareness of the treatment. All the remaining studies were
In seven cases the sequence generation process was not
8, 9, 13, 26, 27, 34, 35
], while all the other
studies showed low selection biases.
3.6 Network Meta-analysis
Due to the high heterogeneity in trials included in the
systematic review, the NMA was limited to those adopting
a time horizon of 6 weeks (or 43 days), which was the
most frequent period reported. Six [
6, 29, 33, 36, 38, 39
out of 21 studies were included in the NMA (see Table 1,
studies with ‘‘a’’ label). Studies reported a mean iron dose
in the range 800—1600 mg for intravenous formulations,
while a daily dose of 975 mg (i.e. 325 mg three times daily
for 6 weeks) was administered for oral comparators.
The analyses focused on the increase of Hb and serum
ferritin levels after iron administration. In details, the
differences between final and initial values of these
parameters when using ferric carboxymaltose were
compared to the differences obtained with the other iron
formulations; the mean difference of these differences
(‘delta’) was estimated for each couple of treatments
(i.e. ferric carboxymaltose vs. competitors) across the
The network of studies considered is reported in Fig. 5,
where numbers indicate how many comparisons were
performed across the different formulations. The best
performing networks were considered: random effects
model (Deviance Information Criterion: 55.86 for random
effects model vs. 74.69 for fixed effects model) for the
serum ferritin NMA and the fixed effects model (Deviance
Information Criterion: 5.50 for fixed effects model vs. 5.91
for random effects model) for the Hb NMA.
As regards serum ferritin (lg/l), the mean difference
over the study period (final value - basal value) was
significantly larger for ferric carboxymaltose compared to oral
iron (delta 172.76; 95 % CI 66.7–234.4) (see Fig. 6).
Ferric carboxymaltose was superior in comparison to
placebo and ferric gluconate with a delta of 65.2 (95 % CI
-66.5 to 192.5) and 1.5 (95 % CI -131.4 to 122.8),
respectively. Iron sucrose was superior to ferric
carboxymaltose with a delta of 21.4 (95 % CI -160.7 to 118.4).
None of the comparisons was statistically significant.
As regards Hb (g/dl), the mean difference over the study
period (final value - basal value) was significantly larger
for ferric carboxymaltose compared to ferric gluconate
(delta 0.6; 95 % CI 0.2–0.9), placebo (delta 2.1; 95 % CI
1.2–3.0) and oral iron (delta 0.8; 95 % CI 0.6–0.9) (see
Fig. 7). Ferric carboxymaltose was superior to iron sucrose
with a delta of 1.1 (95 % CI -1.8 to 3.9) but without
Iron deficiency is a common nutritional deficit, affecting
men and women of all ages, races and ethnic groups. In
some cases, iron stores may be depleted so as to lead to
anaemia (IDA), a severe condition associated with a
number of chronic diseases (mainly of the kidney and the
bowel) and particular events in women’s lives (such as
pregnancy and significant menstrual blood loss in young
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)
Network of connected studies
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
women). Patients suffering from IDA and other ID-related
conditions can benefit from iron therapy. Oral iron is the
first-line treatment for most patients due to its
effectiveness, safety and cost; however, this formulation
presents a number of disadvantages, such as low absorption
of iron and high incidence of gastrointestinal side effects.
Moreover, iron stores are replenished most effectively and
rapidly when intravenous iron supplementation is
administered; therefore, parenteral iron administration was
introduced in clinical practice to overcome limitations and
risks related to oral iron.
Currently, different iron formulations for intravenous
infusion are available. These products are quite similar in
terms of safety profile but differ in the content and
frequency of the doses administered. The present study aimed
at improving the level of evidence to support the indication
of the available intravenous iron formulations and,
particularly, of the most recent preparation, ferric
carboxymaltose, brought into clinical practice.
Twenty-one RCTs involving ferric carboxymaltose, iron
sucrose and ferric gluconate were analysed in order to
retrieve information on clinical efficacy and safety of the
different iron formulations. Ferric carboxymaltose
treatment was shown to be superior in improving IDA
compared to other iron regimens. Ferric carboxymaltose
superiority is justified by the large amount of iron that can
be administered through a small number of injections; this
leads to quicker iron replacements in the body and
consequently a higher success in anaemia correction. A ferric
carboxymaltose dosing regimen was also well tolerated,
with a low number of AEs reported, most minor.
The present systematic literature review mainly
confirms the results already published by other authors [
]. The early response obtained with ferric
carboxymaltose (from day 7 onwards) implies a substantial
improvement in time-to-response and patient convenience and
emphasises the clinical relevance of this treatment. From
the Patient Blood Management (PBM) perspective [
that aims at optimising the care of patients who might need
blood transfusions, ferric carboxymaltose could represent
an effective alternative to transfusions in pre-operative
settings or in cases of severe anaemia (Hb \8 g/dl), while
in patients with non-dialysis-dependent renal failure, ferric
carboxymaltose administration might avoid the use of
erythropoietin-stimulating agents. In this way, PBM can
improve patient outcomes and reduce healthcare costs,
while ensuring that blood components are available for the
patients who need them.
Due to the paucity of RCTs comparing ferric
carboxymaltose with other parenteral iron formulations, a NMA
was performed to combine the highest quality (direct and
indirect) evidence regarding the efficacy of the novel
formulation. The analyses focused on the increase of Hb and
serum ferritin levels after the administration of the iron
formulations considering a time horizon of 6 weeks. Mean
differences in serum ferritin (lg/l) were significantly larger
for ferric carboxymaltose compared to oral iron, and in Hb
(g/dl) compared to oral iron, ferric gluconate and placebo.
Although ferric carboxymaltose superiority over oral iron
and placebo was already demonstrated in several trials [
30, 33, 34, 36, 38–40, 42
], NMA results supported these
findings comparing ferric carboxymaltose also to ferric
gluconate in terms of improvements in serum ferritin
levels. At present, only one trial directly compared ferric
carboxymaltose to ferric gluconate [
]; this study reported
a significant difference in serum ferritin levels achieved by
the two preparations but over a limited period of treatment
(i.e. 4 weeks).
Further RCTs are needed to establish the role of ferric
carboxymaltose with respect to the other intravenous
formulations in patients with IDA. These studies are essential
to provide more direct evidence of the comparisons and
should also focus on a short time horizon (i.e. 2 weeks) to
highlight the formulations suitable to avoid blood
transfusions in pre-operative settings. In the current review, only
two studies [
] reported high haematological
responses for ferric carboxymaltose at 2 weeks, but both
considered placebo as the comparator.
The present study was based on an extensive
bibliographical search that entailed the inclusion of all published
clinical trials addressing different intravenous formulations
considering any ID-related medical condition. However,
this review presents a number of limitations, including
those typical of systematic searches and indirect
comparisons of interventions. First, a selection bias may have
occurred, since only four databases were searched and
‘grey’ literature such as unpublished studies and trial
registers were omitted; the existence of some publication
biases cannot be excluded either. Secondly, clinical
outcomes, time horizon and treatment dose were not consistent
across the studies and a quantitative synthesis of results
was possible for six studies only. Moreover, Hb levels for
inclusion criteria and for the assessment of the primary
outcome varied a lot in the studies; in some studies, only
severe anaemic patients (Hb \10.5 g/dl) were recruited,
while in others these cases were excluded on purpose. In
some articles, the primary outcome was expressed in terms
of difference in Hb levels (g/dl), while in others authors
reported the percentage of patients who recovered from
IDA, thus performing a comparison of treatment effects
In the included studies, no health-related quality-of-life
and economic data were available, thus a comparison in
terms of cost effectiveness of the different intravenous iron
formulations was not feasible. Anyway, some authors
showed the cost effectiveness of ferric carboxymaltose
compared to placebo in patients with chronic heart failure
], while others showed that treatment with ferric
carboxymaltose also improved the quality of life of
anaemic patients in the postpartum  or in patients with IDA
associated with inflammatory bowel disease [
] or heavy
uterine bleeding [
]. Moreover, a recent study conducted
from an Italian perspective showed that ferric
carboxymaltose, due to the low number of infusions needed, might
be a cost-saving option from both national health system
and hospital points of view when compared to ferric
gluconate in the treatment of iron-deficient patients [
A systematic literature review also considering
cost-effectiveness outcomes would be desirable to give a broader
perspective to the analyses.
Despite its appeal in synthesizing all the available
evidence for a treatment, NMA clearly has some limitations as
well. The most critical one is the potentially high
heterogeneity of the studies included in the analysis, both with
regard to the reference study populations and to the
treatment allocation schedule. This may raise some doubts
about the validity of the findings. However, the present
analysis incorporates all the currently available evidence
about iron treatments for IDA and, to the best of our
knowledge, this is the first attempt to systematically and
quantitatively review the literature in this field.
Among the different iron formulations available for the
treatment of IDA, intravenous ferric carboxymaltose was
shown to be superior when compared with other iron
regimens. This new formulation can rapidly improve
haemoglobin levels and re-establish depleted iron stores in
different populations of patients with ID (or IDA) related to
a variety of medical conditions (i.e. chronic kidney disease,
inflammatory bowel disease, heavy uterine bleeding or
postpartum). Moreover, ferric carboxymaltose resulted in a
higher increase of serum ferritin levels in comparison to
ferric gluconate and showed a high safety profile.
From the Patient Blood Management perspective, ferric
carboxymaltose may avoid the use of blood transfusions or
other drugs (e.g. erythropoietin-stimulating agents) in
patients requiring an iron replacement.
The advantages of ferric carboxymaltose should be
further investigated through broader analyses that also
include quality-of-life measures and economic outcomes.
Compliance with Ethical Standards
Funding The present study was funded by Vifor Pharma Italia Srl
through an unrestricted grant to CERGAS, Bocconi University, Via
Roentgen 1, 20136 Milan, Italy. The authors were solely responsible
for carrying out the research project and in writing the manuscript.
Conflict of interest Dr. Melania Marmifero received a fee from
Vifor Pharma Italia Srl to participate in the drafting of this
manuscript. None of the other authors have any conflicts of interest to
Open Access This article is distributed under the terms of the
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License (http://creativecommons.org/licenses/by-nc/4.0/), which
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author(s) and the source, provide a link to the Creative Commons
license, and indicate if changes were made.
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