Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

One-Bag 8-Step Ferric Carboxymaltose Desensitization Protocol for Patients with a History of Hypersensitivity Reactions to Iron Preparations.

INTRODUCTION: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied. METHODS: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization. RESULTS: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients. CONCLUSION: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols.

[Hypophosphatemia associated with use of intravenous ferric carboxymaltose]. / Hipofosfatemia asociada a uso de carboximaltosa férrica endovenosa.

Introduction: Introduction: ferric carboxymaltose (CF) is an intravenous preparation that helps the rapid correction of anemia with a lower risk of adverse reactions. However, an association has been found between the administration of CF and the development of hypophosphatemia. Case report: we present the clinical case of a 57-year-old patient with a history of iron de-ficiency anemia who, after receiving treatment with CF (Ferinjet®) chronically, develops a clinical of severe muscle weakness. Laboratory tests showed hypophosphatemia, normocalcemia, normal vitamin D level (after correction) and increased renal excretion of phosphorus. After study, the diagnosis of chronic hypophosphatemia secondary to the use of CF is reached. Discussion: CF can cause an increase in FGF-23 which acts at the renal level inducing phosphaturia, which can generate severe hypophosphatemia. This case demonstrates the importance of recognizing and treating this clinical entity in time.

Introducción: Introducción: la carboximaltosa férrica (CF) es una preparación intravenosa que ayuda a la corrección rápida de anemia con menor riesgo de reacciones adversas. Sin embargo, se ha encontrado asociación entre la administración de la CF y el desarrollo de hipofosfatemia. Caso clínico: presentamos el caso clínico de una paciente de 57 años con anemia ferropénica que tras recibir tratamiento con CF (Ferinjet®) de forma crónica, desarrolla un cuadro clínico de debilidad muscular severa. En la analítica se aprecia hipofosfatemia, normocalcemia, nivel de vitamina D normal (tras corrección) y aumento de excreción renal de fósforo. Tras estudio se llega al diagnóstico de hipofosfatemia crónica secundaria al uso de la CF. Discusión: la CF puede provocar un aumento de FGF-23 el cual actúa a nivel renal induciendo fosfaturia, pudiendo generar hipofosfatemia grave. Este caso demuestra la importancia de reconocer y tratar esta entidad clínica a tiempo.

What is wrong in doing good?

Hypophosphataemia is a common side-effect in patients with iron deficiency anaemia treated with ferric carboxymaltose, which is not a class effect of all intravenous (IV) iron formulations. The report by Chu et al. shows that moderate and severe hypophosphataemia is common and can even require IV supplementation of phosphate with unknown long-term consequences. Commentary on: Chu et al. Incidence and predictors of hypophosphataemia after ferric carboxymaltose use-a 3-year experience from a single institution in Singapore. Br J Haematol 2023;202:1199-1204.

Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis.

BACKGROUND: Iron deficiency, with or without anemia, is an adverse prognostic factor in heart failure (HF). In AFFIRM-AHF (a randomized, double-blind placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient subjects admitted for acute heart failure), intravenous ferric carboxymaltose (FCM), although having no significant effect on the primary end point, reduced the risk of HF hospitalization (hHF) and improved quality of life versus placebo in iron-deficient patients stabilized after an acute HF (AHF) episode. These prespecified AFFIRM-AHF subanalyses explored the association between hemoglobin levels and FCM treatment effects. METHODS: AFFIRM-AHF was a multicenter, double-blind, randomized, placebo-controlled trial of FCM in hospitalized AHF patients with iron deficiency. Patients were stratified by baseline hemoglobin level (<12 versus ≥12 g/dL). In each subgroup, the primary composite (total hHF and cardiovascular death) and secondary (total hHF; total cardiovascular hospitalizations and cardiovascular death; time to cardiovascular death, and time to first/days lost due to hHF or cardiovascular death) outcomes were assessed with FCM versus placebo at week 52. Sensitivity analyses using the World Health Organization anemia definition (hemoglobin level <12 g/dL [women] or <13 g/dL [men]) were performed, among others. RESULTS: Of 1108 AFFIRM-AHF patients, 1107 were included in these subanalyses: 464 (FCM group, 228; placebo group, 236) had a hemoglobin level <12 g/dL, and 643 (FCM, 329; placebo, 314) had a hemoglobin level ≥12 g/dL. Patients with a hemoglobin level <12 g/dL were older (mean, 73.7 versus 69.1 years), with more frequent previous HF (75.0% versus 68.7%), serum ferritin <100 µg/L (75.4% versus 68.1%), and transferrin saturation <20% (87.9% versus 81.4%). For the primary outcome, annualized event rates per 100 patient-years with FCM versus placebo were 71.1 and 73.6 (rate ratio, 0.97 [95% CI, 0.66-1.41]), respectively, and 48.5 versus 72.9 (RR, 0.67 [95% CI, 0.48-0.93]) in the hemoglobin levels <12 and ≥12 g/dL subgroups, respectively. No significant interactions between hemoglobin subgroup and treatment effect were observed for primary (Pinteraction=0.15) or secondary outcomes. Changes from baseline in hemoglobin, serum ferritin and transferrin saturation were significantly greater with FCM versus placebo in both subgroups between weeks 6 and 52. Findings were similar using the World Health Organization definition for anemia. CONCLUSIONS: The effects of intravenous FCM on outcomes in iron-deficient patients stabilized after an AHF episode, including improvements in iron parameters over time, did not differ between patients with hemoglobin levels <12 and ≥12 g/dL. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02937454.

Intravenous ferric carboxymaltose for the management of iron deficiency and iron deficiency anaemia in children and adolescents: a review.

Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information. CONCLUSION: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary. WHAT IS KNOWN: • Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients. • Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year. WHAT IS NEW: • Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full. • There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

Analysis of transition from intravenous iron sucrose to ferric carboxymaltose infusions in pediatric patients with intestinal failure.

BACKGROUND: Iron supplementation is required for pediatric patients with intestinal failure (IF). There is a paucity of literature on optimal iron formulation and outcomes in this patient population that requires ongoing supplementation. The aim of this study was to assess outcomes in pediatric patients with IF receiving iron sucrose (IS) vs ferric carboxymaltose (FCM) iron infusions. METHODS: This was a single-center observational cohort study of pediatric patients with IF requiring ongoing intravenous iron supplementation. Patients were transitioned from IS to FCM as iron therapy. Longitudinal linear mixed-effects models and generalized estimating equations were used to compare outcomes, including hematologic, iron, and growth parameters for 12-month treatment duration on each iron formulation. Adverse effects were descriptively summarized. RESULTS: Twenty-three patients were included. Sixteen received IS and later switched to FCM, five received IS only, and two received FCM only. Most patients' etiology of IF was short bowel syndrome (FCM: 81%, IS: 83%). No differences were seen over time for iron, hematologic, and growth metrics between IS and FCM. The median number of infusions over 12 months for those taking IS was 15 (interquartile range [IQR] = 13-26) and 2 for FCM (IQR = 1-2). Asymptomatic hypophosphatemia was noted in both groups. Similar central line-associated bloodstream infection rates were noted. CONCLUSION: IS and FCM infusions both maintained hematologic and iron parameters with no significant difference noted between the two types of iron, though the number of FCM infusions was significantly less. No significant adverse effects were noted.

Hypophosphatemic osteomalacia, a side effect of iron carboxymaltose administration.

Carboxymaltose iron (Ferinject®) is a formulation for intravenous (iv) administration, used for the treatment of iron deficiency anemia and/or iron deficiency when oral administration of iron is not effective or due to intolerance. Its safety profile is excellent with few, but not nonexistent, side effects. Hypophosphatemia has been described as one of them. It is usually mild, transient and asymptomatic. However, in some cases it may be accompanied by nausea, asthenia, in addition to muscular and neurological symptoms and hematological alterations. It is, therefore, a potentially serious adverse effect whose prevalence is unknown and which requires high clinical suspicion to be detected.

Effectiveness and safety of an on-demand ferric carboxymaltose infusion strategy in patients with inflammatory bowel disease: a real world experience.

BACKGROUND: We evaluated an on-demand ferric carboxymaltose (FCM) infusion strategy in inflammatory bowel disease (IBD) patients with iron deficiency anemia (IDA). AIMS: The primary outcome was the response rate to single or multiple FCM infusions after 12 months. Secondary outcomes were the response rate to a single FCM infusion after 3 months and the FCM safety profile. METHODS: We retrospectively included 185 IBD patients who received at least one FCM infusion of 500 mg, between 2015 and 2018. FCM was administered to patients with Hb ≤10 g/dL and hypoferritinemia and repeated according to the physician's assessment. Complete response (CR) was defined as Hb ≥12 g/dL (≥13 g/dL for men) or Hb increase ≥2 g/dL. Partial response (PR) was defined as an Hb increase between 1 and 2 g/dL. A univariate analysis was performed at 3 and 12 months. RESULTS: After 12 months, the response rate was 75.1% (CR, 48.6%; PR, 26.4%; mean number of FCM infusions, 1.7 ± 1.1). In total 169/185 patients received a single FCM infusion during the first 3 months and 79.2% achieved response (CR, 56.8%; PR, 22.4%). At univariate analysis, no variable was associated with response. No adverse events were reported. CONCLUSIONS: An on-demand strategy was effective and well-tolerated in treating IDA in IBD patients.