A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

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.

Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability. METHODS: In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations. RESULTS: For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively. CONCLUSIONS: Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.

Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial.

BACKGROUND: Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear. METHODS: We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.v. or usual care in patients being discharged from the ICU with moderate or severe anaemia (haemoglobin ≤100 g L-1). We collected data on feasibility (recruitment, randomisation, follow-up), biological efficacy, and clinical outcomes. RESULTS: Ninety-eight participants were randomly allocated (49 in each arm). The overall recruitment rate was 34% with 6.5 participants recruited on average per month. Forty-seven of 49 (96%) participants received the intervention. Patient-reported outcome measures were available for 79/93 (85%) survivors at 90 days. Intravenous iron resulted in a higher mean (standard deviation [sd]) haemoglobin at 28 days (119.8 [13.3] vs 106.7 [14.9] g L-1) and 90 days (130.5 [15.1] vs 122.7 [17.3] g L-1), adjusted mean difference (10.98 g L-1; 95% confidence interval [CI], 4.96-17.01; P<0.001) over 90 days after randomisation. Infection rates were similar in both groups. Hospital readmissions at 90 days post-ICU discharge were lower in the i.v. iron group (7/40 vs 15/39; risk ratio=0.46; 95% CI, 0.21-0.99; P=0.037). The median (inter-quartile range) post-ICU hospital stay was shorter in the i.v. iron group but did not reach statistical significance (5.0 [3.0-13.0] vs 9.0 [5.0-16.0] days, P=0.15). CONCLUSION: A large, multicentre RCT of i.v. iron to treat anaemia in survivors of critical illness appears feasible and is necessary to determine the effects on patient-centred outcomes. CLINICAL TRIAL REGISTRATION: ISRCTN13721808 (www.isrctn.com).

Efficacy and safety of ferric carboxymaltose infusion in reducing anemia in patients receiving chemotherapy for nonmyeloid malignancies: A randomized, placebo-controlled study (IRON-CLAD).

Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥ 0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. In 244 patients (n = 122, both groups), the percent of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%; p = 0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤ 9.9 g/dL (1.08 vs. 0.42 g/dL; p = 0.01). The percent with ≥ 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%; p = 0.01), occurring in a median 43 versus 85 days (p = 0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA.

Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether iron supplementation in patients on hemodialysis could be delivered by less frequent but higher single doses compared with the currently more common higher-frequency schedules of lower single iron doses is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We carried out an open-label, randomized, controlled noninferiority trial over 40 weeks in patients on prevalent hemodialysis (n=142). We administered in total 2 g iron as 100 mg iron sucrose biweekly in a continuous (20 × 100 mg) fashion or 500 mg ferric carboxymaltose every 10 weeks in a periodic (4 × 500 mg) fashion. The primary end point was the change in hemoglobin at week 40 from baseline with a noninferiority margin of -0.8 g/dl. Secondary end points were changes in ferritin, transferrin, transferrin saturation, and erythropoiesis-stimulating agent use. RESULTS: In total, 108 patients completed the study. At 40 weeks, hemoglobin changed by -0.27 g/dl (95% confidence interval, -0.64 to 0.09) in the iron sucrose arm and by -0.74 g/dl (95% confidence interval, -1.1 to -0.39) in the ferric carboxymaltose arm compared with baseline. Noninferiority was not established in the per-protocol population as hemoglobin changes compared with baseline differed by -0.47 g/dl (95% confidence interval, -0.95 to 0.01) in the ferric carboxymaltose arm compared with the iron sucrose arm. Proportional changes from baseline to week 40 differed by -31% (98.3% confidence interval, -52 to -0.1) for ferritin, by 1% (98.3% confidence interval, -7 to 10) for transferrin, and by -27% (98.3% confidence interval, -39 to -13) for transferrin saturation in the ferric carboxymaltose arm compared with the iron sucrose arm. Erythropoiesis-stimulating agent dosing did not differ between groups. The overall number of adverse events was similar; however, more infections were observed in the iron sucrose arm. CONCLUSIONS: An equal cumulative dose of ferric carboxymaltose administered less frequently did not meet noninferiority for maintaining hemoglobin levels compared with iron sucrose administered more frequently. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Comparison Study of Two Iron Compounds for Treatment of Anemia in Hemodialysis Patients (COPEFER), NCT02198495.

Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. OBJECTIVE: To determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. DATA SOURCES: Electronic medical record i.e. Cerner® system. TARGET POPULATION: Adults patients with iron deficiency anaemia. TIME HORIZON: A 12-month period (01/01/2018-31/12/2018). PERSPECTIVE: Hamad Medical Corporation (HMC, a public hospital). INTERVENTION: IV Ferric Carboxymaltose versus IV Iron Sucrose. OUTCOME MEASURES: With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. RESULTS OF BASE-CASE ANALYSIS: There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. RESULTS OF SENSITIVITY ANALYSIS: Not applicable. LIMITATIONS: The study did not consider the clinical or humanistic outcome. CONCLUSIONS: The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.

Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia.

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.

Intravenous ferric carboxymaltose does not provide benefits in reperfused acute myocardial infarction in the rat with normal iron status.

BACKGROUND: Iron deficiency has been implicated in the pathophysiology of heart failure and myocardial ischemia and reperfusion injury. Moreover, reperfused heart seems to lose iron, thus even subjects with normal iron status could benefit from iron therapy. Impaired mitochondrial respiration and energy starvation may be among possible consequences of myocardial iron deficiency. So far no attempts have been made to treat acute coronary syndromes with iron. Thus our aim was to verify the hypothesis that intravenous iron therapy given during reperfusion of an acute myocardial infarction will reduce left ventricular remodeling and hemodynamic abnormalities in a 2-month follow-up as well as early mitochondrial dysfunction and mortality, in the rat with normal iron status. METHODS AND RESULTS: A single dose of ferric carboxymaltose was administered intravenously at 30 min of reperfusion following 30 min of ischemia in the rat model of myocardial infarction. Ventricular arrhythmias were monitored using a telemetric system, activity of mitochondrial enzymes was assessed using spectrophotometry, serum markers of oxidative stress and inflammation were determined and left ventricular function and remodeling were monitored using echocardiography and pressure-volume loops. Intravenous iron therapy did not affect post-myocardial infarction mortality, left ventricular size or function, ventricular arrhythmias, activity of mitochondrial respiratory chain, oxidative stress or markers of inflammation, but was not associated with any adverse effects. CONCLUSIONS: Although ferric carboxymaltose given at reperfusion was safe, it was ineffective in this model of reperfused myocardial infarction in the rat with normal iron status.

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients: A systematic review and meta-analysis.

INTRODUCTION: Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients. METHODS: We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3. RESULTS: We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], -0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, -0.42 ng/mL; 95% CI, -1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25-1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06-36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35-0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group. CONCLUSION: FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity. TRIAL REGISTRATION: The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).

Attitude changes in prescribing intravenous iron supplementation in different settings at a hospital consortium in Italy.

BACKGROUND: Iron deficiency anaemia is a public health problem. In case oral iron treatment is ineffective, poorly tolerated or contraindicated, the intravenous route becomes the first choice. The aim of the study was to evaluate the shift between ferrous gluconate (FG) and ferric carboxymaltose (FCM) usage at our hospitals over the years. We also performed a cost comparison between pre and post-FCM availability periods, taking into account the acquisition costs of both intravenous iron and red blood cell units (PRBC). STUDY DESIGN AND METHODS: The amount and costs of FG and FCM released by hospital Pharmacy Services from 2010 to 2019 were analysed, along with the number of transfused PRBC units in the same timeframe. RESULTS: Overall, the proportion of FCM usage rose from 8.6 % in 2014 to 71.9 % in 2019, as percentage of total intravenous iron released. After exclusion of haemodialysis, where FG is still widely used, the FCM use in the last four years raised from 12.9% to 92.5%. Despite the higher FCM cost, the mean yearly expenditure for intravenous iron plus PRBC units did not differ between pre- and post-FCM eras (2010-2013, € 2,396,876 € versus 2014-2019, € 2,307,875 - p = 0.234), as a result of a net decrease of PRBC usage, namely from 15,083 to 12,654 (-16.1 %), respectively. DISCUSSION: Intravenous iron has a major role in treating iron deficiency anaemia in several settings. Third generation compounds are paving the way to more updated and safer treatments.

Ferric carboxymaltose treatment for iron deficiency anemia in children with inflammatory bowel disease: Efficacy and risk of hypophosphatemia.

BACKGROUND: Although intravenous ferric carboxymaltose (FCM) is effective in treating iron deficiency anemia (IDA) in paediatric inflammatory bowel disease (pIBD), no data are available on its post-infusion related risks. AIMS: We assessed the efficacy of FCM and the rate of post-infusion hypophosphatemia in a large cohort of children with IBD and IDA. METHODS: All children with IBD with IDA treated with FCM over 5-year period were reviewed. Disease activity, biohumoral assessment and treatments were evaluated at baseline, 4-6 and 12 weeks after each infusion. RESULTS: 128 patients [median age at first infusion: 13 years] were identified, 81 (63.3%) were <14 years, 10 (7.8%) <6 years. Eighty-three children (64.8%) received one infusion, whilst 45 (35.2%) repeated infusions. A significant increase in Hb (p<0.001), iron (p<0.001) and ferritin (p<0.001) was observed 4-6 and 12 weeks post-infusion. Hb gain was unrelated to disease severity. Low baseline iron was the main predicting factor for repeated infusions (p<0.05). Three patients reported infusion reactions, none <6 years. Twenty-five children had low post-infusion serum phosphate (11 were <14 years, 3 <6 years). Two children developed severe hypophosphatemia. CONCLUSIONS: FCM administration is effective for IDA management in pIBD, including children <6 years. Due to the high prevalence of post-infusion hypophosphatemia, serum phosphate monitoring should be mandatory.

Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis.

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.

Parenteral iron therapy and phosphorus homeostasis: A review.

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.

Interventions for treating iron deficiency anaemia in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial. OBJECTIVES: The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials. SELECTION CRITERIA: Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS: We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision). AUTHORS' CONCLUSIONS: Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.

Ferric carboxymaltose for sub-acute and chronic iron deficiency anemia in inherited platelet function defects.

Inherited platelet function defects are characterized by sub-acute and chronic mucocutaneous bleedings leading to iron deficiency anemia (IDA). Oral supplementation is the mainstay of treatment of IDA; however, it can be insufficient to compensate the losses and is often associated with gastrointestinal (GI) side effects. Intravenous (IV) iron is indicated for severe anemia or to overcome GI intolerance. Previous IV iron formulations were limited by the risk of free iron toxicity and immunogenicity, while currently available compounds (ferumoxytol, iron isomaltoside and ferric carboxymaltose (FCM)) allow the administration of high doses with low immunogenicity. There are neither any randomized studies nor case reports evaluating the efficacy of FCM in patients with inherited platelet disorders. We herein present three cases of patients with IDA related to Glanzmann thrombasthenia and Bernard-Soulier syndrome, who have been successfully treated with FCM with increase in hemoglobin levels, reduced hospital visits and improvement in quality of life.

Hypophosphatemia Is Common After Intravenous Ferric Carboxymaltose Infusion Among Patients With Symptomatic Heart Failure With Reduced Ejection Fraction.

Administration of intravenous ferric carboxymaltose (FCM) for iron-deficient patients suffering heart failure with reduced ejection fraction (HFrEF) has been associated with transient hypophosphatemia. We sought to investigate and model the effect of intravenous FCM on phosphate levels in iron-deficient patients with HFrEF. In this single-center retrospective study, serum phosphate levels, recorded for clinical reasons, were collected out to 60 days following intravenous FCM. Hypophosphatemia was defined as a nadir serum phosphate level <0.64 mmol/L. This was further categorized as severe (0.4 to <0.64 mmol/L) and extreme (<0.4 mmol/L). Factors associated with hypophosphatemia and change in serum phosphate over time were explored. Of 173 patients included, 47 (27%) experienced hypophosphatemia, 44 (25%) were classified as severe, and 3 (2%) extreme. Risk of hypophosphatemia was increased for patients with a creatinine clearance between 60 and <90 mL/min (odds ratio, 2.3; 95% confidence interval, 1.0-5.5), while <60 mL/min was protective. The median time to nadir in patients who experienced hypophosphatemia was 8 (interquartile range, 4-16) days, with a return to baseline levels at 6 weeks. Biochemically relevant hypophosphatemia is common following a single dose of intravenous FCM. The median time to nadir was 8 days, and creatinine clearance may influence phosphate levels following intravenous FCM. These observations support the need to increase awareness among clinicians administering intravenous FCM to iron-deficient patients with HFrEF.