Ferric Carboxymaltose Treatment Research Articles

Demir Eksikliği Anemili Kadın Hastalarda İntravenöz Demir Tedavisinin Etkinliği

Abstract: In this study, it was aimed to show the efficacy of intravenous (IV) ferric carboxymaltose treatment for iron deficiency anemia (IDA), which is a public health problem due to its high prevalence in the world and in Turkey. Since it is the first study in the region, its importance is increasing even more. Eighty female diagnosed with IDA and treated with IV iron carboxymaltose, who applied to Siirt Training and Research Hospital Internal Diseases Polyclinics between June 2018 and September 2019, were included in the study. After obtaining voluntary consent of female patients, biochemical data of pre- and post-treatment were included in the study retrospectively. After treatment, hemoglobin (HGB), hematocrit (HTC), mean cell volume (MCV), ferritin, iron and B12 values increased statistically (p

Incidence of Fractures after Intravenous Iron: A Retrospective Analysis Comparing Ferric Carboxymaltose and Ferric Derisomaltose

Background: Hypophosphatemia is a frequent side-effect of certain intravenous (i.v.) iron formulations, and a recent meta-analysis of prospective clinical trials reported that 54% of patients treated with ferric carboxymaltose (FCM) develop hypophosphatemia. While the incidence and time-course of hypophosphatemia are well known, the frequency of clinical consequences of these changes is poorly described. FCM infusions cause high intact fibroblast growth factor 23 (iFGF23), which is associated with hypophosphatemia, hyperphosphaturia, hypocalcitriolemia, hypocalcemia, secondary hypoparathyroidism, which is summarized as the ‘6H-syndrome’ that can ultimately result in osteomalacia. The association between treatment with FCM, high iFGF23, osteomalacia with fractures and nephrolithiasis is well documented in multiple case reports. This is not the case for ferric derisomaltose (FDI). Aims: The aim of the present study was to assess the incidence of fractures or radiological signs of osteomalacia and kidney stone in patients treated with FCM or FDI. Methods: Patients treated with FCM or FDI between January 2010 und December 2019 were identified by retrospective assessment of electronic health records of the University Hospital in Innsbruck, which is a large tertiary referral center in Western Austria. Dose, time of infusion, comorbidities and haematological parameters, serum iron parameters as well as markers of mineral metabolism were extracted from the healthcare records of each patient. Radiological and clinical endpoints included fractures, radiological signs of osteomalacia and kidney stone disease after the first infusion of FCM or FDI. The year before the first infusion was used as a control period. Results: In total, 289 patients were included and the median follow-up time was 5.8 years. Mean age was 44.6 years and 184 of 289 patients (64%) were females. In total 179 patients were treated with FCM and 110 patients received FDI. Grouping patients by drug revealed no differences in cumulative iron dose or number of drug applications. At baseline, serum creatinine was significantly lower in FDI-treated patients, but within the normal range for both groups. Mean hemoglobin concentrations were significantly lower in FCM-treated than in FDI-treated patients (95 g/L vs. 109 g/L) with no statistically significant differences in mean ferritin concentrations between groups at baseline. Assessment of treatment response 1-3 months after i.v. iron treatment showed a robust increase in hemoglobin and serum ferritin in both treatment groups. Baseline phosphate was significantly lower in FDI-treated patients with 3.07 mg/dL versus 3.34 mg/dL in the FCM treatment group. In FCM-treated patients a significantly greater change from baseline to 1-3 months after administration was found for phosphorous and calcium (Table 1). Hypophosphatemia was more commonly documented and more severe in FCM-treated patients, who also showed a significant increase in ALP. In a time to event analysis (fracture, osteomalacia and kidney stones) a significantly higher proportion of patients reached the combined endpoint in the FCM treatment group than in FDI-treated patients (Figure 1). Univariate Cox-regression for fractures after the infusion showed a HR of 4.54 for FCM treatment when compared to FDI (p=0.04). In contrast, no difference in fracture incidence was present in the year before the first iron infusion when both treatment groups were compared. Conclusions: In this retrospective analysis the combined event rate of fracture, radiological signs of osteomalacia and kidney stones was significantly higher among patients treated with FCM than after FDI treatment. This finding suggests that the observed changes in markers of mineral metabolism could indicate that FCM treatment is associated with a significantly higher risk of clinically relevant bone complications and kidney stone disease.

The effect of iron deficiency treatment with intravenous ferric carboxymaltose on the arrhythmic burden of patients with HFrEF and cardiac implantable electronic devices

Abstract Background The deleterious effect of iron deficiency (ID) on cardiomyocyte electrochemical stability is well-documented. In patients with heart failure and reduced ejection fraction (HFrEF), ID represents a key comorbidity associated with increased morbidity and mortality. Thus, it has been hypothesized that treating ID may lead to reduced incidence of arrhythmias in HFrEF patients. Purpose To study the effect of intravenous ferric carboxymaltose (IV FCM) treatment on the iron stores, arrhythmic burden, functional capacity and quality of life in HFrEF patients with ID and cardiac implantable electronic devices (CIEDs). Methods Patients with HFrEF, ID and CIEDs scheduled to receive IV FCM as per ESC guidelines were invited to participate. Follow-up lasted 12 months. The primary outcome was related to the amelioration of patients’ iron status. Secondary outcomes relative to arrhythmic burden included (i) the incidence of device-detected ventricular tachycardias (VTs) between the year before recruitment to the study and the follow-up period, (ii) patients’ Lown and Wolf classification as derived from 24hour Holter monitoring. Data related to non-invasive arrhythmic markers such as late potential, microvolt T-wave alternans and deceleration capacity were also available. Results This real-life cohort included 79 patients (84% male). Patients’ median age was 70.8 [IRQ:11.7] years. Median ferritin increased to 150 [125] ng/mL at 12 months (baseline 55 [68] ng/mL, P<0.001). At their final visit, 45 (57%) patients no longer met the ESC criteria for iron deficiency (P<0.001). The CIED-derived incidence of VT episodes decreased significantly after 12 months of IV FCM treatment (0.26±0.83 episodes per patient per year compared to 0.8±2.36, P = 0.048). Patients were also significantly likely to shift to a more favorable Lown and Wolf arrhythmic burden classification (P = 0.01). Patients’ late potential results and microvolt T-wave alternans also improved significantly (P = 0.01 for both tests). Conclusion The results of this real-life cohort analysis suggest significant reduction of the arrhythmic burden in HFrEF and ID after restitution of iron stores. Further studies are needed to further evaluate the impact of these results.

Seven-Year Single-Center Experience of the Efficacy and Safety of Ferric Carboxymaltose in Cancer Patients with Iron-Deficiency Anemia.

Anemia remains an essential concern affecting the quality of life and the survival of cancer patients. Although there are different approaches to treating anemia in cancer patients, the number of studies reporting the efficacy of iron replacement in cancer patients is limited. In this study, the efficacy and safety of iron carboxymaltose, a parenteral iron treatment option, in the treatment of anemia, were examined retrospectively. A total of 1102 adult patients who received IV ferric carboxymaltose treatment at Hacettepe Oncology Hospital between 2014 and 2020 were included. The mean hemoglobin change observed at the end of the 12th week was 1.8 g/dL, and the rate of patients with an increase in hemoglobin of 1 g/dL or more was 72.1%. It was observed that the treatment demonstrated effectiveness in patients receiving active cancer treatment in all tumor types. The treatment was generally safe, and no grade 3-5 side effects were observed in the patients included in the study. According to one of the most extensive series published in the literature, iron carboxymaltose is an efficient and safe alternative for cancer patients with iron-deficiency anemia.

Hepcidin and Erythroferrone Levels across Human Pregnancy, and the Effect of IV Iron Infusion - a Revamp Substudy

Hepcidin is known to be suppressed in human pregnancy; and while it's known that intravenous iron infusion increases hepcidin levels, it is unknown to what degree this occurs during pregnancy. The REVAMP trial was an open label, individually randomised controlled trial, in 862 Malawian pregnant women in the second trimester, with moderate to severe anaemia (haemoglobin<10.0g/dL). Participants were randomised equally to either intravenous Ferric Carboxymaltose (FCM), or standard of care (Oral iron), and followed up to 28 days post partum. To evaluate hepcidin and erythroferrone levels, a total of 250 participants were randomly selected. This sample was balanced with the main trial with regards to trial arm (FCM 50%, Oral iron 50%), baseline iron deficiency (42.2%), anaemia (96.4%), parity (nulliparous 55.6%), and HIV status (HIV positive 15.3%). Hepcidin and erythroferrone levels were measured by ELISA, on serum samples collected longitudinally across 3 pregnancy timepoints (baseline, 28-days post randomisation, 36-weeks gestation), delivery, and 28-days postpartum. Serum hepcidin levels (reported as: median [IQR]) were not different between the trial arms at baseline (FCM: 11.91ng/ml [5.56-20.53], Oral iron: 12.79ng/ml [6.65-20.40]). At 28 days post randomisation, hepcidin was higher in those treated with FCM (31.92ng/ml [14.80-59.84]) than oral iron (5.85ng/ml [2.50-15.12]), p<0.001. Hepcidin remained significantly increased at 36 weeks gestation (FCM: 21.14ng/ml [11.84-41.62], Oral iron: 10.86ng/ml [8.34-18.03], p<0.001). At delivery levels were higher overall, remaining higher in those who received FCM treatment (80.56ng/ml [25.11-149.6]) than Oral iron (37.39ng/ml [16.35-91.85], p=0.001). At 28days postpartum, hepcidin remained higher in the FCM arm 39.29ng/ml [19.52-76.37] than the Oral arm 17.67ng/ml [11.05-38.21], p<0.001. Erythroferrone levels were not statistically different between arms at any timepoint; values were highest at baseline (FCM median 0.92ng/ml [0.42-1.45], Oral iron 1.06ng/ml [0.52-2.04]). This is the first study examining the effects of modern intravenous iron infusions on hepcidin levels during pregnancy, and demonstrates that there is a statistically significant increase in hepcidin levels after ferric carboxymaltose, throughout pregnancy, persisting to four weeks post partum.

Efficacy and Safety of Intravenous Ferric Carboxymaltose Treatment of Iron Deficiency Anaemia in Patients with Corpus Atrophic Gastritis: A Retrospective Study.

Corpus Atrophic Gastritis (CAG) is characterised by iron malabsorption leading to iron deficiency anaemia (IDA), which rarely responds to oral therapy. Ferric carboxymaltose (FCM), shown to be a safe and effective intravenous iron therapy in other diseases, has not been investigated yet in CAG. Thus, we aimed to assess the safety and efficacy of FCM in CAG-related IDA. A retrospective study on 91 patients identified CAG as the only cause of IDA treated with FCM. Twenty-three were excluded for incomplete follow-up. Sixty-eight were evaluated for safety and efficacy, while three were evaluated for safety only due to infusion interruption for side effects. Haemoglobin and iron storage were evaluated pre-infusion (T0), at 4 weeks (T4) and 12 weeks (T12) after infusion. An eventual IDA relapse was analysed. Two cases reported mild side effects. Haemoglobin significantly increased at T4, and T12, reaching +3.1 g/dL. Ferritin increased at T4, decreasing at T12, while transferrin saturation increased progressively until reaching a plateau. IDA relapsed in 55.4% of patients at a mean of 24.6 months. The only factor associated with relapse was female gender [OR (95% CI): 6.6 (1.5-28.6)]. FCM proved to be safe and effective in treating CAG-related IDA, ensuring quick and long-lasting recovery.

Ferric Carboxymaltose in Patients with Acute Decompensated Heart Failure and Iron Deficiency: A Real-Life Study.

Background: The correction of iron deficiency (ID) with ferric carboxymaltose (FCM) is a recommended intervention in heart failure (HF) with reduced ejection fraction. Our aim is to evaluate, in a real-life setting, the clinical significance of ID screening and FCM treatment in acute decompensated HF (ADHF). Methods: In a cohort of ADHF patients, the prevalence of ID and FCM administration were investigated. Among the 104 patients admitted for ADHF, in n = 90 (median age 84, 53.5% with preserved left ventricular ejection fraction-LVEF), a complete iron status evaluation was obtained. ID was detected in n = 73 (81.1%), 55 of whom were treated with in-hospital FCM. The target dose was reached in n = 13. Results: No significant differences were detected in terms of age, sex, comorbidities, or LVEF between the FCM-supplemented and -unsupplemented patients. During a median follow-up of 427 days (IQR 405-466) among the FCM-supplemented patients, only 14.5% received FCM after discharge; the mortality and rehospitalizations among FCM-supplemented and -unsupplemented patients were similar (p = ns). In a follow-up evaluation, ID was still present in 75.0% of the FCM-supplemented patients and in 69.2% of the unsupplemented patients (p = ns). Conclusions: In this real-life ADHF cohort, FCM was administered at lower-than-prescribed doses, thus having no impact on ID correction. The significance of our findings is that only achieving the target dose of FCM and pursuing outpatient treatment can correct ID and produce long-term clinical benefits.

Patient-Reported Outcomes After Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study.

Iron deficiency anemia (IDA) is a common cause of fatigue and impaired quality of life. The present study aimed to evaluate the impact of intravenous iron supplementation with ferric carboxymaltose (FCM) on fatigue, physical function, and general health among patients with IDA attending routine clinical care. This was a prospective, single arm, observational study of adult patients prescribed with intravenous FCM for the treatment of IDA during routine clinical care. We used Patient-Reported Outcomes Measurement Information System (PROMIS) instruments to evaluate fatigue (PROMIS Short Form v1.0 13a [FACIT-Fatigue]), general health status (PROMIS Scale v1.2), and physical function (PROMIS Short Form v2.0 4a) before and at 3 and 6 months after FCM treatment. A total of 152 patients were enrolled. Mean age was 47.4 ± 16.0 years and 82.2% were female. Mean serum hemoglobin was 10.2 ± 1.4 g/dL at baseline. All patients were treated with at least one FCM dose at baseline, with 77.6% receiving a two-dose treatment course. The mean baseline FACIT-Fatigue score was 61.0 ± 9.0, improving significantly to 50.2 ± 9.5 at 3 months after FCM treatment. A minimum 5-point improvement, pre-defined as clinically meaningful, was seen in the FACIT-Fatigue, PROMIS Global Physical Health, Global Mental Health and PROMIS Physical Function scores for 72.7%, 52.8%, 41.7% and 39.8% of patients at 3 months (p < 0.0001 for each change from baseline), with statistically significant improvement continuing at 6 months. Mean serum hemoglobin was significantly increased at both 3 and 6 months (12.8 g/dL [N = 44] and 12.4 g/dL [N = 54], respectively). IDA patients attending routine clinical practice reported substantial levels of fatigue and impairments in physical function and global health prior to intravenous iron treatment. Patients experienced significant improvements in fatigue symptoms, physical function, and global health at 3 months after treatment with FCM, which were sustained at 6 months.

Efficacy and safety of early ferric carboxymaltose treatment in patients with acute decompensated heart failure

BACKGROUND: The efficacy of intravenous ferric carboxymaltose (FCM) therapy in heart failure (HF) with low ejection fraction with iron deficiency (ID) or ID anemia is known. The aim of this study was to determine the efficacy and safety of intravenous FCM therapy in the early decompensated period in acute decompensated HF with low ejection fraction with ID or ID anemia.METHODS: Patients with acute decompensated HF with low ejection fraction (EF<40%) with ID or ID anemia were included in the study. ID was diagnosed according to serum ferritin and transferrin saturation (TSAT) measurement at admission in 26 patients and before discharge in 26 patients, and intravenous FCM treatment was given at the same time. ID was defined as serum ferritin <100 μg/L (absolute ID) or ferritin 100-299 μg/L with a TSAT<20% (functional ID). Cox regression analysis was used to determine the relationship between the time of intravenous iron therapy and the risk of 30-day hospitalization and 6-month rehospitalization and mortality and Linear regression analysis was used for N-terminal pro-brain natriuretic peptide (NT-proBNP) change at 30 days.RESULTS: All patients have either ID or ID anemia. The mean age was 67.0±13.0 years, 58% female. Anemia was more prevalent at admission blood samples than before discharge (P<0.001), and absolute and functional iron deficiency rates were similar (P=0.38 and P=0.19, respectively). 30-day rehospitalization (Hazar ratio [HR]= 0.80, confidence interval [CI] 0.22-2.98, P=0.74) Sixth-month rehospitalization (HR=0.89, CI 0.36-2.20, P=0.80) and Sixth-month mortality (HR=0.51, CI 0.05-5.56, P=0.58) were similar between treatment groups. There was no significant relationship between the time of administration of FCM treatment and the change in pro-BNP levels measured at baseline and 30-day (P=0.90).CONCLUSIONS: In patients with acute decompensated HF with low ejection fraction and ID or ID anemia, the efficacy and safety of intravenous iron therapy applied at admission are similar to before discharge.

Comparative effects of treatment with ferric carboxymaltose versus ferric derisomaltose in a murine model of iron-deficiency anemia

Intravenous (IV) iron preparations like ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) are used to treat iron deficiency anemia (IDA) due to heavy uterine bleeding, inflammatory bowel disease, and chronic kidney disease. These preparations greatly differ in terms of their side-effect profiles (e.g, hypophosphatemia). However, studies that directly compare FCM and FDI are limited. The objective of this study was to compare the effects of FCM and FDI in a mouse model of IDA and investigate changes in blood parameters and mineral homeostasis. Female C57Bl/6J mice were fed iron-deficient diet for 5 weeks followed by IV bleeding (0.7% of body weight [b.w.]) for 3 consecutive days. On day 0 (last day of bleeding), baseline blood and urine were analyzed for hematocrit, CBC, P i and Ca 2+ . Mice were randomized to vehicle (saline, 2 μl/g b.w.; n=16), FCM (20 mg/kg; n=12), or FDI (20 mg/kg; n=12) treatment via retroorbital injection on day 0 and 7. On day 14, terminal blood, urine, spleen, and heart were collected. At baseline, compared with pre-bleeding, all mice had low hematocrit (22±1 vs 48±0.3%; P&lt;0.05) and microcytic hypochromic anemia. After 14 days, mice treated with FCM and FDI had higher hematocrit compared with vehicle (47±0.4 and 46±0.3 vs 25±1%; P&lt;0.05). WBC were similar on day 14 compared with day 0 for mice treated with FCM (8±1 vs 7±1 x10 9 /L; NS) or FDI (7±1 vs 7±1 x10 9 /L; NS); however, WBC were decreased in vehicle-treated mice (4±1 vs 6±1 x10 9 /L; P&lt;0.05). Thrombocytes were increased in vehicle-treated mice on day 14 compared with day 0 (1405±55 vs 795±23 x10 9 /L; P&lt;0.05); while there was no change in thrombocytes in mice treated with FDI (706±16 vs 831±29 x10 9 /L; NS), they were decreased in FCM-treated mice (583±41 vs 771±30 x10 9 /L; P&lt;0.05). Both FCM and FDI prevented splenomegaly that was seen in vehicle-treated mice (88±3 and 87±20 vs 263±40 mg; P&lt;0.05). Similarly, FCM and FDI prevented greater heart weight that was seen in vehicle-treated mice (0.43±0.01 and 0.45±0.01 vs 0.48±0.01 g/b.w. %; P&lt;0.05). After 14 days, mice treated with FCM and FDI had lower plasma P i compared with vehicle (1.9±0.1 and 2.1±0.1 vs 2.4±0.1 mmol; P&lt;0.05); although FCM-treated mice showed greater hypophosphatemia compared with FDI ( P&lt;0.05). There were no differences between groups for urinary P i . Plasma Ca 2+ was similar between groups on day 14; but compared with day 0, it was higher in vehicle (2.7±0.1 vs 2.5±0.1 mmol; P&lt;0.05) and FCM-treated mice (2.8±0.1 vs 2.5±0.1 mmol; P&lt;0.05). Urinary Ca 2+ /creatinine was higher in mice treated with vehicle compared with day 0 (0.4±0.04 vs 0.1±0.01 mmol/mmol; P&lt;0.05) but was lower with FCM (0.09±0.03 vs 0.14±0.04 mmol/mmol; P&lt;0.05) and FDI (0.08±0.01 vs 0.3±0.06 mmol/mmol; P&lt;0.05). In summary, our study shows that both iron preparations have similar effects on blood parameters, but mice were more hypophosphatemic when treated with FCM vs FDI. We speculate this may be due to variations in PTH and FGF23 levels. This work was supported by 1R01DK110621, VA Merit Award IBX004968A, NIDDK Diabetic Complications Consortium RRID:SCR_001415, DK076169 and DK115255 (all to TR). LT was supported by an AHA Postdoctoral Fellowship (828731). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ferric carboxymaltose and SARS-CoV-2 vaccination-induced immunogenicity in kidney transplant recipients with iron deficiency: The COVAC-EFFECT randomized controlled trial.

Kidney transplant recipients (KTRs) have an impaired immune response after vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Iron deficiency (ID) may adversely affect immunity and vaccine efficacy. We aimed to investigate whether ferric carboxymaltose (FCM) treatment improves humoral and cellular responses after SARS-CoV-2 vaccination in iron-deficient KTRs. We randomly assigned 48 iron-deficient KTRs to intravenous FCM (1-4 doses of 500mg with six-week intervals) or placebo. Co-primary endpoints were SARS-CoV-2-specific anti-Receptor Binding Domain (RBD) Immunoglobulin G (IgG) titers and T-lymphocyte reactivity against SARS-CoV-2 at four weeks after the second vaccination with mRNA-1273 or mRNA-BNT162b2. At four weeks after the second vaccination, patients receiving FCM had higher plasma ferritin and transferrin saturation (P<0.001 vs. placebo) and iron (P=0.02). However, SARS-CoV-2-specific anti-RBD IgG titers (FCM: 66.51 [12.02-517.59] BAU/mL; placebo: 115.97 [68.86-974.67] BAU/mL, P=0.07) and SARS-CoV-2-specific T-lymphocyte activation (FCM: 93.3 [0.85-342.5] IFN-ɣ spots per 106 peripheral blood mononuclear cells (PBMCs), placebo: 138.3 [0.0-391.7] IFN-ɣ spots per 106 PBMCs, P=0.83) were not significantly different among both arms. After the third vaccination, SARS-CoV-2-specific anti-RBD IgG titers remained similar between treatment groups (P=0.99). Intravenous iron supplementation efficiently restored iron status but did not improve the humoral or cellular immune response against SARS-CoV-2 after three vaccinations.

Efficacy of ferric carboxy maltose in treatment of iron deficiency/iron deficiency anaemia during pregnancy.

To evaluate the efficacy of ferric carboxy maltose (FCM) in the treatment of iron deficiency/iron deficiency anaemia (ID/IDA) during pregnancy. Pregnant women ≥ 20 years old diagnosed with ID (serum ferritin < 15 µg/l) and moderate IDA were included in this study for correction of their ID/IDA. The participants received an FCM infusion for correction of their ID/IDA. The pre-treatment ferritin, haemoglobin (Hb), and red blood cell (RBC) indices were compared with the 6- and 12-week post-treatment values to evaluate the efficacy of FCM in the treatment of ID/IDA during pregnancy. The pre-treatment ferritin and Hb significantly increased from 10.3 ±2.3 µg/l and 7.99 ±0.6 g/dl, respectively, to 139.5 ±1.9 and 14.04 ±0.45, respectively, 6-weeks after FCM infusion (p = 0.02 and 0.001, respectively), and to 128.9 ±1.7 and 13.02 ±0.5, respectively, 12-weeks after FCM infusion (p = 0.0008 and 0.02, respectively). In addition, the pre-treatment RBCs mean corpuscular volume and RBCs mean corpuscular haemoglobin (MCH) significantly increased from 72.02 ±3.5 fl and 23.9 ±1.9 pg, respectively, to 90.6 ± 2.8 fl and 29.98 ±1.5 pg, respectively, 6 weeks after FCM infusion (p = 0.01 and p = 0.007, respectively), and to 89.5 ±2.9 fl and 30.2 ±1.5 pg, respectively, 12 weeks after FCM infusion (p = 0.02 and 0.007 respectively). The ferric carboxy maltose was safe and effective for the treatment of ID/IDA during pregnancy within 6 weeks. The serum ferritin and Hb levels and the RBC indices remained significantly high 12 weeks after FCM infusion compared to the pre-treatment values.

Cost-minimization Analysis in Iron-deficiency Anemia Comparing Intravenous Ferric Carboxymaltose to Standard of Care in Pregnant Women in Algeria

Abstract INTRODUCTION: Anemia due to iron deficiency is frequent during pregnancy and increases morbidity and mortality of mothers and infants. The objective of this study was to assess the economic consequences of intravenous ferric carboxymaltose (FCM) in anemic pregnant women in Algeria. METHODS: The economic analysis was a cost-minimization model comparing the strategy for treating pregnant women with intravenous iron sucrose to FCM. The perspective of Algerian health-care providers was adopted to calculate costs savings. Cost related to treatment of iron-deficiency anemia included infusion, iron workup, medical time, iron vials acquisition, and absenteeism. Data were obtained mostly from available scientific literature and public health data and were validated by expert opinion. A budget impact model was also developed for the population of Algerian women needing intravenous iron treatment to evaluate the gross impact on payers’ budget if FCM treatment was prescribed. RESULTS: Treatment of pregnant women with iron-deficiency anemia (mean weight, 65 kg; hemoglobin 7.5 g/dL) needed 7 hospital visits and 14.9 doses for iron sucrose treatment to be compared to 2 hospital visits and 2 doses for FCM treatment. Total cost was Algerian dinar (DZD) 69,222 per patient for iron sucrose and DZD 57,452 for FCM (cost savings per patient: DZD 11,769, i.e., 17%). If all 192,000 pregnant Algerian anemic women eligible for injectable iron treatment received FCM, global cost savings would be DZD 2,259,820,627 per year. CONCLUSION: This economic model suggests that FCM is a cost-saving treatment compared to standard iron sucrose treatment in pregnant women with iron-deficiency anemia in Algeria.

Clinical and economic impact of ferric carboxymaltose treatment for iron deficiency in patients stabilized following acute heart failure: a multinational study

ObjectiveTo estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy.MethodsA decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale.ResultsThe cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of −£14,008,238, −CHF25,456,455 and −€105,295,146 incurred to the UK, Switzerland and Italy, respectively.LimitationsAlthough AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries.ConclusionsThis study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term.

Patient Reported Outcomes after Ferric Carboxymaltose Treatment for Iron Deficiency Anemia: A Prospective Observational Study

Objective: Fatigue is a common symptom reported by iron deficiency anemia (IDA) patients. Iron deficiency has also been shown to reduce physical function independent of anemia. Parenteral iron therapy is indicated for the treatment of iron deficiency anemia (IDA) in patients who are intolerant or nonresponsive to oral iron. This study assessed fatigue symptoms and patient-reported functioning in IDA patients for up to 6 months after treatment with ferric carboxymaltose (FCM). Methods: This prospective, single arm, longitudinal observational study included adult patients diagnosed with IDA who were prescribed FCM under routine clinical care across 7 clinical practice sites in US. Eligible patients had baseline serum hemoglobin of >7 g/dL and <13 for males or <12 for females, no potential contraindications to FCM, and no parenteral iron therapy within 3 months before study enrollment. Patients completed patient-reported outcome (PRO) questionnaires prior to receiving FCM treatment, and at 3 months and 6 months after the first course of FCM. PROs included the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale, the Patient Reported Outcomes Measurement and Information System (PROMIS) Physical Function v2.0 Short Form, and the PROMIS Global Health v1.2 Short Form (physical and mental health). A higher FACIT-Fatigue or a lower PROMIS Physical Function, PROMIS Global Physical Health or Mental Health score indicate more health problems. For each measure, a mean change from baseline of ≥5 points was considered clinically meaningful. Associations between baseline serum hemoglobin and each PRO score were assessed using Spearman's rank correlation coefficient. Results: 152 patients with median IDA history of 2.0 years were included in the intent-to-treat population (mean age=47.4 ± 16.0 years, 82.2% females, 17.1% with inflammatory bowel disease, 13.8% with abnormal uterine bleeding, 9.2% with cancer, mean baseline serum Hgb =10.19±1.35 g/dL). About one-third of patients (34.9%) had oral iron treatment and 2.6% had a blood transfusion within 3 months prior to FCM treatment. A small proportion of patients (6.6%) had parenteral iron treatment in the 12 months before study enrollment. Most patients (83.6%) were prescribed 2 doses of FCM (total dose of 1500mg) at baseline. Within 6 months after the first course of FCM, no patient received treatment with erythropoietin stimulating agents, 1 patient received a blood transfusion, and 14 (9.7%) patients required additional IV iron treatment after the initial course of FCM treatment prescribed at baseline. Median time from baseline to additional IV treatment was 86.5 days. Fatigue symptoms were improved after FCM treatment, as indicated by significantly lower mean FACIT-Fatigue scores at 3 months (50.19 ± 9.51) and at 6 months (52.42 ± 9.31) compared to baseline (61.01 ± 8.96), with p<0.0001 each. A majority of patients had a reduction of at least 5 points in FACIT-Fatigue score from baseline to 3 months (72.7%) and 6 months (67.3%), respectively. Physical function also improved, as indicated by significantly higher mean PROMIS Physical Function score at 3 months (46.08 ± 8.52) and 6 months (45.15±8.85) compared to baseline (41.31±8.63), with p<0.0001 each. Improvements in PROMIS Global Physical Health (p<0.0001) and the PROMIS Global Mental Health score (p=0.0027) were also observed at 3 months and 6 months compared to baseline. Correlations between baseline serum hemogloblin levels and PRO scores were borderline to highly significant, with correlation coefficients of 0.151 (p=0.0647) with PROMIS Global Mental Health, 0.276 (p=0.0006) with Global Physical Health, 0.286 (p=0.0004) with PROMIS Physician Function and -0.294 (p=0.0002) with FACIT-Fatigue. Conclusions: IDA patients treated with FCM reported significant reduction in fatigue symptoms and improvements in physical function, physical health and mental health at 3 months after treatment. These benefits were sustained at 6 months after treatment, with only a small proportion of patients requiring re-treatment with additional IV iron beyond the initial course of FCM treatment. Significant correlations between serum Hgb and PRO scores observed in this study suggest that data collected directly from patients in a real-world setting can provide a valuable supplement to traditional clinical outcomes for evaluating treatment effectiveness. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Assessment of Total Cost of Care in Non-Dialysis Dependent Chronic Kidney Disease Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia

Introduction Iron deficiency anemia (IDA) is a common comorbidity among patients with chronic kidney disease. Iron deficiency occurs in 15% to 48% of non-dialysis dependent chronic kidney disease (ND-CKD) patients with anemia. Parenteral iron therapy is often required in ND-CKD patients with IDA who cannot tolerate or are nonresponsive to oral iron. Available IV iron treatments vary in the amount of iron dose per administration, the number of infusions required to achieve complete iron repletion and drug acquisition cost. The objective of this study was to compare healthcare costs between ferric carboxymaltose (FCM) and low dose IV iron (LDI) for the treatment of IDA in ND-CKD patients. Methods Medical and pharmacy claims from IQVIA PharMetrics® Plus data were analyzed. Adult patients who received first (index) dose of FCM or LDI (i.e., iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019 were included. Eligible patients were required to be continuously eligible 6 months before (baseline) and 12 months after index IV iron infusion and had medical claims associated with diagnosis of chronic kidney disease (ICD-10: N18.1 to N18.5) and IDA (ICD-10: D50.x) anytime during the 18-month study observation period. In addition, eligible FCM patients were required to receive a second dose of FCM within 21 days of index date. Patients who had claims associated with end stage renal disease (ICD-10: N18.5 and N18.6) or dialysis (HCPCS CPT code: 90935-90999) and patients who had received other IV iron products in the 6-month baseline period were excluded. Unadjusted mean number of IV iron infusions, outpatient visits and hospital admissions in the 6 months before and 12 months following index IV iron dose were summarized on a per-patient-per-month basis. Post-index monthly inpatient, outpatient, and total healthcare costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and the Charlson Comorbidity Index (CCI). Sensitivity analyses comparing FCM versus iron sucrose were performed. Results Data from 3,727 FCM patients [mean (SD) age= 67.9 (13.8) years, 61% females, CCI (SD)=1.9 (2.5)] and 5,068 LDI patients [mean (SD) age=64.8 (15.0) years, 60% females, CCI (SD)=1.6 (2.4)] were analyzed. Within the LDI cohort, 3,489 patients received index iron sucrose treatment [mean (SD) age=64.6 (15.1) years, 60% females, CCI (SD)=1.5(2.4)]. Mean (SD) number of IV iron infusions was 0.24 (0.26) for FCM, 0.43 (0.52) for LDI and 0.46 (0.52) for iron sucrose during the post-index period. During the post-index period, FCM has a smaller increase in the number of outpatient visits (mean change from baseline=0.13) than LDI (mean change from baseline=0.64) and iron sucrose (mean change from baseline=0.70). The number of hospital admissions in the post-index period were numerically lower for FCM (mean change from baseline=-0.05) but numerically higher for LDI (mean change from baseline=0.04) and iron sucrose (mean change from baseline=0.05). Mean total health care cost increased during the 12-month period after IV iron treatment compared to baseline in all treatment groups. After adjusting for pre-index cost and other covariates, FCM treatment was associated with significantly lower post-index inpatient costs [adjusted cost ratio (ACR)= 0.73, p<0.0001], ER costs (ACR=0.76, p<0.0001), outpatient costs (ACR=0.73, p<0.0001) and total costs (including IV iron) (ACR = 0.81, p<0.0001) than LDI. Similar results were observed in the comparisons between FCM and iron sucrose. Conclusion Higher drug acquisition cost of FCM compared to LDI was primarily offset by lower inpatient and outpatient costs during the 12 months after FCM treatment for IDA in ND-CKD patients than LDI, resulting in significantly lower overall total health care cost for FCM compared to LDI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical, economical and safety impact of ferric carboxymaltose use in Patient Blood Management programme in Portuguese National Health Service hospitals

Ferric carboxymaltose (FCM) can be used in Patient Blood Management (PBM) to promote the optimization of preoperative haemoglobin (Hb), which aims to minimise the use of allogeneic blood components and improve clinical outcomes, with better cost-effectiveness. This was an observational study conducted in a retrospective and multicentre cohort with adults from elective orthopaedic, cardiac and colorectal surgeries, treated according to local standards of PBM with allogeneic blood product transfusions (ABTs) on demand and with FCM to correct iron deficiency with or without anaemia. In this work, only the first pillar of the PBM model issue by Directorate-General for Health (DGS) was evaluated, which involves optimising Hb in the preoperative period with iron treatment if it’s necessary/indicated. Before the implementation of PBM in Portugal, most patients did not undergo preoperative laboratory evaluation with blood count and iron kinetics. Therefore, the existence of Iron Deficiency Anaemia (IDA) or Iron Deficiency (ID) without anaemia was not early detected, and there was no possibility of treating these patients with iron in order to optimise their Hb and/or iron stores. Those patients ended up being treated with ABTs on demand. A total of 405 patients from seven hospitals were included; 108 (26.7%) underwent FCM preoperatively and 197 (48.6%) were transfused with ABTs on demand. In the FCM preoperative cohort, there was an increase in patients with normal preoperative Hb, from 14.4 to 45.7%, before and after FCM, respectively, a decrease from 31.7 to 9.6% in moderate anaemia and no cases of severe anaemia after FCM administration, while 7.7% of patients were severely anaemic before FCM treatment. There were significant differences (p < 0.001) before and after correction of preoperative anaemia and/or iron deficiency with FCM in Hb, serum ferritin and transferrin saturation rate (TS). In the ABT group, there were significant differences between pre- and postoperative Hb levels (p < 0.001). Hb values tended to decrease, with 44.1% of patients moving from mild anaemia before transfusion to moderate anaemia in the postoperative period. Concerning the length of hospital stay, the group administered with ABTs had a longer hospital stay (p < 0.001). Regarding the clinical outcomes of nosocomial infection and mortality, there was no evidence that the rate of infection or mortality differed in each group (p = 0.075 and p = 0.243, respectively). However, there were fewer nosocomial infections in the FCM group (11.9% versus 21.2%) and mortality was higher in the transfusion group (21.2% versus 4.2%). Economic analysis showed that FCM could reduce allogenic blood products consumption and the associated costs. The economic impact of using FCM was around 19%. The preoperative Hb value improved when FMC was used. Patients who received ABTs appeared to have a longer hospital stay. The FCM group reported fewer infections during hospitalisation. The economic results showed savings of around €1000 for each patient with FCM administration. The use of FCM as part of the PBM program had a positive impact on patients’ outcomes and on economic results. However, it will be essential to perform studies with a larger sample to obtain more robust and specific results.

Evaluation of Minimal Optimal Dose of Intravenous Ferric Carboxymaltose for Treatment of Iron Deficiency Anemia and Risk of Transient Hyperferritinemia.

Iron supplementation is administered orally or intravenously to treat iron-deficiency anemia (IDA). Ferric Carboxymaltose (FCM) "Ferinject®" is an intravenous (IV) iron preparation that has emerged as a safe therapeutic option for treating IDA in the past decade. This study aimed to evaluate safety and efficacy of carboxymaltose in a cohort of patients with IDA not responding to oral therapy. This 12-month retrospective study included 106 patients with IDA, with-or without bariatric surgery, who received (single or multiple doses) of Carboxymaltose 500mg/10mL. Data points included patients' demographics, baseline data for Hb, platelet, ferritin, and MCV pre-and at 1, 2, and 3 months following different doses of IV-Carboxymaltose. Changes in Hb, MCV, platelets, and ferritin levels were recorded in response to Carboxymaltose to assess the optimal dose, risk of hyperferritinemia, and hypophosphatemia. At three months (95 days) follow-up, the median change pre-and post-therapy in hemoglobin was from 9.5 to 11.9g/dL (p < 0.01), MCV 73.6-80.5fL (p < 0.01), and ferritin 5.3-93.8ng/mL. A significant difference was observed between platelet count of patients who underwent bariatric surgery and those who did not. An optimal ferritin response (>30ng/mL) was observed in 87.8% of patients who received first dose, and none of the full three doses showed no response. 37% of patients who received two doses developed hyperferritinemia. Serum phosphate levels were assessed in 28 cases, and hypophosphatemia was observed in 25% of these patients. Carboxymaltose is a reliable option for IDA. IV-FCM therapy helps achieve significant improvement in hemoglobin concentration and MCV from the first dose carrying a low reversible risk of hyperferritinemia following multiple doses. An interesting finding of this study is the discovery of a population of IDA patients requiring periodic assessment for iron reinfusion to sustain normal levels, mostly post-bariatric surgery. Changes in serum phosphate levels reported to occur consecutively with FCM treatment should be further studied.

Safety and effectiveness of ferric carboxymaltose intravenous therapy in pediatric patients with chronic kidney disease.

Iron-deficiency anemia is the most common reason for worsening of the anemia characteristically seen in chronic kidney disease (CKD). Ferric carboxymaltose (FCM) is a macromolecular hydroxide ferric carbohydrate complex that allows high-dose iron to be administered parenterally for gradual, controlled release. The aim of this study was to retrospectively evaluate the safety and effectiveness of FCM treatment in pediatric patients with CKD non-dependent of hemodialysis, seen at a tertiary hospital. Data were collected on demographics, dosage, infusion time, laboratory results, and tolerability of the medicinal product. A total of 79 patients (40.5% girls) were included; the median age [25th percentile (P25) to 75th percentile (P75)] was 9 years (5–13). Laboratory results at 15–45 days post-infusion revealed a median increase of 1.4 g/dL (0.9–1.9) in hemoglobin, 224 μg/L (136–378.5) in ferritin, 37 μg/dL (17.5–71) in serum iron, and 18% (9.3–27.8) in transferrin saturation. All patients tolerated FCM infusions well, and no serious hypersensitivity reactions or anaphylactic reactions were observed. Only one adverse event was identified: drug extravasation at the end of the infusion in a 16-year-old patient. These data provide further evidence for the use of FCM as a safe and effective therapeutic option in pediatric patients with CKD, based on the low incidence of adverse effects, minor intervention required, and anemia improvement based on laboratory results.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment for restless legs symptoms and low serum ferritin in children with autism spectrum disorder

BackgroundRestless legs syndrome (RLS) may be underdiagnosed in children with autism spectrum disorder (ASD) due to difficulty expressing the symptoms in their own words. In addition, administration of oral iron may be particularly difficult in children with ASD. MethodsThis was a retrospective, open-label case series of children with ASD, restless legs (RL) symptoms, and serum ferritin <30 μg/L, who either had failed or did not tolerate oral iron, and were subsequently treated with intravenous (IV) ferric carboxymaltose (FCM). Patients received a single dose of IV FCM, 15 mg/kg up to a maximum dose of 750 mg. Data collected pre- and eight weeks post-infusion included presenting symptoms, serum ferritin, iron profile, and Clinical Global Impression Scale (CGI-Severity pre- and CGI-Improvement post-infusion). Adverse effects were assessed. ResultsNineteen children, 4–11 years old (12 male, median age 6, interquartile range (IQR 4–11) were included. A definite RLS diagnosis was identified in 6 verbal children (31.6%). RL symptoms (designated probable RLS) in the 13 other children met all RLS diagnostic criteria except “improvement of symptoms with movement,” which was not definitively determined. Baseline median values were: ferritin 10 μg/L (IQR 10–16), iron 66.5 μg/dL (IQR 57–96), TIBC 382 μg/dL (IQR 360–411) and transferrin saturation 19% (IQR 14–28). Median CGI-S was 4 (moderate symptoms) (IQR 3–4). At eight weeks after IV FCM, all measures were improved. Median ferritin was 68 μg/L (IQR 62.5–109, p < 0.00045). Median CGI-I was 1 (very much improved) (IQR 1–2). All children meeting definite RLS criteria improved. Three children in the probable RLS group did not improve. Children meeting the full RLS criteria had lower baseline ferritin levels than those with a probable diagnosis (9 μg/L, IQR 9–10 vs. 13 μg/L, IQR 10–16, Mann-Whitney test p < 0.045). Adverse effects included lightheadedness, gastrointestinal discomfort, fever, and headache among others. ConclusionsThe majority of children (84.2%) with ASD, restless legs symptoms, and serum ferritin <30 μg/L had clinical improvement and significantly better serum iron parameters after a single IV FCM infusion. Although larger, randomized trials are needed, IV FCM appears to be a promising treatment for this subset of children with ASD.