Intravenous Iron Formulations Research Articles

Dissimilar ferric derisomaltose formulations – In vitro comparisons between an originator and its intended similars

BackgroundThe complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States. MethodsIron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t½]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®. ResultsIron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t½: 15 h versus 40.3 h); t½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®. ConclusionsSimple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars.

Current approach to the management of preoperative iron deficiency anemia in colorectal cancer patients: a review of literature.

&lt;b&gt;Introduction:&lt;/b&gt; The prevalence of preoperative anemia is the highest in the group of colorectal cancer (CRC) patients and may reach over 75%. The prevalence of anemia in CRC patients increases even further following surgery. Approximately 75-80% of anemic CRC patients present with absolute or functional iron deficiency (ID). Preoperative anemia constitutes an independent risk factor for allogeneic blood transfusion (ABT), postoperative complications, prolonged length of hospital stay, and increased mortality. ABT is itself associated with increased morbidity and mortality.&lt;b&gt;Aim:&lt;/b&gt; The aim of this review article was to present the pathophysiology and the current approach to the diagnostics and treatment of preoperative iron deficiency anemia (IDA) in CRC patients.&lt;b&gt;Material and methods:&lt;/b&gt; Extensive search of medical literature databases was performed (Pubmed, Embase). The key words that were used were as follows: CRC, colorectal surgery, ID, IDA, intravenous iron, Patient Blood Management (PBM).&lt;b&gt;Results:&lt;/b&gt; There are several laboratory parameters that can be used for IDA diagnosis, however, the simplest and most cost- -effective is reticulocyte hemoglobin equivalent (RET-He). Pathophysiologic features of IDA in CRC patients favor treatment with intravenous, as opposed to oral, iron formulations. Applying PBM strategies minimizes the exposure to ABT.&lt;b&gt;Conclusions:&lt;/b&gt; Preoperative IDA is highly prevalent among CRC patients. Preoperative anemia is an independent risk factor for ABT, increased morbidity and mortality, as well as prolonged hospital length of stay. The same negative consequences are associated with ABT. Therefore, preoperative IDA in CRC patients needs to be screened for, diagnosed, and treated before surgery. Effective treatment of preoperative IDA in CRC patients is with intravenous iron formulations. ABT should be the treatment of last resort due to the risk of negative clinical consequences, including an increased rate of cancer recurrence.

Selection of parenteral iron supplement for iron deficiency anemia: A review

The article reviews medicinal products for the treatment of iron deficiency conditions and iron deficiency anemia, the prevalence of which is about 30% among the world population. Iron deficiency is a significant cause of anemia, which can lead to hospitalization and even death. In case of intolerance or ineffectiveness of oral formulations of iron supplements, if it is necessary to replenish the iron level quickly, trivalent iron formulations for intravenous administration are used. These supplements are iron complexes with an iron hydroxide core surrounded by a carbohydrate shell. Iron formulations for intravenous administration can be divided into drugs of the "old" and "new" generation. One of the most studied and popular representatives of the "new" generation is iron carboxymaltose (ICM). The results of clinical studies showed that ICM better and faster increases hemoglobin concentration and replenishes iron stores in patients compared to the "old" generation formulations and also has a more favorable safety profile. Large doses of ICM can be administered in a short time, saving resources and increasing patient satisfaction. The injection of large doses of iron with a small number of infusions in the case of ICM is more economically beneficial for all departments of medical institutions, as it significantly reduces the total cost of medical care. Intravenous iron plays an essential role in the perioperative treatment of iron deficiency anemia, especially in elective surgery. Currently, there is a reliable evidence base confirming the efficacy and safety of intravenous iron formulations in chronic kidney disease, inflammatory bowel disease, heart failure, gynecological and obstetric diseases, and cancer.

Intravenous iron infusions in pediatric patients: A retrospective review of efficacy and safety.

Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.

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

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. 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. 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. Two reviewers independently extracted data from nine selected trials. 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. Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

P-17 Hypophosphatemia related to intravenous iron therapy: A case report

Abstract Introduction Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia. Intravenous iron formulations such as ferric carboxymaltose allow administration of high doses of elemental iron and enable correction of total iron deficit in one or two infusions. An important complication of ferric carboxymaltose is hypophosphatemia caused by increased secretion of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). In this case, we aimed to present our patient with this rare side effect of intravenous iron replacement. Clinical Case A 40-year-old female patient who has no chronic systemic disease was admitted to our endocrinology service for fatigue and weakness. In the patient's history, it was learned that she had been treated with 2500 mg intravenous iron replacement (ferric carboxymaltose) for iron deficiency anaemia in the last month. In the laboratory tests; serum phosphorus 1.05 mg/dl (normal 2.5-4.5 mg/dl), corrected calcium 8.45 mg/dl (normal 8.4-10.2 mg/dl), 25-OH vitamin D 31.4 µg/L (normal &amp;gt;30 µg/L), parathormone 83.2 pg/ml (normal 15-65 ng/ml), alkaline phosphatase 63 U/L (normal 35-105 U/L). Fractional excretion of phosphate (FePO4) confirmed renal phosphate wasting (FePO4: 28.6%; normal &amp;lt;5%). Urinary protein and glucose were negative. FGF23 measured 71 pg/ml (normal &amp;lt;59 pg/mL). Intravenous iron-induced hypophosphataemia was suspected. After initiation of oral phosphate and 1,25-dihydroxyvitamin D3 supplementation, serum phosphate rose to reference range (Figure 1). The patient was taken to outpatient follow-up. Conclusion Physicians should be aware of hypophosphatemia as a common complication of intravenous iron therapy and monitor serum phosphate concentrations in patients receiving repeated doses.Figure 1.Patient phosphorus data during follow-up

Diagnosis and treatment of iron deficiency anemia

The causes of iron deficiency anemia include blood loss, increased demand, insufficient dietary intake, and disorders affecting iron absorption. In certain circumstances, atrophic gastritis, either autoimmune or due to Helicobacter pylori infection, may contribute. On very rare occasions, iron-refractory iron deficiency anemia can develop as a consequence of TMPRSS6 mutations. Iron deficiency anemia is diagnosed by identification of microcytic hypochromic anemia with low serum ferritin levels. In cases of chronic disorders such as chronic kidney disease, chronic heart failure, and chronic inflammatory disorders, the diagnosis may also incorporate transferrin saturation. Treatment of underlying diseases is recommended along with iron supplementation. While oral iron supplements are the first choice, intravenous iron may be considered when oral administration is impractical, iron absorption is impaired, or rapid iron replenishment is necessary. Recently, high-dose intravenous iron formulations became available in Japan, but their use requires caution due to potential risks of allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage. Notably, the benefits of high-dose intravenous iron for patients with heart failure and iron deficiency are recognized in the field of cardiology. This article provides an overview, incorporating recent developments in the field of iron deficiency anemia.

Intravenous iron therapy in pediatrics: who should get it and when is the right time?

Iron-deficiency anemia occurs most commonly in young children due to a low-iron diet and adolescent girls due to menstrual blood loss. However, children with gastrointestinal conditions such as intestinal failure, inflammatory bowel disease, celiac disease, and/or other chronic conditions, including chronic kidney disease and heart failure, also commonly have iron deficiency. Many patients with classic iron-deficiency anemia will improve with oral iron therapy. However, in children who have an incomplete response to oral iron, intravenous iron therapy is increasingly being used. Benefits of intravenous iron therapy include a rapid repletion of iron stores in addition to resolution of anemia, less gastrointestinal side effects, and relief for patients and families struggling with long-term iron supplementation. Indications for first-line therapy with intravenous iron in children with chronic conditions have also increased. Four intravenous iron formulations have approved indications in pediatrics, and many are increasingly used off-label in children as well. Here we discuss the indications and appropriate timing of intravenous iron therapy in children with a wide range of underlying etiologies.

Infusion Reactions with Alternative Therapies during the National Shortage of Iron Dextran

Introduction The national shortage of intravenous iron dextran has required patients to receive more alternative iron infusions, such as iron sucrose and sodium ferric gluconate/sucrose, since January 2023. While prior studies have evaluated rates of infusion reactions among some commonly used intravenous iron formulations, data is lacking among differing doses of iron formulations and especially in the setting of this iron dextran shortage. Clinicians at our institution generally observed more adverse reactions with alternative iron infusions during the national shortage of iron dextran compared to prior. Our study examines the infusion reactions of various iron therapies at differing doses and actions providers and patients took thereafter to assess the impact of the iron dextran national shortage on patients. Methods Patients were included who received iron infusions in three Henry Ford Hospital clinics in metropolitan Detroit, Michigan, from July 2022-June 2023 with the national iron dextran shortage impacting the health system since January 2023. Age, race, sex, reason for iron infusion, iron infusion formulation received, time of infusion, and dosing schedule of infusion were recorded for all participants. We assessed the symptoms experienced and actions taken for patients who had an infusion reaction. The number and type of infusion reactions between different iron infusion formulations and doses were then compared. Results Of the 880 unique patients assessed, 496 (56.4%) received iron dextran, iron sucrose, or sodium ferric gluconate/sucrose between July 2022 and December 2022 prior to the national iron dextran shortage and 384 (43.6%) patients had iron infusions between January 2023 and June 2023 during the shortage. Iron dextran accounted for most of the infusions (n= 356, 71.8%) prior to the shortage whereas iron sucrose was the majority (n=312, 81.3%) during the shortage. Prior to the national shortage, 30 iron infusions reactions occurred, with 18 (60%) associated with iron dextran, 9 (30%) with iron sucrose, and 3 (16.7%) with sodium ferric gluconate/sucrose. During the shortage, 44 reactions occurred, with 1 (2.27%) associated with iron dextran, 41 (93.1%) with iron sucrose, and 2 (4.54%) with sodium ferric gluconate/sucrose. The most reactions (n=41, 55.4%) occurred with iron sucrose at a dose of 500mg across the whole study period. Less reactions (n=9, 12.2%) were reported for iron sucrose at progressively lower doses, comparable to reactions with iron dextran at doses greater than 1000mg (n=8, 10.8%) and at lower doses of iron dextran (n=10, 13.5%). The most common reaction across all infusion types was nausea, vomiting, and/or diarrhea. After an iron infusion reaction, the infusion plan was then most commonly discontinued, with patients either switching to alternative iron infusion formulations, continuing the same infusion type with medications for symptoms, or continuing the same infusion type with lower dose and increased frequency. Conclusion More iron infusion reactions occurred after the national shortage of iron dextran since January 2023 in the setting of more frequent use of alternative iron therapies. The most common infusion formulation associated with a reaction was iron sucrose at its higher recommended dose of 500mg, compared with iron dextran and sodium ferric gluconate/sucrose. Providers should be aware of these associated adverse reactions with the different doses of alternative formulations when recommending infusions for patients, and the need for preemptive intervention.

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.

Disutilities Associated with Intravenous Iron Infusions: Results from a Time Trade-off Survey and Diminishing Marginal Utility Model for Treatment Attributes in China.

Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions. An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model. The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15-30 minutes or 30-60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values <0.01). This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients' quality of life.

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.

Intravenous iron: an update.

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion-related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.

Safety, pharmacokinetics, and pharmacodynamics of intravenous ferric carboxymaltose in children with iron deficiency anemia

BackgroundIron deficiency is the primary cause of anemia in children. Intravenous (IV) iron formulations circumvent malabsorption and rapidly restore hemoglobin.MethodsThis Phase 2, non-randomized, multicenter study characterized the safety profile and determined appropriate dosing of ferric carboxymaltose (FCM) in children with iron deficiency anemia. Patients aged 1–17 years with hemoglobin <11 g/dL and transferrin saturation <20% received single IV doses of undiluted FCM 7.5 mg/kg (n = 16) or 15 mg/kg (n = 19).ResultsThe most common drug-related treatment-emergent adverse event was urticaria (in three recipients of FCM 15 mg/kg). Systemic exposure to iron increased in a dose-proportional manner with approximate doubling of mean baseline-corrected maximum serum iron concentration (157 µg/mL with FCM 7.5 mg/kg; and 310 µg/mL with FCM 15 mg/kg) and area under the serum concentration–time curve (1901 and 4851 h·µg/mL, respectively). Baseline hemoglobin was 9.2 and 9.5 g/dL in the FCM 7.5 and 15 mg/kg groups, respectively, with mean maximum changes in hemoglobin of 2.2 and 3.0 g/dL, respectively.ConclusionsIn conclusion, FCM was well tolerated by pediatric patients. Improvements in hemoglobin were greater with the higher dose, supporting use of the FCM 15 mg/kg dose in pediatric patients (Clinicaltrials.gov NCT02410213).ImpactThis study provided information on the pharmacokinetics and safety of intravenous ferric carboxymaltose for treatment of iron deficiency anemia in children and adolescents.In children aged 1–17 years with iron deficiency anemia, single intravenous doses of ferric carboxymaltose 7.5 or 15 mg/kg increased systemic exposure to iron in a dose-proportional manner, with clinically meaningful increases in hemoglobin.The most common drug-related treatment-emergent adverse event was urticaria.The findings suggest that iron deficiency anemia in children can be corrected with a single intravenous dose of ferric carboxymaltose and support use of a 15 mg/kg dose.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial

Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. Bill & Melinda Gates Foundation (INV-010612).

A continuous quality improvement strategy to strengthen screening practices and facilitate the routine use of intravenous iron for treating anaemia in pregnant and postpartum women in Nigeria: a study protocol

BackgroundPregnancy-related anaemia is a public health challenge across Africa. Over 50% of pregnant women in Africa get diagnosed with this condition, and up to 75% of these are caused by iron deficiency. The condition is a significant contributor to the high maternal deaths across the continent and, in particular, Nigeria, which accounts for about 34% of global maternal deaths. Whereas oral iron is the mainstay treatment for pregnancy-related anaemia in Nigeria, this treatment is not very effective given the slow absorption of the medication, and its gastrointestinal adverse effects which lead to poor compliance by women. Intravenous iron is an alternative therapy which can rapidly replenish iron stores, but fears of anaphylactic reactions, as well as several misconceptions, have inhibited its routine use. Newer and safer intravenous iron formulations, such as ferric carboxymaltose, present an opportunity to overcome some concerns relating to adherence. Routine use of this formulation will, however, require addressing misconceptions and systemic barriers to adoption in the continuum of care of obstetric women from screening to treatment. This study aims to test the options to strengthen routine screening for anaemia during and immediately after pregnancy, as well as evaluate and improve conditions necessary to deliver ferric carboxymaltose to pregnant and postpartum women with moderate to severe anaemia.MethodsThis study will be conducted in a cluster of six health facilities in Lagos State, Nigeria. The study will employ continuous quality improvement through the Diagnose-Intervene-Verify-Adjust framework and Tanahashi’s model for health system evaluation to identify and improve systemic bottlenecks to the adoption and implementation of the intervention. Participatory Action Research will be employed to engage health system actors, health services users, and other stakeholders to facilitate change. Evaluation will be guided by the consolidated framework for implementation research and the normalisation process theory.DiscussionWe expect the study to evolve transferable knowledge on barriers and facilitators to the routine use of intravenous iron that will inform scale-up across Nigeria, as well as the adoption of the intervention and strategies in other countries across Africa.

P352 Occurrence of moderate to severe anaemia and utilization and efficacy of intravenous iron therapies in a nationwide cohort of Inflammatory Bowel Disease patients

Abstract Background Anaemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD), and iron deficiency is the leading cause of IBD-associated anaemia. It is associated with impaired physical and cognitive functioning, increased hospitalization rates, and reduced quality of life. With the advent of newer formulations of intravenous (IV) iron the management of anaemia has undergone a transformation. Our aim was to evaluate the percentage of patients with IBD who developed moderate to severe anaemia over the course of their disease as they are the subset who would benefit most from IV iron. We also evaluated the utilization and efficacy of IV iron therapies among this group of patients in a real-world setting. Methods We conducted a retrospective cohort study utilizing the Veteran Affairs Healthcare System (VAHS) to identify patients who had IBD and were followed in the VAHS. IBD patients who had moderate to severe anaemia over the course of their disease based on WHO criteria (Hemoglobin level: &amp;lt;10g/dl) were included in this study. Among this group of patients with moderate to severe anaemia, we determined how many patients were treated with different IV iron formulations (ferric carboxymaltose, ferumoxytol, iron dextran, iron sucrose and sodium ferric gluconate). From this set of patients treated with IV iron formulations, improvement of Hb levels post therapy defined as achieving a Hb ≥12 g/dl, was ascertained. Results A total of 71,137 patients diagnosed with IBD were identified in the VAHS. Of this group 65, 599 (92.22%) were male. Over the course of their disease the majority were treated with mesalamine (92%) followed by biologics (35%) and thiopurines (25%). Among this group, 21,159 (29.74%) patients developed moderate to severe anaemia over the course of their follow up. Among patients with moderate to severe anaemia, 3,533 (16.7 %) patients received IV iron therapies for the management of their anaemia. 1,132 (32%) of these patients achieved a Hb level ≥12 g/dl post IV iron therapy. Conclusion Almost a third of IBD patients develop moderate to severe anaemia over the course of their disease. Less than a fifth of these patients were treated with IV iron, and among those treated, about a third achieved a Hb level ≥ 12g/dl. Our findings suggest that in the real-world setting, moderate to severe anaemia despite being prevalent is not managed aggressively and efforts should be made to rectify this situation as anaemia has a profound effect on multiple aspects of a patient’s life.

Prevalence of Iron Deficiency Anemia Indicated for Intravenous Iron Treatment in the Korean Population.

We aimed to investigate the number and prevalence of patients indicated for intravenous iron treatment in a large Korean population using criteria based on laboratory test results in an effort to extract indirect information on the need for intravenous iron treatment. Between 1 January 2019 and 31 December 2021, a total of 83,994 Korean patients (30,499 men and 53,495 women) with a median age of 46 years (interquartile range, 30-61) were evaluated using iron deficiency anemia-associated laboratory tests and serum creatinine tests of estimated glomerular filtration rates. The overall prevalence of anemia (Hb ≤ 11 g/dL) was 16.5%, and the proportion of patients with possible chronic kidney disease who had an estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 11.4%. The number of patients indicated for reimbursable intravenous iron treatment was higher in women than in men, higher in older patients, and higher in 2021 than in 2019 (all p < 0.001). The prevalence of patients indicated for reimbursable intravenous iron treatment was up to 30.0% in those ≥ 80 years of age in 2019. The results of this study provide basic knowledge about the use of iron deficiency anemia-associated laboratory tests in planning nutritional support programs using an intravenous iron formulation in Korea.

Modern Intravenous Iron Therapy: A Review on Safety and Practical Aspects

Introduction: Intravenous iron formulations have been approved in Europe and North America for the treatment of iron deficiency if oral iron is not tolerated or not efficacious. Recently-developed intravenous iron formulations exhibit specific physicochemical and immunological properties, with distinct bioavailability, efficacy and safety profiles. Area of Interest: intravenous iron formulations safety and tolerability were reviewed in the framework of a Swiss expert meeting. This work focused on the specificity of each compound with emphasis on the practical aspects of its use. Expert Opinion: Adverse reactions in response to iv formulations can be categorized into two main types: hypophosphataemia and hypersensitivity. Hypophosphatemia follows administration of ferric carboxymaltose at a higher rate in comparison to other formulations, but is mostly mild, transient and asymptomatic. However, the decrease in serum phosphate following repeated administration of iron preparations can affect bone health, particularly in patients at risk for osteomalacia. Severe hypersensitivity reactions are the most lifethreatening adverse reactions to intravenous iron supplementation. Iron (III)- isomaltoside 1000 seems to induce severe hypersensitivity more often (RR 5.6 - 16.2) than ferric carboxymaltose. Further studies are needed to address issues of long-term safety in high dose and prolonged administration of intravenous iron preparations in case of chronic diseases.

EE290 Cost-Effectiveness of Intravenous Iron Formulations in Patients With Iron Deficiency Anaemia and IBD in Sweden

EE290 Cost-Effectiveness of Intravenous Iron Formulations in Patients With Iron Deficiency Anaemia and IBD in Sweden