A Cost-Utility Analysis of Ferric Derisomaltose Versus Ferric Carboxymaltose in Patients with Iron Deficiency Anemia in China.

INTRODUCTION: Intravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) unresponsive to oral iron treatment, in whom oral iron is contraindicated, or where rapid iron replenishment is required. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of patients with IDA in China. METHODS: A previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with body weight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life were obtained from SF-36v2 data from the PHOSPHARE-IBD RCT. RESULTS: Over the 5-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 vs. 6.79). This resulted in iron procurement and administration cost savings of renminbi (RMB) 206 with FDI (RMB 3,519 vs. RMB 3,312). Reduced incidence of hypophosphatemia-related fatigue resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over 5 years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention. CONCLUSIONS: The results showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.

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

BACKGROUND: The 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. METHODS: Iron 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®. RESULTS: Iron 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®. CONCLUSIONS: Simple 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.

[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.

Cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anemia in England.

AIMS: Anemia is the most common extraintestinal complication of inflammatory bowel disease (IBD), with approximately half of cases caused by iron deficiency (ID). Intravenous iron is the preferred ID anemia (IDA) treatment where oral iron is contraindicated, ineffective or not tolerated, or where ID correction is urgent. The objective was to evaluate the cost-utility of ferric derisomaltose (FDI) versus ferric carboxymaltose (FCM) in patients with IBD and IDA in England, in whom IV iron treatment is preferred. MATERIALS AND METHODS: A patient-level simulation model was developed, capturing quality of life (QoL) differences based on SF-36v2 data from the PHOSPHARE-IBD randomized controlled trial, monitoring and incidence of post-infusion hypophosphatemia, and number of iron infusions required. Analyses were conducted over a five-year time horizon from the Department of Health and Social Care (DHSC) perspective, with healthcare provider and societal perspectives adopted in separate analyses. Future costs and effects were discounted at 3.5% per annum and one-way and probabilistic sensitivity analyses were performed. RESULTS: FDI increased quality-adjusted life expectancy by 0.075 QALYs versus FCM from 2.57 QALYs to 2.65 QALYs per patient. Patients receiving FDI required 1.63 fewer iron infusions over the five-year time horizon, driving infusion-related cost savings of GBP 496 per patient (GBP 2,188 versus GBP 1,692) from the DHSC perspective. Costs of monitoring and treating hypophosphatemia after FCM were GBP 226, yielding total savings of GBP 722 per patient (GBP 2,414 versus GBP 1,692) over the five-year time horizon. FDI also led to reduced costs versus FCM in the societal and provider analyses and was therefore the dominant intervention across all three perspectives. LIMITATIONS: The analysis did not capture patient adherence, hypophosphatemic osteomalacia, or fractures. CONCLUSIONS: Results showed that FDI improved patient QoL and reduced direct healthcare expenditure versus FCM in patients with IBD and IDA in England.

Ferric derisomaltose (FDI) is an intravenous iron approved for the treatment of clinically diagnosed iron deficiency in the United Kingdom (UK), and can be an important therapeutic option for patients with inflammatory bowel disease (IBD), who require regular and rapid iron replenishment. Ferric carboxymaltose (FCM) is the sole alternative intravenous iron formulation available in the UK, but is associated with reduced blood phosphate levels, potentially causing fatigue and weakening of the bones. We conducted an economic analysis to weigh the costs and clinical outcomes associated with FDI and FCM in the UK, for patients with IBD and iron deficiency anemia (IDA). The main clinical difference we investigated was reduced blood phosphate levels, which occurred more often after FCM than FDI. We also incorporated recent quality of life data from a clinical study, and calculated the number of infusions (and associated costs) of each iron formulation, that patients would require over five years. Clinical data were obtained from published medical literature, while cost data came from UK sources including the 2022/2023 National Tariff Payment System and the British National Formulary. Our model showed that FDI was associated with quality of life improvements, fewer overall infusions per treatment course, and reduced costs compared to FCM, from the English Department of Health and Social Care perspective, the societal perspective, and the perspective of individual healthcare providers (namely NHS Trusts) within NHS England. FDI is therefore likely to represent the best value intravenous iron for the treatment of IDA with IBD in the UK.

The differential effect of modern intravenous iron on fibroblast growth factor 23 and phosphate in non-dialysis dependent CKD - the exploratory randomized controlled double-blind ExplorIRON-CKD study.

BACKGROUND: Intravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover. METHODS: The single-center double-blind randomized controlled trial "Iron and Phosphaturia - ExplorIRON-CKD" primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1-2 days following iron administration, 2 weeks, 1 month (second iron administration), 1-2 days following second administration, 2 months and 3 months following initial infusion. RESULTS: Twenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1-2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1-203.1) %; p < 0.001 and Baseline to 1-2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 - 25.4) % vs. FCM: 235.1 (138.5-434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI. CONCLUSIONS: The study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019-004370-26 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB ) (First date of trial registration: 03/12/2019).

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.

Administration of intravenous iron through a home-based infusion strategy is safe and has high patient acceptance.

BACKGROUND AND AIMS: To evaluate the safety and patient experience of a hospital-initiated home-based iron infusion service in patients with iron deficiency with or without anaemia. METHODS: Retrospective cohort study, including adult patients who received intravenous iron through a Hospital in The Home service in a single tertiary centre between August 2020 and 2021. A chart review was conducted for documented adverse events (AEs). A telephone survey assessed patient acceptance with three questions on a 5-point Likert scale: (i) How do you perceive the experience of having your infusion given in the home? (ii) Would you like to have the infusion in the same location if you require one in the future? and (iii) Do you feel safe having your infusion at home? OUTCOME MEASURES: Percentage of patients experiencing AEs and patient acceptance of a home-based iron infusion strategy. RESULTS: One hundred ninety-seven patients were included (181 ferric carboxymaltose and 16 ferric derisomaltose). Six (3%) patients (2 of 181 patients who received ferric carboxymaltose compared with 4 of 16 patients who received ferric derisomaltose, P < 0.001, Fisher's exact) experienced AEs, mostly headache and pruritus. Most patients who participated in the telephone survey had a positive experience (57/58 (98%)), felt safe (57/58 (98%)) and preferred future infusions to occur at home (52/58 (90%)). CONCLUSION: A home-based iron infusion strategy was safe and well accepted by patients. Larger studies evaluating the safety profile of different iron formulations in the home setting are required.

The Efficacy, Safety, and Economic Outcomes of Using Ferric Derisomaltose for the Management of Iron Deficiency in China: A Rapid Health Technology Assessment.

Intravenous (IV) iron supplementation is the preferred treatment option for managing severe iron deficiency (ID) and ID anemia (IDA). Three of the available IV iron preparations are ferric derisomaltose (FDI), ferric carboxymaltose (FCM), and iron sucrose (IS). The objective of the present work was to review the published literature about the efficacy, safety, quality of life (QoL), and economic outcomes of using FDI, FCM, and IS for the treatment of ID. A systematic literature search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were assessed for quality using appropriate tools, and data were extracted and analyzed for key outcomes. The evidence synthesis was based on published systematic literature reviews (SLRs), meta-analyses (MAs), indirect treatment comparisons (ITCs), and health technology assessments (HTAs); we also included economic evaluations performed from a Chinese perspective. Out of 337 initial hits, the review included 12 studies. The findings indicated that FDI, FCM, and IS had comparable efficacy in terms of hemoglobin (Hb) improvement. FDI showed a better safety profile with a lower risk of hypophosphatemia, hypersensitivity reactions, and cardiovascular adverse events (AEs) compared to IS and FCM. FDI also demonstrated better cost-effectiveness compared to IS, with potential cost savings attributed to fewer infusions and improved compliance. None of the included studies evaluated QoL after IV iron administration for ID. FDI offers a safe, efficacious, and cost-effective treatment option for ID. It exhibits comparable efficacy to FCM and IS but presents a better safety profile and economic advantage. FDI fulfills the criteria of efficacy, safety, economy, innovation, suitability, and accessibility, making it a promising choice for ID management in China.

Multifocal Abscesses, Necrotizing Fasciitis, Iron Deficiency Anemia, and Hypophosphatemia Induced by Ferric Carboxymaltose Infusions: Report of a Case of Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia in which disrupted angiogenesis leads to increased formation of mucocutaneous telangiectasias or major vascular malformations. Iron deficiency anemia and recurrent abscesses are commonly reported in these patients, reinforcing screening and targeted therapies for these conditions. We report a 50-year-old man with HHT affected by repeated episodes of iron deficiency anemia secondary to recurrent epistaxis requiring frequent intravenous iron infusions. He eventually developed hypophosphatemia and hyperphosphaturia secondary to ferric carboxymaltose. He also had a history of recurrent multifocal abscesses, including a severe presentation of necrotizing fasciitis, requiring multiple surgical interventions. Despite the identification of hypogammaglobulinemia, only after consistent dental treatment and antibiotic prophylaxis did the abscesses stop recurring. We highlight the need for careful consideration of all possible complications inherent to the disease itself but also those related to comorbidities or existing treatments.

Skin Staining Following Intravenous Iron Extravasation in a Patient With Chronic Kidney Disease: A Case Report.

Rationale: Intravenous iron is commonly use in anemia related to chronic kidney disease. Skin staining due to iron extravasation is a rare adverse reaction that can leave a long-term staining of the skin. Presenting Concerns of the Patients: During iron derisomaltose infusion, patient reported iron extravasation. Five months after the incident, the skin stain related to the extravasation was still present. Diagnosis: A case of skin staining due to iron derisomaltose extravasation was diagnosed. Interventions/Outcomes: She was reviewed by dermatology and laser therapy was offered. Teaching Points: Patients and clinicians need to be aware of this complication, and protocol needs to be put in place to minimize extravasation and its complication.

Justification: L'administration de fer par voie intraveineuse est une procédure courante pour traiter l'anémie liée à l'IRC. La coloration cutanée due à l'extravasation du fer est un effet indésirable rare qui peut perdurer à long terme. Présentation du cas: Une patiente ayant signalé une extravasation du fer au cours d'une perfusion de dérisomaltose ferrique. Cinq mois après l'incident, la coloration de la peau liée à l'extravasation était toujours présente. Diagnostic: Un diagnostic de coloration cutanée due à une extravasation de dérisomaltose ferrique a été posé. Interventions/Résultats: La patiente a été revue en dermatologie et une thérapie au laser lui a été offerte. Enseignements tirés: Les patients et les cliniciens doivent être au fait de cette possible complication. Un protocole doit être mis en place pour minimiser l'extravasation et sa complication.

Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis.

INTRODUCTION: AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. MATERIAL AND METHODS: We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. RESULTS: FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2 > 50%) between the trials for any of the analyzed outcomes. CONCLUSIONS: Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while effects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.

A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose.

BACKGROUND: Intravenous iron is the preferred treatment for patients with iron deficiency anemia in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions (HSRs) and, rarely, anaphylactic or anaphylactoid reactions. AIM: The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of HSRs after administration of ferric derisomaltose (FDI) or ferric carboxymaltose (FCM). METHOD: A prospectively-registered systematic literature review was conducted to identify prospective randomized controlled trials comparing FDI and FCM with other intravenous iron formulations or oral iron. Searches were conducted in PubMed (including MEDLINE), EMBASE, and the Cochrane Library in November 2020. The relative incidence of serious or severe HSRs occurring on the day or day after dosing of intravenous iron, recorded under the standardized Medical Dictionary for Regulatory Activities query for anaphylactic reaction. RESULTS: Data were obtained from seven randomized controlled trials of FCM (N = 2683) and ten of FDI (N = 3474) enrolling 10,467 patients in total. The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%). Bayesian inference of proportions showed the event rates to be significantly lower with FDI relative to FCM. CONCLUSION: HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM. Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.

Ferric Derisomaltose Evaluation in Patients with Non-Dialysis-Dependent Chronic Kidney Disease or Peritoneal Dialysis.

Background: Iron deficiency anemia is common in patients with advanced chronic kidney disease (CKD). Ferric derisomaltose (FDI) enables iron repletion in a single dose, unlike other forms of iron for IV administration, which require multiple doses. Protocols are commonly used with other IV irons, but there are limited Canadian data for FDI, and no protocol exists. Objectives: To evaluate the efficacy and safety of FDI for patients with CKD and to ascertain information related to its use in Canadian provinces. Methods: This retrospective cohort study involved patients with non-dialysis-dependent CKD (NDD-CKD) and patients undergoing peritoneal dialysis (PD) who received FDI in a tertiary hospital in Nova Scotia between June 2020 and May 2021. Each patient was followed for a minimum of 6 months. The efficacy outcomes were the changes from baseline in hemoglobin, transferrin saturation (TSAT), and ferritin after the first dose of FDI and at 3 and 6 months. The safety outcomes were the frequency and types of adverse reactions to FDI. Electronic surveys were sent to 33 Canadian renal pharmacists to gather information about FDI use, dosing, administration, monitoring, funding, and safety in their respective organizations. Results: A total of 52 infusions were administered to 35 patients during the study period. The median times between doses 1 and 2 and between doses 2 and 3 were 19.1 and 6.6 weeks, respectively. The median change from baseline to first post-FDI follow-up blood work was significant for hemoglobin (9.0 g/L, p = 0.023), TSAT (11 percentage points, p < 0.001), and ferritin (271.4 µg/L, p < 0.001). Median darbepoetin doses decreased from baseline to 6 months (p < 0.001). Three adverse reactions occurred. At least 15 (65%) of the 23 survey respondents reported that FDI was funded by their province or was listed on their hospital drug formulary. Conclusion: This study provides evidence that FDI is an effective and safe treatment for anemia in NDD-CKD and PD patients.

Contexte: L'anémie ferriprive est fréquente chez les patients atteints d'insuffisance rénale chronique avancée (IRC). Une seule dose de dérisomaltose ferrique (FDI) permet au niveau de fer de se rétablir, contrairement à d'autres formes de fer administrées par IV qui nécessitent, elles, plusieurs doses. Des protocoles sont couramment utilisés avec d'autres fers administrés par IV, mais les données canadiennes sur le FDI sont limitées et il n'existe aucun protocole. Objectifs: Évaluer l'efficacité et l'innocuité du FDI chez les patients atteints d'IRC et vérifier les informations relatives à son utilisation dans les provinces du Canada. Méthodes: Cette étude de cohorte rétrospective comprenait des patients atteints d'IRC sans dialyse (NDD-IRC) et des patients sous dialyse péritonéale (DP) ayant reçu du FDI dans un hôpital de soins tertiaires de la Nouvelle-Écosse entre juin 2020 et mai 2021. Chaque patient a fait l'objet d'un suivi pendant au moins 6 mois. Les résultats d'efficacité étaient les changements par rapport à la base de trois mesures après la première dose de FDI et à 3 et 6 mois, soit l'hémoglobine, la saturation de la transferrine (TSAT) et la ferritine. Les résultats d'innocuité étaient la fréquence et les types de réactions indésirables au FDI. Des sondages ont été envoyés par voie électronique à 33 pharmaciens canadiens spécialisés en néphrologie afin de recueillir des renseignements sur l'utilisation, le dosage, l'administration, la surveillance, le financement et l'innocuité du FDI dans leurs organismes respectifs. Résultats: Au total, 52 perfusions ont été administrées à 35 patients au cours de la période d'étude. Les délais médians entre les doses 1 et 2, et entre les doses 2 et 3 étaient respectivement de 19,1 et 6,6 semaines. Le changement médian entre la base et le premier bilan sanguin de suivi post-FDI était important pour l'hémoglobine (9,0 g/L, p = 0,023), le TSAT (11 points de pourcentage, p < 0,001) et la ferritine (271,4 µg/L, p < 0,001). Les doses médianes de darbépoétine ont diminué par rapport à la base à 6 mois (p < 0,001). Trois effets indésirables se sont produits. Au moins 15 des 23 répondants au sondage (65 %) ont déclaré que le FDI était financé par leur province ou figurait sur les listes de médicaments des hôpitaux. Conclusion: Cette étude fournit des preuves que le FDI est un traitement efficace et sûr de l'anémie chez les patients NDD-IRC et PD.

Ferric derisomaltose for the treatment of iron deficiency anemia with postpartum hemorrhage: Results of a single-arm, open-label, phase 3 study in Japan.

AIM: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). METHODS: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk. RESULTS: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI. CONCLUSIONS: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. CLINICAL TRIAL IDENTIFIER: JapicCTI-194888.

Budget Impact Analysis of Ferric Derisomaltose for the Treatment of Iron-Deficiency in Malaysia

@#Introduction: Untreated iron deficiency (ID) can lead to severe anaemia, requiring blood transfusion, or increased mortality risk. Globally intravenous (IV) iron is increasingly recognised as a recommended option for patients. This study aims to evaluate the budget impact associated with introducing a new intravenous (IV) iron, ferric derisomaltose (Monofer® [IIM]) as one of the treatment options for the management of ID in the Ministry of Health Malaysia (MOHM) setting. Methods: A 5-year budget impact model was developed from 2020 to 2024 for patients with ID that require a high iron dose (≥500 mg), using the perspective of MOHM. The model was built with four external medical specialists, each with experience and deep knowledge of ID management, to support estimations on the future development of iron use in Malaysia. Results: Compared to the current market mix with the existing IV iron products (i.e., iron sucrose and iron dextran), a cost-saving of MYR 53,910 could be achieved with the introduction of IIM in 2020. The uptake of IIM into MOHM over five years is estimated to lead to an overall budget saving of MYR 11,837,524 over a 5-year time horizon. Conclusion: The use of IIM in place of the current IV iron products in MOHM resulted in a significant cost saving by reducing the number of visits required to achieve the targeted iron dose and the shorter IV infusion time with IIM.

Markers of Oxidative Stress, Inflammation and Endothelial Function following High-Dose Intravenous Iron in Patients with Non-Dialysis-Dependent Chronic Kidney Disease-A Pooled Analysis.

Chronic kidney disease (CKD) represents a state of oxidative stress imbalance, which is potentially amplified by iron deficiency. Intravenous iron is considered safe and efficacious in the treatment of iron deficiency anemia, however, concerns remain regarding its potential pro-oxidant effect, leading to inflammatory and endothelial consequences. This pooled analysis of two pilot randomized controlled trials aimed to group and analyze the potential effect of high-dose intravenous iron (ferric derisomaltose, 1000 mg) on markers of oxidative stress (thiobarbituric acid reactive substance), inflammation (C-reactive protein, interleukins 6 and 10) and endothelial response (E-selectin, P-selectin) in patients with non-dialysis-dependent CKD and iron deficiency with/without anemia. Pulse wave velocity as a surrogate measure of arterial stiffness was measured. Thirty-six patients were included. No statistically significant trend was identified for any of the aforementioned markers. Stratification and comparison of data based on CKD stage did not yield statistically significant trajectories with the exception of the C-reactive protein in CKD stage 3b. These results suggest that high-dose intravenous iron does not impact measures of oxidative stress or inflammation; however, the results are not conclusive. Further research in a larger cohort is necessary to characterize the effect of intravenous iron on oxidative status and inflammation and its potential sequela in CKD.

Protocol for a multicenter, double-blinded placebo-controlled randomized controlled trial comparing intravenous ferric derisomaltose to oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy: The IVIDA2 trial.

BACKGROUND: Iron deficiency anemia (IDA) is common during pregnancy and associated with adverse maternal and neonatal outcomes. Treatment with iron supplementation is recommended during pregnancy, but the optimal delivery route is unclear. Oral iron risks has high risk of gastrointestinal side effects and low absorption. Intravenous iron is infused directly but is expensive. The American College of Obstetricians and Gynecologists currently recommends oral iron to treat IDA in pregnancy with intravenous iron reserved as second-line therapy, if needed. This approach is associated with persistent anemia, increasing the risk of peripartum blood transfusion. We aim to provide data on optimal route of iron repletion for IDA in pregnancy. METHODS: In IVIDA2, a double-blind, placebo controlled, multicenter randomized trial in the United States, 746 pregnant people with moderate-to-severe IDA (hemoglobin <10 g/dL and ferritin <30 ng/mL) at 24-28 weeks' gestation will be randomized 1:1 to either a single 1000 mg dose of intravenous ferric derisomaltose and oral placebo (1-3 times daily) or a single placebo infusion with 1-3 times daily 325 mg ferrous sulfate (65 mg elemental iron) tablet. The primary outcome is peripartum blood transfusion (blood transfusion from delivery to 7 days postpartum). Secondary outcomes include adverse medication reactions, maternal and neonatal hematologic indices, and offspring neurodevelopment. ETHICS AND DISSEMINATION: A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of Ethics and dissemination: A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of.

Intravenous ferric derisomaltose versus saccharated ferric oxide for iron deficiency anemia associated with menorrhagia: a randomized, open-label, active-controlled, noninferiority study.

A multicenter, randomized, open-label, phase III study was conducted to compare the efficacy and safety of intravenous ferric derisomaltose (FDI) versus saccharated ferric oxide (SFO) in Japanese patients with iron deficiency anemia associated with menorrhagia. FDI can be administered as a single dose up to 1000 mg, whereas SFO has a maximum single dose of 120 mg. The primary endpoint, which was the maximum change in hemoglobin concentration from baseline, was noninferior for the FDI group compared with the SFO group. The incidence of treatment-emergent adverse events was lower in the FDI group (66.2%) than in the SFO group (90.8%). Notably, the incidence of serum phosphorus level < 2.0 mg/dL was significantly lower in the FDI group (8.4%) than in the SFO group (83.2%), and severe hypophosphatemia (≤ 1.0 mg/dL) occurred in 6.7% of SFO­treated patients compared with none in the FDI group. The percentage of patients who achieved the cumulative total iron dose during the 8-week treatment period was higher in the FDI group (92.8%) than in the SFO group (43.2%). The study met its primary endpoint, and also demonstrated the tolerability of a high dose of FDI per infusion, with a lower incidence of hypophosphatemia.