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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.

Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia.

Background and Aims Intravenous (IV) iron is the preferred treatment for patients with iron deficiency (ID) and iron deficiency anemia (IDA) in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions and, very rarely, anaphylactic reactions. The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of serious or severe hypersensitivity reactions (HSRs) after administration of different IV iron formulations. Methods A prospectively-registered systematic literature review (SLR) was conducted to identify prospective, active comparator randomized controlled trials (RCTs) comparing ferric derisomaltose (FDI) (also known as iron isomaltoside 1000) or ferric carboxymaltose (FCM) with other IV iron formulations or oral iron. The primary endpoint was the incidence of serious or severe hypersensitivity reactions occurring on the day or day after dosing of IV iron, based on pre-specified terms (MedDRA classification). Results Data were obtained from ten prospective, active comparator RCTs of FDI (N=3,474) and seven prospective, active comparator RCTs of FCM (N=2,683), two of which were head-to-head comparisons of FDI and FCM. The trials enrolled a total of 10,467 patients, of whom 6,157 were treated with either FDI or FCM. The number of patients experiencing any serious or severe hypersensitivity reactions was 5/3474 with FDI (0.14%) versus 29/2683 (1.08%) with FCM; Bayesian inference of proportions showed the reaction rates to be significantly lower with FDI relative to FCM (Figure). Conclusions To our knowledge, the present analysis represents the first SLR and meta-analysis of the incidence of serious or severe HSRs after administration of FDI vs FCM based on pre-specified MedDRA terms. The SLR conducted for the present meta-analysis, identified 15 prospective, head-to-head RCTs including 10,467 patients, of whom 3,474 and 2,683 were treated with FDI and FCM, respectively. The analysis demonstrated that serious or severe hypersensitivity reactions were uncommon with the newer high-dose IV iron formulations; and showed a significantly lower incidence of serious or severe hypersensitivity reactions with FDI compared to FCM. Figure 1 Figure 1. Disclosures Biggar: Vifor-Fresenius: Consultancy; Pharmacosmos: Consultancy; Medice: Consultancy. Pöhlmann: Pharmacosmos A/S: Consultancy. Pollock-Wilkins: Pharmacosmos A/S: Consultancy.

Objectives: The benefits of intravenous (IV) iron greatly outweigh the risks, but IV iron formulations carry a small risk of hypersensitivity reactions (HSRs). The objective was to use standardized Medical Dictionary for Regulatory Activities queries (SMQs) to compare the safety of ferric derisomaltose/iron isomaltoside 1000 (FDI), iron sucrose (IS), and ferric carboxymaltose (FCM) using prospective trial data.Methods: Prospective trials reporting the incidence of SMQ-coded serious or severe HSRs were identified in the literature. Four SMQs were used: narrow hypersensitivity terms (A), and broad terms pertaining to potential respiratory HSRs (B), skin HSRs (C), and cardiovascular HSRs (D). Bayesian inference, naive pooling, and adjusted indirect approaches were employed to compare HSR incidence.Results: Twenty one prospective trials including over 8,000 patients receiving FDI, FCM or IS were retrieved. Odds ratios of any serious or severe HSR (all groups) with FDI relative to FCM were 0.41, 0.39, and 0.45 according to the Bayesian, naive and adjusted approaches, respectively.Conclusions: The risk of serious or severe HSRs was lower with FDI relative to FCM and IS. Using data from prospective trials including over 8,000 patients coded using a well-defined standard (SMQs) enabled a robust comparison of HSR incidence between the iron formulations.

In recent years, considerable progress has been made in the detection and treatment of iron deficiency. The results are also relevant for many specialist areas and, in particular, for patients with chronic inflammatory diseases. In daily practice, iron deficiency is often neither identified nor consistently treated.An iron deficiency can - even before anaemia occurs - reduce the quality of life and influence the course of the underlying disease. In patients with chronic diseases , the iron status should be monitored regularly. Especially, the currently available oral iron preparations for these patients are inefficient, because of the limitated tolerability and, furthermore, because of restricted enteral iron uptake due to inflammation. For this reason, various guidelines recommend intravenous iron substitution.In den letzten Jahren konnten wesentliche Fortschritte in der Erkennung und Behandlung des Eisenmangels erzielt werden, deren Ergebnisse auch für viele Fachgebiete und insbesondere mit Patienten mit chronisch-entzündlichen Erkrankungen relevant sind. Allerdings wird in der täglichen Praxis ein Eisenmangel vielfach nicht identifiziert und konsequent therapiert.Ein Eisenmangel kann – auch bevor eine Anämie auftritt – die Lebensqualität einschränken und den Verlauf der Grunderkrankung beeinflussen. Bei Patienten mit chronischen Erkrankungen sollte der Eisenstatus regelmäßig erfasst werden. Gerade bei Patienten mit chronisch-entzündlichen Erkrankungen sind die derzeit verfügbaren oralen Eisenpräparate ineffizient, weil die Verträglichkeit eingeschränkt ist und die enterale Eisenaufnahme durch Inflammation eingeschränkt sein kann. Deshalb empfehlen verschiedene Leitlinien hier eine intravenöse Eisensubstitution.

ZusammenfassungIn den letzten Jahren konnten wesentliche Fortschritte in der Erkennung und Behandlung des Eisenmangels erzielt werden, deren Ergebnisse auch für viele Fachgebiete und insbesondere mit Patienten mit chronisch-entzündlichen Erkrankungen relevant sind. Allerdings wird in der täglichen Praxis ein Eisenmangel vielfach nicht identifiziert und konsequent therapiert.Ein Eisenmangel kann – auch bevor eine Anämie auftritt – die Lebensqualität einschränken und den Verlauf der Grunderkrankung beeinflussen. Bei Patienten mit chronischen Erkrankungen sollte der Eisenstatus regelmäßig erfasst werden. Gerade bei Patienten mit chronisch-entzündlichen Erkrankungen sind die derzeit verfügbaren oralen Eisenpräparate ineffizient, weil die Verträglichkeit eingeschränkt ist und die enterale Eisenaufnahme durch Inflammation eingeschränkt sein kann. Deshalb empfehlen verschiedene Leitlinien hier eine intravenöse Eisensubstitution.

Eisenmangel und Anamie treten insbesondere bei Frauen oder als Komorbiditaten diverser chronischer Erkrankungen auf. Fur die Behandlung eines Eisenmangels oder einer Anamie stehen neben oralen Praparaten auch parenterale Eisentherapien zur Verfugung. Aufgrund der zunehmenden Bedeutung und wachsenden Anzahl von parenteralen Eisenpraparaten werden die Pharmakologie und Applikation sowie die Chronologie der Zulassungen und die Eigenschaften der verschiedenen Praparate hier vergleichend dargestellt. Ubersichtsarbeit Es existieren bisher drei verschiedene Generationen von parenteralen Eisenpraparaten, die sich hinsichtlich Stabilitat, Sicherheit und Dosierung unterscheiden. Insbesondere die Wirkstoffe der dritten Generation, Eisencarboxymaltose, Eisenisomaltosid und Ferumoxytol zeichnen sich durch eine hohe Komplexstabilitat und vergleichbare Sicherheit aus und erlauben eine schnelle Applikation hoher Eisendosen. Hochmolekulares Eisendextran, als Vertreter der Eisenpraparate der ersten Generation, sollte moglichst nicht mehr verwendet werden, da neuere i.v. Eisenpraparate mit deutlich geringerem Risiko fur schwerwiegende anaphylaktische Reaktionen verfugbar sind. Eisengluconat und Eisensucrose, als Vertreter der zweiten Generation, sind sehr effiziente Praparate, erfordern aber haufige Klinik- oder Arztbesuche, da sie aufgrund labilerer Eisenkomplexe nur in niedrigen Dosen verabreicht werden durfen. Die drei parenteralen Eisenformulierungen der dritten Generation weisen im Alltag Vorteile in der Handhabung auf, da sie vergleichbar gute Sicherheitsprofile, eine hohe Komplexstabilitat und hierdurch die Moglichkeit der schnellen Applikation hoher Eisendosen bis hin zu Gesamtdosisinfusionen bieten. Ferner sind Testdosen bei diesen Praparaten nicht erforderlich, was ihren Einsatz zusatzlich vereinfacht.

Anemia is a well-recognized feature in patients with chronic kidney disease (CKD). Recently, two large-scale trials, CREATE and CHOIR, pointed to the complexity of maintaining stable hemoglobin (Hb) levels over time. According to these data, patients failing to achieve the target range of Hb levels between 11–12 g/dL may be at increased risk of dying. Both low and high Hb levels are associated with increased cardiovascular events and death. One reason for failure to achieve stable Hb levels within the target range is Hb cycling. Several causes may be responsible for a cyclic pattern of Hb levels: drug-related factors such as differences in pharmacokinetics and bioavailability in erythropoiesis-stimulating agents (ESAs) as well as difficulties in iron supplementation may induce Hb instability in patients with CKD. Similarly, patient-related factors such as an inflammatory status or protein energy wasting are associated with this phenomenon. Further, variations in fluid balance and bio-compatibility of dialyzer membranes, by differentially affecting inflammation, render the hemodialysis treatment itself a risk factor for Hb cycling. Strategies to reduce Hb cycling are necessary to obtain improved clinical out-comes. This review will describe the phenomenon of Hb cycling, highlighting potential contributing factors and discussing the possible clinical conditions.