Treatment Of Iron Deficiency Anemia In Patients Research Articles

MO525: Iron absorption and phosphate-lowering effects of ferric citrate hydrate are not influenced by gastric secretion inhibitors in patients with chronic kidney disease

Abstract BACKGROUND AND AIMS Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in chronic kidney disease (CKD) patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with CKD not on dialysis. Ingested iron is dissolved at a low pH of the secreted gastric acid in the stomach, which is an important process for its effective absorption [1]. Patients taking gastric acid secretion inhibitors (GASI), such as proton pump inhibitors and histamine-2 receptor antagonists, showed decreased iron absorption and increased risk of iron deficiency, which were dose- and treatment-duration-dependent [2]. The increase in the intragastric pH by concomitantly use of GASI might be affected on FC's iron absorption effect. METHOD We have conducted a retrospective study using data from two previous clinical studies to investigate FC in CKD patients with hyperphosphatemia. A 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study in non–dialysis-dependent (ND) CKD patients (FC, n = 60, ; placebo, n = 30) (CTI-111 435) [3], and a 52-week, phase 3, multicenter, open-label, dose-titration study in CKD patients undergoing hemodialysis (HD) (FC, n = 180) (CTI-111 437) [4] were divided into with or without GASI, and levels of iron and phosphate related parameters were analyzed. RESULTS In ND patients, approximately 25% in FC (n = 14) and 50% (n = 14) in placebo used GASI. Mean [standard deviation (SD)] changes from baseline to end of treatment (EOT) in serum ferritin (ng/mL) were 109.83 (104.46) in FC with GASI, 142.68 (94.28) in FC without GASI, −22.49 (74.85) in placebo with GASI, and −3.43 (43.58) in placebo without GASI (Fig. 1a). Those in transferrin saturation (TSAT, %) were 16.64 (30.13) in FC with GASI, 17.07 (17.56) in FC without GASI, 2.86 (14.68) in placebo with GASI, and 1.31 (9.75) in placebo without GASI (Figure 1b). The mean (SD) dose of FC with or without GASI were 3240 mg/day (approximately 778 mg ferric iron) with GASI (n = 14) and 3445 mg/day (approximately 827 mg ferric iron) without GASI (n = 46), respectively. In HD patients, approximately 50% (n = 95) used GASI. Mean changes (SD) from baseline to EOT in serum ferritin (ng/mL) were 166.32 (153.70) with GASI and 155.16 (139.47) without GASI, and in TSAT (%) were 16.60 (19.44) with GASI and 16.02 (18.81) without GASI, respectively. The mean (SD) dose of FC with or without GASI were 2619 mg/day (approximately 629 mg of ferric iron) with GASI (n = 95) and 2854 mg/day (approximately 685 mg or ferric iron) without GASI (n = 85), respectively. In both studies, there were no differences in the changes from baseline to EOT in serum phosphate between with or without GASI. CONCLUSION GASI did not interfere with iron absorption and phosphate-lowering effects of FC in CKD patients with hyperphosphatemia.

MO519: Ferric Citrate Hydrate Improves Levels of Transferrin Saturation in Hemodialysis Patients With Lower Levels of Transferrin Saturation

Abstract BACKGROUND AND AIMS Iron deficiency identified by transferrin saturation (TSAT) is reported as a risk factor for all-cause mortality and cardiovascular events in non-dialysis dependent (NDD) chronic kidney disease (CKD) [1, 2] and for all-cause mortality in hemodialysis patients [3]. Ferric citrate hydrate (FC, Riona®), an oral iron-based phosphate binder in CKD patients, is also approved as an iron preparation for iron-deficiency anemia (IDA) in Japan in 2021. In the USA, ferric citrate (Auryxia®) is approved as a phosphate binder for dialysis-dependent CKD and an iron replacement product for the treatment of IDA in patients with NDD-CKD. FC or ferric citrate increased TSAT in patients with NDD-CKD and IDA [4]. However, a few data show that whether FC or ferric citrate has the similar effect in hemodialysis patients whose TSAT is <20%. Considering the additional indication of IDA in Japan, we investigated the FC's effect on TSAT by using the data obtained from the ASTRIO study [5], which was conducted in Japanese hemodialysis (HD) patients. METHOD We conducted a retrospective study using the data of ASTRIO study [5], which is a randomized, prospective, open-label, multicenter 24-week study to investigate the FC's effect on anemia management compared with non-iron-based phosphate binders (PBs) in Japanese HD patients with hyperphosphatemia. Ninety-three patients taking non-iron-based PBs were randomized 1:1 to continue PBs (control) or switch to FC. During 24-week study, serum phosphate and hemoglobin were controlled, 3.5–6.0 mg/dL and 10–12 g/dL, respectively. From 93 patients (FC, n = 48; control, n = 45), we extracted 41 patients (FC, n = 21; control, n = 20) whose TSAT at baseline was <20% and compared the levels of TSAT and other iron related parameters between FC group and control group. RESULTS In the ASTRIO study, the mean (SD) levels of TSAT (%) was 14.3 (4.0) at baseline and rapidly increased to 25.0 (11.1) at 4 weeks in the FC group. After that, the levels of TSAT were almost unchanged in the FC group, whereas, in the control group, the mean (SD) levels of TSAT were almost unchanged during the 24-week study. The mean (SD) levels of serum ferritin gradually increased until week 12 and subsequently showed to be stabilized in the FC group, whereas, in the control group, these were almost unchanged during the 24-week study (Table 1). CONCLUSION In Japanese HD patients whose TSAT was <20%, FC rapidly increased TSAT compared with control. We will also investigate the FC's effect on TSAT in HD patients from the post-marketing surveillance study, the prospective, multicenter and observational, up to maximum 2 years treatment.

340 Pre-operative Screening and Treatment of Iron Deficiency Anaemia in Upper GI Cancer Surgery

Abstract Introduction NICE guidelines recommend intravenous iron for patients with iron deficiency anaemia (IDA) before major elective surgery to reduce blood transfusion rate. The aim of this audit was to assess pre-operative screening for anaemia and treatment of IDA in patients undergoing Upper GI (UGI) cancer surgery. Method A retrospective audit of all patients who underwent UGI cancer surgery in year 2019 at a tertiary centre. Data were collected from electronic records. Results Pre-operative haemoglobin level was performed in 110/111 (99.1%) patients. 43 (39.1%) patients were found to be anaemic using the WHO definition and 9/43 (20.9%) were severely anaemic (Hb < 100g/L). All anaemic patients had iron status checked and 26/43 (60.5%) patients were diagnosed with IDA. 17/43 (39.5%) anaemic patients received treatment, including IV iron (n = 8), blood transfusion (n = 3), oral iron (n = 3), and both IV iron and blood transfusion (n = 3). Anaemic patients (n = 17) who received treatment had a significant improvement in anaemia (P = 0.005). Conclusions This audit has demonstrated good pre-operative anaemia and IDA screening; however anaemic patients are not adequately treated, and IV iron is not routinely offered. Pre-operative anaemia treatment is effective in improving haemoglobin level. We have implemented a new anaemia treatment pathway and MDT proforma to improve the quality of care.

Diagnosis and treatment of iron-deficiency anemia in gastrointestinal bleeding: A systematic review.

BACKGROUNDAnemia is considered a public health issue and is often caused by iron deficiency. Iron-deficiency anemia (IDA) often originates from blood loss from lesions in the gastrointestinal tract in men and postmenopausal women, and its prevalence among patients with gastrointestinal bleeding has been estimated to be 61%. However, few guidelines regarding the appropriate investigation of patients with IDA due to gastrointestinal bleeding have been published.AIMTo review current evidence and guidelines concerning IDA management in gastrointestinal bleeding patients to develop recommendations for its diagnosis and therapy.METHODSFive gastroenterology experts formed the Digestive Bleeding and Anemia Workgroup and conducted a systematic literature search in PubMed and professional association websites. MEDLINE (via PubMed) searches combined medical subject headings (MeSH) terms and the keywords “gastrointestinal bleeding” with “iron-deficiency anemia” and “diagnosis” or “treatment” or “management” or “prognosis” or “prevalence” or “safety” or “iron” or “transfusion” or “quality of life”, or other terms to identify relevant articles reporting the management of IDA in patients over the age of 18 years with gastrointestinal bleeding; retrieved studies were published in English between January 2003 and April 2019. Worldwide professional association websites were searched for clinical practice guidelines. Reference lists from guidelines were reviewed to identify additional relevant articles. The recommendations were developed by consensus during two meetings and were supported by the published literature identified during the systematic search.RESULTSFrom 494 Literature citations found during the initial literature search, 17 original articles, one meta-analysis, and 13 clinical practice guidelines were analyzed. Based on the published evidence and clinical experience, the workgroup developed the following ten recommendations for the management of IDA in patients with gastrointestinal bleeding: (1) Evaluation of hemoglobin and iron status; (2) Laboratory testing; (3) Target treatment population identification; (4) Indications for erythrocyte transfusion; (5) Treatment targets for erythrocyte transfusion; (6) Indications for intravenous iron; (7) Dosages; (8) Monitoring; (9) Indications for intravenous ferric carboxymaltose treatment; and (10) Treatment targets and monitoring of patients. The workgroup also proposed a summary algorithm for the diagnosis and treatment of IDA in patients with acute or chronic gastrointestinal bleeding, which should be implemented during the hospital stay and follow-up visits after patient discharge.CONCLUSIONThese recommendations may serve as a starting point for clinicians to better diagnose and treat IDA in patients with gastrointestinal bleeding, which ultimately may improve health outcomes in these patients.

27 UTILIZATION OF AN ELECTONIC MEDICAL RECORD (EMR)-INTEGRATED DASHBOARD IMPROVES IDENTIFICATION AND TREATMENT OF IRON DEFICIENCY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract Background Anemia is frequently encountered in inflammatory bowel disease (IBD) with studies reporting an even greater prevalence among children (16–72%) than adults (4–67%) at any given time during disease course. Anemia is commonly a result of chronic iron deficiency (ID) and inflammation, with the two conditions often overlapping. Many studies have shown that gastroenterologists underecognize and undertreat these conditions. Moreover, there are currently no pediatric-specific guidelines. To align clinical practice with adult guideline recommendations and evidence-based publications, we developed a quality improvement (QI) initiative incorporating an algorithmic framework for recognition and treatment of iron deficiency anemia (IDA) in pediatric IBD. Methods The goals were twofold: improvement in 1) detection and 2) treatment rates of IDA in IBD patients. A multifaceted approach with a series of plan-do-study-act (PDSA) cycles was executed: 1. Public review of our current performance of anemia screening and treatment with all divisional providers (n=60) (11/2017), 2. Development of a new divisional clinical pathway for screening and treatment of IDA in patients with IBD (01/2018), 3. Educational sessions (02-04/2018), 4. Creation of an Epic order set and patient and family education (PFE) (02/2018), 5. Online availability of our pathway (11/2018), and 6. Utilization of an electronic medical record (EMR)-integrated dashboard to track our outcome metrics. A designated coordinator identified patients in the EMR and sent monthly reports to providers based on our automated dashboard which captured the percentage of patients with ordered hemoglobin (Hb) and ferritin, percentage of patients with anemia and/or iron deficiency, and percentage of patients with ordered iron therapy. Baseline data from July 2016 were compared to data after pathway implementation. Results In the pre-intervention period (July 2016-November 2017), 73.5% of our outpatient IBD population had a Hb ordered, with anemia prevalence of 36.3%. Only a minority of patients with anemia were being screened for ID (19.3%). Iron supplementation was prescribed in 38.1% of patients with documented anemia. Following the implementation of this QI initiative, rate of patients with biannual Hb testing completed increased to 80.1%, while prevalence of anemia decreased to 32.1%. Significant improvement was observed with screening and treatment rate increasing to 43.1% and 50.4% respectively by July 2019 as shown in Fig. 1–2. Notably, patients with moderate to severe anemia improved significantly from 48.7% to 62.1%. Conclusion ID and anemia are commonly underdiagnosed and undertreated in children with IBD. An evidence and expert based pathway combined with implementation of provider-based monthly reports using the EMR to support clinical decision may help increase screening and intervention and decrease rates of anemia prevalence. https://www.chop.edu/clinical-pathway

Анемия при воспалительных заболеваниях кишечника: патофизиология, диагностика и лечение

Anaemia is a common secondary syndrome in gastroenterological diseases. Anaemia in patients with inflammatory bowel disease (IBD) is observed in two thirds of patients, which significantly affects the quality of life. Anaemia in IBD has a complex pathogenesis. The most common types of anaemia in patients with IBD are iron deficiency anaemia (IDA) and anaemia of chronic disease, which are often combined. In most cases, laboratory tests can successfully diagnose iron deficiency, in cases when difficulties with differential diagnosis arise, the recently established indicators can be used, such as the soluble transferrin to ferritin ratio or the percentage of hypochromic red blood cells. In the treatment of IDA in patients with IBD, it is very important both to control intestinal inflammation and to correct iron deficiency. Oral iron supplements can be used in patients with mild anaemia and without inflammatory activity, but intravenous iron infusion should be chosen as a first line therapy in patients with haemoglobin < 10 g/dl, in patients with active IBD, in patients with intolerance of oral drugs, and in cases when a fast response is not required. Erythropoietin is needed (in combination with intravenous iron infusion) in patients with anaemia to manage functional iron deficiency, while blood transfusion is restricted to refractory cases or acute, life-threatening conditions. Key words: anaemia, inflammatory bowel disease, iron deficiency anaemia, iron supplements, pathogenesis of anaemia

Usefulness of Oral Ferric Citrate in Patients With Iron-Deficiency Anemia and Chronic Kidney Disease With or Without Heart Failure

Patients with chronic inflammatory conditions including chronic kidney disease (CKD) and heart failure (HF) are undertreated with iron-deficiency anemia (IDA). Progressive inflammation and reduced iron transport associated with CKD and HF may reduce the efficacy of oral iron therapy. Oral ferric citrate improves anemia markers in CKD, but its effects in patients with CKD and concomitant HF have not been described. Patients with CKD not on dialysis and IDA from a phase 2 and 3 trial were treated with ferric citrate (n = 190) or placebo (n = 188); patients with HF were identified from medical histories. Hemoglobin response was defined as a ≥10.0-g/L increase in hemoglobin. Changes in hemoglobin, transferrin saturation, ferritin, and serum phosphate from baseline to week 12 and the incidence of adverse events potentially related to HF were evaluated. HF was reported in 22% (n = 81) of patients. The proportion of patients with hemoglobin response to ferric citrate treatment did not significantly differ in patients with and without HF (43% vs 49%, respectively; p = 0.47); changes from baseline in hemoglobin, iron parameters, and serum phosphate were similar. Adverse events potentially related to HF were noted more frequently in patients with HF (ferric citrate, 23%; placebo, 17%) versus those without HF (ferric citrate, 12%; placebo, 11%). In conclusion, these results indicate a potential role for ferric citrate in the treatment of IDA in patients with CKD not on dialysis and concomitant HF.

Treating iron deficiency in patients with gastrointestinal disease: Risk of re-attendance in secondary care.

BackgroundPatients with gastrointestinal disease may have comorbid iron deficiency anaemia (IDA) and an increased risk of hospitalisation and re-attendance in hospital. The purpose of this study was to determine if oral and intravenous (IV) treatment of IDA in patients with gastrointestinal disease attending hospital were associated with differential rates of subsequent re-attendance.Methods and findingsData from the Clinical Practice Research Datalink (primary care) and Hospital Treatment Insights (secondary care) databases in England were used to conduct this retrospective cohort study. Patients with a coded gastrointestinal disease and IDA who attended hospital (inpatient or outpatient) and were dispensed oral or IV iron between 01/01/2010-31/10/2013 were included. Elective and emergency re-attendances in secondary care within 30 days of the initial attendance were determined. Demographics, medical diagnoses and treatments were extracted. Re-attendance rates following oral or IV iron were compared using chi-square tests and a step-wise logistic regression model to adjust for confounders. 2,844 patients contributed 6,294 initial attendances; 80% of patients received oral iron, 14% received intravenous iron, and 6% received both. Of initial attendances recording oral iron, 77% resulted in re-attendance in hospital, compared to 34% of those recording IV iron (unadjusted odds ratio [OR]: 0.16; adjusted OR: 0.52 [95% CI: 0.44–0.61]). Initial attendances using IV treatment were more likely to result in elective re-attendance (84%) than those recording oral treatment (43%) (p<0.001). Median length of stay in hospital tended to be shorter for patients using IV iron (1.4 days; interquartile range 0.5–3.6 days; oral iron: 5.1 days; interquartile range: 2.2–9.6 days).ConclusionsPatients with gastrointestinal disease and IDA who received IV iron were less likely to re-attend hospital, more likely to re-attend electively, and tended to have a shorter length of stay in hospital. The mode of IDA treatment could have a real-world impact on healthcare utilisation.

Коррекция железодефицитной анемии у пациенток с гинекологическими заболеваниями с использованием липосомального железа

Iron deficiency anemia (IDA) - one of the most common conditions in patients with gynecological diseases. Purpose - to evaluate the clinical efficacy and tolerability iron supplements Sideral forte in the treatment of IDA in patients with gynecological. Materials and methods. The study group consisted of 30 women aged 28 to 50 years with uterine myoma, adenomyosis and menorrhagia with iron deficiency anemia. Diagnosis is based on the results of clinical, laboratory and special methods of investigation. All patients revealed a moderate degree of IDA (WHO classification for non-pregnant women). IDA treatment was carried out drug Sideral forte 1 capsule per day for 6 weeks. Dynamic analysis of hematological and ferrokinetic indicators showed increase in the number of red blood cells, hematocrit, hemoglobin level of 104.5±8.5 to 118.2±8.6 g/l in 75% of patients. The level of serum iron in the dynamics of treatment increased from 5.45±2,3 to 11.63±5.82 mmol/l, to the sixth week of treatment and observation. In the dynamics of therapy showed an increase in the levels of ferritin in the group average from 8.0±4.3 to 12.13±4.7 g/l. The increase in Sideral forte dose to 2 capsules per day was needed in 25% of women due to continuing chronic blood loss. Adverse eventswere in 6.7% of patients in the third week of treatment. Allergic reactions were none of the patients. Conclusion. The liposomal iron can be used as antianemic drug in the complex treatment of mild iron deficiency anemia in patients with uterine myoma, adenomyosis and menorrhagia. The frequency of adverse eventswas 6.7%. Allergic reactions were not. Sideral forte was effective in 75% of patients; 25% of patients were needed to solve the issue about the surgical management of the underlying disease, that resulted in chronic blood loss.

Ferumoxytol versus placebo in iron deficiency anemia: efficacy, safety, and quality of life in patients with gastrointestinal disorders.

IntroductionIron deficiency anemia (IDA) is common in patients with gastrointestinal (GI) disorders and can adversely affect quality of life. Oral iron is poorly tolerated in many patients with GI disorders. Ferumoxytol is approved for the intravenous treatment of IDA in patients with chronic kidney disease. This study aimed to evaluate the efficacy and safety of ferumoxytol in patients with IDA and concomitant GI disorders.Patients and methodsThis analysis included 231 patients with IDA and GI disorders from a Phase III, randomized, double-blind, placebo-controlled trial evaluating ferumoxytol (510 mg ×2) versus placebo in patients who had failed or were intolerant of oral iron therapy. The primary study end point was the proportion of patients achieving a ≥20 g/L increase in hemoglobin (Hgb) from baseline to Week 5. Other end points included mean change in Hgb, proportion of patients achieving Hgb ≥120 g/L, mean change in transferrin saturation, and patient-reported outcomes (PROs).ResultsSignificantly more patients with IDA receiving ferumoxytol achieved a ≥20 g/L increase in Hgb versus placebo (82.1% vs 1.7%, respectively; P<0.001). Mean increase in Hgb (28.0 g/L vs −1.0 g/L, respectively; P<0.001) significantly favored ferumoxytol treatment. Ferumoxytol-treated patients demonstrated significantly greater improvements than placebo-treated patients relative to their very poor baseline PRO scores posttreatment, including improvements in the Functional Assessment of Chronic Illness Therapy–Fatigue questionnaire and various domains of the 36-Item Short-Form Health Survey. Ferumoxytol-treated patients had a low rate of adverse events.ConclusionIn this study, ferumoxytol was shown to be an efficacious and generally well-tolerated treatment option for patients with IDA and underlying GI disorders who were unable to use or had a history of unsatisfactory oral iron therapy.

Iron Deficiency Anemia Associated with Extracorporeal Photophoresis: A Retrospective Analysis

▪Since its emergence as a novel therapy for cutaneous T-cell lymphoma in 1987, extracorporeal photopheresis (ECP) has gained popularity in the fields of solid organ and stem cell transplantation (Perotti et al Transfus Apher Sci 2015). Though ECP is thought to be associated with few adverse effects, we have anecdotally noted that some patients treated with ECP develop iron deficiency anemia. Anemia has been reported in ECP literature at an incidence of anywhere from 0% to 24.5%, however, the etiology of the anemia has not been described (Quaglino et al Int J Dermatol 2013, Flowers et al Blood 2008, Jaksch et al J Heart Lung Transpl 2012, Dignan et al Bone Marrow Transpl 2014). We performed a retrospective chart review to further investigate the magnitude of this potential adverse effect.Adult patients receiving ECP for any indication at Mayo Clinic Hospital-Rochester were eligible for inclusion. Patients with pre-existing iron deficiency anemia (IDA) or physiologic and/or pharmacologic reasons for altered iron homeostasis were excluded from analysis. The primary endpoint was to describe the cumulative incidence of IDA at one year of ECP therapy, utilizing Kaplan-Meier methodology. We defined IDA as a hemoglobin < 12 g/dL (females) or < 14 g/dL (males), plus any of the following: MCV < 80 fL, ferritin < 11 mcg/L, iron < 35 mcg/dL (females) or < 50 mcg/dL (males), total iron binding capacity > 400 mcg/dL, or percent saturation <14%. Secondarily, we aimed to describe the proportion of patients who underwent further diagnostic evaluation of IDA and those that were initiated on iron supplementation for IDA. Patients were followed for the primary endpoint until diagnosis of IDA, death, or date of last ECP session; those who did not develop IDA were censored at the date of last follow-up.Between January 1, 2006 and July 1, 2015, a total of 120 adult patients were treated with ECP at Mayo Clinic in Rochester, MN; 80 patients met inclusion criteria. For the remaining 40 patients, patients were excluded for recent history of transfusions and/or phlebotomy (n=27), incomplete documentation (n=7), IDA at baseline (n=3), or potentially confounding past medical histories (n=3). Treatment of graft-versus-host disease (GVHD) was the foremost ECP indication in our cohort, accounting for 63.8% of our patients. Patients also received ECP for treatment of cutaneous T-cell lymphoma, treatment of solid organ transplant rejection, and other indications (25%, 7.5%, and 3.8%, respectively). Mean age was 55.6 years, 38.7% were female, and the median duration of ECP therapy was 344 days (IQR 130 - 755 days).At 1 year from the start of ECP therapy, the cumulative incidence of IDA in our cohort was 21.1% (95% CI 9% - 31.6%; Figure 1). At 4 years from the start of ECP therapy, the cumulative incidence of IDA was 49.1% (95% CI 26.4% - 64.8%). Of those that developed an IDA at any time during ECP therapy, 6/20 (30%) underwent invasive diagnostic procedures (colonoscopy and/or upper endoscopy) to evaluate the etiology of the IDA. Iron supplementation was initiated in 18/20 (90%) patients; hemoglobin returned to normal in 8 patients (44.4%) based on available follow-up. These data indicate that a substantial number of patients develop IDA while receiving ECP therapy; a finding which may lead to more prompt recognition and treatment of IDA in patients receiving ECP, and perhaps spare expensive diagnostic procedures. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and Safety of IV Ferumoxytol (FER) for Iron Deficiency Anemia (IDA) in Patients with Cancer

▪Background: IDA is common in cancer patients due to blood loss and inflammation. Many do not tolerate oral iron or adequately respond. Two Phase-3 trials investigated the efficacy and safety of IV FER for treatment of IDA in patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. This analysis explored the impact of IV iron treatment on the subgroup of patients with cancer.Methods: Data from patients with cancer were extracted from 2 RCTs (NCT01114139; NCT01114204) in which patients with baseline (BL) Hgb 7-10g/dL, TSAT <20%, were randomized 3:1 to FER (510mg, 2 injections, over 2-8 days) or placebo (PL), and 2:1 to FER or 1g iron sucrose (IS, 200mg, 5 doses over 14 days). Laboratory and safety data were pooled for this analysis. Differences within groups in change from BL Hgb were analyzed with paired t-test, and between groups were explored with ANCOVA adjusted for BL (missing values imputed as 0 change).Results: The ITT population of all 1413 patients who were exposed to study drug included 98 patients with cancer (median age 60.5, 71% female, 65% white, BL TSAT 9.2±9.7%, ferritin 121 ±187ng/mL). Gastrointestinal cancers were most common (42), followed by breast (14), cervix (10), and lung (9). During the studies, 45 patients received chemotherapy, 19 with platinum-based regimens. ESA doses were neither increased >20% nor initiated in any treatment group. Transfusions were received by 3 (23%) of IS and 6 (8%) of FER patients. Treatment with both IV irons was associated with a significant increase in Hgb by end of study (FER 1.8 g/dL, p<0.0001; IS 1.9 g/dL, p=0.002; Figure 1). [Display omitted] However, the response with FER occurred earlier, with a significantly greater increase than IS at week 2 (1.1 vs 0.1, p= 0.007) and greater than PL at week 5 (1.8 vs 0.5 g/dL, p=0.02) (LS means). A summary of the frequency and severity of adverse events among the cancer patients subgroup and the full study populations are provided in Table 1. Abstract 1352. Table 1:Adverse Event SummaryCancer Patients SubgroupPooled Overall Study PopulationAdverse Event (AE) Category,Subjects n(%)FerumoxytolN=75Iron SucroseN=13PlaceboN=10FerumoxytolN=1014Iron SucroseN=199PlaceboN=200All AEs48 (64.0)6 (46.2)8 (80.0)467 (46.1)88 (44.2)86 (43.0)Related AEs (1)6 (8.0)01 (10.0)147 (14.5)32 (16.1)15 (7.5)Serious AEs7 (9.3)1 (7.7)1 (10.0)33 (3.3)5 (2.5)6 (3.0)Related Serious AEs2 (2.7)006 (0.6)00AEs of Special Interest (2)4 (5.3)1 (7.7)033 (3.3)10 (5.0)2 (1.0)AEs Resulting in Study Discontinuation0006 (0.6)2 (1.0)2 (1.0)Death (3)1 (1.3)01 (10.0)3 (0.3)01 (0.5)(1) Classified by investigator as related to study drug. (2) Protocol defined – including hypotension and hypersensitivity (3) Assessed as unrelated by the InvestigatorConclusions: These results indicate that cancer patients with IDA, who had not tolerated or responded to oral iron, responded to both IV FER and IS with a significant increase in Hgb. The response to IV FER appeared earlier. However,given the relatively small N, limited conclusions can be made, and larger studies will be needed to further define the responses. DisclosuresVadhan-Raj:AMAG Pharmaceuticals, Inc.: Research Funding. Off Label Use: Both of the study drugs, ferumoxytol and iron sucrose, are only approved for the treatment of iron deficiency anemia in patients with chronic kidney disease.. Dahl:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Bernard:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Li:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Strauss:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership.

Potential New Treatment Option for Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy- Results of a Phase III, Randomized, Open-Label, Active-Controlled Trial of Ferumoxytol.

AbstractAbstract 2099▪▪This icon denotes a clinically relevant abstract Background:While oral iron is the preferred first-line treatment for patients with iron deficiency anemia (IDA), there are patients who cannot take oral iron, do not tolerate it or do not adequately respond to oral iron. In the US and Canada, the only approved treatment options for these patients are the iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Therefore, many of these anemic patients do not receive IV iron, and remain inadequately treated and symptomatic. In the EU, several IV irons, including iron sucrose (IS), are approved for second line use. Few studies have evaluated the IV irons in head-to-head studies. Ferumoxytol (FER) is a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD) that is formulated to allow for bolus IV injection. This randomized, controlled trial was designed to investigate the efficacy and safety of FER compared to IS for the treatment of IDA in patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Methods:The study was designed to demonstrate non-inferiority and consisted of a 14 day screening period, treatment and a 5 week follow-up period. Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) < 20%. Patients were randomized 2:1 to receive either FER, administered as 2 injections of 510 mg 5±3 days apart, or IS, administered as 5 infusions or injections of 200 mg on 5 non-consecutive days over a 14 day period. Results:A total of 605 subjects were randomized to the 2 treatment arms (FER, n= 406; IS, n=199). FER demonstrated non-inferiority to IS in the proportion of subjects with a >2.0 g/dL increase in Hgb at any time from Baseline to Week 5 (the primary efficacy endpoint), compared to those treated with IS, (FER, 84%; IS 81%) with the lower bound of the 95% CI [-3.89%] above the predefined non inferiority margin [-15%]. In addition at each post-treatment time point, a higher percentage of FER-treated subjects achieved a >2.0 g/dL increase in Hgb compared to those treated with IS. FER also achieved non-inferiority to IS in the mean change in Hgb from Baseline to Week 5 with a robust 2.7g/dL increase in Hgb compared to 2.4g/dL with IS (the lower bound of the 95% CI [0.06g/dL] was above the predefined non-inferiority margin [-0.5g/dL]); this treatment difference (0.3 g/dL) was statistically significant (p=0.0124), and FER actually achieved superiority over IS.The overall rates of adverse events (AEs) and related AEs were lower in the FER group compared to IS-treated subjects. The serious adverse event (SAE) rate was higher in FER-treated subjects (FER, 4.2%; IS, 2.5%), but no pattern or safety trend was observed to suggest a specific safety signal; treatment-related SAEs were reported in 2 (0.5%) FER-treated subjects (1 anaphylactoid reaction and 1 hypertension). Protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were reported at a higher rate in IS-treated subjects compared to the FER treatment group (IS, 5.0%; FER, 2.7%). Cardiovascular AE rates were comparable in the 2 treatment groups (1.0%). Overall, the safety profile of FER was comparable to that of IS and no new safety signals were identified. [Display omitted] Summary of Efficacy and Safety Results by Treatment GroupFER (n=406)IS (n=199)Efficacy Results: (ITT Population)% Subjects with Increase Hgb ≥ 2.0g.dL184%81%Mean change in Hgb2 (g/dL)2.72.4Mean Change in TSAT2 (%)14.510.6Safety Results: (Safety Population)All Treatment Emergent AEs41.4%44.2%Related AEs14.3%16.1%All SAEs4.2%2.5%Related SAEs0.5%0%AEs of Special Interest32.7%5.0%Cardiovascular AEs1.0%1.0%AEs Resulting in Study Discontinuation0.7%1.0%1at any time from Baseline to Week 5.2Least Square Mean change from Baseline to Week 5.3includes protocol-defined signs/symptoms of hypotension and hypersensitivity. Conclusion:In this randomized, controlled trial, the efficacy and safety of 2 doses of FER were shown to be comparable to IS in treating IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. For this IDA patient population, which has limited treatment options in the US and Canada, FER may offer an important, new treatment option with a convenient 2 dose regimen. Disclosures:Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.

Ferumoxytol Treatment Results in Robust Hemoglobin Increases in Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy in a Phase III, Randomized, Placebo-Controlled Trial.

AbstractAbstract 2098▪▪This icon denotes a clinically relevant abstract Background:Although oral iron therapy is often the initial approach to the treatment of iron deficiency anemia (IDA), many patients fail to adequately respond or do not tolerate oral iron. Unfortunately for these patients, approved treatment options are limited in the US and Canada to only the IV iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Many of these patients, therefore, do not get IV iron, and remain inadequately treated and symptomatic. Ferumoxytol (FER), a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD), is being investigated to treat IDA patients without CKD who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used. This randomized, placebo-controlled, double blind trial was designed to assess the efficacy and safety of FER for the treatment of these IDA patients. Methods:Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) <20%. Subjects were randomized 3:1 to receive 2 injections of either FER (510 mg, 5±3 days apart) or placebo (IV normal saline). Efficacy assessments included comparisons of the change in Hgb, TSAT and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the 2 treatment groups between Baseline and Week 5. Results:A total of 808 subjects were randomized to the 2 treatment arms (FER, n=608; placebo, n=200). FER demonstrated superiority to placebo with 81.1% of subjects achieving an increase in Hgb of >2.0 g/dL from Baseline to Week 5 compared to only 5.5% in the placebo group (treatment difference: 75.6%, p<0.0001). At each post-FER treatment time point, a larger percentage of FER-treated subjects had a >2.0 g/dL increase in Hgb compared with those treated with placebo. The superiority of FER was also demonstrated for the mean change in Hgb from Baseline to Week 5 with a robust 2.7 g/dL increase compared to only 0.1 g/dL in the placebo group (treatment difference: 2.54 g/dL, p<0.0001). An increase in TSAT from Baseline to Week 5 was only observed in FER-treated subjects (mean change: FER, 11.0%; placebo −0.1%). In addition, a statistically significant improvement in fatigue from Baseline to Week 5, as measured by the FACIT-Fatigue, was shown for FER-treated subjects compared to placebo (p<0.0001).The rates of adverse events (AEs) and related AEs were higher in the FER group, although no pattern or safety trend was observed to suggest a specific safety signal. The overall rate of serious adverse events (SAEs) was comparable between the 2 treatment groups (FER, 2.6%; placebo, 3.0%), and treatment-related SAEs associated with the class of IV iron products were reported in 4 (0.7%) FER-treated subjects. As expected, protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were noted at a higher rate in FER-treated subjects (FER, 3.6%; placebo, 1.0%). All cardiovascular AEs were considered unrelated by the investigators. Overall, FER was well tolerated and no new safety signals were identified. [Display omitted] Summary of Efficacy and Safety Results by Treatment GroupFER (n=608)Placebo (n=200)p-valueEfficacy Results: (ITT Population)% Subjects with Increase Hgb >2 g/dL181.15.5<0.0001Mean Change in Hgb2 (g/dL)2.70.1<0.0001Mean Change in TSAT2 (%)11.0−0.1<0.0001Safety Results: (Safety Population)All Treatment Emergent AEs49.2%43.0%Related AEs14.6%7.5%All SAEs2.6%3.0%Related SAEs0.7%0%AEs of Special Interest33.6%1.0%Cardiovascular AEs0.8%0%AEs Resulting in Study Discontinuation0.5%1.0%1at any time from Baseline to Week 5.2Least Square Mean change from Baseline to Week 5.3includes protocol-defined signs/symptoms of hypotension and hypersensitivity. Conclusion:In this randomized, placebo-controlled Phase III trial, 2 doses of FER were shown to be highly effective in raising hemoglobin and iron parameters in non-CKD patients with IDA who had a history of unsatisfactory oral iron therapy. FER also significantly reduced fatigue, and was generally well tolerated with no new safety signals being identified. Therefore, FER could provide an important, new treatment option for IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Disclosures:Vadhan Raj:AMAG Pharmaceuticals, Inc.: Research Funding. Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.

The efficacy and safety of current intravenous iron preparations for the management of iron-deficiency anaemia: a review

Iron-deficiency anaemia (IDA) is a major health problem worldwide, but responds well to iron supplementation. New approaches are leading to more effective management of this condition. Iron deficiency (ID) is usually suspected in at-risk patients with declining haemoglobin (Hb) levels and then confirmed by measuring serum ferritin levels and transferrin saturation. However, regular monitoring of these iron indicators and other laboratory parameters in susceptible individuals may lead to early recognition of falling iron stores and facilitate pre-emptive therapeutic intervention before anaemia develops. Patients with ID are commonly prescribed oral iron preparations because of convenience and low cost. However, the efficacy of these agents is limited by their reduced absorption rate and gastrointestinal side-effects. Alternatively, treatment of IDA in patients requiring erythropoiesis-stimulating agents (ESAs) is more predictably achieved by use of intravenous (i.v.) iron. Unfortunately, the development of serious adverse events (SAEs) from high molecular-weight iron dextran has led to reluctance to use i.v. iron in the treatment of IDA. Similarly, but to a much lesser extent, low molecular-weight iron dextran is associated with a number of SAEs, including allergic or anaphylactic reactions. The introduction of second-generation i.v. iron formulations, including iron sucrose and ferric gluconate, was clearly an improvement over i.v. iron dextran. These formulations proved to be effective in the management of IDA and are not associated with the serious allergic reactions encountered with i.v. iron dextran. For these reasons, use of these preparations became more widespread in the treatment of IDA across a wide range of clinical conditions. An important advantage of i.v. iron over oral iron is that it may bypass hepcidin actions by directly loading transferrin and making iron available to macrophages. Despite a reduction in the short-term risks, there is still concern about the potential for long-term toxicity of i.v. iron use (e. g. atherosclerosis development, infection and increased mortality). The association of atherosclerosis with iron overload remains unclear. Alternatively, the relative risk for mortality or hospitalization from infection in patients undergoing haemodialysis (HD) who received i.v. iron was shown not to be higher than that observed in the overall HD population. Indeed, doses of i.v. iron up to 400 mg/month were associated with improved patient survival. Second-generation i.v. iron formulations are more frequently used for treating IDA than i.v. iron-dextran in patients with various chronic conditions including those with chronic kidney disease. In the latter, IDA should be corrected before initiation of ESA therapy, as iron deficiency can lead to hyporesponsiveness to ESA. However, a major limitation of the second-generation i.v. iron agents is that they cannot be administered in large doses and the typical 1000 mg therapy requires several clinic visits. Thus, there is a need for an i.v. iron agent that can be safely administered in a single dose of 1000 mg of iron and therefore requires less frequent clinic visits. This limitation has now been overcome with the introduction of newer i.v. iron preparations. Ferric carboxymaltose offers effective and rapid correction of IDA by overcoming the limitations observed with previous i.v. iron preparations. This agent has been shown to be effective and well tolerated in a number of randomized controlled trials in a variety of chronic conditions.

A Head-to-Head Comparison of the Safety and Efficacy of Ferumoxytol to Iron Sucrose for the Treatment of Iron Deficiency Anemia

AbstractAbstract 5157 BACKGROUND:Iron replacement therapy is essential for increasing iron stores and raising hemoglobin levels in patients with iron deficiency anemia (IDA). Oral iron supplements have limited absorption and are commonly associated with gastrointestinal (GI) side effects that reduce compliance, resulting in limited increases in hemoglobin. In patients without chronic kidney disease (CKD), oral iron therapy is frequently used to treat IDA. However, when oral iron therapy is unsatisfactory or cannot be tolerated, intravenous (IV) iron therapy may be appropriate. In the US, iron dextrans are the only approved IV iron products indicated for the treatment of IDA in non-CKD patients, and have limitations around convenience because they require a test dose and as many as 10 administrations via a slow infusion; iron dextrans have also been associated with a relatively high rate of serious adverse reactions compared to other IV iron products. Other IV irons, such as iron sucrose and sodium ferric gluconate, are only approved in the US for the treatment of IDA in patients with CKD. Like the iron dextrans, both of these products are limited by administration, requiring 5 to 10 clinic visits for the administration of a full therapeutic dose (1 gram of iron). Feraheme® (ferumoxytol) Injection is an IV iron product approved in the US for the treatment of IDA in adult subjects with CKD. Its carbohydrate coating is designed to minimize immunological sensitivity, and it has less free iron than other IV iron preparations. Ferumoxytol is administered as two IV injections of 510 mg (17 mL) 3 to 8 days apart for a total cumulative dose of 1.02 g. METHODS:To date, there have been a limited number of studies that have examined the safety and efficacy of IV irons in a head-to-head manner for the treatment of IDA, and no study has done so in a large number of subjects or in a broad patient population. AMAG, therefore, has initiated a randomized, controlled trial (ClinicalTrials.gov NCT01114204) to compare ferumoxytol with iron sucrose. Iron sucrose is approved in many countries outside the US for the treatment of IDA in patients intolerant to oral iron therapy, and is considered a safer alternative to IV iron dextran. This open-label trial (n=600) will evaluate the efficacy and safety of a 1.02 g of IV ferumoxytol, administered as 2 doses of 510 mg each, compared with 1.0 g of IV iron sucrose, administered as 5 doses of 200 mg each. Enrolled subjects will have IDA associated with a variety of underlying conditions including abnormal uterine bleeding, GI disorders, cancer, postpartum anemia, and others (eg, nutritional deficiency). Endpoints include changes in hemoglobin and transferrin saturation at Week 5, as well as evaluation of the requirement for erythropoiesis stimulating agent therapy and blood transfusion. Patient reported outcomes instruments will be employed to assess the impact of IV iron therapy on anemia symptoms and health-related quality of life (fatigue, energy, etc). Additionally, detailed information on healthcare utilization will be collected. CONCLUSIONIn the US, non-CKD patients with IDA who have a history of unsatisfactory oral iron therapy have limited options for iron replacement therapy. Study NCT01114204 will provide novel information comparing the safety and efficacy of two IV iron therapies for the treatment of IDA in a broad patient population. Disclosures:Poma:AMAG Pharmaceuticals, Inc.: Employment. Diana:AMAG Pharmaceuticals, Inc.: Employment. McLaughlin:AMAG Pharmaceuticals, Inc.: Employment. Kausz:AMAG Pharmaceuticals, Inc.: Employment.

Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients' signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral iron preparations are efficacious but poorly tolerated due to non-absorbed iron-mediated GI side effects. However, oral iron dose may be reduced with no effect on its efficacy while decreasing side effects and patient discontinuation rates. Parenteral iron therapy replenishes iron stores quicker and is better tolerated than oral therapy. Serious hypersensitive reactions are very rare with new intravenous preparations. While data on worsening of inflammatory bowel disease (IBD) activity by oral iron therapy are not conclusive, parenteral iron therapy still seems to be advantageous in the treatment of IDA in patients with IBD, because oral iron may not be sufficient to overcome the chronic blood loss and GI side effects of oral iron which may mimic IBD exacerbation. Finally, we believe the choice of oral vs parenteral iron therapy in patients with IBD should primarily depend on acuity and severity of patients' signs and symptoms.