Abstract
Iron deficiency anemia is common in the elderly. It is an important medical issue particularly in patients with chronic kidney disease (CKD) because of the associated complications, including increased mortality, loss of functional independence, and cognitive and cardiovascular abnormalities. Oral iron replacement is frequently ineffective, being poorly tolerated due to GI side effects. Ferumoxytol, a novel semi-synthetic carbohydrate-coated iron oxide nanoparticle, is being developed as an IV iron therapy to treat iron deficiency anemia in adults and elderly CKD patients. Ferumoxytol is isotonic with plasma, has lower free iron than other available IV products, and can be given as a 510 mg dose via rapid IV bolus. To evaluate the safety and efficacy of iron replacement with ferumoxytol relative to oral iron in adults and elderly subjects with CKD, data were pooled from three open-label, multicenter, randomized Phase III trials (ClinicalTrials.gov identifiers NCT00255437, NCT00255424, and NCT00233597). In a modified ITT Population (subjects randomized and dosed), a total of 884 subjects with CKD stages 1–5 and 5D received either 2 doses of 510 mg of IV ferumoxytol within 5±3 days or 200 mg of elemental oral iron daily for 21 days (Ferro-Sequels®). The mean change from baseline to Day 35 for hemoglobin (Hgb, the primary endpoint in these Phase III studies) was analyzed using an ANOVA with fixed effects for treatment and age categories (<50, 50 to <65, 65 to <75, and ≥75 years) and their interaction. There was a highly significantly greater Hgb response with IV ferumoxytol relative to oral iron across all age groups (mean ± SD were 1.03±1.22 g/dL for ferumoxytol vs. 0.42±1.05 g/dL for oral iron, p<0.0001). The Hgb response to IV ferumoxytol was consistently observed regardless of age and was greater than the response seen with oral iron (see Table for mean ± SD values). By contrast, there appeared to be a diminished response to oral iron with increasing age. Subject incidences of adverse events with ferumoxytol were similar to or lower than those observed with oral iron in all 3 studies. Multiple factors, including patient compliance, concomitant medications, and impaired GI absorption and/or side effects, may contribute to the ineffectiveness of oral iron. Therefore, physicians should consider the use of IV iron to more effectively treat iron deficiency anemia in all adult CKD patients, including the elderly.
Change in Hemoglobin at Day 35 Ferumoxytol 2×510 mg Oral Iron Age N Baseline Hgb Change in Hgb at Day 35 N Baseline Hgb Change in Hgb at Day 35 Relative Change in Hgb (Ferumoxytol vs Oral Iron) All 605 10.15 ± 0.81 1.03 ± 1.22 279 10.33 ± 0.78 0.42 ± 1.05 245% <50 105 10.22 ± 0.96 1.06 ± 1.38 38 10.16 ± 0.96 0.58 ± 1.42 183% 50 to <65 192 10.14 ± 0.80 1.00 ± 1.13 112 10.40 ± 0.79 0.43 ± 1.07 233% 65 to <75 163 10.14 ± 0.76 0.92± 1.19 70 10.33 ± 0.75 0.46 ± 0.89 200% ≥75 145 10.10 ± 0.74 1.17 ± 1.27 59 10.28 ± 0.69 0.25 ± 0.89 468%
Oral Iron Therapy-Induced Neutropenia in Patient with Iron Deficiency Anemia