Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial.

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double-blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least-squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.

Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia: rationale and study design of a randomized double-blind study with a focus on acute hypersensitivity reactions.

BACKGROUND: Intravenous (IV) iron is often used to treat iron deficiency anemia in patients who are unable to tolerate or are inadequately managed with oral iron. However, IV iron treatment has been associated with acute hypersensitivity reactions. The comparative risk of adverse events (AEs) with IV iron preparations has been assessed by a few randomized controlled trials, which are most often limited by small patient numbers, which lack statistical power to identify differences in low-frequency AE such as hypersensitivity reactions. MATERIALS AND METHODS: Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (FIRM) is a randomized, double-blind, international, multicenter, Phase III study designed to compare the safety of ferumoxytol and ferric carboxymaltose (FCM). The study includes adults with hemoglobin <12.0 g/dL (females) or <14.0 g/dL (males), transferrin saturation ≤20% or ferritin ≤100 ng/mL within 60 days of dosing, and a history of unsatisfactory or nontolerated oral iron therapy or in whom oral iron therapy is inappropriate. Patients are randomized (1:1) to ferumoxytol 510 mg or FCM 750 mg, each given intravenously on days 1 and 8. Primary end points are the incidence of moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. All potential hypersensitivity and hypotensive reactions will be adjudicated by a blinded, independent Clinical Events Committee. A secondary safety end point is the composite frequency of moderate-to-severe hypersensitivity reactions, including anaphylaxis, serious cardiovascular events, and death. Secondary efficacy end points include mean change in hemoglobin and mean change in hemoglobin per milligram of iron administered from baseline to week 5. Urinary excretion of phosphorus and the occurrence of hypophosphatemia after IV iron administration will be examined as well as the mechanisms of such hypophosphatemia in a substudy. CONCLUSION: FIRM will provide data on the comparative safety of ferumoxytol and FCM, two IV iron preparations with similar dosing schedules, focusing on moderate-to-severe hypersensitivity reactions, including anaphylaxis, and moderate-to-severe hypotension. The study plans to enroll 2000 patients and is expected to complete in 2017.

A rare cause of pituitary stalk enlargement and panhypopituitarism.

Pituitary stalk involvement is seen in a variety of medical conditions such as infectious diseases, infiltrative diseases and tumors (intracranial and metastatic). Metastatic cancer has a greater propensity to involve the infundibulum and neurohypophysis. We report a case of a 68-year-old man who presented with thickening of the stalk, panhypopituitarism, diabetes insipidus and generalized lymphadenopathy. Lymphoma was diagnosed on axillary lymph node biopsy and lymphomatous involvement of the infundibulum was suspected. Although infundibular thickening resolved and diabetes insipidus improved after chemotherapy, panhypopituitarism persisted.

Diabetes-related morbidity and mortality in a national sample of U.S. elders.

OBJECTIVE: Although the number of elders with diabetes has increased dramatically, there are few data on rates of mortality and serious complications in older populations with diabetes. To determine such rates, we conducted a population-based, nonconcurrent cohort study using claims data from the 1994-1996 Medicare 5% Standard Analytical File. RESEARCH DESIGN AND METHODS: Codes from the ICD-9 were used to identify diabetes and the following complications: amputation, lower extremity infection, gangrene, blindness, acute myocardial infarction, ischemic heart disease, stroke, and metabolic disorders. Using these codes, we assembled a cohort of 148,562 Medicare Part A and B beneficiaries who were > or = 65 years of age, who were alive on 1 January 1995, who were not in managed care in 1994, and who had a diabetes-related claim in 1994. Age-specific rates of death and complications were then calculated. RESULTS: During 24 months of follow-up, 22,044 (14.8%) elders with diabetes died. Death rates in men and women increased significantly with age. Compared with their counterparts in the general U.S. population, elders with diabetes suffered excess mortality at every age group, corresponding to an overall standardized mortality ratio of 1.41 (95% CI 1.39,1.43). The incidence of ischemic heart disease and stroke was 181.5 and 126.2 per 1,000 person-years, respectively, which was higher than the incidence of all other diabetes-related complications. CONCLUSIONS: In every age group, elders with diabetes have significantly higher all-cause mortality rates than the general population. Medicare data may be useful in monitoring trends in diabetes-related morbidity and total mortality in U.S. elders with diabetes.