Iron replacement therapy: assessing today's options to prepare for bundling.

New Medicare rules that set forth a revised reimbursement scheme for dialysis services will introduce significant changes for providers. The new rules will abandon the current system of separate reimbursement for drugs associated with the hemodialysis services, including erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron. These rules will "bundle" these agents and related laboratory tests into a single, case-mix adjusted composite rate. These bundling rules will be gradually phased-in, beginning in 2011. One of the primary effects of the new reimbursement policy will be to discourage over-utilization of ESAs that comprise nearly one-quarter of hemodialysis-related Medicare expenditures. As a result, hemodialysis providers will be challenged to make hemodialysis services more cost-effective, while ensuring that Medicare clinical performance measures are met and patient care is not compromised. i.v. iron has an integral role in making anemia care more cost-effective in the hemodialysis setting by improving measures of iron-deficiency anemia, maintaining necessary iron balance, and reducing the utilization of ESAs. This review discusses the potential benefits of i.v. iron in the management of hemodialysis patients with iron-deficiency anemia. It also focuses on the available i.v. iron options, particularly the established efficacy and safety profile of i.v. iron dextran compared with other i.v. iron formulations as well as cost considerations.

Improving efficiency and value in health care. Intravenous iron management for anaemia associated with chronic kidney disease: linking treatment to an outpatient clinic, optimizing service provision and patient choice.

RATIONALE: The National Service Framework advocates correction of anaemia in patients with chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV) supplementation replenishes and maintains iron stores. In Yorkshire numerous peripheral clinics exist to reduce travel for patients, but patients must travel to the main unit for IV iron therapy. Therefore an outpatient service in tandem with a routine clinic for administration of IV CosmoFer was created. PURPOSE: To evaluate the feasibility and benefits of IV iron therapy in the outpatient clinic during active patient review for CKD patients. DESIGN: A cross-sectional study of patients attending for total dose IV iron (n = 57) at a peripheral clinic. Iron was administered and monitored according to protocol by one of the clinic nurses with medical staff available in the adjoining room. Haemoglobin, ferritin and renal function were recorded pre-infusion and after 4-6 months. Results are given as medians/means +/- standard error. RESULTS: A total of 76 IV infusions were carried out with no reported side effects or haemodynamic instability. Haemoglobin (median 10.9 vs. 11.3 g dL(-1), P = NS), creatinine and estimated glomerular filtration rate (eGFR) over the 6-month period remained stable. Serum ferritin rose significantly [80.9 +/- 6.2 vs. 186.4 +/- 18.2 g L(-1) (P < 0.001)]. Hospital time saved 380 day case bed hours, doctor hours saved 76 hours, and patient hours saved 3 hours/patient. Cost savings for TDI CosmoFer in peripheral clinic versus in centre therapy and versus sucrose, respectively, for 76 treatments was pound 5749.40 and pound 46,320.80 respectively. CONCLUSION: We have demonstrated, in a resource-limited service, the feasibility and cost-effectiveness of a management care pathway for patients with CKD, in a peripheral clinic, to receive total dose IV CosmoFer without disruption of a functioning renal clinic.

Clinical management. Where medicine meets management. Pumping iron.

Non-haemodialysis renal patients requiring intravenous iron therapy are increasing the pressure on renal units. A new form of iron therapy can dramatically reduce patient visits, but takes longer to administer. Sunday provision of nurse-led clinics has enabled a switch to this new therapy. Cost savings have more than offset the additional nurse-led sessions and eliminated waiting lists for this group.

Intravenous iron dextran treatment in predialysis patients with chronic renal failure.

Iron deficiency anemia is common in patients with chronic renal failure not undergoing hemodialysis. Current therapy consists of oral or intravenous (IV) iron dextran (IVID). The standard IV regimen is 100 to 200 mg/dose for a 1-g total dose. We hypothesized that 500 mg/wk of IVID for two doses would be less costly and equally effective as 200 mg/wk for five doses. We prospectively studied 22 patients with creatinine clearances less than 50 mL/min who were not undergoing dialysis and had anemia and evidence of iron deficiency (ferritin level <100 ng/mL or transferrin saturation [TSAT] <20%). Patients were randomized into two groups: group I (n = 8), 200 mg/wk of IVID for 5 weeks, and group II (n = 14), 500 mg/wk of IVID for 2 weeks. All patients tolerated IVID infusions without serious adverse reactions. Over the 6-month follow-up, both groups experienced an increase in hemoglobin levels from baseline. Ferritin levels in both groups increased (P < 0.005), peaked at 2 weeks, then declined thereafter. Over the 6-month follow-up, both groups experienced significant improvement, although the beneficial effects of group II declined at a significantly faster rate than group I (P = 0.003). There was no significant difference in change in ferritin levels between groups. TSAT peaked at 2 weeks in both groups (P < 0. 001). Group I experienced a significant increase in TSAT throughout the 6-month follow-up (P < 0.03), and group II achieved a significant increase in TSAT at 2 weeks, but not at 3 and 6 months. There was no significant difference in pretreatment to posttreatment change in TSAT. Treatment in group II was 35.2% more cost-effective than in group I ($965 versus $1,490, respectively). We conclude that IVID, 500 mg/wk, for 2 weeks is as effective and safe as 200 mg/wk for 5 weeks, but much less costly.

Effective utilization of erythropoietin with intravenous iron therapy.

INTRODUCTION: Iron replacement therapy reduces the demand for erythropoietin (EPO) in some dialysis patients. It has been postulated that iron supply to the bone marrow is a rate-limiting step in the process of erythropoiesis under erythropoietin stimulation. METHODS: We evaluated the economic benefit of intravenous iron therapy for this purpose in a prospective, non-blinded study of 22 haemodialysis patients, 16 male, six female, mean age 62 years (range 24-80 years). All patients had a serum ferritin (SF) of < or = 60 microg/L, despite oral iron therapy. Patients with high aluminium and/or parathyroid hormone (PTH) levels, underlying bleeding/haematological disorders or active inflammatory diseases were excluded. Patients were established on subcutaneous EPO and given intravenous iron over seven consecutive dialysis sessions (total dose 1050 mg) and supplemental monthly doses with regular monitoring for 4 months. RESULTS: The median EPO dose was 4000 units/week (mean 6050 units/week) pre-treatment and 2000 units/week (mean 3700 units) at 6 weeks post intravenous iron therapy (P=0.03). No serious adverse events occurred in the 154 treatment sessions of intravenous iron. Mean haemoglobin (Hb) level remained constant at 6 and 12 weeks (P=0.087). Serum ferritin levels (P< 0.0001) rose significantly, while a reduction in transferrin saturation (TS) became significant at the end of the study (P=0.0047). The use of intravenous iron allowed a substantial monthly cost saving per patient in our unit. CONCLUSION: Intravenous iron therapy is a safe and cost-effective method for maintaining or improving Hb levels with a more effective utilization of EPO in patients with low SF levels despite oral iron therapy.

Cost-effectiveness impact of iron dextran on hemodialysis patients' use of epoetin alfa and blood.

The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

Achieving target hematocrit in dialysis patients: new concepts in iron management.

The management of anemia in dialysis patients involves a comprehensive understanding of the role of erythropoietin deficiency and of the importance of adequate available iron. It is clear that iron and recombinant human erythropoietin (rHuEPO) in concert allow the clinician to achieve a given target hematocrit in dialysis patients. By first repleting and then maintaining iron stores, and with an appreciation of the concept of functional iron deficiency, the nephrologist can achieve target hematocrits with the lowest necessary dose of rHuEPO. Iron repletion and maintenance is difficult to achieve with oral iron, and parenteral iron is needed in most cases. New protocols for ongoing parenteral maintenance therapy with iron dextran or iron gluconate, a form of iron likely to be available soon in the United States, should lead to achievement of target hematocrits in a greater number of patients and be cost-effective in improving patient outcomes.

Hematologic and erythropoietin responses to iron dextran in the hemodialysis environment.

OBJECTIVE: To investigate the hematologic and economic advantages of using iron dextran as the sole supplemental agent to safely increase and maintain hematocrit levels and iron availability while optimizing erythropoietin dosing in patients on chronic hemodialysis. DESIGN: Iron dextran 100 mg (2 ml) was administered i.v. slow push, undiluted three times per week, sometime during the last 30 minutes of each hemodialysis treatment, until a total required ml (determined by using the package insert's formula) was attained. Maintenance doses of either 25 or 50 mg per week (dependent upon body weight) were administered ongoing to compensate for dialytic and gastrointestinal blood losses. The analysis duration was 12 months. SAMPLE/SETTING: A prospective analysis was performed on 13 clinically stable hemodialysis outpatients in a rural community hospital-based dialysis facility (mean age 56.4 years ranging from 24-76; sample included 9 males, 4 females). METHODS: The means and medians were calculated for each variable: hematocrit, ferritin, transferrin saturation, and erythropoietin dose. A one-tailed paired student t test was performed on doses of erythropoietin at -1 and 6 months, -1 and 9 months, and -1 and 12 months. Cost per patient of iron dextran loading dose and maintenance, as well as cost savings from actual erythropoietin dose reductions, were calculated at 3, 9, and 12 months. Cost savings reflected the cost of iron dextran. RESULTS: After 6 months on the protocol, erythropoietin doses decreased an average of 3100 units per patient with an 8% increase in hematocrit and 66% and 78% increase in transferrin saturation and ferritin, respectively. Based on averages in actual reduced erythropoietin dosing, a savings of +5,070 per patient per year was realized. CONCLUSIONS: This analysis found the use of iron dextran in the hemodialysis setting to be an effective and economic means to maintain hematocrit values and iron availability while optimizing erythropoietin dosing.