Ferric citrate improves iron-deficiency anemia in chronic kidney disease

Last Updated: 2017-01-19

By Will Boggs MD

NEW YORK (Reuters Health) - Oral treatment with ferric citrate improves iron-deficiency anemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD), according to a randomized controlled trial.

The reported prevalence of iron-deficiency anemia in NDD-CKD ranges from 48% to 98%, researchers say, and conventional iron preparations have yielded mixed benefits along with frequent adverse gastrointestinal effects. Few patients are treated with intravenous iron owing to a variety of risks.

Dr. Glenn M. Chertow from Stanford University School of Medicine in Stanford, California, and colleagues evaluated the safety and efficacy of oral ferric citrate for treatment of iron deficiency anemia in their phase 3 study of 234 patients with stages 3-5 NDD-CKD.

A 16-week randomized period was followed by an eight-week open-label safety extension period, during which all patients received ferric citrate.

Patients were started on three tablets daily (210 mg elemental iron per tablet) and then titrated by an additional three tablets daily at weeks four, eight, and 12 as needed in an effort to achieve an increase in hemoglobin by more than 1.0 g/dL above baseline (the primary endpoint).

At week 16, significantly more patients in the ferric citrate group (61/117, 52.1%) than in the placebo group (22/115, 19.1%) had achieved the primary endpoint, the researchers report in the Journal of the American Society of Nephrology, online January 12.

"A treatment effect was seen as early as 1-2 weeks after start of treatment," they note. "The response was durable and achieved without the use of erythropoiesis stimulating agents (ESAs)."

Fewer patients in the ferric citrate group (4.3%) than in the placebo group (8.7%) experienced treatment failure due to sustained hemoglobin below 9.0 g/dL.

Patients in the ferric citrate group also achieved greater improvements in transferrin saturation and ferritin levels, and, as an added benefit, ferric citrate significantly reduced serum phosphate and increased serum bicarbonate levels.

Ferric citrate treatment was associated with a greater incidence of diarrhea and constipation, compared with placebo treatment.

Coauthor Dr. Geoffrey A. Block from Denver Nephrology in Denver, Colorado, told Reuters Health by email, "Ferric citrate, if approved by the FDA for the treatment of iron-deficiency anemia in patients with CKD, will become the only approved oral iron for this population and indication. To be able to offer an effective, well-tolerated treatment will represent a change from the current practice pattern."

"Unfortunately, currently the majority of patients with progressive CKD remain untreated until the hemoglobin falls below 10 g/dL, at which time ESA therapy is prescribed," he explained. "Once approved, ferric citrate will offer a treatment option that currently does not truly exist."

"Many clinicians are unaware that the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend a trial of oral iron in patients with CKD and hemoglobin <13 g/dL (males)/12 g/dL (females) prior to any consideration of IV iron or ESA," Dr. Block added. "Ferric citrate will allow us to treat these individuals earlier, modify the otherwise relentless progression of anemia, and to do so with a side effect profile generally similar to placebo. The ancillary 'off-target' effects on phosphate metabolism are a welcome addition."

Dr. Jay B. Wish from Indiana University Health in Indianapolis, who recently reviewed new options for iron supplementation in maintenance hemodialysis patients, told Reuters Health by email, "Ferric citrate appears to be safe and effective in treating iron-deficiency anemia in patients with NDD-CKD, even among patients who were intolerant of or had failed to respond to other oral iron supplements. Since this was a relatively short-term study, no 'hard' outcomes were examined, and it remains to be seen what the relative cost of ferric citrate vs. IV iron (the standard of care for patients who fail oral iron therapy) is in this setting."

"The decrease in serum phosphorus and FGF-23 levels is intriguing, since elevations in these two substances have been implicated as cardiovascular risk factors in patients with CKD," he added. "Long-term trials with ferric citrate as both treatment of iron deficiency and prevention of hyperphosphatemia will be welcome to assess the effect of this agent on 'hard' outcomes."

Keryx Biopharmaceuticals, Inc. sponsored the trial and employed three of the authors.

SOURCES: http://bit.ly/2iMWqXr

J Am Soc Nephrol 2017.