SP657GASTROINTESTINAL SAFETY AND TOLERABILITY OF FERRIC CITRATE IN PATIENTS WITH ESRD ON DIALYSIS: A POOLED ANALYSIS

Abstract

Introduction and Aims: Gastrointestinal (GI) symptoms are common among dialysis patients treated with phosphate binders. Iron‐containing compounds given in the fasting state are also known to increase the rate of GI symptoms and have been limited by GI tolerance to a max dose of approximately 200mg/day. Ferric citrate (FC) is an approved iron‐based phosphate binder given with food to a max dose of 2520mg/day that has been shown to increase serum iron stores while reducing the usage of intravenous iron and erythropoiesis‐stimulating agents in dialysis patients. We currently present the GI safety and tolerability profile of FC in comparison with other non‐iron based phosphate binders in a population with ESRD on dialysis. Methods: Using pooled data from two multicenter, open‐label studies (one randomized, one pragmatic), we compared the GI safety and tolerability profile of ferric citrate to that of sevelamer carbonate and/or calcium acetate (active control, AC) with ESRD subjects on dialysis. The analysis included subjects participating in a randomized control study (RCT) who were initially treated with FC or AC, who then took part in a follow‐up long‐term safety extension study during which they all were treated with FC. Results: In the RCT study, 289 subjects were treated with FC and 149 with AC over 52 wks. Of these, 166 subsequently entered the pragmatic trial in which all were treated with FC over an additional 48 wks. The number of subjects with at least one GI adverse event (AE) including serious and non‐serious events was similar in the FC and AC treated groups, 46.2% vs. 47.7% respectively. Diarrhea was the most common non‐serious AE, with a higher rate in the FC than in the AC group, 20.7% vs. 14.1% respectively. Diarrhea was classified as severe in 5.9% of FC subjects and in 0.7% of AC. Constipation was reported in 7.0% of FC subjects and in 5.4% of AC. Severe constipation occurred similarly in both FC and AC groups, 2.4% and 2.0% respectively. There was less nausea or vomiting in subjects treated with FC than with AC, 12.5% vs. 14.1% and 8.8% vs. 14.8% AC respectively; their reported severity, however, was similar between the two groups. The rate of abdominal pain, dyspepsia, dysphagia, GI hemorrhage, gastro‐esophageal reflux and hematemesis was low and similar between the FC and AC treated group. Feces discoloration was reported in 13.0% of FC subjects while there was no such report with AC. Importantly, the rate of GI‐related serious AE was lower in the FC group compared to AC, 6.2% vs. 12.8% respectively. Conclusions: Consistent with data reported in the primary RCT and now expanded with further data from the pragmatic trial, serious GI adverse events were less frequent among patients treated with FC than those treated with AC. Total GI AEs, including serious and non‐serious events, were similar in the FC and AC treated groups. These data support a favorable GI safety profile of FC as a phosphate binder among dialysis‐treated patients.