Safety and effectiveness of ferric citrate hydrate in serum phosphorus management of patients with chronic kidney disease: a long-term, real-world, observational, post-marketing surveillance study

Abstract

Background: Ferric citrate hydrate (FC) is an oral iron-based phosphate binder that is used to treat hyperphosphatemia in patients with chronic kidney disease (CKD). This post-marketing surveillance study was performed to investigate the long-term safety and effectiveness of FC.

Methods: This prospective, multicenter, observational post-marketing surveillance study was performed in a real-world setting in Japan. The study involved CKD patients with hyperphosphatemia receiving FC who were undergoing either hemodialysis or peritoneal dialysis or were non-dialysis-dependent. Adverse drug reactions, iron- and erythrocyte-related parameters (i.e., levels of serum ferritin, transferrin saturation, and hemoglobin), and serum levels of phosphorus, corrected calcium, and intact parathyroid hormone were monitored for up to 104 weeks.

Results: Safety was evaluated in 2723 patients. Of these patients, 20.5% discontinued FC because of adverse events, and 3.9% discontinued FC because of unsatisfactory effectiveness. Iron-related parameters gradually increased after the initiation of FC treatment but stabilized after week 36. Effectiveness was analyzed in 2367 patients. Serum phosphorus immediately decreased, and the effect persisted for 104 weeks.

Conclusion: In this 104 week surveillance study, no new safety concerns were noted. The safety profile was not obviously different from those in pre-approval clinical trials and the 52 week interim report of this surveillance study. The serum ferritin level of most patients was below the upper limit of the target range, and iron overload risk was not evident. Long-term FC treatment effectively controlled serum phosphorus.

Keywords: Chronic kidney disease; Dialysis; Ferric citrate; Hyperphosphatemia; Long-term safety; Non-dialysis-dependent.

Fig. 1

Patient flow

Fig. 2

Iron- and erythrocyte-related parameters of special interest (safety analysis set) Time-course changes in a serum ferritin, b transferrin saturation, and c hemoglobin. Data represent a median and (b, c) mean ± standard deviation. Error bars in a are from the first to third quartiles. Blue: hemodialysis group (HD), orange: peritoneal dialysis group (PD), green: non-dialysis-dependent group (ND)

Fig. 3

Effectiveness evaluation parameters (effectiveness analysis set) Time-course changes in mean a serum phosphorus, b corrected calcium (cCa), and c intact parathyroid hormone (iPTH). Data represent (a, b) mean ± standard deviation and c median. Error bars in c are from the first to third quartiles. Blue: hemodialysis group (HD), orange: peritoneal dialysis group (PD), green: non-dialysis-dependent group (ND)

Fig. 4

Nine-section charts (effectiveness analysis set) Nine-section charts for patients undergoing (a, b) hemodialysis (HD) and (c, d) peritoneal dialysis (PD) at (a, c) baseline and (b, d) week 104. Green bars designate well-managed serum phosphorus and corrected calcium (cCa)