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.

Effects of ferric citrate hydrate in patients with chronic kidney disease and heart failure: subgroup analysis of a long-term, real-world, post-marketing surveillance study

“…Patient characteristics, iron-and erythrocyte-related parameters and adverse drug reactions were analyzed in the safety-analysis set, and CKD-MBD-related parameters were analyzed in the effectiveness-analysis set. On the basis of data from all Japanese pre-approval clinical studies, we planned to enroll 1000 patients in the HD group, 100 in the PD group, and 500 in the ND group in the post-marketing surveillance study to evaluate longterm safety in the entire CKD population [24]. The current study used the same data set.…”

“…Patients included in the surveillance study have been described in detail in a previous report [24]. Briefly, CKD patients, including patients undergoing hemodialysis (HD group), peritoneal dialysis (PD group), or no dialysis (ND group), were registered within 14 days from the initiation of FC treatment and followed up prospectively.…”

“…The dose was adjusted by physicians according to serum phosphate concentrations or clinical status, with a maximum allowed dose of 6000 mg/day. Concomitant medications (e.g., phosphate binders and iron preparations) were allowed [24].…”

“…In this observational post-marketing surveillance study, 2811 patients with CKD were registered from 573 institutions [24]. Patients whose case report forms were not returned (n = 76) or who underwent combined dialysis (HD and PD) or did not return after the first visit or did not meet registration criteria were excluded.…”

“…Case report forms were collected from participating institutions for up to a maximum of 2 years. Data collection was terminated on April 30, 2020 [24].…”