|
1
|
Kalantar-Zadeh K, Ficociello LH, Zhou M, Anger MS. Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis. BMC Nephrol 2024; 25:197. [PMID: 38886636 PMCID: PMC11184799 DOI: 10.1186/s12882-024-03633-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 06/10/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.
Collapse
Affiliation(s)
- Kamyar Kalantar-Zadeh
- Division of Nephrology and Hypertension and Transplantation, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA
| | | | - Meijiao Zhou
- Fresenius Medical Care, Global Medical Office, Waltham, MA, USA
| | - Michael S Anger
- Fresenius Medical Care, Global Medical Office, Waltham, MA, USA.
| |
Collapse
|
|
2
|
Medaura JA, Zhou M, Ficociello LH, Anger MS, Sprague SM. Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis. Am J Nephrol 2023; 55:127-135. [PMID: 38091973 PMCID: PMC10994597 DOI: 10.1159/000535754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/03/2023] [Indexed: 04/04/2024]
Abstract
INTRODUCTION Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis. METHODS We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year. RESULTS The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p < 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p < 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p < 0.0001 vs. baseline). CONCLUSIONS Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.
Collapse
Affiliation(s)
- Juan A Medaura
- Touro Infirmary, LCMC Health, New Orleans, Louisiana, USA
| | - Meijiao Zhou
- Fresenius Medical Care, Global Medical Office, Waltham, Massachusetts, USA,
| | - Linda H Ficociello
- Fresenius Medical Care, Global Medical Office, Waltham, Massachusetts, USA
| | - Michael S Anger
- Fresenius Medical Care, Global Medical Office, Waltham, Massachusetts, USA
| | - Stuart M Sprague
- Division of Nephrology and Hypertension, NorthShore University Health System-University of Chicago Pritzker School of Medicine, Evanston, Illinois, USA
| |
Collapse
|
|
3
|
Rhee CM, Zhou M, Woznick R, Mullon C, Anger MS, Ficociello LH. A real-world analysis of the influence of age on maintenance hemodialysis patients: managing serum phosphorus with sucroferric oxyhydroxide as part of routine clinical care. Int Urol Nephrol 2023; 55:377-387. [PMID: 35953565 PMCID: PMC9859895 DOI: 10.1007/s11255-022-03327-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 07/25/2022] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Despite the growing number of elderly hemodialysis patients, the influence of age on nutritional parameters, serum phosphorus (sP), and use of phosphate-binder (PB) medications has not been well characterized. We aimed to describe age-related differences in patient characteristics in a large, real-world cohort of maintenance hemodialysis patients, and to examine the impact of age on sP management with sucroferric oxyhydroxide (SO). METHODS We retrospectively analyzed de-identified data from 2017 adult, in-center hemodialysis patients who switched from another PB to SO monotherapy as part of routine clinical care. Changes in baseline PB pill burden, sP levels, and nutritional and dialytic clearance parameters were assessed across varying age groups through 6 months. RESULTS At baseline, older patients had lower mean sP, serum albumin, and pre-dialysis weights compared with younger patients. Prescription of SO was associated with a 62% increase in the proportion of patients achieving sP ≤ 5.5 mg/dl and a 42% reduction in daily pill burden. The proportion of patients achieving sP ≤ 5.5 mg/dl after transitioning to SO increased by 113, 96, 68, 77, 61, 37 and 40% among those aged 19-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years, respectively. CONCLUSIONS Older patients had worse nutritional parameters, lower pill burden, and lower sP at baseline versus younger counterparts. Prescription of SO was associated with improved sP control and reduced pill burden across all ages.
Collapse
Affiliation(s)
- Connie M. Rhee
- grid.266093.80000 0001 0668 7243Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Orange, CA USA
| | - Meijiao Zhou
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | | | - Claudy Mullon
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | - Michael S. Anger
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | - Linda H. Ficociello
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| |
Collapse
|
|
4
|
Bajo MA, Ríos-Moreno F, Arenas MD, Devesa-Such RJ, Molina-Higueras MJ, Delgado M, Molina P, García-Fernández N, Martin-Malo A, Peiró-Jordán R, Cannata-Andia J, Martín-De Francisco ÁL. Safety and effectiveness of sucroferric oxyhydroxide in Spanish patients on dialysis: sub-analysis of the VERIFIE study. Nefrologia 2022; 42:594-606. [PMID: 36739246 DOI: 10.1016/j.nefroe.2021.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 04/12/2021] [Accepted: 04/18/2021] [Indexed: 06/18/2023] Open
Abstract
BACKGROUND AND AIMS In this study, we show the results of the subset of Spanish patients of the VERIFIE study, the first post-marketing study assessing the long-term safety and effectiveness of sucroferric oxyhydroxide (SFOH) in patients with hyperphosphatemia undergoing dialysis during clinical practice. PATIENTS AND METHODS Patients undergoing hemodialysis and peritoneal dialysis with indication of SFOH treatment were included. Follow-up duration was 12-36 months after SFOH initiation. Primary safety variables were the incidence of adverse drug reactions (ADRs), medical events of special interest (MESIs), and variations in iron-related parameters. SFOH effectiveness was evaluated by the change in serum phosphorus levels. RESULTS A total of 286 patients were recruited and data from 282 were analyzed. Among those 282 patients, 161 (57.1%) withdrew the study prematurely and 52.5% received concomitant treatment with other phosphate binders. ADRs were observed in 35.1% of patients, the most common of which were gastrointestinal disorders (77.1%) and mild/moderate in severity (83.7%). MESIs were reported in 14.2% of patients, and 93.7% were mild/moderate. An increase in ferritin (386.66ng/mL vs 447.55ng/mL; p=0.0013) and transferrin saturation (28.07% vs 30.34%; p=0.043) was observed from baseline to the last visit (p=0.0013). Serum phosphorus levels progressively decreased from 5.69mg/dL at baseline to 4.84mg/dL at the last visit (p<0.0001), increasing by 32.2% the proportion of patients who achieved serum phosphorus levels ≤5.5mg/dL, with a mean daily SFOH dose of 1.98 pills/day. CONCLUSIONS SFOH showed a favorable effectiveness profile, a similar safety profile to that observed in the international study with most adverse events of mild/moderate severity, and a low daily pill burden in Spanish patients in dialysis.
Collapse
Affiliation(s)
- María Auxiliadora Bajo
- Hospital Universitario La Paz, Madrid, Instituto de Investigación Sanitaria del HULP (IdiPAZ), Madrid, Spain; Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) del Instituto de Salud Carlos III, Universidad Autónoma Madrid, Madrid, Spain.
| | | | - Maria Dolores Arenas
- Hospital Vithas Perpetuo Socorro, Alicante, Spain; Hospital del Mar, Barcelona, Spain
| | - Ramón Jesús Devesa-Such
- FMC Valencia, Valencia Spain; Servicio de Nefrología, Hospital Universitari y Politècnic La Fe, Valencia, Spain
| | | | | | - Pablo Molina
- Hospital Doctor Peset, Valencia, FISABIO, Valencia, Spain; Departamento de Medicina de la Universitat de València, Valencia, Spain
| | - Nuria García-Fernández
- Departamento de Nefrología, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Alejandro Martin-Malo
- Hospital Universitario Reina Sofía, IMIBIC, REDinREN, Córdoba, Spain; Universidad de Córdoba, Córdoba, Spain
| | | | | | | |
Collapse
|
|
5
|
Bajo MA, Ríos Moreno F, Arenas MD, Devesa Such RJ, Molina Higueras MJ, Delgado M, Molina P, García Fernández N, Martín Malo A, Peiró-Jordán R, Cannata-Andia J, Martín de Francisco ÁL. Seguridad y efectividad del oxihidróxido sucroférrico en pacientes españoles en diálisis: subanálisis del estudio VERIFIE. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
|
|
6
|
Kendrick JB, Zhou M, Ficociello LH, Parameswaran V, Mullon C, Anger MS, Coyne DW. Serum Phosphorus and Pill Burden Among Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide: One-Year Follow-Up on a Contemporary Cohort. Int J Nephrol Renovasc Dis 2022; 15:139-149. [PMID: 35431567 PMCID: PMC9012313 DOI: 10.2147/ijnrd.s353213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 03/19/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018–2019) cohort. Patients and Methods Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1–Q4) and analyzed using linear mixed-effects regression and Cochran’s Q test. These results were contrasted with findings from a historical (2014–2015) cohort (N = 530). Results The proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively; P < 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (P < 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort. Conclusion Despite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.
Collapse
Affiliation(s)
| | - Meijiao Zhou
- Fresenius Medical Care Global Medical Office, Waltham, MA, USA
| | | | | | - Claudy Mullon
- Fresenius Medical Care Global Medical Office, Waltham, MA, USA
| | - Michael S Anger
- Fresenius Medical Care Global Medical Office, Waltham, MA, USA
- Unversity of Colorado School of Medicine, Denver, CO, USA
| | - Daniel W Coyne
- Washington University School of Medicine, St. Louis, MO, USA
- Correspondence: Daniel W Coyne, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA, Tel +1 314-362-7603, Fax +1 314-747-5213, Email
| |
Collapse
|
|
7
|
Coyne DW, Sprague SM, Vervloet M, Ramos R, Kalantar-Zadeh K. Sucroferric oxyhydroxide for hyperphosphatemia: a review of real-world evidence. J Nephrol 2022; 35:875-888. [PMID: 35138627 PMCID: PMC8995279 DOI: 10.1007/s40620-021-01241-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 12/26/2021] [Indexed: 11/28/2022]
Abstract
Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in > 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice.
Collapse
Affiliation(s)
- Daniel W Coyne
- Division of Nephrology, Washington University School of Medicine, 660 S. Euclid Ave., CB 8129, St. Louis, MO, 63110, USA.
| | - Stuart M Sprague
- Division of Nephrology and Hypertension, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, IL, USA
| | - Marc Vervloet
- Department of Nephrology and Amsterdam Cardiovascular Sciences (ACS), Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Rosa Ramos
- NephroCare Spain, Nephrology, Madrid, Spain
| | | |
Collapse
|
|
8
|
Sprague SM, Ketteler M. A safety evaluation of sucroferric oxyhydroxide for the treatment of hyperphosphatemia. Expert Opin Drug Saf 2021; 20:1463-1472. [PMID: 34511018 DOI: 10.1080/14740338.2021.1978973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Hyperphosphatemia is a common complication as chronic kidney disease (CKD) progresses and most patients undergoing dialysis are prescribed oral phosphate binder therapy to control serum phosphate concentrations. Sucroferric oxyhydroxide is an iron-based phosphate binder approved for the treatment of hyperphosphatemia in CKD patients on dialysis. AREAS COVERED This article reviews key safety and effectiveness data for sucroferric oxyhydroxide from both prospective clinical trials and real-world observational studies. EXPERT OPINION Sucroferric oxyhydroxide potently binds dietary phosphate in the gastrointestinal (GI) tract, resulting in effective reduction of serum phosphate concentrations with a relatively low daily pill burden. Data from clinical trials and real-world observational studies show sucroferric oxyhydroxide has a favorable safety and tolerability profile. The most frequent side effects observed with sucroferric oxyhydroxide are GI-related, mainly discolored (black) stools and mild or moderate transient diarrhea, both of which are manageable. There is minimal systemic iron absorption from sucroferric oxyhydroxide, and therefore the drug is associated with a low risk of iron accumulation. Sucroferric oxyhydroxide also displays low potential for drug-drug interactions with other commonly prescribed oral medications. Overall, sucroferric oxyhydroxide offers an effective and well-tolerated treatment option for the management of hyperphosphatemia.
Collapse
Affiliation(s)
- Stuart M Sprague
- NorthShore University Health System, University of Chicago, Pritzker School of Medicine, Evanston, Illinois, USA
| | - Markus Ketteler
- Department of General Internal Medicine and Nephrology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| |
Collapse
|
|
9
|
Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients. Int Urol Nephrol 2021; 54:861-872. [PMID: 34264473 DOI: 10.1007/s11255-021-02952-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/06/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. METHODS Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. RESULTS We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300 ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. CONCLUSION The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.
Collapse
|
|
10
|
Navarro-González JF, Arenas MD, Henríquez-Palop F, Lloret MJ, Molina P, Ríos Moreno F, Macia-Lagier MA, Espinel L, Sánchez E, Lago M, Crespo A, Bover J. Real-world management of hyperphosphataemia with sucroferric oxyhydroxide: the VELREAL multicentre study. Clin Kidney J 2021; 14:681-687. [PMID: 33626111 PMCID: PMC7886585 DOI: 10.1093/ckj/sfaa226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The efficacy and safety of sucroferric oxyhydroxide (SO) have been reported in clinical trials. However, real-life data are scarce. This study presents data on the use, efficacy and safety of SO in real clinical practice. METHODS We performed a retrospective multicentre study, without any influence on the prescription decisions, that included 220 patients from 11 Spanish centres. Demographic, treatment, analytical and nutritional parameters and adherence, side effects and dropout rates were collected during 6 months. RESULTS SO was initiated due to inadequate control of serum phosphate (P) in 70% of participants and in 24.5% to reduce the number of tablets. Monotherapy with SO increased from 44% to 74.1%, with a reduction in the average daily number of sachets/tablets from six to two. Serum P decreased by 20% (4.6 ± 1.2 versus 5.8 ± 1.3 mg/dL; P < 0.001), with a significant reduction in intact parathyroid hormone levels (P < 0.01). The percentage of patients with adequate serum P control at threshold levels of 5 and 4.5 mg/dL increased by 45.4% and 35.9%, respectively. Serum ferritin was not modified, while the transferrin saturation index increased significantly (P = 0.04). Serum albumin and normalized protein catabolic rate, when normalized by serum P, increased, averaging 37% and 39%, respectively (P < 0.001). Adherent patients increased from 28.2% to 52.7%. Adverse effects were reported by 14.1% of participants, with abandonment of treatment in 9.5%. CONCLUSIONS The use of SO in real-life results in better control of serum P, a reduction in the number of tablets and an improvement in therapeutic adherence. In addition, it may be beneficial with regards to secondary hyperparathyroidism and nutritional status.
Collapse
Affiliation(s)
- Juan F Navarro-González
- Servicio de Nefrología y Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
- Red de Investigación Renal (REDINREN – RD16/0009), Instituto de Salud Carlos III, Madrid, Spain
- ERA-EDTA Working Group on CKD-MBD, Parma, Italy
| | | | | | | | - Pablo Molina
- Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, Spain
| | | | | | - Laura Espinel
- Servicio de Nefrología, Hospital Universitario de Getafe, Madrid, Spain
| | - Emilio Sánchez
- Servicio de Nefrología, Hospital Universitario de Cabueñes, Gijón, Spain
| | - Mar Lago
- Servicio de Nefrología, Complejo Hospitalario Universitario Insular, Las Palmas de Gran Canaria, Spain
| | - Antonio Crespo
- Servicio de Nefrología, Hospital Marina Baixa, Alicante, Spain
| | - Jordi Bover
- Red de Investigación Renal (REDINREN – RD16/0009), Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Nefrología, Fundació Puigvert, Barcelona, Spain
| |
Collapse
|
|
11
|
Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins. Toxins (Basel) 2021; 13:toxins13020091. [PMID: 33530404 PMCID: PMC7911578 DOI: 10.3390/toxins13020091] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) is a highly prevalent condition and is associated with a high comorbidity burden, polymedication, and a high mortality rate. A number of conventional and nonconventional risk factors for comorbidities and mortality in CKD have been identified. Among the nonconventional risk factors, uremic toxins are valuable therapeutic targets. The fact that some uremic toxins are gut-derived suggests that intestinal chelators might have a therapeutic effect. The phosphate binders used to prevent hyperphosphatemia in hemodialysis patients act by complexing inorganic phosphate in the gastrointestinal tract but might conceivably have a nonspecific action on gut-derived uremic toxins. Since phosphorous is a major nutrient for the survival and reproduction of bacteria, changes in its intestinal concentration may impact the gut microbiota’s activity and composition. Furthermore, AST-120 is an orally administered activated charcoal adsorbent that is widely used in Asian countries to specifically decrease uremic toxin levels. In this narrative review, we examine the latest data on the use of oral nonspecific and specific intestinal chelators to reduce levels of gut-derived uremic toxins.
Collapse
|
|
12
|
Sanchez-Alvarez JE, Astudillo Cortés E, Seras Mozas M, García Castro R, Hidalgo Ordoñez CM, Andrade López AC, Ulloa Clavijo C, Gallardo Pérez A, Rodríguez Suarez C. Efficacy and safety of sucroferric oxyhydroxide in the treatment of hyperphosphataemia in chronic kidney disease in Asturias. FOSFASTUR study. Nefrologia 2021; 41:45-52. [PMID: 36165361 DOI: 10.1016/j.nefroe.2021.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 06/21/2020] [Indexed: 06/16/2023] Open
Abstract
UNLABELLED Alterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is Sucroferric Oxyhydroxide (SFO). OBJECTIVE To analyse the efficacy and safety of OSF in three cohorts of patients, one with advanced chronic kidney disease not on dialysis (CKD-NoD), another on peritoneal dialysis (PD) and the last on haemodialysis (HD), followed for six months. METHODS A prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. RESULTS Eighty-five patients were included in the study (62 ± 12 years, 64% male, 34% diabetic), 25 with CKD-NoD, 25 on PD and lastly, 35 on HD. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964 ± 323 mg/day. Overall, serum phosphate levels saw a significant reduction at three months of treatment (19.6%, P < 0.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, or the transferrin and haemoglobin saturation indices, although there was a tendency for the last two to increase. Twelve patients (14%) withdrew from follow-up, ten due to gastrointestinal adverse effects (primarily diarrhoea) and two were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1147 ± 371 mg/day. CONCLUSIONS SFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the three groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1000 mg/day. Diarrhoea was the most common side effect, although it generally was not significant.
Collapse
Affiliation(s)
| | - Elena Astudillo Cortés
- Servicio de Otorrinolaringologia, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Miguel Seras Mozas
- Servicio de Nefrología, Hospital Universitario San Agustin, Avilés, Asturias, Spain
| | - Raúl García Castro
- Servicio de Nefrología, Fundación Hospital de Jove, Gijón, Asturias Spain
| | | | | | - Catalina Ulloa Clavijo
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Anna Gallardo Pérez
- Servicio de Nefrología, Hospital Universitario San Agustin, Avilés, Asturias, Spain
| | | |
Collapse
|
|
13
|
Herrero JA, Salomone M, Ramirez de Arellano A, Schaufler T, Walpen S. Estimating hospital inpatient cost-savings with sucroferric oxyhydroxide in patients on chronic hemodialysis in five European countries: a cost analysis. J Med Econ 2021; 24:1240-1247. [PMID: 34761724 DOI: 10.1080/13696998.2021.1996957] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
AIMS Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. MATERIALS AND METHODS All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. RESULTS Annual inpatient cost-savings per patient in the mSO group versus the dSO group were €1,201, €2,097, €2,059, €1,512, and €3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were €327, €1,585, €1,022, €1,100, and €2,204, respectively. LIMITATIONS Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. CONCLUSION SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.
Collapse
Affiliation(s)
| | - Mario Salomone
- Division Nephrology and Dialysis, Maggiore Hospital, Chieri (Turin), Italy
| | | | | | | |
Collapse
|
|
14
|
Ramos R, Chazot C, Ferreira A, Di Benedetto A, Gurevich K, Feuersenger A, Wolf M, Arens HJ, Walpen S, Stuard S. The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis. BMC Nephrol 2020; 21:530. [PMID: 33287733 PMCID: PMC7720479 DOI: 10.1186/s12882-020-02188-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 11/26/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients. METHODS De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH). RESULTS 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day). CONCLUSION In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.
Collapse
Affiliation(s)
- Rosa Ramos
- NephroCare Spain, Nephrology, Madrid, Spain.
| | | | - Anibal Ferreira
- NephroCare Vila Franca de Xira, Nephrology, Vila Franca de Xira, Portugal
| | | | | | | | - Melanie Wolf
- Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany
| | | | - Sebastian Walpen
- Vifor Fresenius Medical Care Renal Pharma, Nephrology, Glattbrugg, Switzerland
| | - Stefano Stuard
- Fresenius Medical Care, Clinical & Therapeutical Governance, Bad Homburg, Germany
| |
Collapse
|
|
15
|
Sanchez-Alvarez JE, Astudillo Cortes E, Seras Mozas M, García Castro R, Hidalgo Ordoñez CM, Andrade López AC, Ulloa Clavijo C, Gallardo Pérez A, Rodríguez Suárez C. Efficacy and safety of sucroferric oxyhydroxide in the treatment of hyperphosphataemia in chronic kidney disease. FOSFASTUR study. Nefrologia 2020; 41:45-52. [PMID: 33239181 DOI: 10.1016/j.nefro.2020.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/01/2020] [Accepted: 06/21/2020] [Indexed: 10/22/2022] Open
Abstract
INTRODUCTION Alterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SFO). OBJECTIVE To analyse the efficacy and safety of SFO in 3 cohorts of patients, one with advanced CKD not on dialysis, another on peritoneal dialysis and the last on haemodialysis, followed for 6 months. METHODS A prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed. RESULTS Eighty-five patients were included in the study (62±12 years, 64% male, 34% diabetic), 25 with advanced CKD not on dialysis, 25 on peritoneal dialysis and lastly, 35 on haemodialysis. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964±323mg/day. Overall, serum phosphate levels saw a significant reduction at 3 months of treatment (19.6%; P<.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, transferrin saturation index or haemoglobin, although there was a tendency for the last 2 to increase. Twelve patients (14%) withdrew from follow-up, 10 due to gastrointestinal adverse effects (primarily diarrhoea) and 2 were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1,147±371mg/day. CONCLUSIONS SFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the 3 groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1,000mg/day. Diarrhoea was the most common side effect, although it generally was not significant.
Collapse
Affiliation(s)
| | - Elena Astudillo Cortes
- Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| | - Miguel Seras Mozas
- Servicio de Nefrología, Hospital Universitario San Agustín, Avilés, Asturias, España
| | - Raúl García Castro
- Servicio de Nefrología, Fundación Hospital de Jove, Gijón, Asturias, España
| | | | | | - Catalina Ulloa Clavijo
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| | - Anna Gallardo Pérez
- Servicio de Nefrología, Hospital Universitario San Agustín, Avilés, Asturias, España
| | - Carmen Rodríguez Suárez
- Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Asturias, España
| |
Collapse
|
|
16
|
Arenas Jiménez MD, Navarro González JF. How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide. Nefrologia 2020; 40:640-646. [PMID: 32564940 DOI: 10.1016/j.nefro.2020.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 02/03/2020] [Accepted: 04/03/2020] [Indexed: 11/28/2022] Open
Abstract
INTRODUCTION The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it. METHODS Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed. RESULTS The percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users' group (62.1-92.9%, p<0.001), but not in the control group (83-83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2-2.3 comp, p<0.001), but not in the control group (5.6-5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8-84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7-78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason. CONCLUSIONS SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.
Collapse
Affiliation(s)
- M Dolores Arenas Jiménez
- Nephrology Department, Hospital Vithas Perpetuo Internacional, Alicante, Spain; Nephrolgy Department, Hospital del Mar, Barcelona, Spain.
| | | |
Collapse
|
|
17
|
Molony DA, Parameswaran V, Ficociello LH, Mullon C, Kossmann RJ. Sucroferric Oxyhydroxide as Part of Combination Phosphate Binder Therapy among Hemodialysis Patients. KIDNEY360 2020; 1:263-272. [PMID: 35372921 PMCID: PMC8809266 DOI: 10.34067/kid.0000332019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/05/2020] [Indexed: 06/14/2023]
Abstract
BACKGROUND Combination therapy with multiple phosphate binders is prescribed to reduce elevated serum phosphorus (sP) concentrations among patients on maintenance hemodialysis. Sucroferric oxyhydroxide (SO), an iron-based phosphate binder, has demonstrated efficacy at reducing sP while also being associated with a low pill burden. Whereas the effects of SO monotherapy have been well characterized in clinical trials and observational cohorts, little is known about the effects of SO-containing combination therapy. METHODS Patients on hemodialysis (N=234) at Fresenius Kidney Care (FKC) who received ≥120 days of uninterrupted phosphate binder combination therapy with SO were included in this retrospective study. Patient data were censored after SO discontinuation, end of care at FKC, or completion of 12 months of follow-up. Quarterly (Q) changes in phosphate binder pill burden, mean sP, and proportion of patients achieving National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI)-recommended sP levels (≤5.5 mg/dl) were compared between baseline (-Q1) and follow-up (Q1-Q4). RESULTS Phosphate binder combination therapy with SO was associated with significant increase in the proportion of patients with sP ≤5.5 mg/dl (from 19% at baseline to up to 40% at follow-up; P<0.001) and reduction in sP at all postbaseline time points (from 6.7 mg/dl to 6.2-6.3 mg/dl; P<0.001). Patients on calcium acetate (N=54) and sevelamer (N=94) who added SO therapy at follow-up resulted in a ≥250% increase in patients achieving sP ≤5.5 mg/dl (all P<0.001). Whereas mean phosphate binder pill burden increased with initiation of phosphate binder combination therapy with SO (15.8 pills/d at Q1 versus 12.3 pills/d at -Q1), continued use of SO was associated with down-titration of non-SO phosphate binders such that, by Q4, mean total PB pill burden reduced to 12.3 pills/d. CONCLUSIONS For patients on hemodialysis with uncontrolled hyperphosphatemia, combination therapy with SO may allow for sustained improvements in sP control without adversely affecting phosphate binder pill burden.
Collapse
Affiliation(s)
- Donald A. Molony
- Division of Renal Diseases and Hypertension, Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School University of Texas, Houston, Texas; and
| | | | | | - Claudy Mullon
- Fresenius Medical Care Renal Therapies Group, Waltham, Massachusetts
| | | |
Collapse
|
|
18
|
Abstract
Rationale & Objective High pill burden associates with reduced phosphate-binder adherence among dialysis patients, contributing to elevated serum phosphorus levels. We compared the real-world effectiveness of sucroferric oxyhydroxide (SO) versus other phosphate binders in hemodialysis patients over 2 years. Study Design Retrospective cohort study. Setting & Participants Adult in-center hemodialysis patients prescribed 2 years of uninterrupted SO therapy (maintenance SO; n = 222) compared with patients who discontinued SO therapy (discontinued SO; n = 596) within 90 days of first prescription and switched to other phosphate binder(s) for 2 years. Exposures Phosphate binders. Outcomes Achievement of serum phosphorus levels ≤ 5.5 mg/dL, pill burden, and hospitalizations. Analytical Approach Comparisons were made quarterly (Q1-Q8) between maintenance SO and discontinued SO using Poisson and mixed-effects linear regression. Results Patients achieving serum phosphorus levels ≤ 5.5 mg/dL increased from baseline in maintenance SO (46 [20.7%] to a maximum of 104 [46.8%; P < 0.001]) and discontinued SO (96 [16.1%] to a maximum of 201 [33.7%]; P < 0.001). 100 (45%) maintenance SO patients achieved target serum phosphorus levels at Q8 with 3.1 fewer pills per day from baseline (7.5 to 4.4 pills per day; P < 0.001), and 190 (31.9%) discontinued SO patients achieved serum phosphorus levels ≤ 5.5 mg/dL at Q8 with pill burden unchanged (9.1 to 9.3 pills per day; P = 0.3). Among all patients during 2 years, mean serum phosphorus levels decreased by -0.66 mg/dL and -0.45 mg/dL (maintenance SO vs discontinued SO; P = 0.014), and mean pill burden decreased in maintenance SO (8.5 to 5.1 pills per day; P < 0.001), but not in discontinued SO (11.6 to 10.9 pills per day; P = 0.2). The serum phosphorus level decrease with SO was confirmed in a sensitivity analysis including patients with SO therapy for 2 or fewer years. Compared with discontinued SO, maintenance SO patients had 35.6 fewer hospitalizations per 100 patient-years (incidence rate ratio, 0.75 [95% CI, 0.58-0.96]). Limitations No data for treatment indication, tolerance, or adherence. Conclusions Patients maintained on SO therapy were more likely to achieve target serum phosphorus levels, use 50% fewer phosphate-binder pills per day, and have fewer hospital admissions than patients switched to treatment with other binders.
Collapse
|
|
19
|
Floege J. Phosphate binders in chronic kidney disease: an updated narrative review of recent data. J Nephrol 2019; 33:497-508. [PMID: 31865608 DOI: 10.1007/s40620-019-00689-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 12/17/2019] [Indexed: 12/11/2022]
Abstract
Chronic kidney disease (CKD) is frequently accompanied by hyperphosphatemia. High serum phosphate usually requires dietary measures, adequate dialysis prescription and/or phosphate binders. For this narrative review a PubMed searched was undertaken to identify new publications on phosphate binders that had been published between January 2015 and July 2019. The present review summarizes this most recent information on dietary measures and their problems in treating hyperphosphatemia in CKD patients, overall effects of phosphate binders on cardiovascular mortality and morbidity, adherence to phosphate binder therapy as well as new data on specific aspects of the various phosphate binders on the market: calcium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), magnesium-containing phosphate binders, lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, and new compounds in development, in particular drugs targeting intestinal phosphate transporters.
Collapse
Affiliation(s)
- Jürgen Floege
- Department of Nephrology and Clinical Immunology, University Hospital, Rheinisch Westfälische Technische Hochschule (RWTH), Pauwelsstr. 30, 52057, Aachen, Germany.
| |
Collapse
|
|
20
|
Kalantar-Zadeh K, Ficociello LH, Parameswaran V, Athienites NV, Mullon C, Kossmann RJ, Coyne DW. Changes in serum albumin and other nutritional markers when using sucroferric oxyhydroxide as phosphate binder among hemodialysis patients: a historical cohort study. BMC Nephrol 2019; 20:396. [PMID: 31664928 PMCID: PMC6820926 DOI: 10.1186/s12882-019-1582-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/03/2019] [Indexed: 12/16/2022] Open
Abstract
Background Elevated serum phosphorus concentrations are common among maintenance hemodialysis patients. Protein is a major source of dietary phosphate, but restriction of protein intake can result in hypoalbuminemia and protein-energy wasting. We hypothesized that sucroferric oxyhydroxide (SO), a potent phosphate binder with a low pill burden, may reduce serum phosphorus levels in hemodialysis patients with hypoalbuminemia without adversely impacting albumin levels or dietary intake of protein. Methods We retrospectively examined de-identified data from 79 adult, in-center hemodialysis patients with baseline hypoalbuminemia (≤ 3.5 g/dL) switched to SO as part of routine clinical care for at least 1 year. Temporal changes (3-month intervals from baseline through Q4) in phosphate binder pill burden, serum phosphorous levels, nutritional markers, and equilibrated Kt/V were analyzed. Data from a matched reference group of non-hypoalbuminemic patients (N = 79) switched to SO were also examined. Results SO therapy was associated with a mean reduction of 45.7 and 45.1% in daily phosphate binder pill burden, and a mean reduction of 0.4 mg/dL and 0.51 mg/dL in serum phosphorus levels for the hypoalbuminemic and non-hypoalbuminemic patients, respectively. Hypoalbuminemic patients demonstrated significant increases in mean serum albumin levels from 3.50 mg/dL at baseline to 3.69, 3.74, 3.70, and 3.69 mg/dL during Q1 through Q4, respectively (P < 0.0001), whereas serum albumin levels remained unchanged in the non-hypoalbuminemic group. Conclusions Both hypoalbuminemic and non-hypoalbuminemic patients switching to SO exhibited significant reductions in serum phosphorus concentrations and daily phosphate binder pill burden. Among hypoalbuminemic patients, the initiation of SO therapy was also associated with increases in serum albumin, suggesting therapy may have allowed patients to increase their dietary intake of protein.
Collapse
Affiliation(s)
| | | | | | | | - Claudy Mullon
- Fresenius Medical Care Renal Therapies Group, Waltham, MA, USA
| | | | - Daniel W Coyne
- Washington University School of Medicine, 660 S. Euclid Ave., CB 8129, St. Louis, MO, 63110, USA.
| |
Collapse
|
|
21
|
Kendrick J, Parameswaran V, Ficociello LH, Ofsthun NJ, Davis S, Mullon C, Kossmann RJ, Kalantar-Zadeh K. One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis. J Ren Nutr 2019; 29:428-437. [PMID: 30679076 PMCID: PMC6642852 DOI: 10.1053/j.jrn.2018.11.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 11/11/2018] [Accepted: 11/20/2018] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN Historical cohort analyses of de-identified electronic medical records. SUBJECTS In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and mean number of PB pills/day. RESULTS Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P < .0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P < .0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women). CONCLUSION Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.
Collapse
Affiliation(s)
- Jessica Kendrick
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Medicine, Denver Health Medical Center, Denver, Colorado
| | | | | | - Norma J Ofsthun
- Fresenius Medical Care North America, Waltham, Massachusetts
| | - Shannon Davis
- Fresenius Medical Care North America, Waltham, Massachusetts
| | - Claudy Mullon
- Fresenius Medical Care Renal Therapies Group, Waltham, Massachusetts
| | - Robert J Kossmann
- Fresenius Medical Care Renal Therapies Group, Waltham, Massachusetts
| | | |
Collapse
|
|
22
|
Gray K, Ficociello LH, Hunt AE, Mullon C, Brunelli SM. Phosphate binder pill burden, adherence, and serum phosphorus control among hemodialysis patients converting to sucroferric oxyhydroxide. Int J Nephrol Renovasc Dis 2019; 12:1-8. [PMID: 30774412 PMCID: PMC6348967 DOI: 10.2147/ijnrd.s182747] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Phosphate binders are widely used to achieve serum phosphorus control in patients with end-stage renal disease. However, the large pill burden associated with these medications may decrease adherence to therapy. In clinical trials, sucroferric oxyhydroxide (SO) demonstrated equivalent control of serum phosphorus to sevelamer, with a lower daily pill burden. We examined changes in phosphate binder pill burden, medication possession ratio (MPR), and phosphorus control among in-center hemodialysis (ICHD) patients converting to SO from another phosphate binder as part of routine care. Materials and methods Patients included in this retrospective analysis (N=490) were ≥18 years old, received ICHD at a large dialysis organization (LDO), and were enrolled in the LDO’s pharmacy service. Patients converting to SO were those who had supply of another phosphate binder, received a first prescription fill for SO, and subsequently did not refill the non-SO phosphate binder. Patients were followed over the 6 months before and 6 months following the first SO fill and were censored from the analysis upon modality change, loss to follow-up, discontinuation of SO, or fill of a prescription for another phosphate binder after SO initiation (number censored=361). Outcome measures assessed were total phosphate binder pill burden and MPR, serum phosphorus, and percentage of patients with serum phosphorus ≤5.5 mg/dL. Results Among patients converting to SO, mean phosphate binder pill burden was 10.8 pills/day during baseline; this decreased to 5.5 pills/day during follow-up (P<0.001). The percentage of patients with serum phosphorus ≤5.5 mg/dL increased from 22.0% to 30.0% (P<0.001). Among patients not using the LDO pharmacy’s automated refill management service (N=30), mean phosphate binder MPR increased from 0.68 during baseline to 0.80 during follow-up (P=0.01). Conclusion In a cohort of ICHD patients, conversion to SO was associated with a reduction in pill burden, better adherence, and improvements in phosphorus control.
Collapse
Affiliation(s)
| | - Linda H Ficociello
- Medical Department, Fresenius Medical Care Renal Therapies Group, Waltham, MA, USA
| | | | - Claudy Mullon
- Medical Department, Fresenius Medical Care Renal Therapies Group, Waltham, MA, USA
| | | |
Collapse
|
|
23
|
Chazot C, Fadel B, Kareche M, Puyoo O, Jean G. [Short-term effects with sucroferric oxyhydroxide in hemodialysis patients: Experience in NephroCare France]. Nephrol Ther 2019; 15:29-34. [PMID: 30639044 DOI: 10.1016/j.nephro.2018.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 07/31/2018] [Accepted: 08/04/2018] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Despite a better management of hyperphosphatemia in haemodialysis patients observed during the past years, most of them remain insufficiently treated and exposed to bone and cardiovascular complications that are associated with this biological abnormality. The availability of calcium-free phosphate binders among therapeutical options is confirmed to significantly reduce serum phosphate levels without the risk of excess exposure to calcium. Currently sucroferric oxyhydroxyde (SO) is the only iron-based phosphate binder available in France. METHODS A cohort of patients prescribed OHS has been extracted from the EUCLID 5 database between June 2016 and December 2017. The effects on bone mineral metabolism and ferritin have been retrospectively studied. RESULTS Two hundred and sixty-two patients with OHS prescription have been identified. The OHS treatment duration median was 4.3 months (1.84-10.99). The average midweek phosphatemia decreased significantly after OHS prescription (from 1.99 to 1.83 mmol/L ; P<0.0001) with a significant increase of the proportion of patients (12.1 to 25.7% ; P<0.0001) reaching the phosphate target of 1.5 mmol/L, without significant change in calcemia and PTH. Ferritinemia significantly increased from 362 to 427 μg/L in 3 months (P=0.0049). OHS therapy has been stopped and replaced in 18% of the cases. DISCUSSION Among the NephroCare cohort, OHS therapy was efficient to decrease phosphatemia and to increase significantly the proportion of patients in target. There were no short term changes in calcemia and PTH. The slight increase in ferritin confirms the findings of the phase III study and its extension. The effects on the pills count and the OHS side-effects are analyzed from literature. The risk of iron overload and the impact on the anemia management including EPO sparing are currently under study. CONCLUSION OHS therapy appears to be a new efficient alternative to non-calcium phosphate binders. A better knowledge of its side effects will help the patients and the physician to optimize the phosphate balance management. The slight increase in ferritin can be considered as an epiphenomenon because of the important iron needs and frequent check of this parameter in the anemia management.
Collapse
Affiliation(s)
- Charles Chazot
- NephroCare France, 47, avenue des Pépinières, 94260 Fresnes, France.
| | | | | | | | - Guillaume Jean
- NephroCare Tassin-Charcot, 69110 Sainte-Foy-Lès-Lyon, France
| |
Collapse
|
|
24
|
Stavroulopoulos A, Aresti V, Papadopoulos C, Nennes P, Metaxaki P, Galinas A. Bicarbonate levels in hemodialysis patients switching from lanthanum carbonate to sucroferric oxyhydroxide. World J Nephrol 2018; 7:123-128. [PMID: 30324087 PMCID: PMC6181871 DOI: 10.5527/wjn.v7.i6.123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 08/02/2018] [Accepted: 08/30/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To examine possible alterations in acid-base parameters in patients switching from lanthanum carbonate (LanC) to sucroferric oxyhydroxide (SFOH).
METHODS Fifteen stable hemodialysis patients were switched from LanC to SFOH. Only nine continued on SFOH, three returned to LanC and the other three switched to sevelamer carbonate. The later six patients served as a control group to the SFOH group of nine patients. Blood was sampled on the 3-d and the last 2-d interval of the week prior to switching and six weeks after. Bicarbonate levels (HCO3-), pH, pO2, pCO2 were measured, and the mean of the two measurements (3-d and 2-d interval) was calculated.
RESULTS Comparing pre-switching to post-switching measurements in the SFOH group, no statistically significant differences were found in any of the parameters studied. The mean pre-switching HCO3- was 22.41 ± 1.66 mmol/L and the mean post-switching was 22.62 ± 2.25 mmol/L (P = 0.889). Respectively, the mean pH= 7.38 ± 0.03 vs 7.39 ± 0.03 (P = 0.635), mean pCO2= 38.41 ± 3.29 vs 38.37 ± 3.62 mmHg (P = 0.767), and Phosphate = 1.57 ± 0.27 vs 1.36 ± 0.38mmol/L (P = 0.214). There were not any significant differences when we performed the same analyses in the control group or between the SFOH group and control group. No correlations were found, either between pre-switching LanC daily dose or between post-switching daily dose of the new binder and the measured parameters.
CONCLUSION In our small study, switching from LanC to SFOH did not have any significant effect on blood bicarbonate levels and gas analysis, indicating that there is no need to change hemodialysis prescription regarding these parameters.
Collapse
Affiliation(s)
| | - Vasiliki Aresti
- Department of Nephrology, IASIO Hospital, General Clinic of Kallithea, Athens 17676, Greece
| | | | - Panagiotis Nennes
- Department of Nephrology, IASIO Hospital, General Clinic of Kallithea, Athens 17676, Greece
| | - Polixeni Metaxaki
- Department of Nephrology, IASIO Hospital, General Clinic of Kallithea, Athens 17676, Greece
| | - Anastasios Galinas
- Department of Nephrology, IASIO Hospital, General Clinic of Kallithea, Athens 17676, Greece
| |
Collapse
|
|
25
|
Sprague SM, Floege J. Sucroferric oxyhydroxide for the treatment of hyperphosphatemia. Expert Opin Pharmacother 2018; 19:1137-1148. [PMID: 29985725 DOI: 10.1080/14656566.2018.1491548] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Sucroferric oxyhydroxide is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in patients with chronic kidney disease undergoing dialysis. Areas covered: Herein, the preclinical development and clinical data for sucroferric oxyhydroxide are reviewed, including the key data from the Phase III registration study and the latest evidence from the real-world clinical setting. Expert opinion: Sucroferric oxyhydroxide displays potent phosphate-binding capacity and clinical studies demonstrate its effectiveness for the long-term reduction of serum phosphorus levels in dialysis patients. Observational study data also show that sucroferric oxyhydroxide provides effective serum phosphorus control for hyperphosphatemic patients in the real-world clinical setting. The serum phosphorus reductions with sucroferric oxyhydroxide can be achieved with a relatively low pill burden in comparison with other phosphate binders, which may translate into better treatment adherence in clinical practice. The Phase III data also indicate that sucroferric oxyhydroxide has a favorable impact on other chronic kidney disease-related mineral bone disease parameters, including a fibroblast growth factor-23-lowering effect. Sucroferric oxyhydroxide is well tolerated and associated with low systemic iron absorption, minimizing the potential for iron accumulation or overload. These attributes render sucroferric oxyhydroxide an attractive non-calcium-containing phosphate binder for the treatment of hyperphosphatemia.
Collapse
Affiliation(s)
- Stuart M Sprague
- a Division of Nephrology and Hypertension , NorthShore University Health System, University of Chicago Pritzker School of Medicine , Evanston , IL , USA
| | - Jürgen Floege
- b Department of Nephrology and Clinical Immunology, Division of Nephrology , RWTH University Hospital Aachen , Aachen , Germany
| |
Collapse
|
|
26
|
Shima H, Miya K, Okada K, Minakuchi J, Kawashima S. Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients. BMC Res Notes 2018; 11:363. [PMID: 29884226 PMCID: PMC5994086 DOI: 10.1186/s13104-018-3483-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 06/05/2018] [Indexed: 12/23/2022] Open
Abstract
Objective Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients. Results Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients. Electronic supplementary material The online version of this article (10.1186/s13104-018-3483-6) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Hisato Shima
- Department of Kidney Disease, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima, 770-0011, Japan.
| | - Keiko Miya
- Department of Internal Medicine, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima, 770-0011, Japan
| | - Kazuyoshi Okada
- Department of Kidney Disease, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima, 770-0011, Japan
| | - Jun Minakuchi
- Department of Kidney Disease, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima, 770-0011, Japan
| | - Shu Kawashima
- Department of Kidney Disease, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima, 770-0011, Japan
| |
Collapse
|
|
27
|
Sprague SM, Ketteler M, Covic AC, Floege J, Rakov V, Walpen S, Rastogi A. Long-term efficacy and safety of sucroferric oxyhydroxide in African American dialysis patients. Hemodial Int 2018; 22:480-491. [PMID: 29656600 DOI: 10.1111/hdi.12663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 02/21/2018] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder that demonstrated sustained serum phosphorus (sP) control, good tolerability, and lower pill burden, vs. sevelamer carbonate ("sevelamer"), in a Phase 3 study conducted in dialysis patients with hyperphosphatemia. This analysis evaluates the efficacy and safety of SFOH and sevelamer among African American (AA) patients participating in the trial. METHODS Post hoc analysis of a 24-week, Phase 3, open-label trial (NCT01324128) and its 28-week extension study (NCT01464190). Patients were randomized 2:1 to SFOH (1.0-3.0 g/day) or sevelamer (2.4-14.4 g/day) for up to 52 weeks. FINDINGS Of 549 patients who completed the Phase 3 study and extension, 100 (18.2%) AA patients were eligible for efficacy analysis (SFOH, n = 48; sevelamer, n = 52). sP concentrations decreased rapidly and comparably with both treatments by Week 8 (mean ± standard deviation change from baseline: -1.9 ± 1.9 mg/dL for SFOH and -2.2 ± 1.8 mg/dL for sevelamer). These reductions were maintained for 52 weeks (-2.1 ± 2.6 and -2.1 ± 1.6 mg/dL) and achieved with a lower mean pill burden (3.4 ± 1.4 vs. 7.6 ± 2.9 tablets/day) with SFOH vs. sevelamer. Treatment adherence rates (adherence within 70%-120% of expected medication intake) were 79.2% with SFOH and 59.6% with sevelamer. The proportion of patients reporting serious adverse events (AEs) was 27.7% with SFOH and 30.7% with sevelamer. More patients withdrew due to treatment-emergent AEs with SFOH vs. sevelamer (18.5% vs. 8.0%). The most common AEs with both treatments were gastrointestinal-related: diarrhea and discolored feces with SFOH, and nausea, vomiting, and constipation with sevelamer. DISCUSSION SFOH is an efficacious and well-tolerated treatment for hyperphosphatemia in AA dialysis patients, with a lower pill burden and an improved adherence rate vs. sevelamer. These findings were consistent with the wider US patient population and the overall study population.
Collapse
Affiliation(s)
| | | | - Adrian C Covic
- 'Gr.T. Popa' University of Medicine and Pharmacy, Iasi, Romania
| | | | | | | | - Anjay Rastogi
- University of California, Los Angeles, California, USA
| |
Collapse
|
|
28
|
Kalantar-Zadeh K, Parameswaran V, Ficociello LH, Anderson L, Ofsthun NJ, Kwoh C, Mullon C, Kossmann RJ, Coyne DW. Real-World Scenario Improvements in Serum Phosphorus Levels and Pill Burden in Peritoneal Dialysis Patients Treated with Sucroferric Oxyhydroxide. Am J Nephrol 2018; 47:153-161. [PMID: 29514139 PMCID: PMC5906196 DOI: 10.1159/000487856] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 02/20/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND A database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care. METHODS Adult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL. RESULTS At baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001). CONCLUSION Among PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed.
Collapse
Affiliation(s)
| | | | | | - Ludmila Anderson
- Fresenius Medical Care North America, Waltham, Massachusetts, USA
| | - Norma J. Ofsthun
- Fresenius Medical Care North America, Waltham, Massachusetts, USA
| | - Christopher Kwoh
- The Kidney Institute, Houston, Texas, USA
- Baylor College of Medicine, Houston, Texas, USA
| | - Claudy Mullon
- Fresenius Medical Care North America, Waltham, Massachusetts, USA
| | | | - Daniel W. Coyne
- Washington University School of Medicine, St. Louis, Missouri, USA
| |
Collapse
|
|
29
|
Dzingarski D, Mladenovska K. Pharmacotherapy in chronic kidney disease hyperphosphatemia – effects on vascular calcification and bone health. MAKEDONSKO FARMACEVTSKI BILTEN 2017. [DOI: 10.33320/maced.pharm.bull.2017.63.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Hyperphosphatemia (HP) in patients with chronic kidney disease (CKD) leads to complications such as renal osteodistrophy, cardiovascular calcification and hemodynamic abnormalities, all of them having a serious impact on the survival rate and quality of life. Also, HP is a key pathogenic factor in the development of secondary hyperparathyroidism (SHPT) in CKD. Having in regard the significance of controlling serum phosphorus levels (Pi), in this paper, the needs and obstacles to successful pharmacological management of HP in CKD are presented, with an overview of major classes of phosphate binders (PBs) and other drugs affecting Pi level, such as active vitamin D sterols and calcimimetics (CMs). In addition, their effects on progression of cardiovascular calcification and bone health are elaborated. In this regard, a PubMed search was carried out to capture all abstracts and articles relevant to the topic of CKD, HP and mineral metabolism, bone disorders and vascular/valvular calcification (VC), published from January 2007 to August 2017. The search was limited to English language, with the search terms including drug name AND hyperphosphatemia or cardiovascular calcification or bone disorder. Comparative studies, clinical studies/trials and meta-analyses related to different classes/representatives of PBs, vitamin D analogues and CMs were reviewed and research data related to their efficacy and safety compared.
Keywords: chronic kidney disease, hyperphosphatemia, phosphate binders, active vitamin D sterols, calcimimetics, bone disorders, cardiovascular calcification
Collapse
Affiliation(s)
- Dimce Dzingarski
- Faculty of Pharmacy, University “Ss Cyril and Methodius”, Mother Theresa St. 47, 1000 Skopje, Republic of Macedonia
| | - Kristina Mladenovska
- Faculty of Pharmacy, University “Ss Cyril and Methodius”, Mother Theresa St. 47, 1000 Skopje, Republic of Macedonia
| |
Collapse
|