24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Predictors of cinacalcet discontinuation and reinitiation in hemodialysis patients: results from 7 European countries

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          The putative benefits of cinacalcet therapy for management of secondary hyperparathyroidism (SHPT) are thought to be most manifested when patients are taking it consistently and as prescribed. Real-world descriptions of cinacalcet prescription discontinuation and reinitiation in European hemodialysis patients are lacking. To address this knowledge gap, we used Dialysis Outcomes and Practice Patterns Study (DOPPS) data, based on dialysis facility medical records, from seven European countries to estimate rates and predictors of cinacalcet prescription discontinuation and reinitiation in hemodialysis patients and to describe the trajectories of CKD-MBD laboratory values after discontinuation.

          Methods

          Cox regression analyses were used to predict (1) cinacalcet discontinuation among 613 patients with ≥3 consecutive months without cinacalcet prescription immediately prior to a new cinacalcet prescription and (2) cinacalcet reinitiation among 415 patients with a newly discontinued cinacalcet prescription immediately after ≥3 consecutive months of prescribed use.

          Results

          Cinacalcet was discontinued in 21 and 35% of new users after 6 and 12 months, respectively. Cinacalcet was reinitiated in 38 and 49% of newly-discontinued users after 6 and 12 months, respectively. Predictors of discontinuation included lower parathyroid hormone (PTH) in the previous month (< 150 pg/ml vs. 150–299, HR = 2.57 [95% CI: 1.52–4.33]) and lower serum calcium in the previous month (< 8.4 mg/dl vs. 8.4–10.19, HR = 1.67 [95% CI: 1.08–2.59]). Predictors of reinitiation included higher PTH in the previous month (300–599 pg/ml vs. 150–299, HR = 1.88 [95% CI = 1.19–2.97]; 600+ pg/ml, HR = 3.02 [95% CI = 1.92–4.76]). After cinacalcet discontinuation, mean serum PTH increased from 408 to 510 pg/ml, mean serum calcium briefly rose from 9.12 to 9.22 mg/dl before declining to 9.06 mg/dl, and mean serum phosphorus showed little change.

          Conclusions

          Nephrologist discontinuation of cinacalcet therapy is common in European countries. Additional research is needed to identify optimal cinacalcet treatment strategies for SHPT management, including comparisons of intermittent cinacalcet therapy versus sustained treatment with reduced dose or frequency.

          Electronic supplementary material

          The online version of this article (10.1186/s12882-019-1355-5) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

          Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism. Copyright 2004 Massachusetts Medical Society
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Nonadherence in hemodialysis: associations with mortality, hospitalization, and practice patterns in the DOPPS.

            Nonadherence among hemodialysis patients compromises dialysis delivery, which could influence patient morbidity and mortality. The Dialysis Outcomes and Practice Patterns Study (DOPPS) provides a unique opportunity to review this problem and its determinants on a global level. Nonadherence was studied using data from the DOPPS, an international, observational, prospective hemodialysis study. Patients were considered nonadherent if they skipped one or more sessions per month, shortened one or more sessions by more than 10 minutes per month, had a serum potassium level openface>6.0 mEq/L, a serum phosphate level openface>7.5 mg/dL (>2.4 mmol/L), or interdialytic weight gain (IDWG)>5.7% of body weight. Predictors of nonadherence were identified using logistic regression. Survival analysis used the Cox proportional hazards model adjusting for case-mix. Skipping treatment was associated with increased mortality [relative risk (RR) = 1.30, P = 0.01], as were excessive IDWG (RR = 1.12, P = 0.047) and high phosphate levels (RR = 1.17, P = 0.001). Skipping also was associated with increased hospitalization (RR = 1.13, P = 0.04), as were high phosphate levels (RR = 1.07, P = 0.05). Larger facility size (per 10 patients) was associated with higher odds ratios (OR) of skipping (OR = 1.03, P = 0.06), shortening (OR = 1.03, P = 0.05), and IDWG (OR = 1.02, P = 0.07). An increased percentage of highly trained staff hours was associated with lower OR of skipping (OR = 0.84 per 10%, P = 0.02); presence of a dietitian was associated with lower OR of excessive IDWG (OR = 0.75, P = 0.08). Nonadherence was associated with increased mortality risk (skipping treatment, excessive IDWG, and high phosphate) and with hospitalization risk (skipping, high phosphate). Certain patient/facility characteristics also were associated with nonadherence.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study.

              Management of secondary hyperparathyroidism is challenging with traditional therapy. The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion. This phase 3, multicenter, randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis (HD) and peritoneal dialysis (PD) patients with PTH > or =300 pg/ml despite traditional therapy. A total of 395 patients received once-daily oral cinacalcet (260 HD, 34 PD) or placebo (89 HD, 12 PD) titrated from 30 to 180 mg to achieve a target intact PTH (iPTH) level of or =30% reduction in iPTH from baseline (65 versus 13%), and proportion of patients with > or =20, > or =40, or > or =50% reduction from baseline. Cinacalcet had comparable efficacy in HD and PD patients; 50% of PD patients achieved a mean iPTH < or =300 pg/ml. Cinacalcet also significantly reduced serum calcium, phosphorus, and Ca x P levels compared with control treatment. The most common side effects, nausea and vomiting, were usually mild to moderate in severity and transient. Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH, Ca x P, calcium, and phosphorus levels in patients who received HD or PD. Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
                Bookmark

                Author and article information

                Contributors
                (734) 665-4108 , Doug.Fuller@ArborResearch.org , http://www.ArborResearch.org/
                dhalle01@amgen.com
                pdluznie@amgen.com
                brunof@amgen.com
                jadoul@nefr.ucl.ac.be
                halm@umich.edu
                fritz.port@gmail.com
                Francesca.tentori@davita.com
                ronald.pisoni@arborresearch.org
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                14 May 2019
                14 May 2019
                2019
                : 20
                : 169
                Affiliations
                [1 ]ISNI 0000 0004 0628 9837, GRID grid.413857.c, Arbor Research Collaborative for Health, ; Ann Arbor, MI USA
                [2 ]ISNI 0000 0001 0657 5612, GRID grid.417886.4, Amgen, Inc., ; Thousand Oaks, CA USA
                [3 ]ISNI 0000 0004 0476 2707, GRID grid.476152.3, Amgen (Europe) GmbH, ; Rotkreuz, Switzerland
                [4 ]ISNI 0000 0001 2294 713X, GRID grid.7942.8, Cliniques Universitaires St-Luc, , Université catholique de Louvain, ; Bruxelles, Belgium
                [5 ]ISNI 0000000086837370, GRID grid.214458.e, Departments of Epidemiology and Environmental Health Sciences, School of Public Health, and Department of Urology, Medical School, , University of Michigan, ; Ann Arbor, MI USA
                [6 ]DaVita, Inc., Minneapolis, MN USA
                [7 ]ISNI 0000 0001 2264 7217, GRID grid.152326.1, Vanderbilt University School of Medicine, ; Nashville, TN USA
                Author information
                http://orcid.org/0000-0002-2448-5896
                Article
                1355
                10.1186/s12882-019-1355-5
                6518810
                31088377
                6817fdf2-d079-483a-b191-44f4698ebe66
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 August 2018
                : 24 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100002429, Amgen;
                Funded by: AstraZeneca Pharmaceuticals LP
                Funded by: FundRef http://dx.doi.org/10.13039/100007658, Baxter Healthcare Corporation;
                Funded by: European Renal Association-European Dialysis & Transplant Association
                Funded by: Fresenius Medical Care Asia-Pacific Ltd
                Funded by: Fresenius Medical Care Canada Inc
                Funded by: German Society of Nephrology (DGfN), Italian Society of Nephrology
                Funded by: FundRef http://dx.doi.org/10.13039/100008897, Janssen Pharmaceuticals;
                Funded by: Japanese Society for Peritoneal Dialysis
                Funded by: Keryx Biopharmaceuticals, Inc
                Funded by: Kidney Care UK
                Funded by: FundRef http://dx.doi.org/10.13039/501100004095, Kyowa Hakko Kirin;
                Funded by: MEDICE Arzneimittel Pütter GmbH & Co K
                Funded by: FundRef http://dx.doi.org/10.13039/100009155, Otsuka America Pharmaceutical;
                Funded by: Proteon Therapeutics, Inc
                Funded by: The Association of German Nephrology Centres
                Funded by: Vifor Fresenius Medical Care Renal Pharma Ltd
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                cinacalcet,hemodialysis,parathyroid hormone
                Nephrology
                cinacalcet, hemodialysis, parathyroid hormone

                Comments

                Comment on this article