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      Economic Benefits of Switching From Intravenous to Subcutaneous Epoetin Alfa for the Management of Anemia in Hemodialysis Patients

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          Abstract

          Background:

          Erythropoiesis-stimulating agents including epoetin alfa have been a mainstay of anemia management in patients with chronic kidney disease. Although the standard practice has been to administer epoetin alfa to patients on hemodialysis (HD) intravenously (IV), subcutaneous (SQ) epoetin alfa is longer acting and achieve the same target hemoglobin level to be maintained at a reduced dose and cost.

          Objective:

          The primary objective of this study was to determine the economic benefits of change in route of epoetin alfa administration from IV to SQ in HD patients. The secondary objectives were (1) to determine the differences in epoetin alfa doses at the pre-switch (IV) and post-switch period (SQ) and (2) to determine serum hemoglobin concentration, transferrin saturation, ferritin level, IV iron dose and cost in relationship to route of epoetin alfa administration.

          Design:

          This retrospective observational study included patients who transitioned from IV to SQ epoetin alfa.

          Setting:

          Two HD sites in southern Saskatchewan (Regina General Hospital, and Wascana Dialysis Unit, Regina) and 2 sites in northern Saskatchewan (St. Paul’s [SPH] Hospital, and SPH Community Renal Health Center, Saskatoon).

          Patients:

          The study includes 215 patients who transitioned from IV to SQ and were alive at the end of 12-month follow-up period.

          Measurements:

          We calculated the dose and cost of different routes of epoetin alfa administration/patient month. Also, serum hemoglobin, markers of iron stores (transferrin saturation and ferritin), IV iron dose, and cost were determined in relation to route of epoetin alfa administration.

          Methods:

          Data were gathered from 6 months prior (IV) to 12 months after switching treatment to SQ. The paired t-test and Wilcoxon signed-rank test were used to compare variables between pre-switch (IV) and post-switch (SQ) period.

          Results:

          The median cost (interquartile range) of epoetin alfa/patient-month decreased from (CAD508.3 [CAD349-CAD900.8]) pre-switch (IV) to (CAD381.2 [CAD247-CAD681]) post-switch (SQ) ( P < .001), a decrease of 25%. The median epoetin alfa dose/patient-month reduced from (38 500 [25 714.3-64 166.5] international unit) pre-switch to (26 750.3 [17 362.6-48 066] IU) post-switch ( P < .001), a decrease of 30.51%. The mean hemoglobin concentration (± standard deviation) for patients in both periods remained stable (103.3 ± 9.2 vs 104.3 ± 13.3 g/L, P = .34) and within the target range. There were no significant differences in transferrin saturation, ferritin, and IV iron dose and cost between the 2 study periods.

          Limitations:

          We were unable to consistently obtain information across all the sites on hospitalizations, inflammatory markers, nutritional status, and gastrointestinal bleeding. In addition, as our study sample was subject to survival bias, we cannot generalize our study results to other populations.

          Conclusions:

          We have shown that administering epoetin alfa SQ in HD patients led to a 30.51% reduction in dose and 25% reduction in cost while achieving equivalent hemoglobin levels. Given the cost sparing advantages without compromising care while achieving comparable hemoglobin levels, HD units should consider converting to SQ mode of administration.

          Trial registration:

          The study was not registered on a publicly accessible registry as it was a retrospective chart review and exempted from review by the Research Ethics Board of the former Regina Qu’Appelle Health Region.

          Abrégé

          Contexte:

          Les agents stimulant l’érythropoïèse, notamment l’époétine alfa, sont un des piliers du traitement de l’anémie chez les patients atteints d’insuffisance rénale chronique. Bien que la pratique courante préconise l’administration intraveineuse (IV) de l’époétine alfa aux patients hémodialysés (HD), il s’avère que son action par voie sous-cutanée (SC) est plus longue et qu’elle atteint les taux d’hémoglobine cibles à une dose et à un coût réduits.

          Objectifs:

          L’objectif principal était d’exposer les avantages sur le plan économique d’un changement de voie d’administration pour l’époétine alfa (IV à SC) chez les patients hémodialysés. Les objectifs secondaires étaient: a) établir les écarts de doses d’époétine alfa entre la période pré-changement (IV) et post-changement (SC), et b) déterminer la concentration d’hémoglobine sérique, la saturation de transferrine, le taux de ferritine, la dose IV de fer et le coût selon la voie d’administration.

          Type d’étude:

          Une étude rétrospective observationnelle sur des patients qui sont passés de la voie IV à la voie SC pour l’administration d’époétine alfa.

          Cadre:

          Deux sites de dialyze du sud de la Saskatchewan (l’hôpital général de Régina et l’unité de dialyze Wascana de Régina) et deux sites du nord de la Saskatchewan (l’hôpital St. Paul et le Community Renal Health Center de Saskatoon).

          Sujets:

          L’étude porte sur 215 patients passés de la voie IV à SC pour l’administration d’époétine alfa et toujours vivants à la fin des 12 mois de suivi.

          Mesures:

          La dose administrée et le coût ont été calculés par mois-patient pour chaque voie d’administration. La concentration d’hémoglobine sérique, les marqueurs des réserves de fer (saturation de transferrine et ferritine), la dose de fer IV et les coûts selon la voie d’administration ont également été calculés.

          Méthodologie:

          Les données des six mois précédant (IV) et des douze mois suivant (SC) le changement ont été colligées. Le test t pour échantillons appariés et le test de rang de Wilcoxon ont été employés pour comparer les variables entre les périodes pré-changement (IV) et post-changement (SC).

          Résultats:

          Le coût médian pour l’administration d’épotine alfa/mois-patient est passé de 508,30 $ CA (voie IV; ÉIQ: 349 – 900,80 $) à 381,20 $ CA (voie SC; ÉIQ: 247 – 681 $) (p<0,001), soit une réduction de 25 % du coût. La dose médiane d’époétine alfa/mois-patient est passée de 38 500 (ÉIQ: 25 714,3 – 64 166,5) à 26 750,3 (ÉIQ: 17 362,6 – 48 066) unités internationales (UI) (p<0,001), soit une baisse de 30,51 %. La concentration moyenne d’hémoglobine (± écart type) est demeurée stable et dans les limites visées pour les deux périodes étudiées (103,3 ±9,2 contre 104,3 ±13,3 grams/liter; p=0,34). Aucune différence significative n’a été observée entre les deux périodes pour la saturation de la transferrine, la ferritine, la dose de fer IV et les coûts.

          Limites:

          L’obtention des données sur les hospitalisations, les taux de marqueurs inflammatoires, l’état nutritionnel des patients et les hémorragies gastro-intestinales s’est avérée inconstante entre les différents sites. De plus, notre échantillon était soumis à des biais de survie, nos résultats ne sont donc pas généralisables à d’autres populations.

          Conclusion:

          Nos résultats montrent que le passage à la voie SC pour l’administration d’époétine alfa chez les patients hémodialysés permet de réduire la dose de 30,51 % et les coûts de 25 %, tout en maintenant un taux équivalent d’hémoglobine sérique. Compte tenu des économies et du fait que ce changement ne compromet en rien les soins et qu’il permet de maintenir un taux comparable d’hémoglobine, les unités d’hémodialyse devraient envisager de passer à la voie SC pour l’administration d’époétine alfa.

          Enregistrement de l’essai:

          L’essai n’a pas été enregistré dans un registre accessible au public puisqu’il s’agit d’un examen rétrospectif des dossiers des patients et qu’il était exempté d’un examen de la part du comité d’éthique de la recherche de l’ancienne région sanitaire Regina Qu’Appelle.

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          Most cited references38

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

          Mechanisms of anemia in CKD.

          Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.
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            • Record: found
            • Abstract: found
            • Article: not found

            Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes.

            Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.
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              • Record: found
              • Abstract: found
              • Article: not found

              Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients.

              Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States. After time-dependent and multivariate adjustment for case mix, quarterly varying administered intravenous iron and ESA doses, iron markers, and nutritional status, hemoglobin levels between 12 and 13 g/dl were associated with the greatest survival. Among prevalent patients, the lower range of the recommended Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl) was associated with a higher death risk compared with the 11.5- to 12-g/dl range. A decrease or increase in hemoglobin over time was associated with higher or lower death risk, respectively, independent of baseline hemoglobin. Administration of any dose of ESA was associated with better survival, whereas among those who received ESA, requiring higher doses were surrogates of higher death risk. In this observational study, greater survival was associated with a baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated with decreased survival. Randomized clinical trials are required to examine these associations.
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                Author and article information

                Journal
                Can J Kidney Health Dis
                Can J Kidney Health Dis
                CJK
                spcjk
                Canadian Journal of Kidney Health and Disease
                SAGE Publications (Sage CA: Los Angeles, CA )
                2054-3581
                4 June 2020
                2020
                : 7
                : 2054358120927532
                Affiliations
                [1 ]Section of Nephrology, Department of Medicine, Regina General Hospital, Saskatchewan Health Authority, Regina, Canada
                [2 ]Department of Pharmacy, Regina General Hospital, Saskatchewan Health Authority, Regina, Canada
                [3 ]Section of Nephrology, Department of Medicine, St Paul’s Hospital, Saskatoon, SK, Canada
                [4 ]Cumming School of Medicine, University of Calgary, AB, Canada
                Author notes
                [*]Bhanu Prasad, Section of Nephrology, Department of Medicine, Regina General Hospital, Saskatchewan Health Authority, 1440, 14th Avenue, Regina, SK, Canada S4P 0W5. Email: bprasad@ 123456sasktel.net
                Author information
                https://orcid.org/0000-0002-1139-4821
                https://orcid.org/0000-0002-7261-2191
                https://orcid.org/0000-0001-5189-8488
                Article
                10.1177_2054358120927532
                10.1177/2054358120927532
                7273547
                3ac88856-d823-4bac-a024-45f1e4cba52f
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 22 January 2020
                : 5 April 2020
                Categories
                Original Clinical Research
                Custom metadata
                January-December 2020
                ts1

                hemodialysis,economic evaluation,end-stage renal disease,cost-effectiveness,epoetin alfa

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