Summary
Background
Dialysis patients, receiving erythropoiesis stimulating agents, typically show signs of hemoglobin variability as a consequence of their dosing patterns, bleeding, infection, etc., which is commonly managed adjusting the dose regimen of the erythropoiesis stimulating agent. However, information on dosing strategies used in daily clinical practice and their outcomes in relation to hemoglobin variability is limited.
Objectives
To investigate clinical practice in Austria in relation with the management of hemoglobin variability, defined as a decrease of ³ 1 g/dL within 4 weeks from ³ 11 g/dL to £ 11 g/dL during maintenance therapy with darbepoetin alfa. The nature and incidence of clinical events related to the hemoglobin drop were also assessed.
Research design and methods
The MAINTAIN non-interventional study was conducted in hemodialysis patients, receiving darbepoetin alfa in accordance to the label approved in the European Union at that time. Patient data were documented retrospectively for the 3 months prior to the hemoglobin drop. Data for the 6 months post hemoglobin drop were collected retrospectively or prospectively, depending on the time of patient inclusion respective to the Hb drop.
Results
A hundred thirty six of 154 patients fulfilled all inclusion/exclusion criteria and had prospective documentation of 6 months. The main causes for the hemoglobin drop included surgical and medical procedures (36.1 %), and infections or infestations (24.4 %). The median treatment period was 273 days. The mean hemoglobin drop was − 1.74 g/dL (95 % confidence interval (CI): − 1.60 to − 1.87). Consequently, 81 % of the patients had their dose of darbepoetin alfa increased within a median Kaplan–Meier time to dose increase of 12.5 days (95 % CI: 6–22). The geometric mean weekly darbepoetin alfa dose increased by a factor of 1.1 from 29.1 mg (95 % CI: 24.6–34.4) in the 3 months before hemoglobin drop to 32.4 (95 % CI: 27.2–38.6) in months 4–6 post hemoglobin drop. Three patients had red blood cell transfusions before hemoglobin drop and nine patients after hemoglobin drop. The mean hemoglobin increase was 0.43 g/dL (95 % CI: 0.24–0.62) from immediately prior to 2 weeks after dose increase. The median Kaplan–Meier time to achieve a hemoglobin ³ 11 g/dL after hemoglobin drop was 36 days (95 % CI: 32–45). Frequent darbepoetin alfa dose adjustments were necessary to sustain maintenance levels. No drug-related adverse events were reported.
Conclusions
This observational study describes physicians’ reactions to a drop in hemoglobin in clinical practice. Using darbepoetin alfa, the drop was generally compensated without leading to overcorrection.
Zusammenfassung
Grundlagen
Bei Dialysepatienten unter Erhaltungstherapie mit Erythropoese-stimulierenden Faktoren beobachtet man häufig Hämoglobinschwankung als Folge von Dosisanpassungen, Blutungen, Infektionen etc. Diesen Schwankungen kann am ehesten durch Dosisanpassung begegnet werden. Über Dosisstrategien in der klinischen Praxis und ihre Auswirkungen, ist bis dato wenig bekannt.
Studienziel
Es wurde die klinische Praxis in Österreich zur Handhabung eines akuten Hämoglobinabfalls von ³ 1 g/dl innerhalb von 4 Wochen von ³ 11 g/dl auf £ 11 g/dl unter Erhaltungstherapie mit Darbepoetin alfa untersucht. Weiters wurde die Art und Inzidenz der kausalen klinischen Ereignisse erfasst.
Studiendesign und Methodik
Die nicht-interventionelle MAINTAIN Studie wurde an Hämodialysepatienten durchgeführt, die Darbepoetin alfa nach der zum Zeitpunkt der Studie geltenden Zulassung der Europäischen Union erhielten. Die Patienten wurden retrospektiv über 3 Monate vor dem Hämoglobinabfall dokumentiert, sowie, je nach Zeitpunkt des Studieneinschlusses, retrospektiv oder prospektiv über 6 Monate danach.
Ergebnisse
Insgesamt wurden 154 Patienten eingeschlossen, 136 erfüllten alle Ein- und Ausschlusskriterien und wurden prospektiv über 6 Monate dokumentiert. Die Hauptursachen für den Hämoglobinabfall waren chirurgische und medizinische Eingriffe (36,1 %), sowie Infektionen oder parasitäre Erkrankungen (24,4 %). Die mediane Behandlungsdauer war 273 Tage. Der mittlere Hämoglobinabfall betrug − 1,74 g/dl (95 % CI: − 1,60 bis − 1,87). Bei 81 % der Patienten wurde die Dosis erhöht. Die mediane Dauer bis zur Dosiserhöhung war 12,5 Tage (95 % CI: 6–22). Die geometrische mittlere Wochendosis stieg um einen Faktor 1,1 von 29,1 mg (95 % CI: 24,6–34,4) in den 3 Monaten vor auf 32,4 (95 % CI: 27,2–38,6) in den Monaten 4 bis 6 nach dem Hämoglobinabfall, 3 Patienten erhielten Blutkonserven davor und 9 Patienten danach. Der mittlere Hämoglobinanstieg von unmittelbar vor bis zwei Wochen nach Dosiserhöhung war 0,43 g/dl (95 % CI: 0,24–0,62). Die mediane Dauer bis zu einem Hämoglobin ³ 11 g/dl nach dem Hämoglobinabfall war 36 Tage (95 % CI: 32–45). Die Stabilisierung und Erhaltung des Hämoglobinwerts erforderte häufige Dosisanpassungen. Es wurden keine auf das Studienmedikament zurückzuführende unerwünschte Ereignisse berichtet.
Schlussfolgerungen
Diese Beobachtungsstudie beschreibt den Umgang mit einem Hämoglobinabfall in der klinischen Praxis. Dieser konnte mit Darbepoetin alfa meist ohne überschießende Reaktionen kompensiert werden.
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Watschinger, B., Salmhofer, H., Horn, S. et al. The MAINTAIN study—managing hemoglobin variability with darbepoetin alfa in dialysis patients experiencing a severe drop in hemoglobin. Wien Klin Wochenschr 125, 71–82 (2013). https://doi.org/10.1007/s00508-012-0311-1
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DOI: https://doi.org/10.1007/s00508-012-0311-1