OPATIJA STUDY: OBSERVATION OF HEMODIALYSIS PATIENTS AND TITRATION OF CERA DOSE JUST SWITCHED FROM ANOTHER ERYTHROPOIESIS STIMULATING AGENT

Abstract

Anemija, posljedica kronične bubrežne bolesti, čija učestalost raste napredovanjem bubrežnog zatajenja, u završnom je stupnju kronične bubrežne bolesti zastupljena u čak do 95% bolesnika. Lijekovi izbora u liječenju bubrežne anemije su pripravci eritropoetina iz skupine lijekova za stimulaciju eritropoeze (LSE). Veliki napredak u liječenju je uporaba metoksipolietilenglikol-epoetina beta, kontinuiranog aktivatora receptora za eritropoetin (CERA). Cilj studije OPATIJA je usporediti postizanje ciljnih vrijednosti hemoglobina (Hb) kao i njegovu varijabilnost uz učinkovitost i sigurnost uporabe u dvije usporedne skupine bolesnika. U jednoj je skupini bolesnika učinjena konverzija s kratkodjelujućih stimulatora eritropoeze na doze CERA navedene na samom proizvodu, dok je druga skupina liječena alternativnim dozama prema individualnim potrebama bolesnika. U ispitivanju je sudjelovalo 79 bolesnika. Bolesnici su bili podijeljeni u dvije usporedne skupine ranije liječene kratkodjelujućim LSE, od kojih je 36 bolesnika bilo u skupini koja je izravno konvertirana na CERA prema preporučenom doziranju navedenom na samom proizvodu. Drugu su skupinu činila 43 bolesnika koji su konvertirani prema dozama prilagođenima prethodnom doziranju kratkodjelujućih LSE. Tijekom osamnaestomjesečnog razdoblja svakom bolesniku u razmacima od najdulje dva mjeseca evidentirani su laboratorijski parametri anemije – razine hemoglobina te parametara statusa željeza (serumsko željezo, TSAT, feritin). Prema navedenim vrijednostima, u slučaju potrebe, prilagođavana je doza CERA te primjenjivana supstitucijska terapija pripravcima željeza. Nakon završetka studije dvije je skupine činio ukupno 51 bolesnik, od kojih je 26 bilo u skupini koja je dobivala preporučenu dozu CERA-e, a 25 bolesnika u skupini koja je dobivala alternativnu dozu. U skupini bolesnika koji su primali preporučene doze CERA prosječna vrijednost hemoglobina tijekom studije iznosila je 104,41 g/L uz prosječne mjesečne doze CERA 104,33 mcg. U skupini bolesnika koji su primali alternativne doze CERA prosječna vrijednost hemoglobina iznosila je 105,33 g/L uz prosječne mjesečne doze CERA 113,08 mcg. U skupini bolesnika koja je dobivala alternativne doze CERA, u 33% slučajeva vrijednosti Hb bile su unutar uskog ciljnog raspona 110-120 g/L. U 30% slučajeva vrijednosti su bile 100-110 g/L, u 29% manje od 100 g/L, a u 8% slučajeva su prelazile 120 g/L. Prosječne vrijednosti Hb na početku i na kraju ispitivanja međusobno se nisu statistički razlikovale osim u skupini bolesnika s nepoželjnim vrijednostima Hb>120 g/L, gdje je 7% bolesnika u skupini s preporučenim doziranjem imalo takve vrijednosti, dok u skupini s alternativnim doziranjem nije bilo bolesnika sa Hb>120 g/L (P=0,017). Varijabilnost hemoglobina s odstupanjima ve im od 10 i 20 g/L zabilježena je u obje skupine uz trend manje pojavnosti u alternativnoj skupini doziranja CERA. U zaključku je preporučeno i alternativno doziranje ime se postižu i održavaju ciljne vrijednosti hemoglobina uz njegovu manju varijabilnost pri primjeni individualiziranog doziranja. Rezultati su potvrdili potrebu individualnog pristupa u liječenju anemije bolesnika koji boluju od završnog stupnja kroničnog bubrežnog zatajenja te se lije e postupcima hemodijalize sukladno najnovijim smjernicama nefrološke struke.Introduction: Anemia is a well-documented consequence of chronic kidney disease, its frequency increases with the progression of renal failure and occurs in up to 95% of patients with end stage renal disease (ESRD). Erythropoietin stimulating agents (ESAs) have become the standard of care in the treatment of renal anemia. The use of methoxy polyethylene glycol-epoetin beta, continuous erythropoietin receptor activator, represents an important beneit in clinical practice. Aim: The aim of the OPATIJA study was to compare the eficacy and safety of maintaining hemoglobin levels in dialysis patients and to assess its variability in a parallel-group design. Patients were randomly assigned to receive methoxy polyethylene glycolepoetin beta once monthly in “normal” dose conversion according to the label of record or “low” or “alternative” dose conversion widely spread according to previous ESA doses. Subjects and Methods: A total of 79 patients were included in the study. The patients who had undergone continuous maintenance intravenous ESA therapy were divided into two parallel groups: group 1 including 36 patients directly switched to CERA according to the manufacturer recommended dosage; and group 2 including 43 patients that were switched by using “low” or “alternative” dose conversion widely spread according to previous ESA doses. During the18-month period, each patient’s anemia parameters, i.e. hemoglobin level, serum iron concentration, TSAT and ferritin, were monitored at intervals not longer than two months. According to hemoglobin levels, the dosage of CERA was adjusted if needed along with oirn supplementation. Results: At the end of the study, the two groups consisted of 51 patients: 26 of those treated with the recommended dose of CERA and 25 treated with the alternative dose. In the normal conversion group, the mean hemoglobin level during the course of the study was 104.41 g/L with the mean monthly dose of 104.33 mcg CERA. In the alternative conversion group, the mean hemoglobin level during the course of the study was 105.33 g/L with the mean monthly dose of 113.08 mcg CERA. In the alternative conversion group, 33% of patients had Hb levels in the tight recommended range of 110-120 g/L. In 30% of patients, Hb levels were 100-110 g/L, in 29% less than 100 g/L, and in 8% more than 120 g/L. The mean Hb levels at the beginning and the end of the study did not differ signiicantly, except for the patient group with Hb levels >120 g/L, where 7% of patients with recommended dosing and none of the patients from the alternative dosing group had such levels (P=0.017). Hemoglobin variability higher than 10 and 20 g/L was recorded in both groups, but less frequently in the alternative CERA dosing group. Conclusion: Both treatments with the recommended and alternative conversion dosing achieved and maintained target hemoglobin level. Study results conirmed the need of individualized approach in the treatment of anemia in ESRD patients receiving hemodialysis, resulting in less potentially harmful hemoglobin variability