POS-287 TREATMENT BURDEN AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH NON–DIALYSIS-DEPENDENT ANAEMIA OF CHRONIC KIDNEY DISEASE RECEIVING ERYTHROPOIESIS-STIMULATING AGENTS: A SYSTEMATIC LITERATURE REVIEW

Abstract

Anaemia of chronic kidney disease (CKD) is associated with morbidity, poor health-related quality of life (HRQoL) and increased mortality. Standard of care includes erythropoiesis-stimulating agents (ESAs), but they are not widely used in non–dialysis-dependent (NDD) patients, due to safety concerns. A broader assessment of patient-centric outcomes is needed. We performed a systematic literature review of treatments for anaemia of CKD in NDD patients. We report the treatment burden, including safety, and HRQoL in patients with NDD anaemia of CKD from ESA trials. We searched electronic databases and other sources to identify randomised controlled trials (phase 2+) for ESAs in the treatment of anaemia of CKD in adults. The search was not limited to outcomes or countries. Other criteria were English publications between database inception and 23 January 2020 (search date). We conducted risk of bias and descriptive assessments of study and patient characteristics, treatment burden and HRQoL. Overall, 4,024 abstracts were screened, and 325 publications were reviewed; 38 ESA NDD-CKD trials of 12,594 randomised patients with anaemia were included. Although 27 trials (71%) had a risk of bias based on quality appraisal, these were included in the descriptive analysis. Overall, 6/38 (16%) trials were phase 3, 24 (63%) were open-label, and 9 (24%) were double-blind. ESAs, such as darbepoetin alfa (DPO) and epoetin alfa, were investigated and often compared with an active comparator, such as other ESAs or iron. Four trials compared high/low haemoglobin (Hb) targets in both ESA treatment arms. Rescue therapy included iron use (45%; 17 trials) and RBC transfusion (3%; 1 trial). Across trials, the mean age was 46.0–84.4 years; baseline Hb range was 8.2–12.2 g/dL. Treatment burden (e.g. discontinuations and adverse events) was evaluated in the safety populations (n=13,082); the burden of treatment administration was not observed. Hypertension was reported frequently as an adverse event across treatment arms (up to 37% of patients) in 18 trials. Treatment discontinuation was reported in 27 trials; common reasons included adverse events, dialysis, treatment failure or other illnesses. The most commonly used HRQoL instruments were Short Form-36 (SF-36; 9 trials), EQ-5D (2 trials), Linear Analogue Self-Assessment (2 trials) and the KDQoL Questionnaire (2 trials). SF-36 scores were statistically significant for ESA vs. placebo as early as 8 weeks (1 trial) and through 1 year (1 trial), though domain-specific results were inconsistent across trials. HRQoL outcomes, such as changes in physical functioning and fatigue scores, were reported in 14 trials; 2 trials evaluated exercise capacity. HRQoL was generally maintained or showed clinically relevant improvements across instruments, particularly for patients receiving ESAs vs. other comparators. Hypertension, as an adverse event was common across treatment arms. Patient-reported treatment burden and HRQoL outcomes were not measured consistently. Questionnaire use was low; SF-36 was mostly frequently used, which is not specific to kidney disease/anemia of CKD. More consideration and consistency of patient-centric outcomes, including complementary evidence from observational studies, may help better understand the holistic impact of ESA treatment on clinical management.