Treating anaemia with epoetin alfa is associated with improvements in quality of life in cancer patients receiving chemotherapy

Anaemia is an important factor in the fatigue experienced by many patients receiving chemotherapy. A recent large-scale, randomised, placebo-controlled trial has shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall quality of life (QoL). In order to examine the relationship between anaemia and QoL more closely, we performed multiple regression analyses, adjusting for possible differences in demographic and clinical characteristics between the treatment groups on the trial data derived from FACT, CLAS and SF-36 QoL assessments. This confirmed that QoL is correlated with haemoglobin levels and that treatment with epoetin alfa is associated with a significant improvement in QoL as measured by validated cancer-specific instruments such as FACT and CLAS. However, the sub-group of patients who suffer disease progression during treatment are not predicted to experience an improvement in QoL, confirming the sensitivity of these scales. Race and tumour type were significantly related to changes in QoL scores, but other factors such as age and gender did not show significant effects on QoL.     

Epoetin alfa offers clinically significant improvements in the quality of life of anaemic cancer patients

Anaemia is a common problem for cancer patients and often causes fatigue and reduces quality of life (QoL). Although randomised trials have repeatedly shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall QoL, such findings may be hard to put into a clinical context and, as a result, cancer-related fatigue remains undertreated. This study gathered data using the FACT-An QoL scale from 1400 people on an internet survey panel. The 1400 were randomly selected and chosen to be representative of the total US population. Survey results were then compared with the findings from a large placebo-controlled study involving 375 anaemic cancer patients. FACT-An showed good psychometric properties in the survey population and was able to distinguish respondents with histories of anaemia and cancer from those without. Comparing the population norm values for FACT-An with the trial data showed that treatment with epoetin alfa led to clinically meaningful improvements in cancer patients' QoL.     

Meta-analysis of the effects of epoetin alfa treatment on quality of life in anaemic cancer patients

Treatment with epoetin alfa has repeatedly been shown to improve the quality of life (QoL) of cancer patients with anaemia. We used meta-analytical techniques to synthesise data from all available (published and unpublished) studies of epoetin alfa in cancer patients receiving chemotherapy that used validated QoL instruments. Results from 23 studies were synthesised. These employed the CLAS, FACT, SF-36 and ECOG (WHO) QoL scales. The meta-analysis indicated that treatment with epoetin alfa was associated with a clear and statistically significant improvement in QoL as measured by all subscales of CLAS, all subscales of FACT, and 5 subscales of SF-36. In contrast, control groups experienced no significant change, or, in some cases, a deterioration in QoL. Improvement was related to treatment duration. The generic ECOG (WHO) performance scale indicated that, even though epoetin alfa treatment is associated with clear benefits in terms of QoL, this population of patients receiving chemotherapy for cancer experience a gradual decrease in functional status over time.     

Benefits of epoetin alfa for cancer patients' quality of life are confirmed after modelling to account for missing data

Incomplete data are inevitable in quality-of-life (QoL) studies involving cancer patients, since a proportion of patients will not complete the trial. Traditional analyses assume that such data are missing at random, but this assumption may be incorrect. We therefore applied mixed-effects statistical models to determine the effects of non-random missing data. Models were applied to results from a large-scale, randomised study of epoetin alfa versus placebo in 375 patients receiving non-platinum-based chemotherapy. The model suggested that QoL data were not missing at random and that analyses based on an assumption of random missing data gave an over-optimistic impression of QoL changes within treatment groups. However, sensitivity analysis demonstrated that the effectiveness of treatment with epoetin alfa compared to placebo in terms of QoL benefits remained highly significant, confirming the original conclusions of the study.     

Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa

ABSTRACT

Objectives: To evaluate the relationship between hemoglobin (Hb) level and quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease receiving epoetin alfa.

Patients and methods: A post-hoc analysis using data from a multicenter, open-label, prospective study of epoetin alfa for anemia in patients with chronic kidney disease not on dialysis was conducted. The relationship between Hb and QOL was analyzed using correlation and longitudinal analyses, the latter adjusting for sample selection bias. The Linear Analog Scale Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used to measure QOL. The impact of an incremental 1?g/dL increase in Hb level on LASA and KDQ scores was determined using an incremental analysis.

Results: A total of 1183 and 1044 patients formed the study populations for the LASA and KDQ analyses, respectively. There was a positive and significant relationship between Hb levels and QOL (?p < 0.05). Using non-linear regression analysis, we characterized the sigmoid-shape of the relationship between Hb levels and QOL scores. Hemoglobin change was a statistically significant determinant of QOL improvement for both LASA and KDQ scales (?p < 0.05). The model predicted that, based on a 2?unit change in Hb, the greatest incremental QOL improvement per unit of Hb increase occurred when Hb was in the range of 11 to 12?g/dL.

Conclusions: This study demonstrates that, beyond the well-known relationship between Hb increases and QOL improvements, the maximal incremental gain in QOL occurred when Hb reached 11 to 12?g/dL. This suggests that treating anemic patients with non-dialysis chronic kidney disease until their Hb level reaches 12?g/dL will result in the greatest QOL improvement per Hb unit increase. The analyses were conducted based on an open-label study of epoetin alfa and could be further validated using a randomized, controlled trial, comparing incremental gains in QOL associated with treatment initiation at varying levels of Hb across arms.     

Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment

ABSTRACT

Objective: To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.

Methods: Patients received epoetin zeta or epoetin alfa intravenously, 1–3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18–75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for ≥ 3 months upon study entry and had achieved a target Hb level of 10.5–12.5?g/dL with a stable epoetin dose.

Main outcome measures: Primary efficacy endpoints were intra-individual differences (test–reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro­poietin antibodies, tolerability, and adverse events (AEs).

Results: In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96–14.22) g/dL and 11.54 (8.74–13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test–reference]: 0.09–0.28?g/dL, within the predefined equivalence range of ±?0.6?g/dL). Mean (range) weekly doses were 92.68 (12.74–398.41) IU/kg/wk and 92.58 (10.53–393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test–reference]: –4.67 and 4.29 IU/kg/wk, within the equivalence range of ±?45.00?IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies.

Conclusions: Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.     

The cost-effectiveness of weekly epoetin alfa relative to weekly darbepoetin alfa in patients with chemotherapy-induced anemia

OBJECTIVE: To compare the cost-effectiveness of epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of chemotherapy-induced anemia (CIA), using dosing regimens approved by the FDA (EPO 40,000 U once weekly and DARB 2.25 U once weekly and DARB 2.25 mcg/kg once weekly). METHODS: The study compared published results of two double-blind, randomized, phase III trials one utilizing EPO (N = 166) and the other, DARB (N = 367). Patients in both trials similar baseline characteristics. Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated (i.e., did not require blood transfusion) during weeks 0-16 and 5-16, respectively. Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost (WAC) and average drug utilization over 16 weeks. Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness. Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs. RESULTS: Estimated drug costs over 16 weeks were $9,039 for EPO and $13,555 for DARB. During weeks 5-16, 85% of EPO patients and 73% of DARB patients were successfully treated, resulting in average cost-effectiveness ratios of $106 for EPO and $186 for DARB per one per cent of successfully treated patients. A 33% reduction in DARB WAC was required to achieve the same drug costs as for EPO. CONCLUSIONS: Utilizing FDA-approved doses, EPO was found to result in lower drug costs and better treatment success when compared to DARB. Hence, EPO is a dominant alternative compared to DARB for the treatment of CIA. The analyses presented here are not without limitations. Specifically, although the studies were comparable, patients were ultimately drawn from different populations.     

Dosing patterns,drug costs,and hematologic outcome in anemic patients with chronic kidney disease switching from darbepoetin alfa to epoetin alfa

ABSTRACT

Objective: To compare real-world dosing patterns, drug costs, and hematologic outcome in anemic chronic kidney disease (CKD) patients, not receiving dialysis, who switched from darbepoetin alfa (DARB) to epoetin alfa (EPO) in a community practice setting.

Research design and methods: This retrospective observational chart review from a US nephrology clinic included 153 anemic CKD patients ≥ 18 years of age who did not receive dialysis during the study period, switched from DARB to EPO between 8/2003 and 8/2005, and received ≥ 2 doses of both agents. Paired t-test and McNemar's chi-square were performed comparing pre-switch and post-switch outcomes.

Results: Mean interval between doses increased from 24.3 ± 11.1 days with DARB to 28.8 ± 19.8 days with EPO (?p = 0.001). Weighted mean pre-switch weekly dose for DARB was 25?µg, while weighted mean post-switch weekly dose for EPO was 7090 Units, resulting in a dose ratio (Units EPO:µg DARB) of 287:1. These doses resulted in mean weekly costs of $110 (DARB) and $86 (EPO). Mean hemoglobin (Hb) levels increased over time from 10.8?g/dL at 6 months pre-switch to 11.1?g/dL 6 months after EPO initiation (?p = 0.0132). Mean Hb levels were > 11?g/dL, but below 12?g/dL, while patients received EPO.

Conclusions: Patients switching from DARB to EPO had a greater mean interval between doses, lower drug costs, and consistently maintained recommended Hb levels over time.

Limitations: The reverse direction (EPO to DARB) was not investigated. Although treatment outcomes were not assessed in a randomized, controlled setting, the study's observational nature provided actual evidence in a real-world setting.     

Stability of multidose, preserved formulation epoetin alfa in syringes for three and six weeks.

The integrity and biological activity of multidose, preserved formulation epoetin alfa stored in syringes at 2-8 degrees C were studied. Three independent 1.0-mL hubless syringes of epoetin alfa 20,000 units/mL were aseptically prepared and refrigerated for three and six weeks (a total of six syringes). Protein integrity was assayed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and glycoprotein detection. Biological activity was determined through a cell-based proliferation assay. The presence or absence of microbial contamination was observed after a one-week culture. A multidose, preserved formulation of epoetin alfa that was opened only at the time of assay served as the reference standard. SDS-PAGE silver-stained gels and immunoblots demonstrated no evidence of erythropoietin degradation after three and six weeks of storage when compared with the reference standard. In addition, SDS-PAGE, immunoblotting, and direct glycoprotein detection found that protein glycosylation was unaffected by the storage. Student's t test detected no significant difference between stored samples and the reference standard in biological activity (p > 0.05). A culture of epoetin alfa in bacterial and eukaryotic cell growth media showed no evidence of contamination. The results suggest that epoetin alfa can be dispensed to patients in prefilled syringes every four to six weeks to coincide with their peritoneal dialysis schedule. The integrity and biological activity of 20,000 units/mL epoetin alfa in prefilled syringes remain intact after three and six weeks when stored at 2-8 degrees C.     

Improvements in health-related quality of life among methadone maintenance clients in Dar es Salaam,Tanzania

BackgroundInjection of heroin has become widespread in Dar es Salaam, Tanzania and is spreading throughout the country. To prevent potential bridging of HIV epidemics, the Tanzanian government established a methadone maintenance treatment (MMT) clinic in February 2011. We assess the effect of MMT on health-related quality of life (HRQOL) and examine factors, particularly HIV infection and methadone dose, associated with changes in HRQOL.MethodsThis study utilized routine data on clients enrolling in methadone from February 2011 to April 2012 at Muhimbili National Hospital. Change in physical (PCS) and mental health (MCS) composite scores, as measured by the SF-12 tool, were the primary outcomes. Backward stepwise linear regression, with a criterion of p < 0.2 was used to identify baseline exposure variables for inclusion in multivariable models, while adjusting for baseline scores.ResultsA total of 288 MMT clients received baseline and follow-up assessments. Mean methadone dose administered was 45 mg (SD ± 25) and 76 (27%) were confirmed HIV-positive. Significant improvements were observed in PCS and MCS, with mean increases of 15.7 and 3.3, respectively. In multivariable models, clients who had previous poly-substance use with cocaine [p = 0.040] had a significantly higher mean change in PCS. Clients who were living with HIV [p = 0.002]; satisfied with current marital situation [p = 0.045]; had a history of suicidal thoughts [p = 0.021]; and previously experienced cognitive difficulties [p = 0.012] had significantly lower mean change in PCS. Clients with shorter history of heroin use [p = 0.012] and who received higher methadone doses [p = 0.028] had significantly higher mean change in MCS, compared to their counterparts.ConclusionAspects of mental and physical health, risk behaviors and quality of life among drug users are intertwined and complex. Our research revealed positive short-term effects of MMT on HRQOL and highlights the importance of sustained retention for optimal benefits. Comprehensive supportive services in addition to provision of methadone are needed to address the complex health needs of people who inject drugs.