Welcome To ANEMIA ALERT!

Nation’s Kidney Doctors Express Concern Over U.S. Food and Drug Administration’s Health Advisory on Anemia Drugs

- Renal Physicians Association States That Changes in Anemia Management Should be Made Carefully and Be Based on Clinical Judgment on A Patient-by-Patient Basis

ROCKVILLE, MD (March 12, 2007) – In response to the F.D.A.'s recent public health advisory citing potential dangers of overusing Erythropoiesis-Stimulating Agents (ESAs), the Renal Physicians Association (RPA) urges caution among its doctors and patients when considering any changes to anemia management regimens. While the F.D.A.'s black box warning should certainly be closely evaluated by nephrologists, RPA is concerned that initial response to the announcement and media reports could lead to unacceptably low hemoglobin levels in patients with Chronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD). Furthermore, RPA believes that the advisory as currently drafted may be misleading and only partly applicable to CKD and ESRD patients, and as a result could cause “considerable confusion” among kidney patients and the kidney community. Anemia-management drugs have been well demonstrated to improve quality of life for CKD patients, both adult and pediatric, and have been accepted for use in this population since approval of ESAs in 1989. Before the advent of ESAs, blood transfusions were the only effective treatment for boosting dangerously low blood counts. The RPA believes that some of the FDA advisory recommendations do not apply to CKD patients. Therefore, the RPA recommends that the risk and benefits for ESA use must be considered on an individual patient basis by the patient's kidney doctor. The clinical standard of care has been to maintain hemoglobin concentration ≥11 g/dL, and evidence-based guidelines should continue to guide therapy. RPA encourages nephrologists to continue making treatment decisions based on clinical judgment, and patients to consult their doctors with any questions about the recent advisory.

RPA Guidance to Nephrology Care Providers Regarding the FDA Public Health Advisory on ESAs

- The FDA issued a public health advisory and black box warning on March 9, 2007 regarding Erythropoiesis-Stimulating Agents (ESAs) that addressed serious and life-threatening side effects in patients treated with these agents. RPA believes that the advisory and black box warning as currently drafted may be misleading and only partly applicable to CKD and ESRD patients, and as a result have caused considerable confusion in the kidney community.

INFORMATION FOR NEPHROLOGY PROVIDERS

The FDA black box warning regarding ESA use states:

• ESAs should be used in the lowest dose sufficient to avoid blood transfusion.
• Target Hgb greater than 12 g/dL increases the risk for death and serious CV events.

The RPA is concerned that the perception from the FDA Advisory and the public press response to the FDA Advisory could lead to unacceptably low Hgb levels.

The RPA notes that the evidence linking increased risks and higher Hgb were for target Hgb levels ≥13 g/dL.

Hgb target ranges are no longer included in the package insert guidelines. The RPA recommends that evidence based targets are helpful and should be reintroduced in the package insert guidelines.

The RPA recommends that the risk and benefits for ESA use must be considered on an individual patient basis. The clinical standard of care has been to maintain Hb concentration ≥11 g/dL, and evidence-based guidelines should continue to guide therapy.

ESAs have been well demonstrated to improve QOL for CKD patients, both adult and pediatric. This has been an approved indication for ESA use since its initial approval in 1989.

The FDA Advisory states that ESAs should not be given to treat symptoms of anemia or poor quality of life (QOL). The RPA believes that this statement should not be directed at chronic kidney disease patients. This is ambiguous in the FDA Advisory and the subsequent public press.

CONSIDERATIONS FOR DISCUSSION WITH PATIENTS

There is a long history of the clear benefit of ESA use.

Any overreaction to the public release of the FDA Advisory should not interfere with best clinical judgment.

The appropriate decisions for use of ESAs with any individual patient should strictly be made by the nephrology provider and their patient.

We believe some of the FDA Advisory recommendations do not apply to CKD patients and this fact has not been fully differentiated in the public press.

Physicians should use their best judgment in the determining the dosing, monitoring and utilization of ESAs.

RPA will continue to be involved in the discussion and rational debate over the FDA position as elaborated in the advisory and will provide the nephrology provider community with clear and concise summaries of our recommendations. The FDA advisory on ESAs is available at www.fda.gov/cder/drug/advisory/RHE2007.htm.

Darbepoetin alfa safe and effective with once monthly dosing in CKD with anemia.

An open-label study of 152 enrolled patients with moderate chronic kidney disease and anemia and a stable hemoglobin (Hb) on darbepoetin alfa every two weeks (Q2W) were transferred over to every month (QM) dosing without significant decrease in safety or efficacy.

The patients all had a glomerular filtration rate of ≥15 and ≤60 ml/min/1.73 m² and were not receiving dialysis. Diabetes (51%) was the most common cause of CKD. The mean age was 66.9 years and 64% or the patients were over 65.

The group, of which 52% were women and 64% white, had anemia treated with Q2W darbepoetin to maintain their Hb in the range of 11.0 to 13.0 g/dL consistent with the guidelines by the National Kidney Foundation Disease Outcome Quality Initiative (KDOQI™). Darbepoetin alfa was administered subcutaneously within 4 days of enrollment and the QM for 28 weeks. Iron replacement therapy was give orally to 106 patients (71%). Twenty patients (13%) received intravenous iron.

The primary end-point was the proportion of subjects who maintained a Hb concentration of ≥11.0 g/dL during the evaluation phase. Secondarily, Hb values and darbepoetin dose were evaluated over the duration of the study. Visits occurred every 2 weeks until week 33 and a follow up was done 4 weeks after administration of the last dose. Adjustment of doses was done to keep the Hb in the study range. The median (95% CI) dose was 125.0µg (115.0 to 150.0). Median QM doses of darbepoetin alfa remained steady throughout the study

The primary end point was achieved by 85% pf the patients while 76% of the patients who had received at least one dose of darbepoetin alfa achieved end point. Adverse events were typical of the study population, occurring in 122 patients (81%), and were mostly mild to moderate. Serious events occurred in 43 patients (29%), but were not considered related to treatment. Only 9 patients (6%) were considered to have a treatment related adverse events: 3 experienced hypertension; 3 patients (2%) withdrew because of adverse events (one from coronary artery disease, another with asthenia, and one with small-cell lung cancer).

NAAC Expert Opinion: Anemia is highly prevalent in patients with CKD. Until recently treatment was either not given, or short-acting erythropoietic stimulators (ESAs) were used. These are effective in this patient population, but require frequent clinic visits for injections. In an attempt to improve convenience for patients and providers, and to improve patient adherence, a longer acting form of ESA , darbepoetin alfa (DA) was developed and approved for use weekly or every other week. Because the half-life of this agent is 48 hours when given subcutaneously it was speculated that once monthly administration would also be effective.

In this study Agarwal and colleagues administered DA once monthly to patients previously stabilized on every other week DA to see if hemoglobin could be maintained and if dose escalation was required for this. They report that conversion from every other week to once monthly DA was able to maintain the Hb stable without a need to increase the dose, likely a reflection of the long half life of this agent. Although the current label does not recommend once-monthly treatment, this study clearly shows that such an approach is reasonable, safe, and likely to improve patient adherence. Future studies need to examine whether there are any other advantages to less frequent administration, such as a decrease in hemoglobin variability, a problem with short acting ESAs.

For additional information on this research, please reference the source article:
Agarwal AK, Silver MR, Reed JE, Dhingra RK, Liu W, Varma V, Stehman-Breen C. An open-label study of darbepoetin alfa administered once monthly for the maintenance of haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis. J Int Med. 2006;260:577-585

Epoetin beta prevents anemia in platinum-based chemotherapy treated patients.

Treating patients with platinum-based chemotherapeutics for solid tumors commonly results in anemia, often severe. These agents damage the renal erythropoietin-producing cells as well as having a direct myelosuppressive effect. Besides anemia's important role in a patient's quality of life (QoL) due to fatigue and other factors, it is also an adverse prognostic indicator in cancer patients.

This study looked at 255 patients with histologically or cytologically confirmed solid tumors and treatment with platinum-based chemotherapy (cisplatin, carboplatin, and oxaliplatin). To be enrolled, the patients had to have a baseline Hb of ≤13g/dL for men and ≤12 g/dL for women, or fell to these levels after one or more chemotherapy cycles.

Patients were treated with 450 IU/kg (about 30,000 units IU) weekly in divided doses until a period of 4 weeks after their last chemotherapy cycle. Doses were increased or decreased if Hb levels fell less than 1 g/dL or rose above 14 g/dL. If a patient's Hb decreased by 1 g/dL despite dose increases, the patient was removed from the study. Iron supplementation was given at the discretion of the treating physician. Transfusions were given if deemed necessary.

Efficacy was assessed based on an anemia prevention response rate (Percent of patients with a Hb response plus the percentage of patients who maintained their Hb at ± 1 g/dL of its baseline.) Hemoglobin response was defined as a rise of Hb level of > 1 g/dL from baseline. Quality of life was measured by the linear analog self-assessment (LASA) for energy level, ability to perform daily activities, and overall QoL.

Forty-one patients either were lost to follow up or did not complete the study treatment period and/or the 30 day follow up assessment. Other withdrawals included adverse events related to epoetin in 4 patients (1.6%), patient decision in 16 patients (6%), and lack of response in 5 patients (2%). Sixty-four percent remained on the starting dose of epoetin beta throughout the study. Twenty-one percent required a dose increase while 3% had a dose decrease.

An anemia prevention response was observed in 92% (234) of the patients. A greater than 1 g/dL response to epoetin beta of was noted in 62.4% (159) of the patients. This response was rapid with 90.5 % improving at the 10,000 IU three times a week (TIW) level. By the 4 week assessment level, 87.4% (139) had responded. Seventy-five patients maintained a Hb of ±1 g/dL versus baseline despite platinum-based chemotherapy. There were no significant differences in response to epoetin beta between patients with different tumor types.

Epoetin beta was well tolerated in this study. Six patients (2.4%) had a treatment related adverse event. Five adverse events in 4 patients were rated as possibly related to epoetin beta therapy. These were a cerebral thrombosis, left inferior thrombosis, a venous thrombosis in the lower limb, and a skin reaction. Two adverse events, venous thrombosis and arterial ischemia, were identified as probably related to epoetin beta therapy.

Quality of life was significantly improved (P<0.01) and performance status was maintained in patients with a response to epoetin beta of >1 g/dL.

The study confirms the use of epoetin beta as an early intervention in patients with solid tumors treated with platinum-based chemotherapy. Ninety-two percent of patients had an increase of Hb levels or maintained their Hb within ± 1 g/dL of baseline.

NAAC Expert Opinion: DeCastro et al. sought to measure the efficacy and safety of epoetin-beta in solid tumor patients receiving platinum-based chemotherapy. In contrast to current recommendations, threshold Hb values were a gram higher in women and 2 grams higher in men, and the recombinant erythropoietin was administered three times weekly (total dose, 30,000U) rather than once weekly. Not surprisingly, the objective of an increment in Hb of 1 gm/dL or greater was achieved in 60% of patients, and an additional 30% maintained a Hb level of ±1gm/dL while on chemotherapy. Twenty-one percent of the patients required dose escalation, while only 3% required dose reduction. Only 12.5% of patients received transfusions, given at physician discretion. However, 12.5% required treatment interruption due to achieving a Hb of 14 gm/dL or greater. Whether these were men or women was not stated. Not unexpectedly, quality of life improved in responsive patients. Most importantly, considering the high initial Hb threshold, and the higher treatment hemoglobins obtained, thrombotic episodes occurred in only 2% of patients.

Unfortunately given the lack of a control arm, this study provides no information as to whether recombinant erythropoietin was necessary to prevent anemia or transfusions in the particular patient population under study. Contrary to the contention of the authors, the low transfusion rate observed is uninterpretable because without a control group, no baseline transfusion requirement could be established. Furthermore, blood transfusion requirements are not just a function of the Hb level. This same criticism applies to the quality of life data.

The 60% overall response rate to recombinant erythropoietin is comparable to what has been observed in other clinical trials. The only useful finding, therefore, is the very low thrombosis rate in a group of anemic cancer patients with Hb levels higher than usually recommended for treatment with recombinant erythropoietin.

For additional information on this research, please reference the source article:
De Castro J, Ordóñez A, Isla D. Sánchez A, Arrivi A, Manzano JL, Barón MG. Early intervention with epoetin beta prevents severe anaemia in patients with solid tumors receiving platinum-based chemotherapy: results of the NeoPrevent study. Cancer Chemother Pharmacol. 2007;59:35-42.

Iron deficiency anemia may be presenting sign of pouchitis post-surgery.

A small study of patients following surgical ileal pouch with anal anastomsis (IPAA) treatment for ulcerative colitis identified a trend suggesting iron deficiency anemia may be a presenting sign of pouchitis, defined for the study as 3 or more episodes of stools per day above postoperative baseline, diarrhea, rectal bleeding, abdominal cramps, fecal urgency, weight loss, fever, chills, tenesmus, and arthralgias.

Eighteen patients with a confirmed diagnosis of ulcerative colitis who had undergone IPAA were enrolled in the study. The majority (61%) were women. Ten (55%) of the 18 had anemia, 8 (72.8%) of these were women. Along with a careful menstrual history in the women, all the patients had regular follow up visits. They were all participating in a IPAA surveillance protocol in a gastroenterology research unit as well as this study.

Other common postoperative complications were also followed, including stricture (44%, all dilated successfully), pouch failure (11.1%), urinary incontinence (11.1%), and fecal incontinence (11.1%).

All ten of the patients with iron deficiency anemia had pouchitis (100%).The anemia preceded the pouchitis in 5 of these 10. The other 5 developed anemia at the same time as they had pouchitis symptoms. Eight patients had normal hemoglobins, but only 4 of these had pouchitis. The median hemoglobin in the anemia group was 9.9 g/dL. Of the 8 women with anemia and pouchitis, 6 had red blood cells that were hypochromic and microcytic. Two (33%) were normochromic and normocytic.

Possible causes of the anemia were insufficient intake, impaired absorption and increased requirements, and/or blood loss. While a trend was suggested by this study, the authors recognized that a larger number of patients need to be studied to confirm the findings.

NAAC Expert Opinion: Inflammatory bowl disease (IBD) carries with it a high incidence of anemia, presumably as a result of gastrointestinal blood loss.  Surgical intervention in selected patients has had an important effect on well-being.  However, it is recognized that the development of anemia is still an issue for many patients.  Drawing on a small group (n=18) of patients with ulcerative colitis who have undergone surgery (ileal pouch with anal anastomosis), the investigators have estimated the frequency of iron deficiency anemia and its association with ‘pouchitis', defined by both clinical criteria and histopathologic findings at endoscopy.  They found that over half of the patients (10 of 18) developed iron deficiency and all 10 had ‘pouchitis.'  Of the non-anemic patients, only 4 of 8 had ‘pouchitis.'  ‘Pouchitis' was said to be asymptomatic in half of the anemic patients.  The authors then go on to speculate what the causes might be, and propose that iron deficiency may be a presenting feature of ‘pouchitis' 

These findings come as no surprise.  What would have lent more value to the study would have been to perform an oral iron absorption test to determine if the patients could absorb medicinal iron or not.  In surgery for IBD or bariatric surgery, iron deficiency anemia is increasingly recognized.  But beyond recognition, it is important in any given patient to understand the mechanism by which iron deficiency is brought about.  Pointless administration of oral iron delays effective treatment and contributes to suboptimal quality of life for these patients.

For additional information on this research, please reference the source article: Pastrana R, Torres E, Arroyo J, Rivera C, Sánchez, Morales L. Iron deficiency anemia in presentation of pouchitis. J Clin Gastroenterol 2007;41-41-44.

Physiologic model of iron status in infancy used to predict risk of iron deficiency.

A logistic regression model were used to determine factors that predicted anemia, iron deficiency (ID)and iron deficiency anemia ( IDA ) in a study of 1657 Chilean children infants at 12 months of age who had birth weights ≥3 kg. Ninety-three percent were randomly assigned at age 6 months into one of three groups: (1). No added supplemental iron. (2). Low iron supplementation. (3). High iron supplementation. The other infants were enrolled in a neurophysiologic trial and excluded from this study.

The research, conducted between 1991 and 1996, followed healthy infants, excluding major problems in demographic details, confounding maternal or perinatal factors, and, exclusive breastfeeding. In 1994, breast feeding was included as a study parameter and was defined as < 250 ml cow milk or formula per day plus breast feeding. All infants were screened for Hb determinations at 5-6 months of age.

The low-iron group received formula averaging 2.3 mg of iron/L. In the high-iron group, those infants whose bottle intake was ≥250 mL/d received formula averaging 12 mg iron/L. Infants taking < 250 mL/d and breast feeding the rest of the time were given vitamins containing 15 mg ferrous sulfate. In the no added-iron group, infants received vitamins without iron whether breast fed or receiving unmodified powdered cow milk, routine in Chile at the time.

The infants were retested at 12 months. Independent variables considered for inclusion in the models were measures of factors influencing iron status in the physiologic framework, such as criterion related to iron at birth were gestational age, birth weight and maternal iron status. Sex and family influences were additional predictors.

At the conclusion of the trial, 571 infants (34.9%) met the criteria of ≥2 abnormal iron measures. Of 186 infants with Hb <11.0 g/dL, 158 (84.9%) had ≥2 abnormal iron measures.

Iron status varied substantially between groups with the no iron-added group having significantly poorer iron status (52.1% total ID and IDA ) than the other groups. The low-iron group had the highest prevalence of ID without anemia (36.7%). The high-iron group had the lowest prevalence of both outcomes (18.6%). There was no statistical significance between the iron-added groups in the prevalence of anemia or IDA . Predictors of anemia and IDA varied depending on iron supplementation, male sex, lower gestational age and lower birth weight (although all infants were born ≥37 wk and ≥3 kg), lower Hb at age 6 months (even though IDA had been excluded and treated), more weight gain over the first year of life, and lower maternal education and SES. Intake of cow milk did not predict IDA . Intake of formula in the high-iron group was an inverse predicator for anemia and a suggested a trend toward IDA with the lower volume intake. A lower Hb and rapid weight gain were also statistically significant risk factors. By far the strongest effect on iron status across all supplementation groups was the Hb at 6 months.

NAAC Expert Opinion: This is a large interventional (prevention) study that examined the risk factors for developing iron deficiency (ID), iron deficiency anemia (IDA) or no anemia in Chilean children.  The study begins at the age of 6 mos. and continues for an additional 6 mos. with evaluation of Hb and iron parameters in groups of children randomized to receive either no, low or high iron supplementation.  Factors that were either known or were predicted to influence the outcomes included Hb level at 6 mos., intake of cow milk, gestational age at birth, gender (male children would be expected to have greater iron requirements because of more rapid growth between 6 and 12 mos. of age), etc.  The criteria for anemia and iron status were carefully outlined.  ID was diagnosed if 2 of 3 iron parameters were abnormal.  These included MCV, free erythrocyte protoporphyrin, and serum ferritin.

“ID was clearly a problem for this population.  At the conclusion, 35% of infants met the criteria for ID and almost all of the anemia was due to ID (85% of anemic children had at least 2 abnormal iron parameters).   For all outcomes, infants in the no iron supplementation group had significantly poorer iron status than did those in the low or high iron supplementation groups.”  This is probably not a surprise and points out the vulnerability of infants to develop iron deficiency.  “For the group that did not receive supplemental iron, several predictors of ID or IDA at 6 mos. were no longer significant in the groups that received supplemental iron.”  In fact, the authors were somewhat surprised that “the only consistent (and strongest) predictor of ID or IDA at age 12 mos. was a lower Hb level at age 6 mos.”  Another result that was stated to be surprising was that “indicators of available iron in the diet (formula or milk) were not strong predictors of iron status in the population.” 

“The analytic approach to the data in this study was chosen to facilitate comparison with a similar study from Europe .  The only congruent finding was that greater formula intake protected against ID in Europe and against anemia in Chile .  Otherwise, no overlap in significant predictors was found.”  Therefore, are these results generalizable?  The authors, appropriately, conclude that they are not.  Variables that make inter-study comparisons problematic include the extent of breastfeeding, use and interpretation of laboratory tests to assess iron status, prevalence of iron status in the mother, etc.  Nevertheless, the value of the study is to remind us, once again, that ID and IDA are common in young children.  Since this study (and others) clearly demonstrates the effectiveness of iron supplementation in preventing ID and IDA , and since ID and IDA can be associated with growth retardation and impaired learning, there can be little doubt about the importance of identifying infants at risk and intervening to prevent the consequences of an inadequate intake of iron. 

For additional information on this research, please reference the source article:
Lozoff B, Kaciroti N, Walter, T. Iron deficiency in infancy: applying a physiologic framework for prediction. Am J Clin Nutr. 2006;84:1412-21

Communication between patient and provider regarding anemia and fatigue studied.

A task force of oncology and linguistic experts was gathered to study objectives, methodology, and linguistic analysis in the interaction between doctor and patient and allied health professionals (AHPs) regarding information exchange about chemotherapy-induced anemia and fatigue in patients with cancer. Thirty-six patient visits were felt to be appropriate for analysis based on previously published work in the field of interactional sociolinguistics.

Six oncologists and 9 hematologist/oncologists met the screening criteria. AHPs were not recruited directly but recorded and interviewed if they participated more than routine patient care. The final sample included 36 patients of which 53% were female. The average age was 62.3 years. None of the participants were aware of the specific focus of the study. After obtaining written consent from all parties, the office was video- and audio-taped. The camera lens was covered at the participant's option while audio taping continued. Post-visit interviews were used to match or mismatch participant's perceptions regarding issues discussed during the visit.

Using linguist evaluative techniques, key areas of investigation were measured. They included quantification of topics discussed and time spent on the topic, word-level analyses of key terms, the number, type and source of questions asked and answered, overall patterns of interaction , and “open door/closed door” of topics that were introduced or blocked in the conversation.

The results showed that conversations about side effects are taking place but are not systematic or goal-driven. Conversations about side effects were routine (34 of 36 visits) and clinician initiated (27 of 34 visits), but lacked quality, were brief, and often minimally interactive. Vocabulary describing the side effects was imprecise, resulting in dialogues that did not allow patients to vocalize their experience. Words such as “listless,” “yucky,” “weak,” or “worn out” were used to describe fatigue, making determining improvement or deterioration difficult in subsequent evaluations of fatigue. Further, fatigue measurement instruments such as Linear Analogue Self-Assessment (LASA) or Functional Assessment of Cancer Therapy ( FACT ) were not used or referenced.

Without systematic evaluation or in-depth communication, the discussions of chemotherapy-induced anemia did not further the clinician's understanding of the true nature of the patient's condition. The implications of the findings raise important questions and suggest several areas that could form the basis for improved communication techniques for clinicians in an era where patient contact is being eroded.

NAAC Expert Opinion: In this innovative observational study, the authors recorded interactions between patients undergoing chemotherapy and their physicians or allied healthcare providers with respect to the discussion of anemia and fatigue. The methodology was sound and the results of interest since they provide a window onto patient-healthcare provider interactions in the community setting. Unfortunately, however, given the wealth of data collected, very little is provided in the article. What comes through clearly though, is the limited time of the patient-healthcare provider encounters, the low rate of patient-initiated discourse about fatigue and the superficial nature of the conversations, at least as they related to anemia and fatigue. Since no laboratory data were provided, the extent to which the degree of anemia or infection impacted on patient or healthcare provider-initiated comments cannot be assessed. At the same time, chemotherapy-naive and experienced patients might be expected to react differently as might patients with mild or extensive disease and this was not factored into the data analysis.

It is unclear to this reviewer why one focus was on anemia, other than for commercial purposes, since patients would not be expected to speak in clinical terms or to necessarily correlate their symptoms with a Hb value or even the concept of anemia. Furthermore, fatigue is a consequence of many more factors than anemia. In addition, given the limited time these community physicians allotted to their patients, the suggested concept of employing validated patient questionnaires to improve communication in the setting of a community clinical practice is an open question.

For additional information on this research, please reference the source article:
Davidson B, Blum D, Cella D, Hamilton H, Nail L, Waltzman R. Communication about chemotherapy-induced anemia. J Support Oncol. 2007; 5:36 -40.

Epoetin delta effective in anemia of chronic kidney disease.

Epoetin delta is the only erythropoietin produced in a human cell line. The glyscosylation is different when compared to currently available epoetins. This study investigates the efficacy and safety of epoetin delta.

Anemia associated with Chronic Kidney Disease (CKD) has been well established. In this study, 75 epoetin-naïve patients with CKD were treated with epoetin delta. They were randomized to 15, 50, 150 or 300 IU/kg doses of epoetin delta or epoetin alfa at 50 IU/kg. Baseline Hb was < 10.0 g/dL. Patients initially were entered into a correction phase where the aim was to achieve two consecutive weekly Hb measures of ≥11.5 g/dL or a ≥13.0 g/dL single Hb measurement.

Safety evaluation was performed on all patients receiving at least one epoetin delta dose (75/78). The efficacy population (67/78; 85.9%) studied all treated patients who had at least two Hb values during the correction phase along with a baseline Hb. Baseline hematological parameters for the study population (n=63; Hb 8.66 ±0.94 g/dL) were similar to the epoetin alfa groups (n=15; Hb 8.57 ±0.82 g /dL).

Total success in the epoetin delta dose group 150 IU/kg and 300 IU/kg was 55.6% (15/27) compared with the lowest (15 IU/kg) dosing group (4.5% (1/22)) (p=0.0002).

As dose increased, success increased with a significant trend across the epoetin delta dosing groups (p=0.0001). Pairwise analyses of total success indicated significant differences between the 15 IU/kg dosing group and the 150 IU/kg group (p=0.0026) and 15 IU/kg group and the 300 IU/kg group (p=0.0004). No significant difference was noted between the epoetin delta 15 IU/kg group and the 50IU/kg epoetin alfa group.

Safety and tolerance were similar between epoetin delta (93.4%) and epoetin alfa (92.9%) and consistent for this patient group. Possibly related adverse events occurred in 11.5% of patients in the epoetin delta group and 0% in the epoetin alfa group. These events included puritis, diarrhea, headache, hypertension, neuropathy, paresthesia, thrombocytosis, and thrombosis. All but one of these events were considered to be mild-to-moderate. There was no evidence of any adverse event being related to dose. No patient developed neutralizing anti-erythropoietin antibodies in this study.

Further investigations are needed to examine whether the differences between epoetin delta and recombinant, CHO cell line-derived erythropoietins lead to any clinical benefit.

NAAC Expert Opinion: Although epoetin alfa dominates the erythropoietic stimulator ( ESA ) market, epoetin beta and epoetin omega, are additional forms of short-acting ESA that have been in clinical use throughout the world. Spinowitz and colleagues report on the safety and efficacy of another short-acting ESA , epoetin delta. This compound is different from other short-acting ESAs because it is produced in human, rather than CHO cells.

This study compared various doses of epoetin delta in hemodialysis patients and showed that higher doses led to a higher fraction of “responders” defined by change in Hb level, not a surprising finding. At the doses used, however, fewer responders were seen than would be with typical doses of other ESAs, suggesting that additional studies with higher doses are needed. The side-effect profile for epoetin delta was similar to that reported with other ESAs. It was not clear from the discussion what advantage this agent would have over other ESAs, and with other more innovative approaches to anemia management on the near horizon, EPO mimetics and HIF-PH inhibitors, for example, this compound will seemingly face a difficult battle differentiating itself to clinicians.

For additional information on this research, please reference the source article:
Spinowitz B, Pratt R. Epoetin delta is effective for the management of aenemia associated with chronic kidney disease . Curr Med Res Opin. 2006;22(12):2507-2513