Prophylaxis with recombinant factor IX Fc fusion protein reduces the risk of bleeding and delays time to first spontaneous bleed event in previously untreated patients with haemophilia B: A post hoc analysis of the PUPs B-LONG study.

OBJECTIVES: Haemophilia B (HB), characterised by deficient factor IX (FIX), leads to spontaneous bleeds. Severe cases require prophylactic FIX replacement. This post hoc analysis assessed the first spontaneous bleeds among previously untreated patients (PUPs) with HB treated with recombinant FIX Fc fusion protein (rFIXFc) (NCT02234310) to identify factors influencing bleeds. METHODS: Subjects included paediatric PUPs with HB (≤2 IU/dL endogenous FIX). Analyses described treatment patterns (on demand [OD] vs. prophylaxis) and prophylaxis type (started on vs. switched to prophylaxis). Kaplan-Meier analyses assessed the time to first spontaneous bleed, including median time to event and fitting models with predictors for treatment regimen and/or baseline age. RESULTS: PUPs B-LONG enrolled 33 subjects. Baseline age did not influence the time to first spontaneous bleed for any rFIXFc regimen. Those who started on prophylaxis with rFIXFc (n = 11), compared with those treated OD (n = 22), had an extended time to first spontaneous bleed. Starting prophylaxis afforded a 93% reduced risk of first spontaneous bleed versus starting OD (hazard ratio [95% confidence interval]: 0.071 [0.009-0.592]) (p = .015). CONCLUSION: rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs.

A post hoc analysis of previously untreated patients with severe hemophilia A who developed inhibitors in the PUPs A-LONG trial.

ABSTRACT: Inhibitor development is a major therapeutic complication for people with hemophilia. The phase 3 PUPs A-LONG study evaluated the safety and efficacy of efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, herein referred to as rFVIIIFc) in previously untreated patients (PUPs) with severe hemophilia A. Male PUPs <6 years old were enrolled and received rFVIIIFc; inhibitor development was the primary end point. Post hoc analyses, including patient treatment regimen patterns and timing of inhibitor development, descriptive and Kaplan-Meier analyses of time to first inhibitor-positive test by treatment regimen and by titer, and consumption, were performed to describe patients who developed inhibitors during PUPs A-LONG. We investigated patient characteristics (eg, demographics and genotype) and nongenetic risk factors (eg, intense factor exposure and central venous access device [CVAD] placement) that may predict inhibitor development and characteristics of inhibitor development (low-titer vs high-titer inhibitor). Baseline characteristics were similarly distributed for age, race, and ethnicity across both patients who were inhibitor-positive and those who were inhibitor-negative (all P > .05). High-risk F8 variants were associated with development of high-titer inhibitors (P = .028). High-titer inhibitor development was often preceded by the presence of a low-titer inhibitor. Patients whose low-titer inhibitor progressed to a high-titer inhibitor received a higher mean dose per infusion (98.4 IU/kg, n = 5) compared with those whose low-titer inhibitor resolved spontaneously (59.2 IU/kg, n = 7; P = .033) or persisted (45.0 IU/kg, n = 5; P = .047). There was no association between CVAD placement surgery and inhibitor development. Post hoc analyses suggest that F8 genotype and dose of factor are as important as inhibitor risk factors and require further investigation. This study was registered at ClinicalTrials.gov as #NCT02234323.

Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

Once-weekly prophylaxis regimen of nonacog alfa in patients with hemophilia B: an analysis of timing of bleeding event onset.

In a pivotal, multicenter, open-label study, 25 patients aged 12-54 years with moderately severe/severe hemophilia B received on-demand nonacog alfa (6 months; dose at investigator's discretion) followed by once-weekly prophylaxis with nonacog alfa 100 IU/kg (12 months). During prophylaxis, patients had a median spontaneous annualized bleeding rate (sABR) of 1.0 and significant reductions in ABR (P < 0.0001). This post hoc analysis examined the time of onset of spontaneous bleeding events (sBEs) and spontaneous target joint bleeding events (sTJBEs). The postdosing day (D) of onset of sBEs observed during prophylaxis and steady-state FIX activity data (FIX:C) between 144 and 196 h postdose were collected at weeks 26 and 78. Twelve patients (48%) had no sBEs; the remaining 13 (52%) had the following onset of sBEs: less than 1 D (0%), 1 to less than 2D (5%), 2 to less than 3 D (22%), 3 to less than 4 D (9%), 4 to less than 5D (22%), 5 to less than 6D (23%), 6 to less than 7D (11%), and at least 7D (8%). Reductions in sBEs and sTJBEs during on-demand versus prophylaxis treatment were experienced by all 13 patients. Target joint sABR during prophylaxis was 0 for 5/13 patients. ABR reduction ranged from 66.1% (27.2→9.2) to 97.8% (46.2→1.0); sTJBE reductions ranged from 6.2% (2.1→2.0) to 100% (from 40.1, 19.1, 3.9, 9.0, 6.1--0). During prophylaxis, 47% (8/17) of trough FIX activity samples were more than 2%. In sBE patients, ABR and number of TJBEs were reduced with once-weekly nonacog alfa. When sBEs occurred, they followed no apparent pattern for day of occurrence. Clinicaltrials.gov identifier: NCT01335061.

First open-label, single-arm, prospective study of real-world use of FIX replacement therapy in a predominantly pediatric hemophilia B population in China.

BACKGROUND: Nonacog alfa (recombinant factor IX [FIX]) is approved in China for the control and prevention of bleeding events in patients with hemophilia B. This was the first study to assess prophylaxis and on-demand therapy with recombinant FIX replacement in a real-world setting in China. This study aimed to evaluate the safety and efficacy of nonacog alfa in Chinese patients with hemophilia B. METHODS: In this open-label, multicenter study (clinicaltrials.gov identifier NCT02336178), patients received on-demand or prophylactic treatment with intravenous nonacog alfa for approximately 6 months or 50 exposure days, whichever occurred first. The primary safety outcome was medically important events (i.e., development of FIX inhibitors, allergic reactions, and thrombotic events). Key secondary efficacy outcomes included the annualized bleeding rate for on-demand treatment and prophylaxis, response to on-demand treatment, the number of infusions per bleeding event, and the number of breakthrough bleeding events within 48 hours of prophylaxis. RESULTS: Seventy male patients (mean [standard deviation] age 7.8 [7.2] years) were enrolled (on-demand, n = 37; prophylaxis, n = 57 [24 patients were included in both groups]). Thirty-eight (54%) patients had up to 50 FIX exposure days before the study. The only medically important event was a transient low-titer FIX inhibitor (incidence 1.4%, 95% confidence interval, 0-7.7). The mean annualized bleeding rate was 26.3 for on-demand treatment and 6.5 for prophylaxis. A mean (standard deviation) of 1.5 (1.7) nonacog alfa infusions were given per bleeding episode; 78.8% of episodes resolved with 1 infusion. Response was "excellent" or "good" for 88% of the on-demand infusions. Twenty-three bleeding events (n = 11 patients) occurred within 48 hours of 2032 prophylaxis doses (1.13%). CONCLUSION: In the real-world setting, nonacog alfa is safe and effective for on-demand treatment and for prophylaxis for patients with hemophilia B in China.

Safety and Efficacy of Moroctocog Alfa (AF-CC) in Chinese Patients with Hemophilia A: Results of Two Open-Label Studies.

INTRODUCTION: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China. METHODS: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥6 years, previously treated with ≥1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery. RESULTS: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study. CONCLUSION: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A.

Assessment of Relative Bioavailability of Moroctocog Alfa and Moroctocog Alfa (AF-CC) in Subjects With Severe Hemophilia A.

An open-label, single-dose, randomized, two-period, crossover study comparing the pharmacokinetics of factor VIII activity in plasma (FVIII:C) after administration of an albumin-free presentation of moroctocog alfa (test) and moroctocog alfa manufactured using the previous technique (reference) was conducted in 30 (25 evaluable) male subjects who had severe hemophilia A (FVIII:C < 1 IU/dL). Blood samples were collected for 48 h after administration of each dose. FVIII: C was assayed using a chromogenic substrate assay. The FVIII:C pharmacokinetic parameters were calculated using noncompartmental analysis. The presentations would be bioequivalent if the 90% confidence limits of the ratio of the geometric mean values of AUCinf and recovery fell within the interval of 80-125%. The bioequivalence criteria were met. A total of 10 treatment-related adverse events were observed in a total of nine subjects. All were mild and none was determined to be related to administration of study medication.

Thrombogenicity evaluation in 221 patients with haemophilia B treated with nonacog alfa.

: Risk for thrombotic events with factor IX replacement therapy in patients with haemophilia B remains a concern for patients, those who treat them, and regulatory agencies, based on experience with early use of prothrombin complex concentrates. The current post hoc analysis assessed the incidence of thrombotic events and changes in prothrombin fragment 1 + 2, thrombin-antithrombin complex, and D-dimer in 221 patients with haemophilia B who received nonacog alfa in clinical studies. Thrombotic event and coagulation marker data were collected from 8 interventional studies utilizing on-demand, prophylactic, and preventive regimens in patients with haemophilia B. Mean age was 25 years (min-max, 0-69), with 51 (23%) patients aged less than 12 years and 15 (7%) aged less than 2 years. None tested positive for inhibitors. Mean time on study was 60.9 ±â€Š32 weeks and mean number of exposure days was 69.3 (min-max, 1-496). Sixty-nine (31%) patients regularly received infusions that were approximately 100 IU/kg as part of a routine prophylaxis regimen, and 29 (13%) patients underwent surgical procedures. No clinical thrombotic events were reported, and no patient experienced clinically significant changes in coagulation markers between baseline and end-of-study testing. These collective data support the low thrombotic risk associated with nonacog alfa in paediatric, adult, and surgical patients with haemophilia B receiving different treatment regimens, including doses of approximately 100 IU/kg. Although careful thrombotic clinical evaluation is important, regular coagulation marker monitoring does not appear to be warranted in patients with haemophilia B.

Confirmation of longer FIX activity half-life with prolonged sample collection after single doses of nonacog alfa in patients with haemophilia B.

A multicentre, single-dose study enrolled 12 previously treated patients with moderately severe to severe (factor IX [FIX] levels ≤2 IU/dl) haemophilia B to assess FIX pharmacokinetics after nonacog alfa administration and to evaluate the impact of length of sampling time on half-life (t½). After refraining from FIX replacement for four days, patients received 50 IU/kg as an intravenous (IV) infusion over 10 minutes. Blood samples were collected predose and 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72, and 96 h post dose. Tolerability and safety were assessed by monitoring adverse events and were subsequently summary tabulated. FIX activity was measured by a one-stage clotting assay with a lower limit of quantification of 0.010 IU/ml, and inhibitors to FIX were measured using the Bethesda assay. Pharmacokinetic parameters were calculated by noncompartmental analysis and were descriptively summarised. Half-life estimates were calculated first using all available data, then excluding 96-h observations (truncated at 72 h) and, finally, excluding both 72- and 96-h observations (truncated at 50 h). No patient was positive for FIX inhibitors. No treatment-emergent adverse events were reported. Prolonging the duration of the sample collection to 96 h resulted in a terminal t½ estimate of 39.6 ±7.4 h in the eight patients aged 18 years and older, which was longer than the estimates obtained using shorter periods of observation: 29.6 ± 5.5 h (truncated at 72 h) and 27.2 ± 7.0 h (truncated at 50 h). To accurately assess an adult patient's t½, sampling should be continued for at least 96 h.

Pharmacokinetics, Efficacy, and Safety of Nonacog Alfa in Previously Treated Patients with Moderately Severe to Severe Hemophilia B.

PURPOSE: Nonacog alfa, a recombinant factor IX (FIX) product, is used for FIX replacement in the treatment and prevention of bleeding events in patients with hemophilia B. This study aimed to provide supplemental pharmacokinetic (PK), efficacy, and safety data for nonacog alfa when administered as part of usual hemophilia care, including on-demand treatment, routine prophylaxis, and surgical prophylaxis. METHODS: Men with previously treated severe or moderately severe hemophilia B (FIX activity ≤2%) were enrolled in this prospective, open-label, nonrandomized, multicenter study. An initial 72-hour PK assessment was performed wherein patients received a single dose of nonacog alfa (75 IU/kg) as an infusion over 10 minutes. A final 72-hour PK assessment was performed at the patient's last visit, after a minimum washout period of 4 days. Correlations between Cmax after the first dose and body weight and body mass index (BMI) were assessed post hoc using Spearman test after evaluating normality. FINDINGS: In total, 23 patients (age, 12-59 years; weight, 44-173 kg; and BMI, 16.3-45.1) with previous exposure to FIX products (median, 460 days; range, 150-2400 days) were enrolled; 21 were evaluable for efficacy. The median number of exposure days per efficacy-evaluable patient in this study was 48 (range, 31-103). The FIX activity profiles showed multiphasic disposition characteristics, with initial mean (SD) PK profiles as follows: Cmax, 61.4 (12.5) IU/dL; AUC∞, 1055 (227) IU·h/dL; t½, 23.7 (5.6) hours; and recovery, 0.818 (0.167) IU/dL. Mean plasma FIX activity versus time profiles were essentially identical upon initial exposure and after repeated use (n = 17), and bioequivalence was confirmed. No apparent relationship was observed between Cmax and either body weight (P > 0.1732) or BMI (P > 0.1235). IMPLICATIONS: The FIX activity profile after administration of nonacog alfa is predictable and is not altered after repeated exposure during usual hemophilia care. PK parameters are consistent with nonacog alfa use for FIX replacement in on-demand treatment, routine prophylaxis, and surgical prophylaxis in patients with hemophilia B.

Nonacog alfa: an analysis of safety data from six prospective clinical studies in different patient populations with haemophilia B treated with different therapeutic modalities.

Nonacog alfa is a recombinant factor IX (FIX) product indicated for treatment and prevention of bleeding episodes in patients with haemophilia B. This posthoc analysis evaluated the safety of nonacog alfa in key clinical studies across 15 years. Data were pooled from six prospective studies that utilized on-demand, prophylactic and preventive nonacog alfa regimens: three open-label, nonrandomized studies that assessed efficacy and safety; a bioequivalence study of original and reformulated nonacog alfa; an open-label, randomized study that compared on-demand and prophylactic treatment; and a noninterventional observational registry study that evaluated safety. Safety assessments included adverse events, serious adverse events (SAEs) and events of special interest. In total, 412 patients received nonacog alfa treatment. Adverse events occurred in 220 patients (53.4%), the most common being pyrexia (n = 63), nasopharyngitis (n = 53) and cough (n = 52). Forty-eight patients (11.7%) experienced treatment-related adverse events; the most common were hypersensitivity (n = 6), urticaria (n = 6), FIX inhibition (n = 5) and pyrexia (n = 4). Seventy-four patients (18.0%) developed SAEs. Thirty-seven events of special interest occurred in 31 (7.5%) patients. Events of special interest included allergic-type manifestations (n = 15), inhibitor development (n = 5), lack of effect (n = 8), red blood cell agglutination in tubing or syringe (n = 7), and thrombogenicity (n = 2). Six patients (1.5%) withdrew due to seven adverse events: hypersensitivity (n = 3), drug eruption, pruritic rash, urticaria and decreased therapeutic response (n = 1 each). Four patients died during the study; no deaths were related to study medication. This pooled safety analysis in haemophilia B patients confirmed the safety of nonacog alfa across various patient populations.

Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

[Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer]. / Variables predictivas de respuesta a la eritropoyetina recombinante humana en pacientes con anemia y cáncer.

The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

Factors that influence the bleeding phenotype in severe hemophilic patients.

Hemophilia A and B are rare, X-linked bleeding disorders resulting from a partial or total deficiency of functionally active coagulation factor VIII or factor IX, respectively. Endogenous factor levels have traditionally been used to characterize the severity of the disorder, with severe hemophilia considered as circulating levels of factor less than 1% of normal. Identifying patients with severe hemophilia is essential to effective treatment, since these patients are at highest risk of spontaneous life or limb-threatening bleeding and disability resulting from repeated joint bleeding and are most likely to benefit from prophylaxis. However, there is variability in bleeding tendency, even among patients with severe hemophilia. This article will review potential modifiers of hemophilia-associated bleeding other than endogenous factor activity, which may influence bleeding tendencies and complications in hemophilic patients considered to have severe hemophilia. These potential modifiers include physiologic factors, such as elements of the hemostatic system; pathophysiologic factors, such as hemophilic arthropathy, associated inflammation, and angiogenesis; and others, such as seasonal variation, body weight, and physical activity.

The role of transfusion-transmitted virus in patients undergoing hemodialysis.

GOALS: To study transfusion-transmitted virus (TTV) infection in 75 patients on hemodialysis and examine its relationship with age, sex, duration of dialysis, history of transfusion, and chronic elevation of alanine aminotransferase (ALT) levels. STUDY: Serum TTV was analyzed by polymerase chain reaction (PCR), TTV genotypes by restriction fragment length polymorphism, and hepatitis C virus (HCV) RNA by PCR. RESULTS: Transfusion-transmitted virus was detected in 32 patients (42.7%). Transfusion-transmitted virus genotypes were as follows: G1 in 16 patients; G2, 3; G3, 1; G4, 2; G2-G5, 6; and unclassified, 4. Mean duration of dialysis was 37 +/- 32 months for TTV-positive patients and 43 +/- 37 months for TTV-negative patients (not significant). Twenty-seven (84%) TTV-positive patients and 27 (63%) TTV-negative patients had a history of transfusions ( p = 0.04). Chronic ALT elevation was observed in 9 patients; 5 of them were TTV-positive (16%) and 4 were TTV-negative (9%) (not significant). Four (40%) HCV RNA-positive patients and 5 (8%) HCV RNA-negative patients had chronic ALT elevation ( p = 0.003). Three TTV-positive patients with chronic ALT elevation were also infected with HCV. The two patients with isolated TTV infection did not have another clinical feature to explain their ALT elevation. CONCLUSIONS: Transfusion-transmitted virus had a high prevalence in the patients on hemodialysis; genotype G1 accounts for half of the cases. Transfusion-transmitted virus infection depends on the transfusional antecedent but not on the duration of dialysis. Chronic ALT elevation is significantly associated with HCV infection but not TTV infection. However, TTV could be a causative agent of chronic ALT elevation in some patients.

Tratamiento de la anemia en pacientes en hemodiálisis crónica con dosis bajas de eritropoyetina recombinante asociada o no a andrógenos / Anemia treatment in patients in chronic hemodialysis with low dosis of recombinant eritropoyetin associated or not with androgens

La utilización de Eritropoyetina Humana Recombinante (rHuEpo)es efectiva en el tratamiento de la anemia en pacientes en hemodiálisis crónica (HDC). El costo del tratamiento es un factor limitante en su utilización en la población de escasos recursos económicos. Los andrógenos han demostrado tener acción sinérgica con la rHuEpo probablemente por dos mecanismos: 1)estimular la liberación de la eritropoyetina (EPO), 2)aumentar la sensibilidad de los profenitores eritroides a la misma. Realizamos un estudio prospectivo asociando rHuEpo y andrógenos en pacientes con anemia en HDC. De acuerdo a los resultados, pensamos que la asociación de rHuEpo/andrógenos podría ser un esquema terapéutico alternativo en pacientes de escasos recursos económicos. (AU)

Tratamiento de la anemia en pacientes en hemodiálisis crónica con dosis bajas de eritropoyetina recombinante asociada o no a andrógenos / Anemia treatment in patients in chronic hemodialysis with low dosis of recombinant eritropoyetin associated or not with androgens

La utilización de Eritropoyetina Humana Recombinante (rHuEpo)es efectiva en el tratamiento de la anemia en pacientes en hemodiálisis crónica (HDC). El costo del tratamiento es un factor limitante en su utilización en la población de escasos recursos económicos. Los andrógenos han demostrado tener acción sinérgica con la rHuEpo probablemente por dos mecanismos: 1)estimular la liberación de la eritropoyetina (EPO), 2)aumentar la sensibilidad de los profenitores eritroides a la misma. Realizamos un estudio prospectivo asociando rHuEpo y andrógenos en pacientes con anemia en HDC. De acuerdo a los resultados, pensamos que la asociación de rHuEpo/andrógenos podría ser un esquema terapéutico alternativo en pacientes de escasos recursos económicos.

Empleo de eritropoyetina recombinante humana en la anemia de la insuficiencia renal crónica / The use of recombinant-human erythropoietin in the anemia of chronic renal failure

La anemia progresiva es una complicación frecuente de la insuficiencia renal crónica (IRC) y reconoce como causa mayor, la deficiencia relativa de eritropoyetina (Epo). Muchas evidencias clínicas avalan la utilidad terapéutica de la eritropoyetina recombinante humana (rHuEpo) en este tipo de anemia. El objetivo del protocolo fue demostrar la eficacia y seguridad de la administración a largo plazo de la rHuEpo en los niños para corregir su anemia. Treinta y cuatro niños portadores de IRC fueron tratados con rHuEpo bajo protocolo prospectivo. Dieciocho de ellos estaban sometidos a hemodiálisis crónica (HDC), nueve a diálisis peritoneal contínua ambulatoria (DPCA) y siete se encontraban en etapa predialítica (EPD). El 97.3 por ciento de los pacientes analizados respondieron adecuadamente, superando la hemoglobina blanco (10 g. por ciento) preestablecida. Un solo paciente, en quien la biopsia de médula ósea mostró fibrosis severa (mielofibrosis) tuvo respuesta parcial. Las dosis medias requeridas en el grupo HDC fueron mayores que los grupos DPCA y PD. Se observaron algunos efectos adversos similares a los previamente descriptos en adultos y niños. La exarcebación de la hipertensión arterial fue el más frecuente. En ningún caso debió suspenderse la administración de rHuEpo. Conclusión: la rHuEpo es efectiva y segura para corregir la anemia asociada a la IRC en los niños, evitando con su empleo las transfusiones sanguíneas repetidas.