Influence of recombinant human erythropoietin (rHuEPO) on plasma levels of selected hormones in females with rheumatoid arthritis Polish
Polskie Archiwum Medycyny Wewnetrznej. 2005;114((2):):731-7.
During recent years, it was shown, that treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis in patients both with renal and nonrenal anaemia. Additionally in patients with chronic renal failure treated with rHuEPO a significant, however only transient, influence on function of endocrine glands was also found. The present study aimed to asses for the first time the influence of rHuEPO on function of endocrine organs in anaemic patients with rheumatoid arthritis and normal renal function. Twenty two woman with rheumatoid arthritis and concomitant anaemia (Ht < or = 30%) were enrolled into the study. In 13 of them rHuEPO was used during 4 months (5000 IU 2 times per week s. c. ). The rest 9 woman with similar degree of anaemia did not receive rHuEPO therapy. In woman of both groups intensive clinical and biochemical monitoring during 4 months period was performed. Blood samples were withdrawn before and after 4 months of rHuEPO therapy or clinical observation only. In these blood samples plasma concentrations of somatotropin (HGH), insulin (IRI), aldosterone (ALD), atrial natriuretic peptide (ANP), 25-hydroxycholecalciferol (25OHD3), intact parathyroid hormone (iPTH) and plasma renin activity (PRA) were estimated. After 4 months of rHuEPO therapy significant increase of plasma IRI, ANP concentrations and significant decrease of PRA and plasma ALD, HGH concentrations were found. Therapy with rHuEPO does not influence significantly plasma iPTH and 25OHD3 concentration. During 4 months of clinical observation in patients not treated with rHuEPO, plasma concentrations of HGH, IRI, ALD, ANP, 25OHD3, iPTH and plasma renin activity (PRA) did not change significantly. Results obtained in this study suggest, that rHuEPO therapy does influence the function of endocrine organs also in patients with rheumatoid arthritis with normal renal function.
Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures
Rheumatology International. 1999;18((5-6):):201-6.
Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P < 0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = -0.47, P < 0.01), Hb (r = 0.37, P < 0.01) and changes in both DAS (r = -0.74, P < 0.01) and Hb (r = 0.44, P < 0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.
Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial
Annals of Internal Medicine. 1997;126((10):):782-7.
BACKGROUND Anemia often complicates Crohn disease and affects quality of life. OBJECTIVE To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease. DESIGN Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase. SETTING University-based gastroenterology outpatient clinic. PATIENTS 40 patients with Crohn disease and a hemoglobin concentration of 10.5 g/dL or less. INTERVENTION All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo. MEASUREMENTS Response was defined as an increase in hemoglobin concentration of 2 g/dL or more. RESULTS 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03). CONCLUSIONS Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.
Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis
Rheumatology International. 1997;17((2):):67-73.
Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.
Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis
American Journal of Medicine. 1990;89((2):):161-8.
PURPOSE To administer recombinant erythropoietin to patients with rheumatoid arthritis who had significant anemia, while monitoring hematologic and rheumatologic clinical responses as well as potential toxicity. PATIENTS AND METHODS Seventeen patients with rheumatoid arthritis from five rheumatology care settings were studied. The patients had initial hematocrits of 34% or less and stable clinical status, and were not being treated with second-line drugs or corticosteroids. An 8-week randomized double-blind study involving various dosages of recombinant erythropoietin, as well as placebo, was followed by a 24-week open-label study in which dosage could be titrated to achieve a normal hematocrit. RESULTS In the 8-week randomized study, four of 13 patients who received injections of recombinant erythropoietin showed a hematologic response, arbitrarily defined as at least a 6-unit increase in hematocrit. None of four placebo-treated patients showed a meaningful hematologic response. All 11 patients who completed the subsequent 24-week open-label study reached a normal hematocrit level at some time during the study, and 10 of 11 showed an increase of hematocrit 6 units or greater. At least one adjustment, i.e., an increase, decrease, or omission of the erythropoietin dosage, was required in all patients to maintain the hematocrit at a target range of 35% for women or 40% for men. Meaningful changes were not seen in patients' capacity to perform activities of daily living or pain levels during either the 8-week randomized study or the 24-week open-label study. No adverse effects were associated with recombinant erythropoietin therapy. CONCLUSION Patients with rheumatoid arthritis showed excellent hematologic responses to recombinant erythropoietin, without toxicity, during careful monitoring for appropriate dosage adjustment, although a meaningful change in rheumatologic clinical status was not seen.