Recombinant human erythropoietin treatment: investigational new drug protocol for the anemia of the acquired immunodeficiency syndrome. Overall results.

BACKGROUND: Anemia associated with human immunodeficiency virus infection may be due to reduced erythropoiesis related to the disease itself or to concomitant medications (eg, zidovudine). Clinical studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in correcting the anemia of zidovudine-treated patients infected with human immunodeficiency virus with baseline serum erythropoietin levels of 500 U/L or less. A treatment investigational new drug protocol that provided r-HuEPO to 1943 anemic patients with the acquired immunodeficiency syndrome was studied. METHODS: Enrollment criteria included a clinical diagnosis of acquired immunodeficiency syndrome, serum erythropoietin level of 500 U/L or less, hematocrit less than 0.300, and age of 12 years or more. The initial r-HuEPO dosage was 4000 U subcutaneously for 6 days each week. On the basis of response, the r-HuEPO dosage could be increased sequentially to 8000 U subcutaneously for 6 days per week. This was an open-label multicenter treatment protocol. A total of 1943 patients were treated by 510 investigators. Efficacy evaluations were based on the effect of r-HuEPO on hematocrit levels and transfusion requirements relative to baseline. Adverse experiences that were considered by the investigator to be possibly related to r-HuEPO therapy were collected to assess safety. RESULTS: Therapy with r-HuEPO resulted in an increase in mean hematocrit from a baseline of 0.280 to 0.331 at week 12 and 0.338 at week 24. This increase was sustained throughout the course of the study to week 54. Overall, 40% of patients (769/1943) required at least one transfusion in the 6-week interval immediately preceding study entry (baseline). After 12 and 24 weeks of r-HuEPO treatment, corresponding percentages were 22% (311/1387) and 18% (119/650), respectively. Response to therapy, defined as an increase of 0.060 from baseline in hematocrit, with no transfusions within 28 days before achieving that hematocrit, was observed in 44% of patients. Adverse experiences not clearly related to acquired immunodeficiency syndrome were reported by 11% of patients. CONCLUSION: In a study population of 1943 anemic patients with acquired immunodeficiency syndrome treated with r-HuEPO, the hematocrit increased and blood transfusion requirements decreased. Therapy with r-HuEPO was well tolerated.

Recombinant human erythropoietin and health-related quality of life of AIDS patients with anemia.

To evaluate the effect of recombinant human erythropoietin on anemia and health-related quality of life in patients with acquired immunodeficiency syndrome (AIDS), we initiated an observational study with an open-label multicenter treatment protocol that involved multiple academic and community physicians in the United States. Our subjects comprised 251 anemic (i.e., hematocrit < 30%) patients with a clinical diagnosis of AIDS using 1987 CDC criteria, age > or = 12 years, and serum erythropoietin level < or = 500 IU/L. The initial dosage of recombinant human erythropoietin was 4,000 units subcutaneously for 6 days each week. Based on the patient's response to therapy, the dosage was increased sequentially to 8,000 units subcutaneously for 6 days per week. Our measurements included changes in mean hematocrit and health-related quality of life. The interview included measures of energy/fatigue; physical, social, role and cognitive function; depression; health perceptions; and life satisfaction. Adverse experiences were also documented to assess safety. Changes in mean hematocrit level from a baseline of 27.9% to 33.6% at week 12 (p < .0001) and 34.5% at week 24 (p < .0001) were observed in patients treated with recombinant human erythropoietin. Adverse experiences, not clearly associated with AIDS, were reported by 10% of patients. Increases in energy (p < .05) were observed after 12 and 24 weeks of drug therapy, and increases in health perceptions were seen after 24 weeks (p < .05). No statistically significant increases or decreases were observed on measures of physical functioning, cognitive functioning, depression, social functioning, or home management activities over the 24-week follow-up. Anemia correctors (defined as hematocrit > or = 38%) showed greater improvement in energy, health perceptions, home management, and role function than noncorrectors. Study dropouts and those who died had significantly worse scores for health-related quality of life at baseline compared to study completers. Thus, the AIDS patients with anemia and serum erythropoietin levels < or = 500 IU/L treated with recombinant human erythropoietin showed increased mean hematocrit and improved health perceptions and energy levels. The drug therapy was associated with increased feelings of energy, but it was not associated with other changes in health status and well-being in the AIDS patients completing the study. These observations need to be confirmed in randomized clinical trials.