SAT0116 Safety and Efficacy of Ara290, a Non-Hematopoietic Erythropoietin Derived Peptide, in a 4 Weeks Phase II Open Label Trial in Patients with Active Rheumatoid Arthritis

Background Erythropoietin, a well-known stimulator of erythrocyte production, also has nonhematopoietic activities, that can generally be summarized as counteracting the actions of proinflammatory cytokines. It has been suggested previously that erythropoietin reduces disease activity in RA,1 2 but given the side effects of administering high doses of erythropoietin, this treatment option has not been further investigated. Objectives To assess the safety and efficacy of ARA290, a non-hematopoietic erythropoietin derived peptide, in active rheumatoid arthritis patients in an open-label trial. Methods Fifteen patients were randomized to 4 weeks of intravenous treatment with 2mg of ARA290 either once or 3x/week. The latter was the highest dosing scheme tested in healthy volunteers. Safety was assessed weekly by history taking and laboratory tests. Disease activity, using the disease activity score (DAS), functional ability, using the Health Assessment Questionnaire (HAQ), and pain on a visual analogue scale (VAS pain) were measured weekly. Paired t tests or Wilcoxon matched-pair signed-rank tests were performed where appropriate to examine the difference between baseline and after treatment. Results Patient groups were similar in demographics and baseline disease characteristics: median disease duration was 8 years, in 93% rheumatoid factor and in 87% anti-citrullinated protein antibodies were present, 86% had erosive disease and half of the patients had failed on ≥1 biological. Three patients experienced a non-serious infection, leading to study withdrawal in one patient. One patient (treated 3x/week) was hospitalized in week 4 for observation of subjective paraesthesias where no abnormalities were found. One patient, who was treated 3x/week, had a good EULAR response, one (treated 1x/week) had a moderate response, two (one from each group) achieved low disease activity without a DAS decrease >0.6 points and one (treated 3x/week) had a decrease >0.6 points but still a DAS >3.7. There was a (numerical) decrease in median VAS pain of 27 mm in the group treated 1x/week, p=0.03, and of 29 mm in the group treated 3x/week, p=0.2, and a decrease in median VAS global of 29 mm in the group treated 3x/week, p=0.03. No relevant changes in ESR and CRP or tender and swollen joint counts were observed. Conclusions This small open-label trial showed no major safety issues and possible (subjective and/or analgesic) efficacy of ARA290 in patients with active rheumatoid arthr