Biosimilar erythropoiesis-stimulating agents and the risk of developing anti-drug antibodies-a systematic review.

purposeWe systematically reviewed published observational studies and randomized controlled trials (RCT) reports of clinical trials on erythropoiesis-stimulating agents (ESA's). Only studies evaluating the risk of developing anti-drug antibodies (ADA) of both original and biosimilar drugs were chosen.

methodsDatabases including PubMed, EMBASE and Cochrane Library were searched up to 17 March 2015. Two reviewers independently assessed the relevant studies for risk of bias.

resultsTwenty-one publications were included. The overall prevalence of ADA in the studies was about 0.2 to 0.5 %. Most studies were not designed to monitor the development of ADA and often the study duration was too short (less than 6 months) and the patient population too small. Moreover, in many studies, the assays used only determined the presence of ADA and did not measure therapy failure due to ADA. In one RCT, as many as 13 cases (4 %) of ADA were identified.

conclusionADA development seems to be low in short-term studies with ESA. None of the efficacy and safety issues for ESA biosimilars were judged to be adequately addressed in the evaluated literature, with respect to ADA formation, due to the study design and the assay method used.