Background Regulatory approval of biosimilar versions of innovator biotherapeutics requires that new biological products be highly similar to innovator products, with no clinically meaningful differences in safety, purity, and potency.1,2 Pre-specified margins for equivalence in efficacy have been met in comparative trials of biosimilars of tumour necrosis factor inhibitors (TNFis) in rheumatoid arthritis (RA)3 and plaque psoriasis (PsO),4 supporting biosimilarity, but differences in treatment responses between originator pivotal trials and biosimilar trials have posed some interesting questions.
Objectives To compare American College of Rheumatology 20% response (ACR20) and Psoriasis Area Severity Index 75% (PASI75) responses to originator TNFis in pivotal trials with those to originator TNFis and TNFi biosimilars in biosimilar trials in RA and PsO.
Methods Historical data from originator pivotal trials (averaged across trials) were obtained from published systematic literature reviews. Searches were conducted to identify comparative randomized clinical trials of approved or proposed biosimilars of adalimumab (ADA), etanercept (ETN), and infliximab (INF) using Embase®, MEDLINE®, the Cochrane Central Trials Register and Database of Systematic Reviews, and other Cochrane Library databases, and 2015/16 congress abstracts. To reduce variability, only studies conducted in disease-modifying antirheumatic drug-experienced patients treated with the same biologic dosages and assessed at the same time points were selected for analysis.
Results Of 83 publications initially identified, 16 publications were included for analysis (RA: originators, n=4; biosimilars, n=6; PsO: originators, n=3; biosimilars, n=3). Higher proportions of ACR20 responders were found among RA patients receiving the originator biologics and biosimilars in biosimilar trials, than among patients receiving the originator biologics in pivotal trials (Table). Insufficient data were available from ADA and INF biosimilar studies in PsO; in ETN studies in PsO, a difference was also observed in the proportions of PASI75 responders between biosimilar and pivotal trials.
Conclusions Differences were observed in treatment response rates between originator pivotal trials and more recent trials of originator biologics and their respective biosimilars. Such differences in outcomes may be attributable to fundamental differences in study design and/or baseline patient characteristics, which require further analysis. Additional research is also needed to explore the clinical relevance of these differences.
US Food and Drug Administration. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM291128.pdf.
European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/01/WC500180219.pdf.
Emery P, et al. Ann Rheum Dis. 2017;76:51–7.
Griffiths CE. Br J Dermatol. 2016. Oct 27 [e-pub].
Disclosure of Interest R. Moots Grant/research support from: Novartis, Pfizer, Consultant for: Abbvie, BMS, Cellgene, Chugai, C. Curiale Shareholder of: Pfizer, Employee of: Pfizer, D. Petersel Shareholder of: Pfizer, Employee of: Pfizer, C. Rolland Employee of: Envision Pharma Group, H. Jones Shareholder of: Pfizer, Employee of: Pfizer, E. Singh Shareholder of: Pfizer, Employee of: Pfizer, E. Mysler Consultant for: Abbvie, BMS, Pfizer, Roche, Pharma, GEMMA, Mabxience