THU0184 Impact of immunogenicity on clinical efficacy and administration related reaction in tnf inhibitors: a pooled-analysis from three biosimilar studies in patients with rheumatoid arthritis
Authors: P. Emery, M. Weinblatt, J.S. Smolen, E. Keystone, M. Genovese, J. Vencovsky, J. Kay, E. Hong, Y. Baek, J. Ghil
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> SB4, SB2, and SB5 are biosimilars of reference etanercept, infliximab, and adalimumab, respectively. The phase III randomised, double-blind clinical studies comparing the efficacy and safety of each biosimilar with its reference product had similar study designs, patient demographics, and the same primary endpoint of the ACR20 response rate. In each study immunogenicity was measured using a validated ECL assay tagged with the biosimilar. <h3>Objectives</h3> To assess the immunogenicity of three TNFi and examine the potential impact of anti-drug antibodies (ADAbs) on efficacy and injection site reactions (ISR) or infusion related reactions (IRR) by a pooled analysis of three biosimilar studies.<sup>1–3</sup> Data to the time of the primary endpoint for each study (week 24 for etanercept and adalimumab studies and week 30 for infliximab study) are presented. <h3>Methods</h3> Data from patients who had immunogenicity results from each phase III study were pooled. Efficacy (ACR responses, clinical response [defined as good or moderate EULAR response], change in disease activity [DAS28, SDAI, CDAI]) and ISR/IRR were evaluated in relation to the presence of ADAb (at least one ADAb positive result up to when the primary endpoint was measured). <h3>Results</h3> The analysis included 1710 patients and the incidence of ADAb by treatment group is presented in the table 1. Across treatment groups, efficacy was greater in patients without ADAb compared to those with ADAb. In all treatments combined, the ACR20 response rate was lower in the presence of ADAb (OR 2.06, 95% CI: 1.63–2.60, p&lt;0.0001) (figure 1) and the mean improvement in DAS28 was significantly greater in patients without ADAb (estimated difference: 0.383, 95% CI: 0.24–0.52, p&lt;0.0001). The ADAb effect on reducing ACR20 response rates as well as other efficacy parameters was similarly observed in other treatment groups. In all treatments combined, the presence of ADAb was associated with increased ISR/IRR (OR 1.73, 95% CI: 1.02–2.96, p=0.043), predominantly with the infliximab combined (OR 2.67, 95% CI: 1.04–6.89, p=0.041) rather than the etanercept combined (OR 1.72, 95% CI: 0.38–7.77, p=0.478) and adalimumab combined (OR 1.00, 95% CI: 0.35–2.88, p=0.998). <h3>Conclusions</h3> In a pooled analysis, the development of ADAbs to TNFi is associated with reduced clinical efficacy and increased incidence of ISR/IRR in patients with RA. <h3>References</h3> [1] Emery, et al. Ann Rheum Dis2017Jan;76(1):51–57. [2] Choe, et al. Ann Rheum Dis2017Jan;76(1):58–64. [3] Weinblatt, et al. Arthritis Rheumatol2018Jan;70(1):40–48. <h3>Disclosure of Interest</h3> P. Emery Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Sanofi, Consultant for: AbbVie, Amgen, Novartis, Roche, GlaxoSmithKline, Merck, Samsung, Crescendo Bioscience, and AstraZeneca, and Bristol-Myers Squibb, Lilly, Pfizer, and UCB, J. Smolen Grant/research support from: AbbVie, Janssen, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Astro-Pharma, Celgene, GSK, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Novo Nordisk, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, E. Keystone Consultant for: Abbott, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, F. Hoffmann-La Roche, Genentech, Janssen, Lilly, Merck, Pfizer, UCB, Samsung Bioepis, M. Genovese Consultant for: Samsung, Merck, Abbvie, Amgen, BI, J. Vencovsky Consultant for: Samsung Bioepis, Biogen, J. Kay Consultant for: Alexion; Amgen; AbbVie; AstraZeneca; Boehringer Ingelheim; BMS; Crescendo Bioscience; Eli Lilly; Epirus; Genentech; GlaxoSmithKline; Hospira; Janssen; MSD; Novartis; Pfizer; Samsung Bioepis; Sandoz; Roche; UCB, E. Hong Employee of: Samsung Bioepis, Y. Baek Employee of: Samsung Bioepis, J. Ghil Employee of: Samsung Bioepis