Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: SB4, SB2, and SB5 are biosimilars of reference etanercept, infliximab, and adalimumab, respectively. The phase III randomized, 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 this study, the immunogenicity of three TNFi and the potential impact of anti-drug antibodies (ADAbs) on efficacy and injection site reactions (ISR) or infusion related reactions (IRR) were assessed by a pooled analysis of three biosimilar studies.1,2,3
Methods: In each study immunogenicity was measured using a validated ECL assay tagged with the biosimilar and patients who had immunogenicity results from each phase III study were pooled. 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 included. 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).
Results: The analysis included 1710 patients and the incidence of ADAb by treatment group is presented in the Table.
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 2.01, 95% CI: 1.60-2.53, p<0.0001) (Figure) and the mean improvement in DAS28 was significantly greater in patients without ADAb (estimated difference: 0.33, 95% CI: 0.19-0.48, p<0.0001). The ADAb effect on reducing efficacy parameters was similarly observed in other treatment combinations.
In all treatments combined, the presence of ADAb was associated with increased ISR/IRR (OR 1.78, 95% CI: 1.05-3.02, p=0.033), 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 1.14, 95% CI: 0.41-3.13, p=0.804).
Conclusion: 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.
References: 1. Emery et al. Ann Rheum Dis. 2017 Jan;76(1):51-57; 2. Choe et al. Ann Rheum Dis. 2017 Jan;76(1):58-64; 3. Weinblatt et al. Arthritis Rheumatol. 2018 Jan;70(1):40-48
To cite this abstract in AMA style:Emery P, Weinblatt ME, Smolen JS, Keystone EC, Genovese MC, Vencovsky J, Kay J, Hong E, Ghil J. 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 [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/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/. Accessed February 3, 2023.
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