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Abstract Number: 1532

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

Paul Emery1, Michael E Weinblatt2, Josef S. Smolen3, Edward C. Keystone4, Mark C. Genovese5, Jiri Vencovsky6, Jonathan Kay7, Evelyn Hong8 and Jeehoon Ghil8, 1University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom, 2Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 3Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria, 4Mount Sinai Hospital, Toronto, ON, Canada, 5Stanford University Medical Center, Palo Alto, CA, 6Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine, Charles University, Czech Republic, Prague 2, Czech Republic, 7UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, 8Samsung Bioepis Co., Ltd., Incheon, Korea, Republic of (South)

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: , ,

Session Information

Date: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Treatments Poster II: PROs, Safety and Comorbidity

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

 

Disclosure: P. Emery, Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly, 5; M. E. Weinblatt, Amgen, BMS, Crescendo Bioscience, Sanofi/Regeneron, 2,Abbvie, Amgen, BMS, Crescendo Bioscience, Corrono, GSK, Gilead, Eli Lilly and Company, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Set Point, UCB, 5,Lycero, Can-fite, Scipher, Vorso, Inmedix, 1; J. S. Smolen, AbbVie, Janssen, MSD, Pfizer, Roche and UCB, 2,AbbVie, Amgen, AstraZeneca, Astro-Pharma, Celgene, GSK, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Novo Nordisk, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB, 5; E. C. Keystone, Abbott, AstraZeneca, Bristol-Myers Squibb, Crescendo Bioscience, F. Hoffmann-La Roche, Genentech, Janssen, Lilly, Merck, Pfizer, UCB, Samsung Bioepis, 5; M. C. Genovese, Samsung, Merck, Abbvie, Amgen, BI, 5; J. Vencovsky, Samsung Bioepis, Biogen, 5; J. Kay, Alexion; Amgen; AbbVie; AstraZeneca; Boehringer Ingelheim; BMS; Crescendo Bioscience; Eli Lilly; Epirus; Genentech; GlaxoSmithKline; Hospira; Janssen; MSD; Novartis; Pfizer; Samsung Bioepis; Sandoz; Roche; UCB, 5; E. Hong, Samsung Bioepis, 3; J. Ghil, Samsung Bioepis, 3.

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 .

ACR Meeting Abstracts - 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/