AB0198 EFFICACY AND SAFETY AFTER TRANSITION FROM REFERENCE ADALIMUMAB TO CT-P17 (ADALIMUMAB BIOSIMILAR: 100 MG/ML) IN COMPARISON WITH THE MAINTAINED TREATMENT (CT-P17 OR REFERENCE ADALIMUMAB) IN PATIENTS WITH MODERATE-TO-SEVERE ACTIVE RHEUMATOID ARTHRITIS: 1-YEAR RESULT
Authors: D. Furst, E. Keystone, J. Kay, J. Jaworski, R. Wojciechowski, P. Wiland, A. Dudek, M. Krogulec, S. Jeka, A. Zielinska, J. Trefler, K. Bartnicka-Masłowska, M. Krajewska-Wlodarczyk, P. Klimiuk, S. J. Lee, S. H. Kim, Y. Bae, G. Yang, J. Yoo, T. Kim
Journal: Annals of the Rheumatic Diseases (2021)

Background: Therapeutic equivalence of CT-P17 to reference adalimumab (ref-adalimumab) has been shown in patients with moderate-to-severe active rheumatoid arthritis (RA) through primary 24-week results [1]. Here, efficacy, pharmacokinetics (PK), safety and immunogenicity results up to 52-week, including transition data from ref-adalimumab to CT-P17 are presented. Objectives: To evaluate efficacy, PK, safety and immunogenicity when switched from ref-adalimumab to CT-P17 compared to maintaining CT-P17 or ref-adalimumab. Methods: In this study, 648 moderate-to-severe active RA patients despite methotrexate treatment were randomized (1:1) to either CT-P17 or ref-adalimumab and treated with doses of 40 mg every 2 weeks up to Week 24. Prior to dosing at Week 26, 608 patients were randomized again to either maintaining their treatments or being switched from ref-adalimumab to CT-P17. Efficacy, PK, safety, and immunogenicity were assessed up to Week 52. Results: After the second randomization, 303 patients continued with CT-P17, 153 patients continued with ref-adalimumab and 151 patients switched from ref-adalimumab to CT-P17 treatments, up to Week 48. Demographics and baseline characteristics were similar among the 3 groups. Sustained and comparable efficacy in terms of ACR20/50/70 response rates was achieved not only in the maintenance groups (CT-P17 or ref-adalimumab) but also in the switched from ref-adalimumab to CT-P17 group up to Week 52 (Figure 1). Figure 1. ACR 20/50/70 Response Rates up to 1 YearAbbreviation: ref-adalimumab, reference adalimumab.Note. There were patients who could not visit the study site due to COVID-19 pandemic and were counted as nonresponder for ACR response at Week 52. In terms of PK, mean trough serum concentration (Ctrough) were maintained after Week 24 in all 3 groups. The observed mean Ctrough were within the reported therapeutic ranges of ref-adalimumab trough levels in RA patients (5-8 μg/mL). The safety profile after transition was comparable among the 3 groups (Table 1). The most common treatment-emergent adverse events (TEAEs) was neutropenia. Similar proportions of patients in all 3 groups experienced at least 1 TEAE: injection site reactions, hypersensitivity/allergic reactions and infections. One malignancy (basal cell carcinoma; unrelated) was reported in the ref-adalimumab maintenance group. Safety data accumulated over 1 year also showed comparable results among the 3 groups. Anti-drug antibody (ADA) and neutralizing antibody (NAb) results were similar among the 3 groups. At Week 52, the proportions of patients who had ADA/NAbs were 28.4%/24.8% patients in CT-P17 maintenance, 27.0%/24.3% patients in ref-adalimumab maintenance and 28.3%/26.3% patients in switched to CT-P17 groups. Conclusion: Single transition from ref-adalimumab to CT-P17 was efficacious and safe without increase in immunogenicity. Also, efficacy, PK, safety and immunogenicity profiles were comparable between CT-P17 and ref-adalimumab up to Week 52. References: [1]J Kay et al, 2020. Poster Presented at ACR Convergence 2020. Table 1. Overview of TEAEs from Weeks 26 to 52 (Safety Population – second random subset) Patients, n (% ) Second Randomization CT-P17 Maintenance (N=303 ) Ref-ada Maintenance (N=152 ) Switched to CT-P17 (N=152 ) ≥1 TEAE 121 (39.9) 69 (45.4) 73 (48.0) ≥1 TESAE 6 (2.0) 3 (2.0) 5 (3.3) ≥1 TEAE leading to study drug discontinuation 3 (1.0) 2 (1.3) 5 (3.3) ≥1 TEAE classified as hypersensitivity/allergic reactions 2 (0.7) 1 (0.7) 0 (0) ≥1 TEAE classified as injection site reactions 1 (0.3) 4 (2.6) 1 (0.7) ≥1 TEAE classified as infection 54 (17.8) 41 (27.0) 28 (18.4) ≥1 TEAE classified as malignancy 0 (0) 1 (0.7) 0 (0) Abbreviations: Ref-ada, reference adalimumab; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event. Disclosure of Interests: Daniel Furst Speakers bureau: CME, Consultant of: Amgen, Corbus, Galapagos, Horizon, Kadmon, Pfizer, Talaris, Grant/research support from: Corbus, CSL Behring, Galapagos, Gilead, GSK, Horizon, Kadmon, Novartis, Pfizer, Roche/Genetech, Talaris, Edward Keystone Speakers bureau: Amgen, AbbVie, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Novartis, Pfizer Pharmaceuticals, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion Inc., Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc., Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm, Jonathan Kay Consultant of: AbbVie, Inc., Boehringer Ingelheim GmbH, Celltrion Healthcare Co. Ltd., Jubilant Radiopharma, Merck &amp; Co., Inc., Pfizer Inc., Samsung Bioepis, Sandoz Inc., Scipher Medicine, UCB, Inc., Grant/research support from: Paid to the University of Massachusetts Medical School: Gilead Sciences Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Janusz Jaworski: None declared, Rafal Wojciechowski: None declared, Piotr Wiland Speakers bureau: Eli Lilly, Sanofi Aventis, Novartis, Sandoz, Consultant of: Eli Lilly, Novartis, Sandoz, Anna Dudek: None declared, Marek Krogulec: None declared, Sławomir Jeka Speakers bureau: Novartis, Pfizer, Roche, Lilly, Teva, MSD, Abbvie, Sandoz, Egis, Medac, Consultant of: Novartis, Pfizer, Roche, Lilly, Teva, MSD, Abbvie, Sandoz, Egis, Medac, Agnieszka Zielinska: None declared, Jakub Trefler: None declared, Katarzyna Bartnicka-Masłowska: None declared, Magdalena Krajewska-Wlodarczyk Speakers bureau: Abbvie, Eli Lilly, Novartis, Roche, Piotr Klimiuk: None declared, Sang Joon Lee Employee of: Celltrion, Inc., Sung Hyun Kim Employee of: Celltrion, Inc., YunJu Bae Employee of: Celltrion, Inc., GoEun Yang Employee of: Celltrion, Inc., JaeKyoung Yoo Employee of: Celltrion, Inc., TaeKyung Kim Employee of: Celltrion, Inc.