FRI0201 Immunogenicity of certolizumab pegol without concomitant methotrexate and clinical response in rheumatoid arthritis patients: post-hoc analysis of the hikari study
Authors: T. Takeuchi, K. Yamamoto, H. Yamanaka, N. Ishiguro, Y. Tanaka, K. Eguchi, A. Watanabe, H. Origasa, Y. Wada, T. Shoji, N. Miyasaka, T. Koike
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Immunogenicity and subsequent reduction in clinical response is an issue for biological agents in rheumatoid arthritis (RA) treatment. <h3>Objectives</h3> To assess immunogenicity and clinical response to certolizumab pegol (CZP), a PEGylated Fc-free anti-TNF, in RA patients (pts) without concomitant methotrexate (MTX). <h3>Methods</h3> Post-hoc analysis of a 24-wk, double-blind (DB) study of CZP 200mg without concomitant MTX (HIKARI study) and subsequent open-label extension (OLE) in Japanese pts with active RA (116 pts).<sup>1</sup> <h3>Results</h3> Anti-CZP antibodies (Abs) were detected in 18 pts (15.5%) at any visit during the first 24 wks. Two anti-CZP profiles were observed: 1) Abs peaked between Wk8–Wk12 (early development, n=7); 2) Abs peaked at/after Wk24 (late development, n=11) (Figure). In 6 pts with early development, anti-CZP Abs decreased to below threshold (≤2.4units/mL) at Wk24, and their plasma CZP level increased at Wk24 (median CZP concentration of 7.7µg/ml), following a drop at Wk8 (35.3 and 2.2µg/ml at Wk6 and Wk8, respectively). In contrast, in pts with late development, Abs appeared mostly at Wk24, and plasma CZP level slowly decreased from Wk8 (median CZP concentrations 27.5 and 2.4µg/ml at Wk8 and Wk24, respectively). ACR20/ACR50/ACR70 responses of early development pts (n=7) were greater than those with late development (n=11) (Table). These results suggest that early, transient development of anti-CZP Abs was not associated with poor long-term clinical response, whereas later development led to loss of response. This observation suggests that when anti-CZP Abs with low affinity to CZP are developed early, they may be adsorbed by the high level of plasma CZP. In contrast, late-developed anti-CZP Abs may reside longer and lead to sustained drug clearance, similar to Abs against other anti-TNF biologics. <h3>Image/graph</h3> <h3>Conclusions</h3> Anti-CZP Abs were detected in 15.5% of RA pts during 24 wks of treatment without concomitant MTX. Better long-term clinical responses were observed in patients with early vs late anti-CZP Abs development. <h3>References</h3> Yamamoto K. Arthritis Rheum 2011;63(Suppl10);S476 <h3>Acknowledgements</h3> The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. <b>Disclosure of Interest</b>: T. Takeuchi Grant/research support from: Abbott, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon Shinyaku, Otsuka, Pfizer, Sanofi-Aventis, Santen, Takeda, Teijin, Consultant for: AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe, Asahi Kasei, Speakers bureau: Abbott, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, K. Yamamoto Grant/research support from: Pfizer, Abbott, Santen, Mitsubishi-Tanabe, Eisai, UCB Pharma, Consultant for: Pfizer, Abbott, BMS, Roche, Chugai, Mitsubishi-Tanabe, Eisai, H. Yamanaka Grant/research support from: Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, UCB Pharma, Consultant for: Abbott, Astellas, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, UCB Pharma, N. Ishiguro Grant/research support from: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Speakers bureau: Takeda, Mitsubishi-Tanabe, Astellas, Chugai, Abbott, BMS, Eisai, Janssen, Kaken, Pfizer, Taisho-Toyama, Otsuka, Y. Tanaka Grant/research support from: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, Abbott, Eisai, Janssen, Speakers bureau: Mitsubishi-Tanabe, Abbott, Eisai, Chugai, Janssen, Santen, Pfizer, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Otsuka, Actelion, Eli Lilly, Nippon Kayaku, Quintiles Transnational, Ono, UCB Pharma, K. Eguchi Consultant for: UCB Pharma, A. Watanabe Grant/research support from: Astellas, Daiichi-Sankyo, Kyorin, Shionogi, Taisho, Dainippon-Sumitomo, Taiho, Toyama Chemical, Meiji Seika, Speakers bureau: Abbott, MSD, Otsuka, GSK, Shionogi, Daiichi-Sankyo, Taisho-Toyama, Dainippon-Sumitomo, Mitsubishi-Tanabe, Toyama Chemical, Bayer, Pfizer, H. Origasa Consultant for: Astellas, UCB Pharma, Y. Wada Employee of: UCB Pharma, T. Shoji Employee of: UCB Pharma, N. Miyasaka Grant/research support from: Pfizer, Takeda, Mitsubishi-Tanabe, Chugai, Abbott, Eisai, Astellas, T. Koike Speakers bureau: Pfizer, Chugai, Abbott, Mitsubishi-Tanabe, Takeda, Eisai, Santen, Astellas, Taisho-Toyama, BMS, Teijin, Daiichi-Sankyo, UCB Pharma