THU0114 CERTOLIZUMAB PEGOL IN PATIENTS WITH RHEUMATOID ARTHRITIS: POOLED EFFICACY ANALYSIS OF PHASE 3 CLINICAL TRIALS ACROSS BASELINE RHEUMATOID FACTOR QUARTILES
Authors: Y. Tanaka, Z. Li, N. Inanc, R. Xavier, N. Tilt, C. Cara, C. Saadoun, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2020)

Background: The presence of rheumatoid factor (RF) in patients (pts) with rheumatoid arthritis (RA) is associated with higher disease activity, 1 and is regarded as a risk factor for more aggressive RA. 1 Most studies on anti-tumour necrosis factor (TNF) monoclonal antibodies such as infliximab, etanercept and adalimumab have shown better response in pts with negative versus positive and low versus high baseline RF titres. 2-3 Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF, has shown rapid and sustained reduction in signs and symptoms of moderate to severe RA, inhibition of radiographic progression and improvements in physical function in pts with an inadequate response to methotrexate (MTX). 4–7 The efficacy of CZP in pts with different baseline RF levels has not been studied. Objectives: To assess the efficacy of CZP, as measured by Disease Activity Score 28-erythrocyte sedimentation rate (DAS28[ESR]), in pts with active RA across baseline RF levels. Methods: In this post-hoc analysis, data were pooled from four clinical trials of CZP in RA: two global trials (RAPID 1, NCT00152386 and RAPID 2, NCT00175877 ), a Japanese trial (J-RAPID, NCT00791999 ) and a Chinese trial (RAPID-C, NCT02151851 ). Pts ≥18 years with adult onset RA for ≥6 months (defined by ACR 1987 criteria), who received MTX for ≥6 months (≥3 months for RAPID-C) prior to baseline, were randomised 1:1 to receive placebo (PBO) every two weeks (Q2W)/CZP 400 mg Q2W/CZP 200 mg Q2W (CZP 400 mg at Weeks [Wks] 0/2/4) plus MTX for at least 24 Wks. Complete study design and pt characteristics were reported previously. 4–7 Here we include only pts who received CZP 200 mg Q2W (CZP 400 mg at Wks 0/2/4). RF titres were measured by validated assays in local hospital laboratories. Pts were stratified into quartiles based on pooled baseline RF levels: &lt;25.0, &lt;78.5, &lt;207.0 and ≥207.0 IU/mL. DAS28(ESR) categories were adopted to stratify pts: remission (REM), DAS28(ESR) &lt;2.6; low disease activity (LDA), DAS28(ESR) ≤3.2. Missing values were imputed using last observation carried forward. Results: Data were pooled from 1,017 and 504 pts in the CZP 200 mg Q2W and PBO Q2W groups, respectively. At baseline, mean [SD] DAS28(ESR) was similar with PBO vs CZP across RF quartiles (6.5 [0.9] – 7.0 [0.9] vs 6.6 [0.9] – 7.0 [0.9]). Compared with the PBO group, numerically higher DAS28(ESR) REM and LDA rates were observed for CZP 200 mg Q2W group at Wk 24 across RF quartiles (Figure 1). DAS28(ESR) REM and LDA responder rates increased to Wk 24 in pts treated with CZP. In general, LDA and REM rates were similar across RF quartiles at all timepoints (Figure 2). Conclusion: Over 24 Wks of treatment, trends showed steady efficacy of CZP across baseline RF quartiles in pts with active RA. In this pooled post-hoc analysis, efficacy of CZP appeared to be consistent and independent of RF levels; observed efficacy may be related to the unique molecular structure of CZP. CZP treatment in association with MTX may be a feasible option in pts with RA regardless of baseline RF status. References: [1]Aletaha D. Arthritis Research &amp; Therapy 2015;17:229; [2]Bobbio-Pallavicini F. Ann Rheum Dis 2007;66:302–7; [3]Potter C. Ann Rheum Dis 2009;68:69–74; [4]Keystone E. Arthritis Rheum 2008;58:3319–29; [5]Smolen J. Ann Rheum Dis 2009;68:797–804; [6]Yamamoto K. Mod Rheumatol 2014;24:715–24; 7. Bi L. Clin Exp Rheumatol 2019;37:227–234. Acknowledgments: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical, Singapore. Disclosure of Interests: Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Zhanguo Li: None declared, Nevsun Inanc: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Nicola Tilt Employee of: UCB Pharma, Carlos Cara Employee of: UCB Pharma, Carine Saadoun Employee of: UCB Pharma, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi &amp; Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.