P106 Do high rheumatoid factor titres impact response to tumour necrosis factor inhibitors? Comparison of certolizumab pegol and adalimumab in patients with rheumatoid arthritis and high titres of rheumatoid factor: a post hoc analysis of a phase 4 trial.

Abstract Background/Aims In patients with rheumatoid arthritis (RA), high rheumatoid factor (RF) titres are considered a poor prognostic factor and are associated with higher disease activity, risk of radiographic progression and decreased response to TNF inhibitors (TNFis). Recent data suggests that patients with RA and high RF titre may achieve and maintain greater clinical improvement with TNFis without a crystallisable fragment (Fc) compared to TNFis with an Fc. In this analysis of the EXXELERATE trial, we assessed efficacy outcomes of certolizumab pegol (CZP), a PEGylated Fc-free TNFi, versus adalimumab (ADA; Fc-containing TNFi) in patients with RA and high RF titres. Methods The phase 4 EXXELERATE trial (NCT01500278) compared the efficacy and safety of CZP to ADA. Patients were randomised 1:1 to CZP 200 mg every two weeks (Q2W) plus methotrexate (MTX) or ADA 40 mg Q2W plus MTX. At Week 12 (Wk), patients were classified as responders or non-responders; non-responders were switched to the other TNFi with possible follow-up to Wk104. Here, we report drug plasma concentrations, mean disease activity score (DAS)28-CRP score and proportion of patients achieving low disease activity (LDA; threshold: DAS28-CRP ≤2.7) to Wk104. Results are stratified by RF titre quartile (≤Q3: ≤203 IU/mL; >Q3: >203 IU/mL; measured by Roche Tina-quant®) and reported as observed data. Results Baseline data by RF quartile were available for 453 CZP-randomised patients (≤Q3: n = 334; >Q3: n = 119) and 454 ADA-randomised patients (≤Q3: n = 347; >Q3 n = 107). Baseline characteristics were similar between CZP- and ADA-randomised patients across the RF titre quartiles. At Wk12, 66 CZP-treated patients switched to ADA and 59 ADA-treated patients switched to CZP. At Wk104, mean ADA concentrations were 22.9% lower in patients with RF >Q3 (mean [SD] 4.8 [3.0]) vs those with RF ≤Q3 (6.2 [4.0]); in CZP-treated patients, this difference was smaller (13.0%) in patients with RF >Q3 (23.3 [15.4]) vs those with RF ≤Q3 (26.7 [13.1]). For patients in RF ≤Q3, mean DAS28-CRP scores were similar between CZP- and ADA-treated patients through Wks0-104 (mean [SD] DAS28 at Wk104: 2.48 [1.18] CZP vs 2.49 [1.14] ADA). However, for patients in RF >Q3, mean [SD] DAS28-CRP scores were nominally lower in CZP- vs ADA-treated patients (Wk104: 2.50 [1.18] CZP vs 2.93 [1.22] ADA). A similar pattern was observed for the proportion of patients achieving LDA at Wk104 (≤Q3: 64.8% CZP vs 65.1% ADA; >Q3: 65.7% CZP vs 48.3% ADA). Conclusion CZP-treated patients with RA and high titre RF had similar drug concentrations and clinical responses to patients with RA and low titre RF, a pattern not observed in ADA-treated patients. These data, together with previous reports where CZP showed consistent efficacy irrespective of baseline RF titre, suggest CZP may be a suitable therapy for patients with RA and high RF titre. Disclosure J.S. Smolen: Honoraria; AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, R-Pharma, Roche, Samsung, Sanofi, and UCB Pharma. Grants/research support; AbbVie, AstraZeneca, Eli Lilly, Novartis and Roche. Other; Editor of Annals of the Rheumatic Diseases, Co-editor of Rheumatology 7E/8E, Convenor of EULAR Task Forces and T2T Task Forces. P.C. Taylor: Consultancies; AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Sanofi and UCB Pharma. Grants/research support; Galapagos. Y. Tanaka: Honoraria; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho, Taisho. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, Gilead, GSK, Pfizer, Taiho and Taisho. Grants/research support; Chugai, Eisai, Mitsubishi-Tanabe, Taisho. C. Cara: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. B. Lauwerys: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. R. Xavier: Consultancies; AbbVie, AstraZeneca, Janssen, Organon, UCB Pharma. Member of speakers’ bureau; AbbVie, AstraZeneca, Janssen, Organon, and UCB Pharma. J.R. Curtis: Consultancies; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. Grants/research support; AbbVie, Amgen, BMS, Corrona, Crescendo, Genentech, Janssen, Pfizer, Roche, UCB Pharma. T.R. Mikuls: Consultancies; Horizon Therapeutics, Pfizer, Sanofi, UCB Pharma. Royalties; Elsevier, Wolters Kluwer Health (UpToDate). Grants/research support; Horizon Therapeutics. M. Weinblatt: Consultancies; AbbVie, Aclaris, Amgen, Aqtual, BMS, CorEvitas, Eli Lilly, GSK, Gilead, Horizon, Johnson and Johnson, Prometheus, Pfizer, Rani, Revolo, Sanofi, Scipher, Sci Rhom, Set Point, UCB Pharma. Grants/research support; AbbVie, Aqtual, BMS, Janssen.