Certolizumab Inhibits Radiographic Progression Even in RA Patients with High Rheumatoid Factor Levels: A Pooled, Post-Hoc Analysis of Two Phase 3 Trials

Josef Smolen¹, Gerd Burmester², Yoshiya Tanaka³, Tsutomu Takeuchi⁴, Jeffrey Curtis⁵, Ted Mikuls⁶, Clementina López Medina⁷, Peter C. Taylor⁸, Nicola Tilt⁹, Bernard Lauwerys¹⁰, Baran Ufuktepe¹¹ and Thomas Huizinga¹², ¹Medical University of Vienna, Vienna, Austria, ²Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Berlin, Germany, ³Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan, ⁴Department of Internal Medicine, Keio University, Tokyo, Tokyo, Japan, ⁵The University of Alabama at Birmingham, Birmingham, AL, ⁶University of Nebraska Medical Center, Omaha, NE, ⁷Reina Sofia University Hospital, Cordoba, Spain, ⁸University of Oxford, Oxford, United Kingdom, ⁹UCB Pharma, Slough, United Kingdom, ¹⁰UCB Pharma, Brussels, Belgium, ¹¹UCB Pharma, Istanbul, Turkey, ¹²Department of Rheumatology, Leiden University, Leiden, Netherlands

Meeting: ACR Convergence 2024

Keywords: clinical trial, prognostic factors, rheumatoid arthritis, Rheumatoid Factor, TNF-blocking Antibody

Session Information

Date: Monday, November 18, 2024

Title: RA – Treatment Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: In patients (pts) with rheumatoid arthritis (RA), including those treated with disease-modifying antirheumatic drugs, high rheumatoid factor (RF) levels are a poor prognostic factor, associated with higher disease activity and risk of radiographic progression.^1,2,3 Such pts have reduced response to monoclonal antibodies targeting TNF,⁴ but may experience greater clinical response to TNF inhibitors without a fragment crystallizable (Fc) portion, such as certolizumab pegol (CZP).^5,6,7 This post-hoc analysis assessed radiographic progression in CZP+methotrexate (MTX) vs placebo (PBO)+MTX-treated pts with RA, stratified by RF level, in the C-EARLY (NCT01519791) and C-OPERA (NCT01451203) phase 3 randomized trials.

Methods: A pooled analysis of pts with early (≤1 year active disease) moderate-to-severe RA with poor prognostic factors in the C-EARLY and C-OPERA trials is presented (full analysis set). At Week (Wk)24, PBO-treated non-responders could switch to CZP for the remaining 28 wks (early escapers). Pts were stratified by baseline (BL) RF level (low: < 200 IU/mL; high: ≥200 IU/mL), per published strata.^1,6 Change from BL in modified total sharp score (mTSS) and proportions of pts experiencing minimum clinically important difference (worsening) of mTSS ( >5) at Wk24 and Wk52, and mTSS over time are reported.

Results: 813 CZP-treated (low RF: N=571; high RF: N=242) and 367 PBO-treated (low RF: N=242; high RF: N=125) pts with BL RF measurements were included; 56 PBO-treated pts were early escapers. BL characteristics were similar between CZP- and PBO-treated pts within each RF stratification. However, pts with high RF had more severe disease at BL than those with low RF, with higher mean C-reactive protein, anti-citrullinated protein antibodies, mTSS, and erosion scores (Table 1).

By Wk52, mean mTSS increased from BL in PBO-treated pts with both high RF (change from BL [CfB]: 2.36±6.20) and low RF (CfB: 1.37±3.43), but was comparable in CZP-treated pts (high RF: CfB: 0.28±2.63; low RF: CfB: 0.14±3.11) (Table 2).

The proportion of pts with meaningfully worsening radiographic progression was higher in PBO-treated pts with high RF compared to low RF at both Wk24 (6.48% vs 2.84%) and Wk52 (17.59% vs 10.43%) (Figure 1). By contrast, a smaller proportion of CZP-treated pts experienced meaningful worsening and was similar between pts with high and low RF (Wk24: 0.00% vs 1.05%; Wk52: 5.29% vs 3.14%, respectively).

Conclusion: Pts with high BL RF levels had more severe RA and BL radiographic damage than those with low RF. Worsening radiographic damage was observed in PBO-treated pts, with slightly greater progression in high-RF pts than low-RF. In contrast, irrespective of BL RF levels, CZP-treated pts demonstrated consistently lower radiographic progression, suggesting RF does not adversely influence radiographic response to CZP.

References: 1. Vastesaeger N. et al, Rheum 2009;48:1114–21. 2. Cuchacovich M. et al, Clin Rheumatol 2014;33(12):1707–14. 3. Smolen J. et al, Ann Rheum Dis 2023;82(1):3–18. 4. Takeuchi T. et al, Arthritis Res 2017;19:194. 5. Nakayama Y. Rheumatol Int 2022;42:1227–1234. 6. Smolen J. Arthritis Rheumatol 2023;75(suppl 9). 7. Bidgood S. et al, Ann Rheum Dis 2024;83 (suppl 1):727.

Table 1. Baseline demographics and disease characteristics stratified by baseline RF level

Table 2. Change from baseline in mTSS scores, stratified by baseline RF (low [<200 IU/mL] vs high [≥200 IU/mL]) over time (OC)

Figure 1. Individual pt CfB in mTSS at Wk24 and Wk52, stratified by baseline RF level (low [<200 IU/mL] vs high [≥200 IU/mL])

Disclosures: J. Smolen: Abbvie, 5, 6, Amgen, 6, Astra-Zeneca, 5, 6, Astro, 6, Bristol-Myers Squibb, 6, Celgene, 6, Celltrion, 6, Chugai, 6, Eli Lilly, 5, 6, Gilead, 6, ILTOO, 6, Janssen, 6, Merck Sharp & Dohme, 6, Novartis, 5, 6, Pfizer, 6, Roche, 5, 6, R-Pharma, 6, Samsung, 6, Sanofi, 6, UCB Pharma, 6; G. Burmester: AbbVie, 2, Amgen, 2, BMS, 2, Galapagos, 2, Lilly, 2, MSD, 2, Pfizer, 2, Sanofi, 2; Y. Tanaka: AbbVie, 6, Asahi-kasei, 6, Astellas, 6, AstraZeneca, 6, Boehringer Ingelheim, 5, 6, Chugai, 5, 6, Daiichi Sankyo, 6, Eisai, 6, Gilead, 6, GSK, 6, Lilly, 6, Pfizer, 6, Taisho, 5, 6, UCB, 6; T. Takeuchi: AbbVie, 4, 6, Astellas, 2, 6, Eisai, 4, 6, Eli Lilly Japan, 2, 6, Gilead, 2, 6, Pfizer Japan, 6; J. Curtis: AbbVie, 2, 5, Amgen, 2, 5, AstraZeneca, 2, 5, Bendcare, 2, 5, Eli Lilly, 2, 5, Genentech, 2, 5, GlaxoSmithKline, 2, 5, Horizon, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, Sanofi, 2, 5, Scipher Medicine, 2, 5, Setpoint, 2, 5, UCB Pharma, 2, 5; T. Mikuls: Elsevier, 9, Horizon Therapeutics, 2, 5, Pfizer, 2, Sanofi, 2, UCB Pharma, 2, Wolters Kluwer Health (UpToDate), 9; C. López Medina: AbbVie, 2, 5, 6, Eli Lilly, 2, 5, 6, Janssen, 6, MSD, 6, Novartis, 2, 5, 6, UCB Pharma, 2, 5, 6; P. Taylor: AbbVie, 2, Acelyrin Inc., 2, Biogen, 2, Eli Lilly, 2, Fresenius, 2, Galapagos, 2, 12, Participation on a Data Safety Monitoring Board/Advisory Board, Gilead, 2, GSK, 2, Immunovant, 12, Participation on a Data Safety Monitoring Board/Advisory Board, Janssen, 2, Kymab, 12, Participation on a Data Safety Monitoring Board/Advisory Board, Nordic Pharma, 2, Pfizer, 2, Sanofi, 12, Participation on a Data Safety Monitoring Board/Advisory Board, UCB Pharma, 2; N. Tilt: UCB Pharma, 3, 11; B. Lauwerys: UCB Pharma, 3, 11; B. Ufuktepe: UCB Pharma, 3, 11; T. Huizinga: Abblynx, 2, 5, 6, Abbott, 2, 5, 6, Boehringer, 2, 5, 6, Bristol Myers Squibb, 2, 5, 6, Eli Lilly, 2, 5, 6, Galapagos, 2, 5, 6, Janssen, 2, 5, 6, Merck, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, Roche, 2, 5, 6, Sanofi-Aventis, 2, 5, 6, UCB, 2, 5, 6.

To cite this abstract in AMA style:

Smolen J, Burmester G, Tanaka Y, Takeuchi T, Curtis J, Mikuls T, López Medina C, Taylor P, Tilt N, Lauwerys B, Ufuktepe B, Huizinga T. Certolizumab Inhibits Radiographic Progression Even in RA Patients with High Rheumatoid Factor Levels: A Pooled, Post-Hoc Analysis of Two Phase 3 Trials [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/certolizumab-inhibits-radiographic-progression-even-in-ra-patients-with-high-rheumatoid-factor-levels-a-pooled-post-hoc-analysis-of-two-phase-3-trials/. Accessed .

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