Post hoc analysis showed meaningful efficacy of certolizumab pegol for RA patients with high Rheumatoid Factor (RF) levels

• A post hoc analysis from the EXXELERATE trial shows that 65.7 percent of certolizumab pegol-treated patients, and 48.3 percent of adalimumab-treated patients, with rheumatoid arthritis (RA) and high rheumatoid factor (RF) levels achieved low disease activity at Week 104¹ 
• Certolizumab pegol maintained drug concentrations and achieved Low Disease Activity regardless of RF levels in patients with established RA until the end of the study period (w104)¹
• The results are in line with previous analyses from independent studies that demonstrate the consistent efficacy of certolizumab pegol across the entire RA population, while TNFis with an Fc fragment showed a decline in efficacy in high RF patients. 
• In patients with RA and high RF levels, who are at increased risk of disease progression, certolizumab pegol has the potential to deliver meaningful outcomes¹
   

Brussels (Belgium), 11 November 2023 – 07:00 (CEST) – UCB, a global biopharmaceutical company, will present a post hoc analysis of the EXXELERATE trial examining the efficacy of certolizumab pegol and adalimumab in patients with rheumatoid arthritis (RA) with high rheumatoid factor (RF) levels. The data are being presented at the American College of Rheumatology (ACR) Convergence 2023 in San Diego, U.S., November 10–15.¹

In the initial EXXELERATE trial comparing the efficacy of certolizumab pegol and adalimumab, the primary endpoints of superiority were not met. The post hoc analysis assessed the efficacy of certolizumab pegol, a PEGylated fragment crystalized (Fc)-free tumor necrosis factor inhibitor (TNFi) and adalimumab, an Fc-containing TNFi in patients with RA across RF subgroups.¹ Patients were randomized 1:1 to certolizumab pegol 200 mg every 2 weeks plus methotrexate (MTX) or adalimumab 40 mg every 2 weeks plus MTX. At Week 12, patients were classified as responders or non-responders, non-responders were switched to the other TNFi with possible follow-up to Week 104. The results of this post hoc analysis showed that for patients in the higher RF quartile (≤Q3: ≤203 IU/mL; >Q3: >203 IU/mL; measured by Roche Tina-quant^®), 65.7 percent of 453 patients treated with certolizumab pegol achieved low disease activity at Week 104 and 48.3 percent of 454 patients treated with adalimumab achieved low disease activity.¹

“It is well known that high rheumatoid factor (RF) levels are associated with a poor prognosis². In addition, high pre-treatment RF levels may lead to decreased drug concentrations of monoclonal antibodies and potentially lower response to TNFis in patients with rheumatoid arthritis (RA)^1,3. The results of this analysis highlight how certolizumab pegol maintained constant blood concentrations and therapeutic responses regardless of RF levels,” said Professor Josef Smolen, Emeritus Professor of Internal Medicine, Medical University of Vienna, Division of Rheumatology, Vienna, Austria. “These data may be of clinical relevance in the context of using a personalized medicine approach for patients with RA and high RF levels¹.”

RA is a chronic disease that causes inflammation throughout the body and commonly presents as joint pain, swelling and deformity, which results in a decline in physical function and quality of life.^4,5 It is estimated that, as of 2019, more than 18 million people worldwide live with this disease.⁶ High RF is associated with a more aggressive and destructive disease course, which is often more difficult to treat.⁷ One reason for this is the high levels of RF autoantibodies binding with the Fc parts of TNFis to form large immune complexes that are then degraded by macrophages, resulting in lower bioavailability of the biologic drugs.^8,9

To treat RA when high RF levels are present, American College of Rheumatology 2021 guidelines recommend biologic disease-modifying anti-rheumatic drugs (bDMARDS), if there is no observed improvement with MTX treatment.¹⁰  However, many bDMARDs such as TNFis contain an Fc region that RF antibodies bind to, which can result in a lower clinical efficacy and the need for additional interventions.^11,12,13 The distinctive, FC-free structure of certolizumab pegol could mean RF may not bind to the drug, which may allow its concentration to remain stable over time.¹⁴

“At UCB, we aspire to achieve long-lasting remission for as many patients living with rheumatoid arthritis (RA) as possible,” said Emmanuel Caeymaex, Executive Vice President, Immunology Solutions & Head of U.S., UCB. “The data presented at this year’s ACR Convergence demonstrate the benefits of certolizumab pegol, as it continues to deliver value for those with high unmet need late into its lifecycle and beyond. We are excited to continue exploring its scientific potential as a personalized solution for RA patients with high levels of rheumatoid factor (RF)¹.”  

Abbreviations: ACR: American College of Rheumatology, Fc: fragment crystalized, MTX: methotrexate, RA: rheumatoid arthritis, RF: rheumatoid factor, TNFis: tumor necrosis factor-α inhibitors.