Post Hoc Analysis Showed CIMZIA Resulted in Meaningful Efficacy for RA Patients with High Levels of Rheumatoid Factor (RF)

ATLANTA, Nov. 11, 2023. CB, a global biopharmaceutical company, will present a post hoc analysis of the EXXELERATE trial examining the efficacy of CIMZIA (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, November 10–15.¹

In the initial EXXELERATE trial comparing the efficacy of CIMZIA and adalimumab, the primary endpoints of superiority were not met. In the post hoc analysis, efficacy outcomes in CIMZIA and adalimumab were assessed in patients with RA across RF subgroups.¹ Patients were randomized 1:1 to CIMZIA 200 mg every two weeks plus methotrexate (MTX) or adalimumab 40 mg every two 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. Results showed that for patients in the higher RF quartile, 65.7 percent of 453 patients treated with CIMZIA and 48.3 percent of 454 patients treated with adalimumab achieved low disease activity at Week 104.¹

“It is well known that high rheumatoid factor (RF) levels are associated with a poor prognosis.² In addition, high 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, through its fragment crystallizable (Fc)-free molecular structure, 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 levels.”¹

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 2021, approximately 1.5 million people in the United States 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 biologic drugs.^8,9

To treat RA when high RF levels are present, American College of Rheumatology 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 CIMZIA means RF may not bind to the drug, allowing its concentration to remain stable over time.¹⁴

“At UCB, we aspire to achieve long-lasting drug-free 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

About the EXXELERATE trial methodology and patient population
In patients with RA, high RF levels are considered a poor prognostic factor and are associated with higher disease activity, risk of radiographic progression, and decreased response to TNF inhibitors (TNFis).⁷ Recent data suggest that patients with RA and high RF levels may achieve and maintain greater clinical improvement with TNFis without a crystallizable fragment (Fc) compared with TNFis with an Fc.¹² In this post hoc analysis of the EXXELERATE trial, we assessed efficacy outcomes of CIMZIA (CZP), a PEGylated, Fc-free TNFi, and adalimumab (ADA; Fc-containing TNFi) in patients with RA across different RF levels.¹

About CIMZIA in the U.S.¹⁵
CIMZIA is the only Fc-free, PEGylated anti-TNF (tumor necrosis factor). CIMZIA has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha.

CIMZIA is also indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA), adults with active psoriatic arthritis (PsA), adults with active ankylosing spondylitis (AS), and adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

CIMZIA is indicated for the treatment of moderate-to-severe plaque psoriasis (PSO) in adults who are candidates for systemic therapy or phototherapy.

In addition, CIMZIA is indicated for reducing signs and symptoms of Crohn’s disease (CD) and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

About UCB
UCB, Brussels, Belgium is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 8,700 people in approximately 40 countries, the company generated revenue of €5.5 billion in 2022 UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA.

Forward looking statements
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Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations.

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction.

Abbreviations: ACR: American College of Rheumatology, bDMARDS: biologic disease-modifying anti-rheumatic drugs, AS: Ankylosing spondylitis, axSpA: Axial spondyloarthritis, CRP: C-reactive protein, DMARDs: disease-modifying antirheumatic drugs, EEA: European Economic Area, EU: European Union, MRI: Magnetic Resonance Imaging, NSAIDS: non-steroidal anti-inflammatory drugs, HBV: hepatitis B, Fc: fragment crystallizable, MTX: methotrexate, RA: rheumatoid arthritis, RF: rheumatoid factor, TNFis: tumor necrosis factor-α inhibitors, UCB: Union Chimique Belge.

References
¹ Smolen J, Taylor P, Tanaka Y, et al. Do High RF Titers Impact Response to TNF Inhibitors? Comparison of Certolizumab Pegol and Adalimumab in Patients with RA and High Titers of RF: A Post Hoc Analysis of a Phase 4 Trial. Arthritis Rheumatol. 2023;75 (suppl 9). ACR Convergence 2023. 2148.
² Albrecht K, Zink A. Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies. Arthritis Res Ther. 2017;19(1):1-8.
³ Tiwari V, Jandu JS, Bergman MJ. Rheumatoid Factor. In: StatPearls [Internet]. Treasure Island. 2023.
⁴ Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019;170(1):ITC1-ITC16.
⁵ Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023–38.
⁶ Arthritis Foundation (October 15, 2021). Rheumatoid Arthritis: Causes, Symptoms, Treatments and More. Available at: https://www.arthritis.org/diseases/rheumatoid-arthritis. Last accessed: October 2023.
⁷ Watanabe R, Hashimoto M, Murata K, et al. Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort. Immunol Med. 2022;46(1):35-44.
⁸ Laurent L, Anquetil F, Clavel C, et al. IgM rheumatoid factor amplifies the inflammatory response of macrophages induced by the rheumatoid arthritis-specific immune complexes containing anticitrullinated protein antibodies. Ann Rheum Dis. 2015;74(7):1425-31.
⁹ Aletaha D, Alasti F, Smolen JS. Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity. Ann Rheum Dis. 2012;72(6):875-80.
¹⁰ Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-39.
¹¹ Takeuchi T, Miyasaka N, Inui T, et al. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study. Arthritis Res Ther. 2017;19(1):194.
¹² Nakayama Y, Watanabe R, Murakami K, et al. Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study. Rheumatol Int. 2022;42(7):1227-34.
¹³ Calvo Gutierrez J, Ortega Castro R, Ábalos-Aguilera MC, et al. Impact of baseline rheumatoid factor titers and anti-TNF molecular structure on the retention rate in patients with rheumatoid arthritis. Ann Rheum Dis. 2023;82:1400-1.
¹⁴ Senolt L. Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies. F1000Res. 2019;8:F1000 Faculty Rev-1549.
¹⁵ CIMZIA (certolizumab pegol) US Prescribing Information. Available at: Cimzia_09_11_2019_en.pdf (ucb.com). Last accessed: November 2023.

SOURCE UCB

Posted: November 2023

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