A Podcast for Rheumatologists
A Podcast for Rheumatologists
Right Fit Report

A podcast for rheumatologists, brought to you by UCB

Dr. Brown: 
Welcome to the Right Fit Report, with rheumatology insights brought to you by UCB. I’m Dr. Adam Brown of the Cleveland Clinic, and I’m joined today by my colleague, Dr. Monica Schwartzman of Schwartzman Rheumatology in New York.

Dr. Schwartzman: 
Hi, everyone.

Dr. Brown:
Today we’re discussing rheumatoid factor, or RF. RF is more than just a diagnostic marker of rheumatoid arthritis. We’ll cover how high RF levels can impact RA pathogenesis, and how RF itself interacts with certain biologics, most notably TNF inhibitors.

Dr. Schwartzman: 
In particular, we’ll focus on CIMZIA, a TNF inhibitor with a unique molecular design that is engineered without an Fc region. CIMZIA is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis. Important Safety Information will be read at the end of this podcast. For more safety information, please visit CIMZIAhcp.com.

Dr. Brown:  
When patients with RA come to us, they don’t talk about cytokines or antibodies. They talk about pain, swelling, and stiffness. These symptoms are the result of the underlying mechanism of disease. Two important factors to consider in RA are tumor necrosis factor, or TNF, a key driver of inflammation, and RF, a biomarker associated with prognostic implications.

Dr. Schwartzman: 
Right. TNF drives inflammation in rheumatologic diseases like RA. When elevated, TNF sets off an inflammatory cascade in the synovium and recruits more inflammatory mediators, leading to the swelling, pain, and stiffness that characterize RA. Over time, articular cartilage and juxta-articular bone are destroyed, resulting in joint erosion. TNF is a pro-inflammatory cytokine that activates mediators such as leukocytes, endothelial cells, synovial fibroblasts, and other cytokines, to induce an inflammatory response.

Dr. Brown: 
RF is an autoantibody, most often IgM, that targets the Fc portion of IgG. In RA, RF binds to Fc regions on IgG antibodies and forms immune complexes. These complexes activate the complement system and immune cells, which amplifies the inflammatory response. Immune complexes can activate macrophages, leading to the secretion of pro-inflammatory cytokines, such as TNF-alpha and IL-6, and other inflammatory mediators.

Dr. Schwartzman: 
Our understanding of rheumatoid factor is evolving beyond its role as a diagnostic marker. RF has been gaining increasing attention in recent years, with new evidence demonstrating an impact of RF on the formation of immune complexes and subsequent role in the pro-inflammatory cascade and therapeutic response. RF levels matter because higher levels are associated with more aggressive disease, characterized by joint destruction, erosion, faster radiographic progression, disability, and lower likelihood of therapeutic response. There are also cardiovascular implications. This is significant because high RF levels can help identify patients who may have a poor clinical response to some TNFis. For example, higher RF levels have been linked to reduced drug concentrations for certain biologics.

Dr. Brown: 
TNFis like CIMZIA neutralize TNF. But higher RF levels may help explain why some patients respond differently to certain RA treatments – more on this to come.

Dr. Brown: 
Now of all the TNFis out there, what’s unique about CIMZIA?

Dr. Schwartzman: 
Most TNFis are full antibodies that include an Fc region. CIMZIA is different—it’s the only Fc-free TNFi.

Dr. Brown: 
So we know CIMZIA is built differently than other TNF inhibitors. It’s both Fc-free and PEGylated. But let’s talk more about what that means in practice.

Dr. Schwartzman: 
CIMZIA is a monoclonal antibody fragment that binds to and neutralizes TNF-alpha, interrupting the downstream inflammatory cascade that drives RA symptoms and joint damage.

Dr. Brown:
And since CIMZIA lacks an Fc region, it’s hypothesized that it does not bind to molecules such as RF. While the clinical relevance of CIMZIA’s mechanism of action is unknown, its PEGylated Fab' fragment is thought to help prolong its half-life, extend bioavailability, and slow drug clearance.

Dr. Schwartzman: 
So, big picture: By directly neutralizing TNF-alpha, CIMZIA is thought to inhibit the inflammatory cascade responsible, in part, for the joint destruction and clinical disease in rheumatoid arthritis.

Dr. Brown:
Understanding the difference in structure among the different TNF inhibitors is critical. For example, it has been shown in pharmacokinetic studies that rheumatoid factor binds to the Fc region of certain TNFis, creating large protein complexes and driving increased clearance. 
Higher RF levels have also been associated with lower drug concentrations of certain TNFis compared with lower RF levels. Because CIMZIA lacks an Fc region, this decrease in drug concentration is not seen.
These characteristics suggest that CIMZIA's Fc-free structure may be relevant when treating patients with RA who have higher RF levels.
Dr. Schwartzman: 
That’s why understanding the difference between Fc-containing TNFis and the only Fc-free TNFi, CIMZIA, can help us better tailor treatment decisions for our patients with high RF.   
Dr. Brown: 
Thanks so much for joining me, Dr. Schwartzman.

Dr. Schwartzman: 
It’s been a pleasure.

Dr. Brown: 
And thank you to our listeners for joining us on the Right Fit Report.

In our next episode, we’ll dive into the RAPID trial, which was CIMZIA’s pivotal study in rheumatoid arthritis. We’ll also look at EXXELERATE, the head-to-head study comparing CIMZIA with adalimumab, and we’ll explore a post hoc analysis from EXXELERATE that focused specifically on patients with high RF levels.
For more details on CIMZIA and the role of high RF in RA, check out the references linked on our episode page.  

And now, please stay tuned for the full Important Safety Information. And to learn more about how CIMZIA may be the right fit for your patients with RA, including those with high RF, visit the RA pages at CIMZIAhcp.com.

Until next time!

Aletaha D, Alasti F, Smolen JS. Rheumatoid factor determines structural progression of rheumatoid arthritis dependent and independent of disease activity. Ann Rheum Dis. 2013;72(6):875-880. doi:10.1136/annrheumdis-2012-201517

Bidgood SR, et al. Fragment crystallizable (Fc)-free certolizumab pegol is not bound by rheumatoid factors, while Fc containing biological DMARDs are, driving immune complex formation and cellular clearance. Abstract presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC.

CIMZIA [prescribing information]. Smyrna, GA: UCB, Inc.

Farrugia M, Baron B. The role of TNF-α in rheumatoid arthritis: a focus on regulatory T cells. J Clin Translat Res. 2016;2(3):84-90.

Fazeli MS, Khaychuk V, Wittstock K, et al. Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies. Clin Med Insights Arthritis Musculoskelet Disord. 2021;14:11795441211028751. doi:10.1177/11795441211028751

Martinez-Feito A, Plasencia-Rodriguez C, Novella-Navarro M, et al. Influence of rheumatoid factor on serum drug levels of TNF inhibitors with different structures in rheumatoid arthritis. Clin Exp Rheumatol. 2024;42(5):999-1005.

Oliveira VDRS, Reis APMG, Brenol CV, et al. High-Titer Rheumatoid Factor is Associated with Worse Clinical Outcomes and Higher Needs for Advanced Therapies in Rheumatoid Arthritis Under Real-Life Conditions. Rheumatol Ther. 2025;12(1):123-136. doi:10.1007/s40744-024-00730-w

Porter C, Armstrong-Fisher S, Kopotsha T, et al. Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer. J Reprod Immunol. 2016;116:7-12.

Smolen JS, Taylor PC, Tanaka Y, et al. Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis. Rheumatology (Oxford). 2024;63(11):3015-3024.

Tanaka Y, Takeuchi T, Haaland D, et al. Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: post-hoc analysis of clinical trials. Int J Rheum Dis. 2023;26(7):1248-1259. 

Togashi T, Ishihara R, Watanabe R, et al. Rheumatoid factor: diagnostic and prognostic performance and therapeutic implications in rheumatoid arthritis. J Clin Med. 2025;14(5):1-20. doi:10.3390/jcm14051529

Episode 1

How Could CIMZIA’s (certolizumab pegol) Different Molecular Structure Be Meaningful for Patients With High RF?

Join Dr. Monica Schwartzman and Dr. Adam Brown as they explore the impact of high rheumatoid factor (RF) levels on rheumatoid arthritis and discuss how CIMZIA's fragment crystallizable (Fc)-free structure could make it the right fit for patients with high RF.

Featured Guests:
Monica Schwartzman, MD, MS
Monica Schwartzman, MD, MS
New York, NY
Adam Brown, MD
Adam Brown, MD
Cleveland, OH
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Episode 1

How Could CIMZIA’s (certolizumab pegol) Different Molecular Structure Be Meaningful for Patients With High RF?

The healthcare professionals featured in this podcast have been compensated by UCB, Inc. for their time and participation.

Explore EXXELERATE data
Explore polyarticular juvenile idiopathic arthritis (pJIA)

IMPORTANT SAFETY INFORMATION & INDICATIONS

Serious and sometimes fatal side effects have been reported with CIMZIA, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens (such as Legionella or Listeria). Patients should be closely monitored for the signs and symptoms of infection during and after treatment with CIMZIA. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member.

INDICATIONS

CIMZIA is a tumor necrosis factor (TNF) blocker 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
  • Treatment of adults with moderately to severely active rheumatoid arthritis (RA)
  • Treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older
  • Treatment of adult patients with active psoriatic arthritis (PsA)
  • Treatment of adults with active ankylosing spondylitis (AS)
  • Treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation
  • Treatment of adults with moderate-to-severe plaque psoriasis (PSO) who are candidates for systemic therapy or phototherapy

IMPORTANT SAFETY INFORMATION (CONT’D)

CONTRAINDICATIONS

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria.

SERIOUS INFECTIONS

Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue CIMZIA if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before CIMZIA use and during therapy. Initiate treatment for latent TB prior to CIMZIA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with CIMZIA prior to initiating therapy in the following patients: with chronic or recurrent infection; who have been exposed to TB; with a history of opportunistic infection; who resided in or traveled in regions where mycoses are endemic; with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with CIMZIA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

  • Do not start CIMZIA during an active infection, including localized infections.
  • Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
  • If an infection develops, monitor carefully and initiate appropriate therapy.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which CIMZIA is a member.

  • Consider the risks and benefits of CIMZIA treatment prior to initiating or continuing therapy in a patient with known malignancy.
  • In clinical trials, more cases of malignancies were observed among CIMZIA-treated patients compared to control patients.
  • In CIMZIA clinical trials, there was an approximately 2-fold higher rate of lymphoma than expected in the general U.S. population. Patients with rheumatoid arthritis, particularly those with highly active disease, are at a higher risk of lymphoma than the general population.
  • Malignancies, some fatal, have been reported among children, adolescents, and young adults being treated with TNF blockers. Approximately half of the cases were lymphoma, while the rest were other types of malignancies, including rare types associated with immunosuppression and malignancies not usually seen in this patient population.
  • Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including CIMZIA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis, and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treating with CIMZIA in these patient types.
  • Cases of acute and chronic leukemia were reported with TNF blocker use.

HEART FAILURE

  • Worsening and new onset congestive heart failure (CHF) have been reported with TNF blockers. Exercise caution and monitor carefully.

HYPERSENSITIVITY

  • Angioedema, anaphylaxis, dyspnea, hypotension, rash, serum sickness, and urticaria have been reported following CIMZIA administration. If a serious allergic reaction occurs, stop CIMZIA and institute appropriate therapy. The needle shield inside the removable cap of the CIMZIA prefilled syringe contains a derivative of natural rubber latex that may cause an allergic reaction in individuals sensitive to latex.

HEPATITIS B VIRUS REACTIVATION

  • Use of TNF blockers, including CIMZIA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
  • Test patients for HBV infection before initiating treatment with CIMZIA.
  • Exercise caution in patients who are carriers of HBV and monitor them before and during CIMZIA treatment.
  • Discontinue CIMZIA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming CIMZIA after HBV treatment.

NEUROLOGIC REACTIONS

  • TNF blockers, including CIMZIA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, seizure disorder, optic neuritis, peripheral neuropathy, and Guillain-Barré syndrome.

HEMATOLOGIC REACTIONS

  • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with CIMZIA.
  • Consider stopping CIMZIA if significant hematologic abnormalities occur.

DRUG INTERACTIONS

  • Do not use CIMZIA in combination with other biological DMARDs.

AUTOIMMUNITY

  • Treatment with CIMZIA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.

IMMUNIZATIONS

  • Avoid use of live vaccines during or immediately prior to initiating CIMZIA. Update immunizations in agreement with current immunization guidelines prior to initiating CIMZIA therapy.

ADVERSE REACTIONS

  • The most common adverse reactions in CIMZIA clinical trials (≥8%) were upper respiratory infections (18%), rash (9%), and urinary tract infections (8%).

 

Please refer to full Prescribing Information.

US-CZ-2600076