Certolizumab Pegol Offers Consistent Benefit, Regardless of Rheumatoid Factor Levels

James Galloway, MBChB
Credit: Galapagos Health

New data from the European Congress of Rheumatology (EULAR 2024), is underlying the potential benefits of among certolizumab pegol (Cimzia) in patients with rheumatoid arthritis (RA), regardless of rheumatoid factor levels at baseline.

An analysis of the phase 3b REALISTIC trial, results of the study provide an overview of the benefit-risk profile of certolizumab pegol relative to placebo across varying rheumatoid factor levels, with data pointing to a consistent benefit with use regardless of rheumatoid factors levels.¹

“For people living with RA, high [rheumatoid factor] levels are associated with more severe disease activity, risk of progression and loss of treatment efficacy, so the encouraging results of the REALISTIC study may impact treatment choices for people living with RA and high [rheumatoid factor] levels who have previously had an inadequate response to TNFis,” said study investigator James Galloway, MBChB, professor of Rheumatology at King’s College London and an honorary consultant in Rheumatology at King’s College Hospital, London.² “The [rheumatoid factor]-drug interaction research also presented at EULAR provides important molecular insights in to why we see more consistent drug concentrations among high [rheumatoid factor] patients treated with certolizumab pegol compared with Fc-containing TNFis.”

Published in 2012, which was 3 years after the agent received FDA approval for RA in 2009, REALISTIC was a 12-week, double-blind, placebo-controlled phase 3b trial launched with the intent of exploring the effects of certolizumab pegol among a cohort of patients with RA who had an inadequate response to at least 1 DMARD. Per trial protocol, 1063 patients were randomized 4:1 to certolizumab pegol or placebo therapy, with patients stratified by previous TNF inhibitor use, concomitant methotrexate use, and disease duration. The overall trial concluded use of certolizumab pegol was associated with rapid and consistent clinical responses across the study population, with benefit over placebo observed regardless of concomitant or previous therapy.^3,4

In the current study, Galloway and colleagues sought to further explore data from the trial, with a specific intent of assessing 36-week outcomes for Disease Activity Score 28 C-reactive protein (DAS28-CRP) score, DAS28-CRP less than 2.6, Clinical Disease Activity Index (CDAI) score, and CDAI remission. For the purpose of analysis, investigators stratified patients according to baseline rheumatoid factor levels and prior TNF inhibitor use. Of note, stratification for rheumatoid factor level was considered as being in the highest or lowest quartile.¹

Of the 1063 included in the original trial, 751 patients randomized to certolizumab pegol and 179 randomized to placebo therapy were included were included. Investigators pointed out demographics were similar between patients with elevated rheumatoid factor relative to their counterparts with reduced rheumatoid factor, including number of previous DMARDs.¹

Results indicated TNF-naïve patients treated with certolizumab pegol achieved a lower DAS28-CRP than placebo-treated patients, regardless of baseline rheumatoid factor levels, at week 12. Analysis of 36-week data from the trial indicated the proportion of certolizumab pegol-treated patients who achieved DAS28-CRP less than 2.6 was similar across rheumatoid factor levels and prior TNF inhibitor use.¹

Further analysis demonstrated TNF-naïve patients receiving certolizumab pegol had lower CDAI scores than those receiving placebo therapy, regardless of rheumatoid factor levels at week 12. Among those with a history of prior TNF inhibitor use, greater mean differences were observed for CDAI score among the certolizumab pegol group relative to the placebo group in patients with elevated rheumatoid factor. Investigators also pointed out the proportion of patients who achieved CDAI remission at week 36 was similar in certolizumab pegol group across subgroups defined by rheumatoid factor levels and prior TNF inhibitor use.¹

“Chronic rheumatological diseases such as axSpA, RA, and PsA are multifactorial and present significant treatment challenges, particularly as patients progress through different stages of life, such as family planning, pregnancy and breastfeeding, or disease progression,” said Oseme Etomi, MBBS, a consultant rheumatologist and Obstetric Physician, Guy’s and St Thomas Hospitals.² "The new clinical data we’ve seen at EULAR are valuable to support more personalized treatment that is tailored to the individual needs, lifestyle choices and clinical profile of each patient.”

References:

1. ^{Smolen JS, Mikuls T, Galloway J, et al. DO HIGH RHEUMATOID FACTOR LEVELS IMPACT RESPONSE TO CERTOLIZUMAB PEGOL IN PATIENTS WITH INADEQUATELY CONTROLLED RHEUMATOID ARTHRITIS? A POST HOC ANALYSIS OF THE PHASE 3B REALISTIC TRIAL. Abstract presented at European Congress of Rheumatology, EULAR 2024. Vienna, Austria. June 12-15, 2024.}
2. ^{UCB. New data support the value of CIMZIA[®] for women living with chronic rheumatic diseases throughout pregnancy and post-partum, and for people living with RA and high rheumatoid factor levels. UCB. June 13, 2024. Accessed June 13, 2024. https://www.ucb.com/stories-media/Press-Releases/article/New-data-support-the-value-of-CIMZIAR-for-women-living-with-chronic-rheumatic-diseases-throughout-pregnancy-and-post-partum-and-for-people-living-with-RA-and-high-rheumatoid-factor-levels.}
3. ^{Weinblatt ME, Fleischmann R, Huizinga TW, et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology (Oxford). 2012;51(12):2204-2214. doi:10.1093/rheumatology/kes150}
4. ^{UCB. UCB’s CIMZIA® (certolizumab Pegol) approved by the U.S. FDA for adult patients suffering from moderate to severe rheumatoid arthritis. UCB. May 14, 2009. Accessed June 13, 2024. https://www.ucb.com/stories-media/Press-Releases/article/UCB-s-CIMZIA-certolizumab-pegol-approved-by-the-U-S-FDA-for-adult-patients-suffering-from-moderate-to-severe-rheumatoid-arthritis.}