Certolizumab Pegol Effective for Treating Rheumatoid Arthritis With High RF Levels

Josef S Smolen, MD

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Certolizumab pegol (CZP; Cimzia) was associated with maintained drug concentration and efficacy in patients with rheumatoid arthritis (RA) and high rheumatoid factor (RF) levels and may therefore be a more suitable therapeutic option than TNF inhibitors (TNFis) with a crystallizable fragment (Fc) fragment than adalimumab.¹

“In patients with RA, high RF levels are considered a poor prognostic factor and are associated with more aggressive and destructive disease, higher disease activity, higher cardiovascular risk and higher risk of radiographic progression,” lead investigator Josef S Smolen, MD, Emeritus Professor of Medicine, Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria, and colleagues wrote.¹

Smolen and colleagues conducted the phase 4 EXXELERATE (NCT01500278) 104-week, randomized, single-blind (double-blind until week 12; investigator blind thereafter) study comparing CZP (n = 453) with adalimumab (n = 454) in patients with RA for whom baseline data by RF quartiles were available (≤Q3, ≤204 IU/ml; >Q3, >204 IU/ml).¹

The investigators found that from week 12, the area under the curve (AUC) of adalimumab concentration was lower in patients in the upper quartile of RF concentration compared with patients below the upper quartile whereas the AUC of CZP concentration was similar in patients with higher and lower RF concentrations. Accordingly, patients under the upper quartile of RF concentration had similar disease activity scores (DAS28)-CRP between those treated with CZP (2.5; standard deviation [SD]. 1.2) and adalimumab (2.5; SD, 1.2; P = .917) through week 104 but were lower in patients in the upper quartile of RF concentration treated with CZP (2.5; SD, 1.2) than with adalimumab (2.9; SD, 1.2; P = .046).¹

Patients in the upper quartile of RF concentration treated with CZP (n = 46/70; 65.7%) were more likely to achieve DAS28-CRP low disease activity at week 104 than those treated with adalimumab (n = 28/58; 48.3%; 36% relative increase in CZP-treated patients). Non-responder imputation yielded similar findings. Number needed to treat (NNT) for DAS28-CRP LDA number at week 104 in patients under the upper quartile of RF concentration was 52.1 in patients treated with CZP compared with adalimumab (95% CI,193.5–297.6) and 5.5 (95% CI: 0.3–10.7) in patients in the upper quartile of RF concentration.¹

“To conclude, patients with RA and high levels of RF are a subgroup of patients with poor clinical outcomes. In ADA-treated patients, clinical outcomes were poorer and drug concentration lower in patients with high RF levels compared with lower RF levels,” Smolen and colleagues concluded.¹ “However, in CZP-treated patients, those with high levels of RF had similar drug concentration and clinical outcomes to patients with lower levels of RF. Thus, the current data are the first from a head-to-head trial comparing CZP and ADA to show that response to therapy in patients with RA and high levels of RF is influenced by the presence or absence of an Fc-portion, which is in line with previous findings.”

Recent data from Smolen and colleagues presented at the European Congress of Rheumatology (EULAR 2024) further underscored the potential benefits of among CZP in patients with RA, regardless of RF levels at baseline. The phase 3b REALISTIC trial demonstrated the benefit-risk profile of CZP relative to placebo across varying RF levels, with TNF-naïve patients treated with CZP achieving a lower DAS28-CRP than placebo-treated patients, regardless of baseline RF levels, at week 12. Analysis of 36-week data from the trial indicated the proportion of CZP-treated patients who achieved DAS28-CRP less than 2.6 was similar across rheumatoid factor levels and prior TNF inhibitor use.²

REFERENCES

1. 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. Rheumatol (Oxford). 2024, 00; 1–10 doi: 10.1093/rheumatology/keae435
2. 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.