November 11, 2023
Post Hoc Analysis Reveals Certolizumab Pegol's Meaningful Efficacy in Rheumatoid Arthritis Patients with High Rheumatoid Factor Levels
A post hoc analysis derived from the EXXELERATE trial sheds light on the significant efficacy of certolizumab pegol in patients with rheumatoid arthritis (RA) who exhibit high levels of rheumatoid factor (RF). The analysis indicates that, at Week 104, 65.7 percent of patients treated with certolizumab pegol achieved low disease activity, surpassing the 48.3 percent seen in adalimumab-treated patients.
Certolizumab pegol consistently maintained drug concentrations and achieved low disease activity irrespective of RF levels, offering sustained benefits until the end of the study period (Week 104). This finding aligns with earlier independent studies, showcasing the uniform efficacy of certolizumab pegol across the entire RA patient population. In contrast, tumor necrosis factor inhibitors (TNFis) with an Fc fragment displayed diminishing efficacy in patients with high RF levels.
While the initial EXXELERATE trial did not meet the primary endpoints of superiority in comparing certolizumab pegol and adalimumab, the subsequent post hoc analysis focused on evaluating the efficacy of these TNF inhibitors across RF subgroups. Patients were randomly assigned to receive certolizumab pegol or adalimumab in combination with methotrexate (MTX). Responders and non-responders at Week 12 underwent a switch to the alternative TNFi, with potential follow-up until Week 104.
The analysis results indicated that, among patients in the higher RF quartile, 65.7 percent treated with certolizumab pegol and 48.3 percent treated with adalimumab achieved low disease activity at Week 104.
Notably, the distinctive Fc-free structure of certolizumab pegol may prevent RF from binding to the drug, ensuring its concentration remains stable over time. This characteristic sets certolizumab pegol apart as a potential solution for RA treatment, particularly in cases where high RF levels pose challenges.
By the American College of Rheumatology 2021 guidelines, which recommend biologic disease-modifying anti-rheumatic drugs (bDMARDs) for RA treatment when there is insufficient improvement with MTX alone, certolizumab pegol emerges as a compelling option. Unlike many bDMARDs that contain an Fc region susceptible to RF antibody binding, certolizumab pegol's unique structure may offer stability and sustained efficacy without the need for additional interventions.
November 07, 2023
Phase 2 Nipocalimab Data Confirm Mechanism of Action in Rheumatoid Arthritis, Supporting Progression into Combination Studies
Janssen Pharmaceutical has unveiled significant data from the Phase 2a IRIS-RA clinical study, a step forward in treating adults dealing with moderate to severe active rheumatoid arthritis (RA). This pioneering study, evaluating the efficacy and safety of nipocalimab—an anti-neonatal Fc (FcRn) inhibitor—in individuals with inadequate responses or intolerance to anti-tumor necrosis factor (anti-TNF) therapy, establishes the proof of mechanism for nipocalimab in RA.
The study showcased nipocalimab's effectiveness in reducing levels of circulating IgG antibodies, including ACPAs (anti-citrullinated protein antibodies), suggesting their potential role in driving RA disease activity. Notably, participants with higher baseline ACPAs demonstrated more than twice the placebo-adjusted DAS28-CRP remission compared to the overall study population.
Nipocalimab demonstrated positive outcomes across primary and secondary efficacy endpoints at Week 12, including improvements in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) (11.2% reduction in remission for all patients), American College of Rheumatology (ACR) responses (10.2% improvement for all patients, n=53), DAS28-CRP remission, and Health Assessment Questionnaire – Disability Index (HAQ-DI).
The encouraging results pave the way for the next phase, with a trial investigating the combination of nipocalimab with an anti-TNFα treatment in RA patients recently initiated.
With a favorable benefit-risk profile, nipocalimab demonstrates its potential as a valuable addition to the therapeutic options for individuals in this refractory RA population.