Certolizumab Inhibits Radiographic Progression Even in Rheumatoid Arthritis Patients with High Rheumatoid Factor Levels: A Pooled, Post Hoc Analysis of Two Phase 3 Trials
Bibliographic record
Abstract
Objectives To assess radiographic progression in certolizumab pegol (CZP)+methotrexate (MTX) vs placebo (PBO)+MTX-treated patients (pts) with rheumatoid arthritis (RA), stratified by rheumatoid factor (RF) level, in the C-EARLY ( NCT01519791 ) and C-OPERA ( NCT01451203 ) phase 3 randomized trials. Methods A pooled analysis of pts with early (≤1 year active disease) moderate-to-severe RA with poor prognostic factors in the C-EARLY and C-OPERA trials is presented (full analysis set). At Week (Wk)24, PBO-treated non-responders could switch to CZP for the remaining 28 wks (early escapers). Pts were stratified by baseline (BL) RF level (low: <200 IU/mL; high: ≥200 IU/mL), per published strata.[1,2] Change from BL in modified total Sharp score (mTSS) and proportions of pts experiencing minimum clinically important difference (worsening) of mTSS (>5) at Wk24 and Wk52 are reported. Results 813 CZP-treated (low RF: N=571; high RF: N=242) and 367 PBO-treated (low RF: N=242; high RF: N=125) pts with BL RF measurements were included; 56 PBO-treated pts were early escapers. BL characteristics were similar between CZP- and PBO-treated pts within each RF stratification. However, pts with high RF had more severe disease at BL than those with low RF, with higher mean C-reactive protein, anti-citrullinated protein antibodies, mTSS, and erosion scores. By Wk52, mean mTSS increased from BL in PBO-treated pts with both high RF (change from BL [CfB]: 2.36±6.20) and low RF (CfB: 1.37±3.43) but was comparable in CZP-treated pts (high RF, CfB: 0.28±2.63; low RF, CfB: 0.14±3.11). The proportion of pts with meaningfully worsening radiographic progression was higher in PBO-treated pts with high RF compared to low RF at both Wk24 (6.48% vs 2.84%) and Wk52 (17.59% vs 10.43%) (Figure). By contrast, a smaller proportion of CZP-treated pts experienced meaningful worsening and this was similar between pts with high and low RF (Wk24: 0.00% vs 1.05%; Wk52: 5.29% vs 3.14%, respectively). Figure. Individual pt CfB in mTSS at Wk24 and Wk52, stratified by baseline RF level (low [<200 IU/mL] vs high [≥200 IU/mL]) Conclusion Pts with high BL RF levels had more severe RA and BL radiographic damage than those with low RF. Worsening radiographic damage was observed in PBO-treated pts, with slightly greater progression in high RF pts than low RF. In contrast, irrespective of BL RF levels, CZP-treated pts demonstrated consistently lower radiographic progression, suggesting RF does not adversely influence radiographic response to CZP. Previously submitted to: ACR 2024. [1.] Vastesaeger N. Rheumatology (Oxford) 2009;48:1114-21; [2.] Smolen J. Arthritis Rheumatol 2023;75(suppl 9).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.022 | 0.016 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.016 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".