P-096 The Relative Efficacy of Methotrexate and Thiopurines in Preventing Anti-Drug Antibodies To Certolizumab Pegol in Patients with Crohnʼs Disease
Bibliographic record
Abstract
Tumor necrosis factor (TNF) antagonists are established agents for the treatment of moderate to severe Crohn's disease (CD). However, these foreign proteins can induce antidrug antibodies (ADAs) that decrease drug efficacy. Co-administration of immunomodulators such as azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX), may reduce the risk of sensitization and increase efficacy. However, no data exist regarding the relative efficacy of these agents in preventing formation of ADAs in patients receiving certolizumab pegol (CZP) therapy for CD. Data from 9 clinical trials of CZP for moderate to severe Crohn's disease were pooled for this analysis. Patients who were treated concurrently with CZP and either MTX or AZA/6MP for at least 90 days versus no concurrent immunomodulators were analyzed for ADA. Descriptive statistics and Kaplan-Meier analyses were used. The mean (SD) age of patients treated with AZA/6MP or MTX (n = 700) was 36 (12) years old and of those not treated with immunomodulators (n = 1315) was 38 (12) years old; 57% in each category were female. The disease severity in each group had similar mean (SD) CDAI scores of 300 (60) and 301 (62), respectively. In these analyses, patients treated with AZA/6MP or MTX were less likely to develop ADAs to CZP than those who were not treated with immunomodulators (Table). Likewise, the time to developing ADAs to CZP was shorter for patients not receiving immunomodulators concomitantly with CZP (P < 0.0001). No clinically significant difference was observed in ADA incidence between the AZA/6-MP and MTX concurrent groups (Table). The analysis of ADAs to CZP based on administered MTX dose suggests that at least 15 mg per week is a minimum effective dose for reducing ADAs to CZP. Conversely, no dose response relationship was found between AZA/6-MP and risk of ADA formation (Figure). In these analyses, AZA/6MP and MTX were similarly effective at reducing formation of ADAs to CZP. An MTX dose of at least 15 mg/week was most effective in preventing formation of ADAs to CZP, but no such threshold was seen for AZA/6MP.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".