Week 12 Reduction in Modified Multiplier of the Simple Endoscopic Score for Crohn’s Disease is Predictive of Delayed Response to Upadacitinib in Crohn’s Disease
Bibliographic record
Abstract
BACKGROUND & AIMS: Delayed clinical response to biologics and small molecules has been observed in inflammatory bowel disease, but little is known about the characteristics and outcomes of delayed responders to upadacitinib in Crohn's disease (CD). We aimed to evaluate early endoscopic and biochemical markers to help identify patients with CD who exhibit delayed response to upadacitinib compared with nonresponders. METHODS: This was a post-hoc analysis of patient-level data from the U-EXCEED and U-EXCEL clinical trials. Patients with moderate-to-severe CD randomized to upadacitinib 45 mg once daily were assessed for clinical response at week 12. Those who did not achieve clinical response by week 12 were offered an additional 12 weeks of open-label upadacitinib at 30 mg daily, and those with week 24 clinical response were considered delayed responders. The primary outcome was week 24 clinical response, defined as a decrease ≥30% in the average daily frequency of very soft or liquid stools or in the abdominal pain score with neither worse than baseline. Logistic regression was used to assess the likelihood of achieving outcomes of interest. RESULTS: Among 665 patients randomized to upadacitinib, 194 (29.2%) were nonresponders at week 12. Of these, 122 had week 24 data available, with 64 (52.5%) achieving delayed response at week 24. Most delayed responders had achieved at least a 20% reduction in Modified Multiplier of the Simple Endoscopic Score for Crohn's Disease (MM-SES-CD) by week 12 (51/64; 79.7%). Patients who failed to achieve at least a 20% reduction in the MM-SES-CD at week 12 were unlikely to achieve a delayed clinical response (13/39 [33.3%] vs 51/83 [61.5%]; adjusted odds ratio, 0.22; 95% confidence interval, 0.09-0.53; P = .001). Similar findings were observed for achievement of MM-SES-CD <22.5 by week 12. Improvement in endoscopic burden defined using the SES-CD and reduction in inflammatory biomarkers including C-reactive protein or fecal calprotectin by week 12 were not predictive of week 24 delayed response to upadacitinib. CONCLUSIONS: Delayed clinical response to upadacitinib occurs in a substantial proportion of initial nonresponders. Failure to achieve week 12 reduction in MM-SES-CD is associated with a high likelihood of delayed nonresponse, supporting its utility in guiding treatment decisions.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| 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".