Efficacy and Safety of Dose Adjustment and Delayed Response to Ustekinumab in Moderate - Severe Crohnʼs Disease Patients: Results from the IM-UNITI Maintenance Study: 2016 ACG Presidential Poster Award
Bibliographic record
Abstract
Introduction: Ustekinumab (UST) has been shown to induce and maintain clinical response and remission in moderate-severe Crohn's disease (CD) in 2 induction(UNITI-1 and 2) and 1 maintenance (IM-UNITI) randomized, placebo controlled Phase 3 trials. We evaluated the efficacy of UST in 2 additional groups in IM-UNITI: patients(pts) who underwent dose adjustment following loss of response (LOR) and pts who did not have a clinical response to IV UST during induction and had an additional subcutaneous(SC) dose. Methods: Pts achieving clinical response after single dose IV induction were randomized to SC placebo (PBO), UST 90 mg every 12wks(q12w) or every 8wks(q8w). Pts who met LOR criteria, defined as a CDAI score of ≥220 and a ≥100 point increase from the maintenance baseline CDAI score, between wks 8 and 32 of the maintenance trial could undergo a single dose adjustment as follows:PBO→q8w, q12w→q8w, and q8w→q8w (no dose adjustment) and were assessed for clinical response (≥100 point decrease in CDAI) and clinical remission (CDAI < 150) 16wks later. Separately, UST pts not in clinical response 8wks after the IV induction dose were given SC UST 90mg and if in clinical response 8wks later were continued on q8w dosing.Table 1: Proportion of subjects achieving clinical response and remission 16 weeks after dose adjustmentResults: 51(39%), 29(23%), and 28(22%) pts in the PBO, q12w and q8w groups, respectively, underwent dose adjustment after meeting LOR criteria. Among these pts, clinical remission and clinical response were observed in 39% and 71% of pts adjusting PBO→q8w(a situation similar to a drug holiday), 41% and 55% in the q12w→q8w group, and 32% and 46% in the q8w→q8w group when assessed 16wks later(Table). Median change in CDAI after adjustment was -121, -141 and -78.5 in the PBO→q8w, q12w→q8w and q8w→q8w groups, respectively. Of 467 pts not in response to UST following IV induction in UNITI1&2, 50.5% and 28.9% were in clinical response and remission 8wks after one additional UST dose (90mg SC). Among the 251 of these pts continuing dosing at wk8 of maintenance, 68.1% were in response and 50.2% were in remission at wk44. No increases or changes in patterns of adverse events were seen among pts who dose adjusted. Conclusion: In pts who met LOR criteria, dose adjustment from UST 90mg q12w to 90mg q8w provided some additional clinical benefit compared to pts who remained on UST 90mg q8w. Additionally, pts who were initial induction non-responders can benefit from continued treatment with at least 1 SC UST dose 8wks after IV induction.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".