A Pooled Safety Analysis from the Ustekinumab Crohnʼs Disease and Psoriatic Diseases Phase 2 and 3 Clinical Trial Programs: 2016 ACG Presidential Poster Award
Bibliographic record
Abstract
Introduction: Ustekinumab (UST) is a well-established therapy in psoriasis (PsO) and psoriatic arthritis (PsA) with up to 5 years safety experience from psoriasis clinical trials with 3117 pts & 8998 patient years (PY) of follow-up. However, limited safety data have been presented in Crohn's disease (CD). In pts with CD, Phase 2/3 data show that UST is safe & effective. Herein we present CD safety results & compare these with the safety profile in psoriatic diseases. Methods: Safety data from 5 CD (2 Ph2/3Ph3) trials were analyzed with the previously reported PsO (1 Ph2/3Ph3) & PsA (1 Ph2/2 Ph3) randomized controlled trials. All psoriatic pts received UST 45 or 90mg SC; Ph3 CD pts received a single IV UST induction dose of 130mg or ˜6 mg/kg followed by 90mg SC q8 or q12 wks. In PsO trials, no concurrent treatment was permitted; concomitant MTX was permitted in PsA trials & concomitant immunomosuppressives & corticosteroids were permitted in CD trials. All pts who received ≥1 dose of UST were included. Safety outcomes are presented as events per 100 PYs. Results: Through the PBO-control period across all indications, 3636 pts were treated with UST (1582 PsO, 692 PsA & 1362 CD). Treated pts with ≥1 reported event PBO vs UST in pooled indications (incidence/100 PY of f/u): AEs 556.1 vs594.3; SAEs 19.5 vs16.4; infections 135.8 vs138.1; serious infections 2.9 vs 3.3; MACE 0.26 vs 0.60; malignancies 0.26 vs 0.12; deaths 0 vs 0.12. Through 1 year, 5884 pts were treated with UST (3117 PsO, 1018 PsA, & 1749 CD) with 4521 PY of follow-up. Rates of AEs, SAEs, infection/serious infection were similar between UST group and PBO (Table) across the pooled indications. Event rates in the combined CD studies were also similar between treatment groups (PBO & UST groups) with overall AEs, & infections occurring more frequently in CD pts. Conclusion: UST has a favorable safety profile in CD with IV induction dosing up to 6mg/kg & SC maintenance dosing up to 90mg q8wks. Evaluation of the CD experience did not alter the safety profile of UST previously defined in pts with psoriatic disease treated with up to 5 years of therapy.Table 1: Key safety events through 1yr of follow-up
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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 | 0.027 | 0.022 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.013 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".