P625 Ustekinumab use in Crohn's disease: effectiveness of dose escalation
Bibliographic record
Abstract
Background: Efficacy of ustekinumab (UST) in Crohn's disease (CD) has been demonstrated in clinical trials. In the absence of therapeutic drug monitoring, empirical dose escalation has been considered as a strategy to optimize response in patients with either primary or secondary non-response. Efficacy and safety of UST 90mg subcutaneous (SC) every 4 weeks is not known. Methods: A retrospective, observational study of compassionate use of UST in CD was conducted at a Canadian tertiary centre. A subset of patients in whom dose escalation (90mg SC every 4 weeks) had occurred was identified. Symptomatic response, defined as physician documentation of improvement of CD-associated symptoms and continuation of therapy, following dose escalation was assessed, as was biochemical or endoscopic response if available. Results: Ustekinumab was dose escalated in 16 patients (9 males) of median age 47 (IQR 34–54); disease duration of 12.5 years (IQR 8–18) and location of ileal (4); colonic (4) and ileocolonic (8), with accompanying perianal involvement in 8 patients. All patients were anti-TNF experienced. Fourteen patients had been induced with standard SC dosing (90mg Weeks 0, 1, 2) and 4 with higher SC dosing (270mg Week 0; 180mg Weeks 1 and 2). Dose escalation occurred for primary and secondary nonresponse to UST in 7 and 9 patients respectively. Nineteen percent (3/16) of patients had a response to dose escalation, while 10 patients have ceased therapy. A myopathy developed in one patient and was considered possibly related to UST; dose has been subsequently de-escalated. No additional significant adverse events were reported in the remaining patients who received dose escalated UST. Conclusions: In this subset of real-life experience of UST use in patients with CD, maintenance dose escalation to 90mg every 4 weeks had a modest benefit in achieving a clinical response. This may be suggestive of the mechanism of loss of response to UST being driven by factors other than low bioavailability due to processes such as rapid clearance. Further assessment in larger cohorts as well as the use of therapeutic drug monitoring will be important to evaluate the usefulness of dose escalation for patients on UST.
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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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".