A257 EARLY PROACTIVE THERAPEUTIC DRUG MONITORING WITH USTEKINUMAB THERAPY IN PAEDIATRIC CROHN’S DISEASE
Bibliographic record
Abstract
Abstract Background Ustekinumab (UST) is an effective therapy for adults with moderate to severe Crohn’s disease (CD), but data concerning optimal dosing in children are sparse. Aims To examine real-world post-induction PK and efficacy in a prospective multicentre cohort study of paediatric CD (Canadian Children IBD Network (CIDsCaNN)). Methods Children 2-17 years-old with CD were eligible for this analysis if they received IV UST for treatment of luminal CD and had serum UST levels measured at week 8. Median with interquartile range (IQR) UST dose and serum trough levels at weeks 8 and 16 were compared between children ampersand:003C40 kg and ≥40 kg with Mann-Whitney U test. Clinical remission was defined as weighted Pediatric CD Activity Index (wPCDAI) ampersand:003C12.5. UST durability was compared between those with a week 8 serum UST level ampersand:003C5 versus ≥5 µg/mL (log-rank p-value). Results Between 21/04/2017 and 30/04/2023, 39 children were eligible (74% M; median age 13.5 (IQR 11.9-15.6) y; median weight 44.7 (IQR 30.4-55.0) kg, 12 children ampersand:003C40 kg; 84% bio-naïve). Median disease duration at UST start was 4 (IQR 1-17) months; CD location distal ileal ± limited cecal (18%), colonic (26%), ileocolonic (54%). Median follow-up duration was 10.0 (IQR 6.7-12.7) months. All children received UST IV induction (67% 260 mg, 18% 390 mg) followed by 90 mg SC every 8 weeks. Induction doses in mg per kg were higher in those ampersand:003C40 kg (median 9.11 (IQR 8.68-10.08)) compared to those ≥40 kg (5.77 (IQR 5.24-6.45) mg/kg), pampersand:003C0.001. Induction doses in mg per body surface area (BSA) in m2 were similarly higher in those ampersand:003C40 kg (median 251.66 (IQR 244.16-258.99) versus 195.15 (IQR 172.71-224.11) mg/m2, pampersand:003C0.001). Despite higher induction doses, week 8 trough levels were numerically lower in those ampersand:003C40 kg (median 4.32 (IQR 1.33-8.36) versus 6.96 (IQR 5.38-8.90) µg/mL, p=0.29). Week 16 serum UST levels were also numerically lower in ampersand:003C40 kg versus ≥40 kg (median 4.04 (IQR 1.92-6.98) versus 5.50 (IQR 3.17-8.27) µg/mL, p=0.57). Interval shortening during maintenance to every 4 weeks occurred in 7 children prior to week 16, and in 14 children prior to 6 months. By 4 months, 19 of 33 children with available data (56%) achieved clinical remission. Overall, 8/39 (21%) ceased UST. Those who discontinued UST had significantly lower week 8 levels than those who continued UST (median 3.52 (IQR 1.19-6.12) versus 7.15 (IQR 5.09-10.15) µg/mL, p=0.027). In survival analysis, week 8 trough level ampersand:003C5 µg/mL was associated with an increased risk of UST discontinuation (log-rank p=0.032) (Figure 1). Conclusions Higher UST concentration at week 8 is associated with greater drug durability. A higher BSA-based induction for children ampersand:003C40 kg is supported by higher serum drug levels and improved drug durability. Figure 1. Ustekinumab durability by week 8 serum drug level Funding Agencies CIHR
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".