OP011 Etrolizumab treatment leads to early improvement in symptoms and inflammatory biomarkers in anti-TNF-refractory patients in the open-label induction cohort of the phase 3 HICKORY study
Bibliographic record
Abstract
Background: Etrolizumab, an anti-β7 mAb targeting integrins α4β7 and αEβ7, showed significantly greater clinical remission at wk 10 vs placebo (PBO) in the phase 2 EUCALYPTUS trial. We assessed changes in symptoms and inflammatory biomarkers in aTNF refractory or intolerant (aTNF-IR) pts treated in a non-pivotal open-label induction (OLI) cohort of a phase 3 study. Methods: HICKORY is a multicentre, randomised, double-blind, PBO-controlled phase 3 study (NCT02100696) evaluating the safety and efficacy of etrolizumab during induction and maintenance in aTNF-IR pts with moderate-to-severe UC. The study includes a non-pivotal OLI cohort that treated 130 pts with etrolizumab 105 mg every 4 wk for 14 wk. Symptomatic improvement in this cohort was assessed based on the change in weekly mean rectal bleeding (RB) and stool frequency (SF) scores (each scored on a scale of 0–3), derived from pts' daily eDiary entries. SF remission was defined as a weekly mean score of ≤1 (rounded to the nearest integer) with ≥1 point reduction from baseline (BL). RB remission was defined as a weekly mean score of 0 (rounded to the nearest integer) with ≥0.5 point reduction from BL. Faecal calprotectin (FC) and C-reactive protein (CRP) were measured at BL and wk 14 or early termination. Changes in SF, RB, PRO score (SF + RB), FC and CRP were assessed descriptively. Results: Of 130 treated pts, 97% received all induction doses, 80% had a BL Mayo Clinic endoscopic score of 3, and 45% had received ≥2 prior aTNFs. RB remission rates improved from BL to wk 4 (∼30%) and 14 (∼50%). SF remission rates improved from BL to wk 4 (∼10%) and 14 (∼25%). PRO scores improved regardless of disease severity and irrespective of prior treatment with 1 or ≥2 aTNFs. The mean (± SE) decrease in PRO was 22% (±3%) at wk 4 and 36% (±3%) at wk 14; this decrease mirrored mean reductions in FC and CRP. Overall, FC and CRP levels decreased at wk 14 by a mean (95% CI) of 57% (42 to 69) and 33% (15 to 47), respectively. Mean decrease in CRP in pts with CRP levels >2.87 mg/L (ULN) at BL was 47%. Mean decreases in FC and CRP levels at wk 14 were greater in pts in SF remission (FC, 83%; CRP, 54%) and in pts in RB remission (FC, 69%; CRP, 49%). Etrolizumab demonstrated favourable safety and tolerability. Figure 1 Conclusions: aTNF-IR pts with moderate-to-severe UC reported symptom improvement as early as wk 4 during OLI treatment with etrolizumab. Clinically meaningful improvement in disease activity was observed in pt-reported SF and RB scores, serum CRP and FC by wk 14.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Open science | 0.000 | 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".