S849 Real-World Clinical Effectiveness and Safety of Vedolizumab and Ustekinumab in Bio-Naïve Patients With Complex Crohn’s Disease: Results From the EVOLVE Expansion Study
Bibliographic record
Abstract
Introduction: Effectiveness of Crohn’s disease (CD) treatment (Tx) may vary per CD complexity. This analysis compared real-world clinical effectiveness and safety of vedolizumab (VDZ) and ustekinumab (UST) in bio-naïve patients (pts) with complex CD. Methods: Multicenter, observational, retrospective EVOLVE Expansion chart review study (NCT05056441) included bio-naïve pts with CD (≥ 18 years old) who initiated VDZ or UST in Australia, Belgium, or Switzerland from 2016 to 2021. A subgroup analysis analyzed outcomes in pts with complex CD (defined as at least 1 of: active fistula at Tx initiation and/or any prior CD-related surgeries during disease duration and/or CD-related hospitalizations in 12 months before Tx initiation). Data were collected from Tx initiation to the first of: chart abstraction initiation, Tx discontinuation, death, or loss to follow-up. Cumulative rates of clinical response, clinical remission, mucosal healing (all assessed using published algorithms1) and Tx persistence over 36 months of Tx were estimated in time-to-event analysis using Kaplan-Meier method. Safety was evaluated as serious adverse events (SAEs) and serious infections (SIs); healthcare resource utilization (HCRU) was evaluated as CD exacerbations, CD-related hospitalizations, and CD-related surgeries. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics between cohorts. P< 0.05 denoted statistical significance. Results: In total, 198 pts (VDZ 103, UST 95) with complex CD were included in this analysis. Baseline characteristics between groups were similar after IPTW (Table 1). During 36 months of Tx, pts from VDZ and UST cohorts had similar rates of clinical response (VDZ 76.4%, UST 80.2%; P=0.47), clinical remission (VDZ 79.9%, UST 83.1%; P=0.40), mucosal healing (VDZ 92.6%, UST 78.7%; P=0.05), and Tx persistence (VDZ 73.1%, UST 70.0%; P=0.81). There were no significant differences in the risk of SAEs (HR=0.84; 95% CI, 0.38-1.85; P=0.66), CD exacerbations (HR=0.89; 95% CI, 0.49-1.65; P=0.72), CD-related surgeries (HR=3.39; 95% CI, 0.97-11.84; P=0.06), and CD-related hospitalizations (HR=0.81; 95% CI, 0.42-1.57; P=0.53) during 36 months. Conclusion: In a real-world clinical setting, pts with complex CD had similar cumulative rates of clinical response, clinical remission, mucosal healing, and Tx persistence as well as similar risk of SAEs and HCRU outcomes between VDZ and UST cohorts during 36 months. Reference: 1. Bressler B, et al. J Crohns Colitis. 2021;15(10):1694-1706. Table 1. - Baseline characteristics of bio-naïve patients with complex CD initiating first-line biologic treatment with vedolizumab or ustekinumab Unweighted Weighted Baseline characteristic VDZ n=103 UST n=95 P value* VDZ n=101 UST n=97 Std Diff after IPTW Age, mean±SD, y 51.3±17.3 47.6±16.6 0.13 50.6±17.0 50.4±16.8 0.015 Male, n (%) 56 (54.4) 51 (53.7) 0.92 53 (52.6) 51 (52.2) 0.008 Smoking status, n (%) 0.56 0.169 Current 22 (21.4) 15 (15.8) 40 (39.4) 36 (36.9) Former 23 (22.3) 27 (28.4) 24 (24.3) 29 (30.1) Never 43 (41.7) 36 (37.9) 21 (21.2) 15 (15.7) Disease duration Median (min, max), y 6.2 (0.0, 52.6) 9.2 (0.0, 46.0) 0.81 9.7 (1.4–22) 8.5 (1.0–22) 0.060 CD location at Tx initiation, n (%) 0.41 Colonic with/without upper GI disease 19 (18.4) 9 (9.5) 14 (14.2) 10 (9.8) 0.028 Ileal with/without upper GI disease 52 (50.5) 49 (51.6) 43 (43.1) 43 (43.9) 0.012 Ileocolonic with/without upper GI disease 28 (27.2) 31 (32.6) 35 (34.8) 32 (32.4) 0.040 Disease behavior at Tx initiation, n (%) 0.62 0.016 Non-stricturing, non-penetrating 56 (54.4) 43 (45.3) 46 (46.1) 40 (41.3) Penetrating 12 (11.7) 15 (15.8) 16 (15.7) 16 (16.7) Stricturing 30 (29.1) 32 (33.7) 26 (25.7) 23 (23.8) Disease severity at Tx initiation, n (%) 0.60 Normal 12 (11.7) 9 (9.5) 10 (10.4) 11 (11.2) Mild 20 (19.4) 26 (27.4) 20 (20.1) 29 (29.7) Moderate 50 (48.5) 44 (46.3) 50 (49.8) 41 (42.6) 0.027 Severe 11 (10.7) 6 (6.3) 9 (8.6) 7 (6.9) 0.022 Fistula† prior to Tx initiation, n (%) 30 (29.1) 24 (25.3) 0.54 27 (26.4) 27 (27.3) 0.040 CD-related surgeries since CD diagnosis, n (%) 71 (68.9) 63 (66.3) 0.69 72 (71.6) 68 (69.9) 0.038 CD-related hospitalizations in the 12 months prior to Tx initiation, n (%) 53 (51.5) 54 (56.8) 0.45 53 (53.0) 51 (52.6) 0.008 *Unadjusted P values are reported.†Enterocutaneous, perianal, rectovaginal, other, or unknown.CD, Crohn’s disease; GI, gastrointestinal; IPTW, inverse probability of treatment weighting; Std Diff, standardized difference; Tx, treatment; UST, ustekinumab; VDZ, vedolizumab; y, years.
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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 | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".