Vedolizumab Demonstrates Early Symptomatic Improvement in Crohnʼs Disease (CD): A GEMINI 2 Post hoc Analysis
Bibliographic record
Abstract
Introduction: Vedolizumab (VDZ), a humanized monoclonal anti-α4β7 integrin antibody, is approved for the treatment of adults with moderately to severely active CD1. Improvements in patient-reported symptoms remain important treatment goals for patients (pts) and key indicators of treatment response for physicians. We aimed to characterize early response with VDZ by evaluating the timing of symptomatic improvements through a post hoc analysis of GEMINI 2. Methods: Pts with active CD were randomized to receive double-blind placebo (PBO) or VDZ at weeks (wks) 0 and 2 during the 6-wk induction phase. The two patient-reported components of the Crohn's disease activity index (CDAI) score- abdominal pain subscores (APS) and number of liquid or very soft stools subscore (NLVSS)- were evaluated at 0, 2, 4 and 6 wks. Mean percentage change from baseline (BL) was reported for the overall population and in those who were tumor necrosis factor antagonist (anti-TNF) naive. The difference in adjusted percentage change from BL between VDZ and PBO was determined using an ANCOVA model with treatment as a factor and BL as a covariate. Results: Percentage decreases in APS and NLVSS from BL over time were examined in anti-TNF-naive and overall populations. Significantly greater percentage decreases in APS were observed with VDZ than PBO at wks 2, 4 and 6 in both populations (Fig 1). Similarly, greater percentage decreases in NLVSS were observed with VDZ than PBO, reaching statistical significance at wks 2 and 6 (Fig 2). A composite score of APS and NLVSS showed similar trends with significantly greater percentage decreases with VDZ than PBO at all time points (Fig 3). Overall, differences in percentage change between VDZ and PBO were greater in naive pts than in the overall population. Notably, differences in percentage APS decrease from BL in naive pts were about 2-times as much as in the overall population [% decrease in naive vs overall: -19.4 vs -10.4; -22.0 vs -11.2; -21.1 vs -11.7 at wks 2, 4 and 6, respectively](Fig 1).Figure: Percentage change from baseline in CDAI abdominal pain score *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL APS=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; APS, abdominal pain subscore; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Figure: Percentage change from baseline in CDAI number of liquid or very soft stool subscore *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL NLVSS=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Figure: Percentage change from baseline in CDAI composite score of the number of liquid or very soft stool and abdominal pain *Data points represent adjusted % change from BL mean, where adjustment is for BL value and treatment. Error bars represent standard error. †Diff in adjusted % change from BL=adjusted mean % change for VDZ - adjusted mean % change for PBO. Upper limit of 95% CI <0 indicates statistical significance at a nominal significance level of 0.05. Patients with BL value=0 were excluded from this analysis. Abbreviations: anti-TNF, tumor necrosis factor antagonist; BL, baseline; CDAI, Crohn's disease activity index; CI, confidence interval; Diff, difference; PBO, placebo; VDZ, vedolizumab.Conclusion: Symptomatic improvements were achieved with VDZ as early as wk 2, with greater differences from PBO observed in anti-TNF-naive pts compared with the overall population. These results highlight that rapid onset of action of VDZ in CD may be observed in some pts; however, for those who exhibit a more gradual response, assessing efficacy at wk 14 and beyond is recommended to inform clinical practice.
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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 | 0.008 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".