Vedolizumab Demonstrates Early Symptomatic Improvement in Crohnʼs Disease (CD): A GEMINI 2 Post hoc Analysis
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,008 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».