A116 LOSS OF RESPONSE TO VEDOLIZUMAB MAINTENANCE THERAPY IN CROHN`S DISEASE
Notice bibliographique
Résumé
Vedolizumab is a gut-specific alpha-4-beta-7 integrin antagonist that has demonstrated efficacy in induction and maintenance of clinical response and remission in Crohn’s disease randomized controlled trials. To evaluate the long-term maintenance of response achieved with vedolizumab therapy in Crohn’s disease in the real-world setting. A retrospective cohort study was performed at the University of Calgary of adult (≥18 years) CD patients responding to vedolizumab within 6 months of standard induction therapy (vedolizumab 300mg IV at weeks 0, 2, and 6) followed by a scheduled maintenance vedolizumab IV regimen. The primary outcome was composite loss of response (LOR) in follow-up, defined by worsening symptoms requiring vedolizumab dose escalation, rescue medical therapy with corticosteroids or immunomodulators, or vedolizumab discontinuation. Survival analysis with Kaplan-Meier plots was performed to assess median time to LOR and probability of LOR in follow-up. 109 CD patients with symptomatic response within 6 months to vedolizumab induction therapy were followed for a mean duration of 46.3 weeks (SD ±31.3 weeks). Mean Harvey Bradshaw Index (HBI) at induction was 6.3 (± 3.2); 68.8% (75/109) of patients had previously failed biologic therapy and 45 patients (41.3%) had previously failed multiple biologic agents. Composite loss of response occurred in 36 patients (33.0%) in follow-up at a mean time of 35.2 weeks (± 20.9 weeks). Dose escalation of vedolizumab to 300mg IV every four weeks was required in 22 patients (20.1%) to optimize primary clinical response in the context of ongoing symptoms despite every eight week therapy. Dose escalation for secondary loss of response occurred in 10 patients (9.2%) at a mean time of 38.9 weeks (± 5.0 weeks). Addition of rescue corticosteroids or immunomodulators was attempted in six patients (5.5%). Vedolizumab was discontinued due to loss of response in 22 patients (20.2%); mean time to drug discontinuation was 42.3 weeks (± 23.3 weeks). At 52 weeks, the probability of developing a composite loss of response was 36.7% [95% CI: 26.6 – 49.2%]. The probability of continuing on vedolizumab therapy at 52 weeks among initial symptomatic responders was 75.6% [95% CI: 62.8 – 84.5%]. Over three quarters of patients who respond symptomatically to vedolizumab induction therapy continue on treatment at one year, but 1/3 of patients will experience a loss of response and approximately 20% will discontinue treatment due to loss of response during maintenance therapy. Figure 1: Kaplan-Meier survival curve for probability of composite loss of response among 109 Crohn’s disease patients with primary clinical response/remission within 6 months of induction. None
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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 | 0,002 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».