Loss of Efficacy to Anti-TNF Therapy in the Management of Crohnʼs Disease: A Brazilian Multicenter Observational Study
Notice bibliographique
Résumé
Besides the great benefit of anti-TNF agents in the management of Crohn's disease (CD), it is known that efficacy of both Infliximab (IFX) and Adalimumab (ADA) can be reduced over time. Loss of response to these agents can be explained by immunological issues, such as antibody formation or even lower trough levels of the drugs. There is lack of real life data in Latin American CD patients regarding the issue of loss of efficacy (LOE) to anti-TNF therapy. The primary objective of this study was to analyze the incidence of LOE to both IFX and ADA in a cohort of Brazilian CD patients. The secondary objectives were to define the timing of LOE to the drugs and to identify possible risk factors for its appearance. This was a retrospective, observational cohort study, with CD patients treated with anti-TNF therapy from 5 referral IBD centres from Brazil. Inclusion criteria: CD patients, responders to the first biological agent (anti-TNF naive) with completed induction regimen. Exclusion criteria: undetermined IBD, primary non-responders and patients previously exposed to anti-TNF agents. Patients were allocated in two groups, regarding the drug administered (IFX or ADA). Electronic chart review was performed and a specific protocol was ful-filled. Variables analyzed: demographic data, Montreal classification, concomitant medications, smoking, perianal CD, time of follow-up, presence of LOE, timing and the reasons for its occurrence. LOE was defined as one of the following characteristics: need for steroids, occurrence of abdominal surgery during treatment, dose increase, interval shortening or switching of the anti-TNF agent. Statistical analysis was performed with student's t test, Mann Whitney, Fischer or chi-square tests to demonstrate comparability of the groups. Log-rank test (Kaplan Meier) was performed to analyze the timing of loss of efficacy. Cox regression multivariate analysis was also performed to define risk factors, with P < 0.05 considered significant. A total of 175 patients were included in the study (117 in the IFX and 58 in the ADA group). The groups were considered homogeneous regarding demographic data, Montreal classification, smoking status and perianal CD. There were more patients exposed to steroids and azathioprine in the IFX group. Medium follow-up period was 17.3 (±12.4) months on the IFX and 13.1 (±11.3) months on the ADA group. Overall, LOE occurred in 47/117 (40.2%) of the IFX and in 9/58 (15.5%) ADA patients (P = 0.001). Medium timing for LOE was 11.8 (±8.1) months on IFX and 13.3 (±12.3) months on ADA patients (P = 0.073), without significant difference on the reasons for its occurrence (P = 0.125). On multivariate analysis, younger patients (Montreal A1) were at risk for LOE (P = 0.032). On COX regression analysis, a higher risk for LOE was noticed when IFX was administered (OR = 3.33; P = 0.006) and in patients with perianal CD (OR = 2.23; P = 0.026). Loss of efficacy (LOE) was observed in 40.2% of the IFX and in 15.5% of the ADA patients, without any significant difference in timing and reasons for its occurrence. These data were similar to the literature of other countries. The risk for the development of LOE was higher in younger patients, on IFX therapy and with perianal CD.
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 | 0,002 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,000 |
| 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 ».