Therapeutic Drug Monitoring of Adalimumab in Patients With Inflammatory Bowel Disease
Notice bibliographique
Résumé
The introduction of antitumor necrosis factor (TNF) such as infliximab (IFX) and adalimumab (ADA) has revolutionized the management landscape of inflammatory bowel disease (IBD). However, the response rate to those medications remains sub-optimal with many patients with Crohn’s disease (CD) and ulcerative colitis (UC), showing evidence of primary nonresponse or failing to maintain remission on those medications. One pivotal factor that may play a role in predicting the response to anti-TNF agents is serum drug level. Therapeutic drug monitoring (TDM), defined as the assessment of drug concentrations and antibodies, is an important tool toward optimizing biological therapy.1 TDM can be either reactive, in response to symptoms, signs and/or biomarkers of active disease, or proactive with adjustment of the medication to a target trough level in patients in remission. The DIAMOND study group reported a significant difference in week 26 ADA levels and antibodies between those adults with CD who were in remission at week 52 when compared with those who were not (7.7 ± 3.3 versus 5.4 ± 4.3 Ug/mL: P < 0.001) with less antibodies against ADA in those with higher 6-thioguanine nucleotide (TGN).2 A recent pediatric-randomized study examined the value of proactive versus reactive TDM in a cohort of children and young adults with CD on ADA. Higher corticosteroid-free sustained remission rates were associated with the proactive strategy.3 In a real-world experience, Park et al4 examined the association between ADA trough levels and IBD activity in 236 patients. The study did not find a significant difference between ADA trough levels in patients with active disease versus in those with quiescent disease except for mean tough levels that were significantly higher in patients with a normal CRP compared with those with a high CRP (6.7 ± 6.4 versus 4.7 ± 4.2 mcg/mL; P = 0.023) while the median was not. Nonetheless, there was a significant difference in trough levels between those in endoscopic remission versus those who were not. Higher trough levels were associated with endoscopic and radiological remission. The study was not powered enough to examine the effect of having an immunosuppressive agent on ADA trough levels in those who were on combination therapy versus those who were ADA. On the other hand, TDM was proven effective in guiding clinical management in the majority of patients. The study by Park et al is another step toward confirming the value of reactive TDM in a better guidance of managing patients with IBD. Funding: None. Conflict of Interests: W.E.M. served as an advisory board member for Janssen and AbbVie Canada.
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 | 0,001 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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 | 0,001 | 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 ».