Reaching the therapeutic ceiling in IBD: Can Advanced Combination Treatment (ACT) offer a solution?
Notice bibliographique
Résumé
The term Advanced Combination Treatment involves the combination of at least two biologics or the use of a biologic with a small molecule drug, each with different mechanisms of action. This narrative review evaluates the current evidence supporting ACT in inflammatory bowel disease (IBD), focusing on preclinical studies, real-world evidence, and randomised controlled trials. A systematic review of randomized controlled trials has concluded that ACT significantly improves clinical outcomes, without significant safety concerns in patient with IBD. However, variability in trial designs and the lack of standardized outcome measures have led to initiatives aimed at mitigating these issues through a clear expert consensus. While the evidence for ACT in IBD is compelling, substantial challenges remain in standardizing treatment protocols and ensuring long-term safety. In the meantime, the use of ACT in clinical practice remains off-label and requires careful consideration of patient-specific factors. Future clinical trials should consider robust biomarkers for patient selection and leverage mechanistic insights to select combination components. • Combination Approaches: Advanced Combination Treatment (ACT) has emerged as the preferred terminology, emphasizing a strategic focus on leveraging multiple therapeutic mechanisms for more effective disease control. • Viable Treatment Option: Current evidence supports ACT as a promising alternative for IBD patients, offering targeted treatment that contrasts with traditional monotherapy strategies. • Ideal Candidates: ACT should be prioritized for patients with refractory disease, high-risk phenotypes, or concomitant EIMs or IMIDs, where conventional therapies have failed or are unlikely to succeed. • Optimal Timing and Setting: Begin combination therapy when disease risks outweigh treatment risks, and ideally in specialized centres with multidisciplinary teams for comprehensive care and access to clinical trials. • Monitoring and Adjustment: Regularly reassess treatment every six months to ensure efficacy and safety. Adjust or discontinue agents as necessary, and prioritize therapies with well-established safety profiles, such as vedolizumab or ustekinumab, when possible. Research Agenda • Mechanistic Approaches: Further investigation into the biological mechanisms underlying ACT will enhance the precision of therapy selection and optimize treatment outcomes. • Bispecific Antibodies: Explore bispecific antibodies, like SOR102, which can target multiple inflammatory pathways simultaneously, to improve disease control. • Extended half-life mAbs against alpha4beta7 (SPY001), TL1A (SPY002), and IL-23 (SPY003) are under development as combination therapies for IBD. • Consensus Initiatives: Develop standardized definitions, guidelines, and consensus frameworks for ACT to enable broader clinical adoption and improve consistency in treatment approaches. • Cost-effectiveness: As biosimilars become more widely available, the cost-effectiveness of combination therapies is expected to improve, making ACT more accessible and affordable for a wider patient population. • Future Research Needs: Research should focus on determining whether ACT is beneficial not only in refractory cases but also in early-stage disease, with the goal of improving long-term disease outcomes. Key trials such as VICTRIVA, DUET-CD, DUET-UC, and Target CD (NCT06548542) are exploring promising combination regimens to refine treatment strategies.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,007 | 0,007 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».