Drug Repurposing in Crohn's Disease Using Danish Real-World Data.

Crohn’s disease drug repurposing inflammatory bowel disease intestinal fibrosis machine-learning real-world data

Journal

Pragmatic and observational research
ISSN: 1179-7266
Titre abrégé: Pragmat Obs Res
Pays: New Zealand
ID NLM: 101688693

Informations de publication

Date de publication:
2024
Historique:
received: 08 12 2023
accepted: 08 02 2024
medline: 26 2 2024
pubmed: 26 2 2024
entrez: 26 2 2024
Statut: epublish

Résumé

Drug repurposing, utilizing electronic healthcare records (EHRs), offers a promising alternative by repurposing existing drugs for new therapeutic indications, especially for patients lacking effective therapies. Intestinal fibrosis, a severe complication of Crohn's disease (CD), poses significant challenges, increasing morbidity and mortality without available pharmacological treatments. This article focuses on identifying medications associated with an elevated or reduced risk of fibrosis in CD patients through a population-wide real-world data and artificial intelligence (AI) approach. Patients aged 65 or older with a diagnosis of CD from 1996 to 2019 in the Danish EHRs were followed for up to 24 years. The primary outcome was the need of specific surgical procedures, namely proctocolectomy with ileostomy and ileocecal resection as proxies of intestinal fibrosis. The study explored drugs linked to an increased or reduced risk of the study outcome through machine-learning driven survival analysis. Among the 9179 CD patients, 1029 (11.2%) underwent surgery, primarily men (58.5%), with a mean age of 76 years, 10 drugs were linked to an elevated risk of surgery for proctocolectomy with ileostomy and ileocecal resection. In contrast, 10 drugs were associated with a reduced risk of undergoing surgery for these conditions. This study focuses on repurposing existing drugs to prevent surgery related to intestinal fibrosis in CD patients, using Danish EHRs and advanced statistical methods. The findings offer valuable insights into potential treatments for this condition, addressing a critical unmet medical need. Further research and clinical trials are warranted to validate the effectiveness of these repurposed drugs in preventing surgery related to intestinal fibrosis in CD patients.

Identifiants

pubmed: 38404739
doi: 10.2147/POR.S444569
pii: 444569
pmc: PMC10894518
doi:

Types de publication

Journal Article

Langues

eng

Pagination

17-29

Informations de copyright

© 2024 Shakibfar et al.

Déclaration de conflit d'intérêts

Dr Tine Jess reports personal fees from Ferring, outside the submitted work. Dr Julien Kirchgesner reports personal fees from Janssen, personal fees from Abbvie, personal fees from Pfizer, personal fees from Galapagos, personal fees from Takeda, personal fees from Tillots, personal fees from Amgen, personal fees from Lilly, outside the submitted work. The authors report no other conflicts of interest in this work.

Auteurs

Saeed Shakibfar (S)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Kristine H Allin (KH)

Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

Tine Jess (T)

Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

Maria Antonietta Barbieri (MA)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Vera Battini (V)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Pharmacovigilance & Clinical Research, International Centre for Pesticides and Health Risk Prevention, Department of Biomedical and Clinical Sciences (DIBIC), ASST Fatebenefratelli-Sacco University Hospital, Università Degli Studi Di Milano, Milan, Italy.

Eva Simoncic (E)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Julien Kirchgesner (J)

Department of Gastroenterology, INSERM, Institut Pierre Louis d'Epidémiologie Et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France.

Trond Ulven (T)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Maurizio Sessa (M)

Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Classifications MeSH