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

Abstract

Saeed Shakibfar,1 Kristine H Allin,2 Tine Jess,2 Maria Antonietta Barbieri,1,3 Vera Battini,1,4 Eva Simoncic,1 Julien Kirchgesner,5 Trond Ulven,1,* Maurizio Sessa1,* 1Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; 2Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; 3Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 4Pharmacovigilance & 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; 5Department of Gastroenterology, INSERM, Institut Pierre Louis d’Epidémiologie Et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France*These authors contributed equally to this workCorrespondence: Saeed Shakibfar, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark, Email [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: Crohn’s disease, drug repurposing, inflammatory bowel disease, intestinal fibrosis, machine-learning, real-world data

Keywords

• crohn’s disease
• drug repurposing
• inflammatory bowel disease
• intestinal fibrosis
• machine-learning
• real-world data.