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. 2024 Feb 21:15:17-29.
doi: 10.2147/POR.S444569. eCollection 2024.

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

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 Sessa #  1
Affiliations

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

Saeed Shakibfar et al. Pragmat Obs Res. .

Abstract

Aim: 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.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Hazard ratio of drugs associated with an increased risk of the study outcome.
Figure 2
Figure 2
Risk difference of drugs associated with an increased risk of the study outcome.
Figure 3
Figure 3
Lasso regression for variable selection prolonging time interval from CD to the study outcome. Log(λ) = 4.5 was chosen to get the optimal number of features.
Figure 4
Figure 4
Hazard ratio of drugs associated with a prolonged time interval from the initial diagnosis of CD to the study outcome.
Figure 5
Figure 5
Risk difference of drugs associated with an increased time interval from CD diagnosis date to the study outcome date.
See this image and copyright information in PMC

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