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

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

Data Sharing Statement

Data are stored on secure servers on Statistics Denmark and cannot be shared according to Statistics Denmark regulations. Access to Statistics Denmark servers and the associated data can be granted by Statistics Denmark upon adequate permissions.

Acknowledgments

VB is enrolled in the PhD in Experimental and Clinical Pharmacological Sciences, Università degli Studi di Milano, which supports her fellowship.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

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.

Additional information

Funding

The manuscript received funding from Novo Nordisk Foundation, grant NNF21OC0069019.