Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study

Narula N 1 , Wong ECL 2 , Pray C 2 , Marshall JK 2 , Rangarajan S 3 , Islam S 3 Show all authors , Bahonar A 4 , Alhabib KF 5 , Kontsevaya A 6 , Ariffin F 7 , Co HU 8 , Al Sharief W 9 , Szuba A 10 , Wielgosz A 11 , Diaz ML 12 , Yusuf R 13 , Kruger L 14 , Soman B 15 , Li Y 16 , Wang C 16 , Yin L 16 , Mirrakhimov E 17 , Lanas F 18 , Davletov K 19 , Rosengren A 20 , Lopez-Jaramillo P 21 , Khatib R 22 , Oguz A 23 , Iqbal R 24 , Yeates K 25 , Avezum Á 26 , Reinisch W 27 , Moayyedi P 28 , Yusuf S 3

Affiliations 

  • 1 Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address: Neeraj.narula@medportal.ca
  • 2 Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  • 3 Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada
  • 4 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  • 5 Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud Medical City, King Saud University, Riyadh, Saudi Arabia
  • 6 National Research Center for Therapy and Preventive Medicine, Russian Federation, Moscow, Russia
  • 7 Primary Care Medicine, Faculty of Medicine Universiti Teknologi MARA, Selangor, Malaysia
  • 8 University of the Philippines College of Medicine, Manila, Philippines
  • 9 Family Medicine Department, Medical Education and Research Department, Dubai Health Authority, Dubai, United Arab Emirates
  • 10 Department of Angiology, Hypertension and Diabetology, Wroclaw Medical University, Wroclaw, Poland
  • 11 University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  • 12 Estudios Clínicos Latinoamérica Rosario, Santa Fe, Argentina
  • 13 Independent University, Bashundhara R/A, Dhaka, Bangladesh
  • 14 Africa Unit for Transdisciplinary Health Research, Potchefstroom, South Africa
  • 15 Health Action by People, Thiruvananthapuram, Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India
  • 16 Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • 17 Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
  • 18 Universidad de La Frontera, Temuco, Chile
  • 19 Al-Farabi Kazakh National University, Health Research Institute, Almaty, Kazakhstan
  • 20 Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Västra Götaland Region Region, Sweden
  • 21 Masira Research Institute, Medical School, Universidad de Santander, Bucaramanga, Colombia
  • 22 Advocate Aurora Research Institute, Advocate Aurora Health, Downers Grove, Illinois; Institute of Community and Public Health, Birzeit University, Birzeit, Palestine
  • 23 Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine, Istanbul, Turkey
  • 24 Department of Community Health Sciences, Aga Khan University, Karachi City, Sindh, Pakistan
  • 25 Department of Medicine, Queen's University, Kingston, Ontario, Canada
  • 26 International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
  • 27 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  • 28 Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Ontario, Canada
Clin Gastroenterol Hepatol, 2023 Sep;21(10):2649-2659.e16.
PMID: 36528284 DOI: 10.1016/j.cgh.2022.11.037

Abstract

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort.

METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs.

RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity.

CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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