Prescriptions for antibiotics in childhood and risk of inflammatory bowel disease: A matched case-control study in the UK Clinical Practice Research Datalink

Date of ISAC Approval: 
30/11/2018
Lay Summary: 
Over the past decades, the number of people suffering from inflammatory bowel disease (IBD) has increased. The term IBD includes Ulcerative colitis and Crohn's disease which are both defined by long-lasting inflammation of the digestive tract. The inflammation usually causes severe diarrhoea, abdominal pain, fatigue and weight loss. An estimated 2.5-3 million patients in Europe have this disease. IBD can cause severe symptoms in the gastrointestinal tract as well as in the skin, eyes and joints. In addition, patients with IBD are more likely to develop different types of cancer. The cause of IBD is unknown, however, it is suggested that factors affecting the normal bacterial in the bowel are risk factors for disease development. Antibiotics are commonly used drugs in the treatment of different infections in the body. While the antibiotic agent kills the disease-causing bacteria, some of the "good" bacteria in the bowel are killed too. In this study, we will investigate whether use of antibiotics in childhood may be a risk factor for developing IBD later in life.
Technical Summary: 
Exposure to antibiotics is associated with a temporary disruption of the human gut microflora which could possibly be a risk factor for developing inflammatory bowel disease (IBD). In this matched case-control study, we will count the number of prescriptions for different antibiotics in childhood among patients in the UK Clinical Practice Research Datalink (CPRD) with IBD and compare this number to matched IBD-free controls. Cases will consist of all patients in the CPRD with a recorded diagnosis of IBD. To be selected as a case, the patients must fulfil the following criteria; 1) at least one prescription for IBD-therapy after the date of IBD-diagnosis, 2) at least 10 years of history in the CPRD prior to the IBD-diagnosis and 3) no prior diagnosis of cancer (except non-melanoma skin cancer), Down Syndrome or diverticular diseases. Based on the same eligibility criteria, we will match the IBD-cases to up to 4 IBD-free controls on age (+/- 2 year), sex, general practice, number of active years in CPRD (within +/- 1 year) and index date (date of their matched case's IBD-diagnosis date). Using conditional logistic regression models, we will estimate the crude and adjusted odds ratios and their 95% confidence intervals for IBD stratified on ever or non-use of antibiotics, number of prescriptions for all antibiotics and number of prescriptions for different types of antibiotics.
Health Outcomes to be Measured: 
Inflammatory bowel disease (i.e. Ulcerative colitis or Crohn's disease)
Collaborators: 

Dr Susan S Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Frederikke Troelsen - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Dr Susan S Jick - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program