Rheumatoid arthritis (RA) is an autoimmune condition that causes systemic inflammation leading to joint pain and swelling. It is one of the most common forms of inflammatory arthritis in the UK and can occur due to a combination of genetic, environmental and constitutional risk factors. Recently a link between antibiotic use and RA has been suggested. Antibiotics are widely prescribed to treat a wide range of bacterial infections including respiratory tract, gastrointestinal (GI) tract, and urinary tract infections. In the UK, around 30% of all registered patients in primary care receive at least one antibiotic prescription per year. However, antibiotics as well as targeting bacteria responsible for underlying infection can also disturb normal composition of very useful bacteria in our gut. There is now a growing body of evidence indicating that antibiotic usage, particularly during childhood, may be a major risk factor for infections and certain autoimmune conditions. However, it is not clear if antibiotic use is associated with the onset of rheumatoid arthritis. Using routinely collected health information from the Clinical Practice Research Datalink (CPRD), we propose to assess whether those prescribed antibiotics are more likely to develop RA.
An association between antibiotic use and certain autoimmune conditions (e.g. inflammatory bowel disease) has been suggested, however it is not clear if antibiotics are associated with the onset of rheumatoid arthritis. If such an association exists, then antibiotic use could be potentially considered as a modifiable risk factor for RA, especially in primary care where such drugs are overprescribed. The proposed study will 1) assess risk of RA among those prescribed one or more courses of antibiotics; 2) assess the association between antibiotic type (bacteriostatic or bactericidal) and RA.
Method and data analysis
We will identify individuals with first ever recorded diagnosis of RA between 1990 and 2018 using Read codes. Each case will be individually matched to 5 controls on year of birth, gender and general practice and assigned an index date corresponding to the date of their matched case. Exposure will be defined as any systemic antibiotic prescription recorded more than one year before the index date. Conditional logistics regression will be used to assess the association between antibiotic exposure and the risk of incident RA. We will adjust our estimates for a wide range of confounding factors using a multivariable regression model.
Incident rheumatoid arthritis
Christian Mallen - Chief Investigator - Keele University
Sara Muller - Corresponding Applicant - Keele University
Alyshah Abdul Sultan - Collaborator - AstraZeneca Ltd - UK Headquarters
Ian Scott - Collaborator - Keele University
Lindsay Hall - Collaborator - Quadram Institute
Samantha Hider - Collaborator - Keele University
Toby Helliwell - Collaborator - Keele University