Rheumatoid arthritis (RA) is a chronic inflammatory disease that brings about a lot of ailments and difficulties for the affected patient. Osteoporosis commonly known as brittle bones and osteoporotic (OP) fractures are one of those complications, which are very dangerous and deadly. There are several factors that play a part in the raised risk of OP fractures in RA including the medicine that RA patients use.
Perhaps, the most important drugs in RA with a role in osteoporosis are oral glucocorticoids (GCs). Still, RA patients take other drugs that could also affect bones; they are prescribed non-steroidal anti-inflammatory drugs (NSAIDs) as pain-killers and as these drugs could develop stomach upset and peptic ulcer, other medication such as proton pump inhibitors (PPIs) do normally accompany them to reduce the stomach acidity and the chance of having peptic ulcer. Previous studies showed that PPIs could also increase the risk of an OP fracture.
But to date, there is no study that considers use of both GCs and PPIs together and fracture risk in RA patients. Thus, in this study we examine the association between use of both GCs and PPIs together and the risk of fracture among patients with RA in the UK. Also, we examine the use of GCs and PPIs separately and different doses of GCs and PPIs and its effect on OP fracture risk, and among various OP fracture sites such as hip, vertebrae, humerus, forearm, pelvis, and rib.
Objectives: To investigate the association between concomitant use of glucocorticoids (GCs) and proton pump inhibitors (PPIs), and the risk of fracture among patients with rheumatoid arthritis (RA).
Design: Retrospective cohort study using the Clinical Practice Research Datalink (CPRD).
Participants: All adults aged 50 years and older diagnosed with RA in CPRD between 1997 and 2017. The index date will be the RA diagnosis, recorded as the first read code for RA during valid data collection.
Primary exposure: There will be two primary exposures of interest in this study. First, the use of oral GCs, and secondly, the use of PPIs. Exposure to treatment will be assessed time-dependently, and in 30-day follow-up periods.
Outcome: The outcome in our study is occurrence of the first incident osteoporotic (OP) fracture in RA patients after the index date, which include hip/femur, clinical symptomatic vertebral, humerus, forearm, pelvic, and rib fractures.
Statistical analyses: Cox proportional-hazards models will be used to conduct the statistical analysis. The first and main analysis will compare the OP fracture risk between RA patients who are current users of both GCs and PPIs, and RA patients who take neither of them. Separate analyses will be conducted for various OP fracture sites. Also, the only use of either of these medications, i.e. GCs, or PPIs, will be compared to the control group, in order to estimate the fracture risk of any of these drugs, individually. Furthermore, recent and past use of either of these drugs will be compared to non-use. The secondary analysis will focus on average daily and cumulative dose of current GC and average daily dose and duration of current PPI use in RA patients and will be compared to non-use of both drugs. All calculations will be adjusted for the potential confounders.
Occurrence of an osteoporotic fracture, including hip/femur, clinical symptomatic vertebral, humerus, forearm, pelvic, and rib fractures.
Frank de Vries - Chief Investigator - Utrecht University
Frank de Vries - Corresponding Applicant - Utrecht University
Andrea Burden - Collaborator - ETH Zurich
Anna Elise (Annelies) Boonen - Collaborator - Maastricht University Medical Centre
Johanna Driessen - Collaborator - Utrecht University
Joop van den Bergh - Collaborator - Maastricht University
Patrick Souverein - Collaborator - Utrecht University
Shahab Abtahi - Collaborator - Utrecht University
Tjeerd van Staa - Collaborator - University of Manchester