Prescribing of medication to prevent glucocorticoid harms in patients with Polymyalgia Rheumatica: a cross-sectional study and two emulated target trials in the Clinical Practice Research Datalink Aurum

Abstract Objectives Polymyalgia rheumatica (PMR) is a common indication for long-term glucocorticoid (GC) treatment. Bone- and gastro-protective medications are recommended for those at high-risk of adverse events from GCs but no trials have evaluated their effectiveness in PMR. We describe bone-/gastro-protective medicine prescribing in people with PMR and evaluate its impact on adverse GC outcomes using a target trial approach. Methods A sample of >40,000 individuals aged ≥50 years, with a coded PMR diagnosis from January 2010-March 2022, prescribed GCs within 21 days of first PMR diagnosis code, was constructed in CPRD Aurum. Prescriptions were defined as prevalent (pre-PMR diagnosis), incident (at diagnosis), or late (post-diagnosis, still GC-treated), reported stratified by age/gender/deprivation. A target-trial approach assessed the effect of: a) bisphosphonates on fragility fractures and b) proton-pump inhibitors/H2-receptor antagonists (PPIs/H2RAs) on gastrointestinal (GI) ulceration/bleeding. Treatment effect, adjusted for confounders, was modelled using targeted maximum likelihood estimation. Results 67.2% were co-prescribed bisphosphonates and 78.6% PPIs/H2RAs. Males and those in more deprived areas were less likely to receive bisphosphonates. 1.40% (95%CI 1.10%,1.70%) of those prescribed vs 2.32% (2.12%,2.52%) of those not prescribed bisphosphonates for 12 months experienced a fracture (risk difference 0.92% points [0.56%,1.27%], NNT 109). Prescribing gastro-protective medications was not associated with serious GI events. Conclusion Rates of prescribing to mitigate GC harms are higher than previously reported. Bisphosphonates are associated with approximately one less fragility fracture per year for every 100 people treated. Gastro-prophylaxis is not associated with reduced risk of GI ulceration/bleeding, suggesting potential to reduce prescribing for this indication.