Association of Therapies for Axial Spondyloarthritis on the Risk of Hip and Spine Fractures

OBJECTIVE: People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with receiving tumor necrosis factor inhibitors (TNFis) and nonbiologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in patients with axSpA, relative to receiving nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We conducted a nested case-control study using 2006 to 2021 data from the Merative MarketScan Database. We included adults 18 to 65 years old with at least one inpatient or at least two outpatient axSpA International Classification of Diseases, Ninth Revision (ICD-9), or International Classification of Diseases, Tenth Revision (ICD-10), diagnosis codes separated by at least seven days. The primary outcome was hip and/or spine fracture, defined by ICD-9 or ICD-10 diagnosis or procedure codes. For each patient with fracture (cases), we selected up to 10 controls without fracture. We evaluated medication exposure (TNFis, csDMARDs, NSAIDs referent, or none) hierarchically using pharmacy claims and procedure codes. We assessed the relation of medication exposure with hip and spine fracture risk using unconditional logistic regression with confounder adjustment. RESULTS: Our main analysis included 13,519 individuals with axSpA, comprising 1,229 patients with fracture and 12,290 controls. Individuals receiving TNFis had 29% lower odds of fracture compared to those receiving NSAIDs (odds ratio OR 0.71, 95% confidence interval CI 0.59-0.85), accounting for age, sex, and diagnosis year. Results were similar in the fully adjusted model (OR 0.75, 95% CI 0.62-0.91) and when stratified by sex. CONCLUSION: Using a large US insurance claims database, we found evidence for a protective effect of receiving TNFis on fracture risk in patients with axSpA underscoring a potential impact of TNFis in diminishing comorbidities linked with axSpA.