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 tumor necrosis factor inhibitors (TNFi) and non-biologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a nested case-control study using 2006-2021 data from the MerativeTM MarketScan® Database. We included adults 18-65 years old with ≥1 inpatient or ≥2 outpatient axSpA ICD-9 or 10 diagnosis codes separated by ≥7 days. The primary outcome was hip and/or spine fracture, defined by ICD-9 or 10 diagnosis or procedure codes. For each fracture case, we selected up to 10 controls without fracture. We evaluated medication exposure (TNFi, 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. Our main analysis included 13,519 individuals with axSpA, comprising 1,229 cases and 12,290 controls. Individuals on TNFi had 29% lower odds of fracture compared to those on NSAIDs (OR 0.71, 95% 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. Using a large US insurance claims database, we found evidence for a protective effect of TNFi on fracture risk in axSpA underscoring a potential impact of TNFi in diminishing comorbidities linked with axSpA.
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