Comparative risk of osteoporosis and osteoporotic fractures according to exposure to two groups of biologics in patients with ankylosing spondylitis

Objective To assess the comparative risk of osteoporosis and fractures associated with biological disease-modifying anti-rheumatic drug (bDMARD) exposure in patients with ankylosing spondylitis (AS). Methods This nationwide cohort study analyzed 37,708 patients with AS. The outcomes of interest were osteoporosis, vertebral fracture, and hip fracture, defined based on diagnosis codes. The follow-up period was from the AS diagnosis date to December 2021. Multivariable time-varying Cox regression models were used to assess the comparative risk of each outcome comparing tumor necrosis factor inhibitors (TNFi) vs. bDMARD-naïve; interleukin-17 inhibitors (IL-17i) vs. bDMARD-naïve; and IL-17i vs. TNFi. For comparing IL-17i vs. TNFi, we matched the line of bDMARD treatment between the TNFi and IL-17i groups in a 4:1 ratio. Results The TNFi (adjusted hazard ratio [aHR]=0.83, 95% confidence interval [CI]=0.76–0.90, p<0.01) and IL-17i (aHR=0.19, 95% CI=0.10–0.38, p<0.01) exposures were associated with lower osteoporosis risk compared with the bDMARD-naïve group. Further, IL-17i (aHR=0.23, 95% CI=0.11–0.46, p<0.01) was associated with lower osteoporosis risk than TNFi. The TNFi (aHR=0.64, 95% CI=0.59–0.70, p<0.01) exposure was associated with lower vertebral fracture risk than the bDMARD-naïve group. IL-17i (vs. bDMARD-naïve) was associated with lower vertebral fracture risk, although this did not reach statistical significance (aHR=0.52, 95% CI=0.25–1.09, p=0.09). Hip fracture risk did not differ across different groups. Conclusion TNFi and IL-17i exposures may be associated with a lower risk of osteoporosis, but not hip fractures, compared with bDMARD-naïve. TNFi exposure, but not IL-17i exposure, may be associated with a lower risk of vertebral fracture compared with bDMARD-naïve.