Comparative Risk of Osteoporosis and Osteoporotic Fractures According to Exposure to 2 Groups of Biologics in Patients With Radiographic Axial Spondyloarthritis

Objective To assess the comparative risk of osteoporosis and fractures associated with biologic disease-modifying antirheumatic drug (bDMARD) exposure in patients with radiographic axial spondyloarthritis (r-axSpA).

Methods This nationwide cohort study analyzed 37,708 patients with r-axSpA. The outcomes of interest were osteoporosis, vertebral fracture, and hip fracture, defined based on diagnosis codes. The follow-up period was from the r-axSpA diagnosis date to December 2021. Multivariable time-varying Cox regression models were used to assess the comparative risk of each outcome comparing the following groups: tumor necrosis factor inhibitor (TNFi) vs bDMARD-naïve, interleukin-17 inhibitor (IL-17i) vs bDMARD-naïve, and IL-17i vs TNFi. For comparing IL-17i vs TNFi, the line of bDMARD treatment was matched between the TNFi and IL-17i groups at a 4:1 ratio.

Results Exposure to TNFi (adjusted hazard ratio [aHR] 0.83; 95% CI 0.76-0.90, P < 0.01) and IL-17i (aHR 0.19, 95% CI 0.10-0.38; P < 0.01) was associated with a lower risk of osteoporosis compared with that of the bDMARD-naïve group. Further, IL-17i (aHR 0.23, 95% CI 0.11-0.46; P < 0.01) was associated with a lower risk of osteoporosis than TNFi. Exposure to TNFi (aHR 0.64, 95% CI 0.59-0.70; P < 0.01) was associated with a lower risk of vertebral fracture than that of the bDMARD-naïve group. IL-17i (vs bDMARD-naïve) was associated with a lower risk of vertebral fracture, 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 groups.

Conclusion Exposure to TNFi and IL-17i may be associated with a lower risk of osteoporosis, but not hip fracture, compared with the bDMARD-naïve group. Exposure to TNFi, but not IL-17i, may be associated with a lower risk of vertebral fracture compared with the bDMARD-naïve group.