In this nationwide observational study, ixekuzumab was mainly used in patients with axSpA and PsA who had previously failed multiple b/tsDMARDs, including other IL-17 inhibitors. Although prior IL-17 treatment was associated with increased risk of withdrawal in both groups, the relatively high retention rates and improvements in all disease outcomes suggest ixekizumab as a viable option for challenging patients with multiple b/tsDMARD failures.