Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase III Randomized, Double‐Blind, Placebo–Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (r‐axSpA) and prior inadequate response or intolerance to 1 or 2 TNF inhibitors (TNFi). Methods: In this randomized, double‐blind placebo‐controlled, Phase 3 trial, adult patients with inadequate response/intolerance to 1 or 2 TNFi and an established diagnosis of axSpA and fulfilling ASAS criteria for r‐axSpA with radiographic sacroiliitis defined per modified NY criteria and ≥1 SpA feature were recruited and randomized 1:1:1 to placebo or 80‐mg subcutaneous ixekizumab every 2 (IXEQ2W) or 4 (IXEQ4W) weeks, with a 80‐mg or 160‐mg starting dose. The primary endpoint was ASAS40 response at Week 16. Secondary outcomes and safety were also assessed. Results: In total, 316 patients were randomized to placebo (N=104), IXEQ2W (N=98), or IXEQ4W (N=114). At Week 16, significantly higher proportions of IXEQ2W (N=30 [30.6%]; p=0.003) or IXEQ4W (N=29 [25.4%]; p=0.017) patients achieved ASAS40 versus placebo (N=13 [12.5%]), with statistically significant differences reported as early as Week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal MRI inflammation were observed with 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events (AE) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W). Conclusion: Ixekizumab treatment for 16 weeks in patients with active r‐axSpA and previous inadequate response or intolerance to 1 or 2 TNFi yielded rapid and significant improvements in the signs and symptoms of r‐axSpA versus placebo.