Background/Purpose: Ixekizumab (IXE) is a high affinity monoclonal antibody that selectively targets IL-17A. The objective of this analysis is to report the integrated safety of IXE in 2 pivotal trials in patients with active PsA.

Methods: The SPIRIT phase 3 trials consist of patients with active PsA who were bDMARD-naive (SPIRIT-P1, NCT01695239) or were inadequate responders to TNF-inhibitors (SPIRIT-P2; NCT02349295). Patients were randomized to 80 mg IXE every 4 weeks (Q4W, N=229) or 2 weeks (Q2W, N=225) after a 160 mg starting dose or PBO (N=224). Integrated safety data are presented from the PBO-controlled treatment periods (Weeks 0-24). Safety was assessed for patients who received at least 1 dose of study drug. At Week 16, patients deemed Inadequate Responders received rescue therapy and were included in this dataset only up to Week 16. Data was analyzed using a Cochran-Mantel-Haenszel test stratified by trial.

Results: The percentage of patients with ≥1 treatment emergent adverse event (TEAE) was significantly greater in the IXE compared to PBO treatment groups (Table 1). No clear difference was seen between groups for the percentage of patients with ≥1 serious adverse event (SAE) or discontinued early from study drug. Infection-related SAEs were reported in a significantly higher percentage of IXE Q2W than PBO patients. Treatment-emergent infections were numerically more frequent with IXE treatment compared to PBO (Table 2); upper respiratory tract infections, nasopharyngitis, and sinusitis were the most common infections. One PBO, 4 IXE Q4W, and 8 IXE Q2W-treated patients had ≥1 Candida infection. Injection site reactions were reported in a significantly higher percentage of patients in the IXE than the PBO treatment groups; most were of mild or moderate severity. Allergic reactions/hypersensitivity events were reported in a significantly higher percentage of IXE Q2W than PBO patients; no case of anaphylaxis was reported. Two cases of malignancy were reported (both IXE Q4W patients): prostate cancer and basal cell carcinoma. There were no major adverse cardiac events (MACE). While there were no reports of Crohn’s disease or ulcerative colitis, 1 IXE Q2W patient had SAEs of anal abscess and anal fistula, considered to represent inflammatory bowel disease; this patient continued study drug. There were no deaths or reports of suicide or suicidal ideation.

Conclusion: The safety profile of IXE during the placebo-controlled treatment period was consistent with published findings in patients receiving ixekizumab for moderate-to-severe plaque psoriasis¹.

¹Strober, B et al. JAAD. 2017 76(3):432