Background/Purpose: Ixekizumab (IXE) is a high-affinity monoclonal antibody that specifically targets IL-17A. Pooled safety data from IXE studies in moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA) have been reported previously.^{1, 2} The purpose of this analysis is to report integrated safety results of IXE collected as of March 21, 2019.

Methods: All safety data from controlled and uncontrolled trials were integrated from 14 PsO and 4 PsA studies. The longer-term follow-up was 5 years for PsO trials and 3 years for PsA trials. Safety data were integrated from an all IXE exposure-safety population (defined as all patients receiving ≥1 dose of IXE) by indication. We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals (over the entirety of exposure) for up to 5 years for adverse events (AEs). Major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated by an external adjudication committee.

Results: A total of 6091 (17499.3 PY) patients from PsO trials and 1401 (2228.6 PY) patients from PsA trials were analyzed. The Table summarizes safety results for both treatment populations over 1-year intervals. Overall, the IRs for treatment-emergent AEs (TEAEs), serious AEs, and serious infections remained stable with continued IXE exposure, whereas the IRs of patients reporting infections or injection site reactions decreased over time. The most common TEAEs in PsO and PsA were nasopharyngitis, upper respiratory tract infection, and injection-site reaction; most were reported as mild or moderate in severity Opportunistic infections were limited to oral and esophageal candidiasis and localized herpes zoster. Over the entirety of exposure in PsO and PsA studies, respectively, IRs for AEs leading to study drug discontinuation (2.8 and 5.1), serious SAE (5.4 and 6.0) and death (0.2 and 0.3) were reported. The rate of suicide ideation or behavior was 0.1in PsO studies and less than 0.1 in PsA studies. There were no completed suicides in both PsO and PsA studies. In both PsO and PsA studies, IRs for safety topics of special interest in PsO and PsA included, IBD (adjudicated; 0.2 and 0.1), depression (1.2 and 1.7), non-melanoma skin cancer (0.3 and 0.4), other malignancies (0.5 and 0.3) and MACE (0.5 and 0.5), respectively.

Conclusion: The results support a favorable and consistent long-term safety profile of IXE treatment in patients with moderate-to-severe PsO (17499.3 PY) or active PsA (2228.6 PY).

References:

1. Langley RG, et al. J Eur Acad Dermatol Venereol. 2018;epub ahead of print.
2. Mease P, et al. Arthritis Care Res (Hoboken) 2018 Aug 29.

Table

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-profile-of-ixekizumab-treatment-in-patients-with-moderate-to-severe-plaque-psoriasis-and-psoriatic-arthritis-integrated-analysis-of-18-clinical-trials/