Ixekizumab Demonstrates Consistent Safety Profile in Long-Term Analysis

Atul Deodhar, MD

Credit: OHSU

A long-term, integrated safety analysis demonstrated the consistent safety profile of ixekizumab, according to a study published in Arthritis Research and Therapy.¹

Ixekizumab is a high-affinity monoclonal antibody designed to selectively target interleukin (IL)-17A, an inflammatory cytokine linked to the pathogenesis of numerous autoimmune conditions. The drug is currently approved for moderate to severe plaque psoriasis (PsO), psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA), ankylosing spondylitis (AS), and pediatric PsO.²

“Because of the immunomodulatory effects of biologic medications, the potential for adverse events (AEs), the prolonged treatment periods typically required to manage these immune-mediated diseases, and the increased burden of comorbidities experienced by patients, continued safety monitoring is essential,” wrote lead investigator Atul Deodhar, MD, professor of medicine and medical director of rheumatology clinics at the Division of Arthritis & Rheumatic Diseases in Oregon Health & Science University, and colleagues.

The end-of-study safety outcomes from 25 randomized clinical trials (RCTs) evaluating ≥ 1 dose of ixekizumab in patients with PsO (n = 17), PsA (n = 4), or axial spondyloarthritis (axSpA, n = 4), were collected. The axSpA cohort included patients with nr-axSpA and AS diagnoses. Data were analyzed over 5 years in the PsO cohort and up to 3 years in the PsA and axSpA cohorts.

The rates of treatment-emergent adverse events (TEAEs), selected AEs of interest, and serious adverse events (SAEs) were assessed by both years of therapy and overall. AEs of interest included infections, depression and suicide/self-injury, Candida infection, latent tuberculosis, injection site reactions, inflammatory bowel disease (IBD), uveitis, malignancies, and major adverse cerebro-cardiovascular events (MACE). Exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) both overall and at yearly intervals were reported and evaluated.

A total of 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA were included in the analysis, with a cumulative ixekizumab exposure of 22,371.1 PY.

The IRs per 100 PY for any TEAE were 50.3 in the PsA cohort, 38.0 in the axSpA cohort, and 32.5 in the PsO cohort (80.7%, 85.6%, and 85% of patients, respectively). The most common TEAEs (≥ 10%) among groups were nasopharyngitis (23.1% PsO, 18.9% axSpA, 14.4% PsA) and injection site reactions (10.1% PsO, 10.0% axSpA, and 11.1% PsA). During the observation period, TEAEs did not increase with treatment exposure, and most were categorized as mild or moderate.

IRs of discontinuation of ixekizumab due to AE were 2.9 in the PsO group, 5.1 in the PsA group, and 3.1 in the axSpA group. SAEs were observed in 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8).

Other adverse events included injection site reactions (IRs per 100 PY: 11.6 in the PsA group, 7.4 in the axSpA group, and 5.9 in the PsO group), Candida (IRs per 100 PY: 2.0, 1.2, and 1.9, respectively), depression, malignancies, and MACE (IRs per 100 PY: ≤1.6 across all conditions). The adjudicated IRs per 100 PY of IBD were .8 in the axSpA cohort, and .1 in both the PsA and PsO cohorts.

Investigators noted the duration of study periods coupled with a relatively small patient sample size comprised of mostly White patients (> 70%) as limitations of the study.

“These final, end-of-study program results surrounding the long-term use of ixekizumab in patients with PsO, PsA and axSpA should serve as an important point of reference for physicians considering ixekizumab treatment in these patients, over an extended period,” investigators concluded.

References

1. ^{Deodhar A, Blauvelt A, Lebwohl M, et al. Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials. Arthritis Res Ther. 2024;26(1):49. Published 2024 Feb 12. doi:10.1186/s13075-023-03257-7}
2. ^{Liu L, Lu J, Allan BW, Tang Y, Tetreault J, Chow CK, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39–50.}