Background/Purpose: Tildrakizumab (TIL) is a high‐affinity, humanized, immunoglobulin G1κ, anti–interleukin-23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis. We evaluated adverse events related to liver function in the clinical development program for TIL.

Methods: This post hoc analysis included patients with moderate to severe chronic plaque psoriasis in 1 phase 2b (P05495, NCT01225731) and 2 phase 3 trials (reSURFACE 1 and 2, NCT01722331 and NCT01729754). In P05495, patients received placebo (PBO) or TIL 5, 25, 100, or 200 mg. In reSURFACE 1 and 2, patients received PBO or TIL 100 or 200 mg; reSURFACE 2 had an additional etanercept (ETN) 50 mg arm up to week (W)28. Patients were treated at W0 and W4 and then every 12 weeks, and were followed for up to W52 (P05495/reSURFACE 2) or 64 (reSURFACE 1). The primary safety population was all subjects as treated (≥1 dose of study treatment). We evaluated liver function test (LFT) findings in patients receiving TIL 100 or 200 mg using pooled safety data from the base studies (P05495, n = 355; reSURFACE 1, n = 771; reSURFACE 2, n = 1090). LFT events of clinical interest were defined as elevated aspartate or alanine transaminase (AST or ALT) levels ≥3 times the upper limit of normal (ULN) and elevated total bilirubin (BILI) levels ≥2 times the ULN combined with alkaline phosphatase levels (ALP) < 2 times the ULN. Extension study data are also provided.

Results: In the PBO-controlled periods, 2 patients (0.6%) in the PBO and 1 (0.1%) in the TIL 200 mg group discontinued due to elevated LFT. In the base study periods, the numbers of patients (patients with events/100 patient-years) with elevated LFT leading to treatment discontinuation were similar between PBO (2 [0.91]) and TIL (4 [0.21]) groups. No patients discontinued in the ETN group due to elevated LFT. Two patients had elevated LFT events of clinical interest not related to study treatment. During the extension, no patients met the criteria for elevated LFT events of clinical interest. In the base study safety pool, there were no patterns of worsening in AST, ALP, and BILI levels over the study course for patients with continuous TIL 100/200 mg exposure. Of patients with normal ALT levels at baseline, 26% had a high ALT result at some point during the study. Similar patterns were seen in the extension.

Conclusion: Patients receiving TIL had low rates of increased liver function or drug-induced liver injury, similar to patients receiving PBO or ETN. There were no consistent signals for LFT worsening over the study course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/no-increased-risk-of-liver-dysfunction-from-tildrakizumab-treatment-post-hoc-analyses-of-the-tildrakizumab-psoriasis-clinical-program/