Guselkumab Not Linked to Worsening Liver Fibrosis in Psoriasis, 3-Year Study Finds

Guselkumab therapy does not contribute to liver fibrosis progression in patients living with psoriasis, new findings suggest, although longer psoriasis duration is suggested to be a significant factor linked to elevated Fibrosis-4 (FIB-4) index levels.1

These results were the conclusions drawn from an investigative team that sought to examine guselkumab’s long-term impact on liver fibrosis in 154 individuals with psoriasis using the FIB-4 index. The research was authored by a team of investigators, such as Edoardo Mortato, from the department of systems medicine at the University of Rome Tor Vergata in Italy.

The team highlighted that prior findings on the relationship between the FIB-4 index and characteristics of patients with psoriasis, as well as the impacts of interleukin (IL)-23 inhibitors on the FIB-4 index, had been published. Such data pointed to reductions in FIB-4 index after treatment with IL-23 inhibitors at 6 months in patients with higher scores at baseline.2

“Motivated by these findings, our study aimed to evaluate changes in the FIB-4 index in psoriasis patients treated with the IL-23 inhibitor guselkumab in a real-life setting and in the long term, over 3 years,” Mortato and colleagues wrote.1

The investigative team involved adult trial subjects who lived with moderate-to-severe psoriasis and had been undergoing treatment with guselkumab for a single year at minumum, with follow-up extending to 3 years. The team calculate subjects’ FIB-4 index, which they noted is a noninvasive marker for liver fibrosis. They did so annually using the formula suggested by the American Association for the Study of Liver Diseases, beginning prior to participants’ initiation of guselkumab.3

The investigators did not include patients who lacked essential laboratory values, including serum ALT, AST, or platelet counts. In their full cohort, the team included 154 individuals at baseline. Follow-up data were available for 154, 106, and 63 participants at the 1, 2, and 3-year marks, respectively. The analysis also involved a separate evaluation of a subset of 100 subjects aged 35 - 65 years, given that FIB-4 was known to provide more accurate estimates of fibrosis risk among this age cohort.

The research team used 2 groups to categorize the study participants, basing the cohorts on subjects’ initial FIB-4 scores. Specifically, the team created a higher-risk arm of the study (FIB-4 ≥ 1.3) and a lower-risk arm (FIB-4 < 1.3). They used a variety of statistical methods to assess FIB-4 trends over time, including Wilcoxon signed-rank, Friedman, and Mann–Whitney U tests, with significance set at P < .05.

Across all of the cohorts assessed by the investigative team, stability in mean FIB-4 values was shown to have remained. The team highlighted a lack of statistically significant shifts, noting that subjects placed in the high-risk group reported minor fluctuations that did not reach significance.

Among those deemed to be low-risk (FIB-4 < 1.3), the investigators noted that FIB-4 values trended upward slightly over time. They commented that this likely reflected age-related changes. Notably, however, the findings suggest that longer duration of psoriasis is a significant factor linked to elevated FIB-4 levels. In the team’s univariate analysis, participants showing a disease duration of 20 years or more showed an increased likelihood of presenting with a high-risk FIB-4 index (odds ratio, 2.13; 95% CI, 1.06–4.27; P = .034). This was seen in 40% compared to only 23.7% among those with a shorter disease history.

These findings suggest that guselkumab therapy is not linked to progression of liver fibrosis in patients with psoriasis. However, future analayses utilizing more sensitive techniques such as imaging or liver biopsy may be necessary to further validate hepatic safety of IL-23 inhibitors in the long term, such as guselkumab. The team also noted their study’s limitations.

“The declining sample size, especially after the second year, reduced statistical power,” they concluded.1 “Patient loss to follow-up and withdrawals may have affected result reliability. Additionally, FIB-4 is an indirect marker influenced by factors like platelet count and age, which were not controlled for. The lack of liver biopsy data limits histological assessment, and the extended follow-up may have diluted short-term treatment effects.”

References

1. Mortato E, Marcelli L, Tofani L, et al. Effects of Guselkumab on the FIB-4 Index in Psoriasis Patients (EGIPT): A Three-Year Study. J Dermatol. Published online April 16, 2025. doi:10.1111/1346-8138.17752

2. Takeshima R, Kamata M, Suzuki S, et al. Interleukin-23 inhibitors decrease Fibrosis-4 index in psoriasis patients with elevated Fibrosis-4 index but not inteleukin-17 inhibitors. J Dermatol. 2024;51(9):1216-1224. doi:10.1111/1346-8138.17277

3. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. doi:10.1002/hep.29367