Hepatic Safety of IL-17 Inhibitors in Psoriasis and Psoriatic Arthritis: A 12-Month Retrospective Cohort Evaluation Using the FIB-4 Index
Keywords:
Psoriasis, Psoriatic Arthritis, IL-17 inhibitors, Secukinumab, IxekizumabAbstract
Introduction: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated diseases frequently associated with metabolic dysfunction–associated steatotic liver disease (MASLD). Interleukin-17 (IL-17) contributes to both psoriatic inflammation and hepatic fibrogenesis. However, long-term real-world data on the hepatic safety of IL-17 inhibitors remain limited.
Objectives: To evaluate longitudinal changes in hepatic fibrosis risk using the Fibrosis-4 (FIB-4) index in PsO and PsA patients treated with IL-17 inhibitors and to assess concurrent trends in skin activity and liver enzymes in a dual-center, retrospective cohort.
Methods: Adults with PsO ± PsA who received secukinumab or ixekizumab for ≥12 months at two tertiary centers were retrospectively analyzed. FIB-4 index, liver enzymes (AST, ALT, GGT), and Psoriasis Area and Severity Index (PASI) were assessed at baseline, 3, 6, and 12 months. Patients with chronic liver disease, hepatotoxic drug exposure, or incomplete follow-up were excluded.
Results: A total of 123 patients (mean age 45.2 ± 11.7 years; 59.3% male; 79.7% with PsA) were included. Median baseline FIB-4 was 1.06 (IQR 0.84–1.32); 17.9% of patients were in the intermediate-high risk category. FIB-4 values and risk distribution remained stable over 12 months (P=0.76). Liver enzyme levels did not change significantly, and no hepatotoxic event occurred. Median PASI improved from 12.3 (IQR 7.9–18.7) to 1.1 (IQR 0.5–2.2) at month 12 (P<0.001), with 68.1% of patients achieving PASI ≤1. There was no correlation between changes in PASI and FIB-4 (ρ= -0.08; P=0.27).
Conclusions: IL-17 inhibitors provided substantial clinical efficacy and stable hepatic fibrosis risk over 12 months, including among patients with intermediate-high baseline FIB-4. These findings support the hepatic safety of IL-17 blockade in psoriatic disease and highlight the importance of routine fibrosis monitoring in metabolic-risk populations.
References
Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-994. DOI:10.1016/S0140-6736(14)61909-7. PMID: 26025581.7
Ogdie A, Grewal SK, Noe MH, et al. Risk of incident liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis: A population-based study. J Invest Dermatol. 2018;138(4):760–767. DOI:10.1016/j.jid.2017.10.024. PMID: 29104161.
Miele L, Vallone S, Cefalo C, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):778–786. DOI:10.1016/j.jhep.2009.06.008. PMID: 19664838.
Heitmann J, Frings VG, Geier A, Goebeler M, Kerstan A. Non-alcoholic fatty liver disease and psoriasis—is there a shared proinflammatory network? J Dtsch Dermatol Ges. 2021;19(4):517–528. DOI:10.1111/ddg.14425. PMID: 33768700.
Gisondi P, Targher G, Zoppini G, Girolomoni G. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):758–764. DOI:10.1016/j.jhep.2009.04.020. PMID: 19560226.
Tan Z, Qian X, Jiang R, et al. IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. J Immunol. 2013;191(4):1835–1844. DOI:10.4049/jimmunol.1203013. PMID: 23842754.
Meng F, Wang K, Aoyama T, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012;143(3):765–776.e3. DOI:10.1053/j.gastro.2012.05.049. PMID: 22687286.
Lemmers A, Moreno C, Gustot T, et al. The interleukin-17 pathway is involved in human alcoholic liver disease. Hepatology. 2009;49(2):646–657. DOI:10.1002/hep.22680. PMID: 19177575.
Fabre T, Kared H, Friedman SL, Shoukry NH. IL-17A enhances the expression of profibrotic genes through upregulation of the TGF-β receptor on hepatic stellate cells in a JNK-dependent manner. J Immunol. 2014;193(8):3925–3933. DOI:10.4049/jimmunol.1400861. PMID: 25210118.
Menter A, Strober BE, Kaplan DH, et al. Joint AAD–NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029–1072. DOI:10.1016/j.jaad.2018.11.057. PMID: 30772098.
Girolomoni G, Mrowietz U, Paul C, et al. Psoriasis: rationale for targeting interleukin-17. Br J Dermatol. 2012;167(4):717–724. DOI:10.1111/j.1365-2133.2012.11099.x. PMID: 22934909.
Takamura S, Teraki Y, Katayama E, et al. Effects of interleukin-17 inhibitors on hepatic fibrosis index in patients with psoriasis and metabolic dysfunction-associated fatty liver disease: Directed acyclic graphs. Clin Mol Hepatol. 2022;28(2):269–272. DOI:10.3350/cmh.2022.0040. PMID: 35164434.
Armijo-Borjon G, Miranda-Aguirre AI, Garza-Silva A, et al. Biologic therapy for psoriasis is associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD): A study on the association of cardiometabolic conditions with psoriasis treatment. Arch Dermatol Res. 2025;317(1):195. DOI:10.1007/s00403-024-03688-5. PMID: 39775081.
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. 2025;52(6):1113–1117. DOI:10.1111/1346-8138.17752. PMID: 40237394.
McPherson S, Hardy T, Dufour JF, et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol. 2017;112(5):740–751. DOI:10.1038/ajg.2016.453. PMID: 27725647.
Sanyal AJ, Castera L, Wong VW. Noninvasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023;21(8):2026–2039. DOI:10.1016/j.cgh.2023.03.042. PMID: 37062495.
Feng G, Targher G, Byrne CD, et al. Global burden of metabolic dysfunction-associated steatotic liver disease, 2010 to 2021. JHEP Rep. 2024;7(3):101271. DOI:10.1016/j.jhepr.2024.101271. PMID: 39980749.
Eslam M, Sanyal AJ, George J, et al. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158(7):1999–2014.e1. DOI:10.1053/j.gastro.2019.11.312. PMID: 32044314.
Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317–1325. DOI:10.1002/hep.21178. PMID: 16729309.
Castera L, Friedrich-Rust M, Loomba R. Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156(5):1264–1281.e4. DOI:10.1053/j.gastro.2018.12.036. PMID: 30660725.
Wattacheril JJ, Abdelmalek MF, Lim JK, Sanyal AJ. AGA clinical practice update on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease: Expert review. Gastroenterology. 2023;165(4):1080–1088. DOI:10.1053/j.gastro.2023.06.013. PMID: 37542503.
Hagström H, Shang Y, Hegmar H, Nasr P. Natural history and progression of metabolic dysfunction-associated steatotic liver disease. Lancet Gastroenterol Hepatol. 2024;9(10):944–956. DOI:10.1016/S2468-1253(24)00193-6. PMID: 39243773.
Polistena B, Calzavara-Pinton P, Altomare G, et al. The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: An analysis based on Italian actual clinical practice. J Eur Acad Dermatol Venereol. 2015;29(12):2411–2416. DOI:10.1111/jdv.13307. PMID: 26370321.
Poniewierska-Baran A, Tabarkiewicz J, Radzikowska U, Tynecka M, Eljaszewicz A. The pivotal role of IL-17A in hepatic stellate cell activation. Cent Eur J Immunol. 2024;49(4):331. DOI:10.5114/ceji.2024.146900. PMID: 39944263.
Loomba R, Adams LA. Advances in non-invasive assessment of hepatic fibrosis. Gut. 2020;69(7):1343–1352. DOI:10.1136/gutjnl-2018-317593. PMID: 32066623.
López Tórrez SM, Ayala CO, Ruggiro PB, et al. Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: A meta-analysis of over 40,000 participants. Front Nutr. 2024;11:1284509. DOI:10.3389/fnut.2024.1284509. PMID: 38419854..
Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD–NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073–1113. DOI:10.1016/j.jaad.2018.11.058. PMID: 30772097.
Sheikh MY, Younus MF, Shergill A, Hasan MN. Diet and lifestyle interventions in metabolic dysfunction-associated fatty liver disease: A comprehensive review. Int J Mol Sci. 2025;26(19):9625. DOI:10.3390/ijms26199625. PMID: 41096891.
Abdelnabi MN, Hassan GS, Shoukry NH. Role of the type 3 cytokines IL-17 and IL-22 in modulating metabolic dysfunction-associated steatotic liver disease. Front Immunol. 2024;15:1437046. DOI:10.3389/fimmu.2024.1437046. PMID:39156888.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–1339. DOI:10.1056/NEJMoa1412679. PMID:26422723..
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202–209. DOI:10.1016/j.jhep.2020.03.039. PMID:32278004.
González Fernández J, Prieto-Torres L, Ara Martín M, Martínez-Domínguez SJ. MASLD and liver fibrosis in patients with psoriasis receiving IL-17 or IL-23 inhibitors: A systematic review. Ther Adv Gastroenterol. 2025;18:17562848251335824. DOI:10.1177/17562848251335824. PMID:40417712.
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829–846. DOI:10.1016/j.jhep.2017.05.016. PMID:28545937.
Younossi ZM, Noureddin M, Bernstein D, Kwo P, Russo M, Shiffman ML, et al. Role of noninvasive tests in clinical gastroenterology practices to identify patients with nonalcoholic steatohepatitis at high risk of adverse outcomes: Expert panel recommendations. Am J Gastroenterol. 2021;116(2):254–262. DOI:10.14309/ajg.0000000000001054. PMID:33284184.
González Fernández J, Prieto-Torres L, Ara Martín M, Martínez-Domínguez SJ. MASLD and liver fibrosis in patients with psoriasis receiving IL-17 or IL-23 inhibitors: A systematic review. Ther Adv Gastroenterol. 2025;18:17562848251335824. DOI:10.1177/17562848251335824. PMID:40417712.
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