Does Skyrizi (Guselkumab) Cause Elevated Liver Function Tests?
Skyrizi (guselkumab) does not cause clinically significant elevations in liver function tests and does not require routine hepatic monitoring in patients with psoriasis or psoriatic arthritis. 1
Evidence for Hepatic Safety
Guselkumab, as an IL-23 inhibitor, has demonstrated a favorable hepatic safety profile distinct from other systemic psoriasis therapies:
No hepatotoxicity signal identified: In the integrated analysis of 11 phase II/III clinical studies involving 4,399 guselkumab-treated patients followed for 10,787 patient-years, no specific hepatotoxicity concerns were reported, and adverse event rates remained consistently low throughout long-term treatment. 2
No baseline or ongoing liver monitoring required: Unlike methotrexate, which requires extensive hepatic monitoring including baseline liver function tests, monthly monitoring for the first 6 months, and consideration of liver biopsy after cumulative doses, guselkumab guidelines do not mandate any hepatic laboratory surveillance. 1
Contrast with hepatotoxic systemic agents: Methotrexate causes hepatotoxicity in up to 16% of patients with risk factors including obesity, diabetes, and hyperlipidemia—all common psoriasis comorbidities—and requires FIB-4 index monitoring in at-risk patients. 1 Guselkumab has no such requirements.
Specific Context: Concomitant LTBI Treatment
An important clinical scenario demonstrates guselkumab's hepatic safety even under challenging conditions:
Safe with hepatotoxic TB medications: In pooled VOYAGE 1 and VOYAGE 2 data through week 100, patients receiving concomitant latent tuberculosis infection (LTBI) treatment with guselkumab showed comparable adverse event rates to those not receiving LTBI treatment. 3
Expected transaminase elevations from LTBI drugs, not guselkumab: Through week 16, greater proportions of LTBI+ patients (those on anti-TB medications) reported ALT and AST elevations compared with LTBI- patients across all treatment groups, reflecting the known hepatotoxicity of isoniazid and rifampin rather than the biologic therapy. 3
Long-term tolerability maintained: Through week 100, proportions of patients experiencing adverse events and serious adverse events were comparable between LTBI+ and LTBI- patients treated with guselkumab. 3
Clinical Implications and Monitoring Recommendations
No routine liver function monitoring is recommended for guselkumab therapy. 1 This represents a significant practical advantage over traditional systemic agents:
Methotrexate requires monthly liver function tests for 6 months, then every 1-3 months, with liver biopsy consideration after 3.5-4.0 g cumulative dose in patients without risk factors, or after only 1.0-1.5 g in those with hepatotoxicity risk factors. 1
Acitretin causes transaminase elevations in up to 16% of patients and requires increased monitoring in patients with underlying liver disease. 1
Leflunomide can cause severe liver injury, including fatal outcomes, most commonly within 6 months of therapy, requiring monthly CBC and liver function tests for the first 6 months. 1
Important Caveats
While guselkumab itself does not cause hepatotoxicity, clinical judgment remains essential:
Pre-existing liver disease: Patients with chronic hepatitis B or C, nonalcoholic steatohepatitis, or cirrhosis may still warrant baseline assessment before initiating any systemic therapy, though this reflects general medical practice rather than guselkumab-specific concerns. 1
Concomitant hepatotoxic medications: If patients require concurrent use of known hepatotoxic agents (such as LTBI treatment, methotrexate for psoriatic arthritis, or other medications), monitor liver function based on the requirements of those agents, not guselkumab. 3
Drug interactions are minimal: Unlike methotrexate, which has extensive drug interactions requiring careful monitoring, guselkumab as a monoclonal antibody has minimal drug-drug interactions affecting hepatic metabolism. 1
Comparison with Other Biologics
The hepatic safety profile of guselkumab aligns with other biologic agents for psoriasis:
IL-17 inhibitors (secukinumab): Demonstrated neutral effects on liver enzymes over 52 weeks in phase 3 studies, with no routine hepatic monitoring required. 4
TNF inhibitors: Similarly do not require routine liver function monitoring in the absence of other risk factors. 1
IL-23 inhibitors as a class: The American Academy of Dermatology provides Grade A recommendations for guselkumab without any hepatic monitoring requirements, reflecting the favorable safety profile of this drug class. 1