Can Skyrizi (Risankizumab) increase liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST)?

Can Skyrizi Increase Liver Enzymes?

Yes, Skyrizi (risankizumab) can increase liver enzymes, particularly in patients with psoriatic arthritis and Crohn's disease, though elevations are generally mild and rarely lead to serious hepatic events.

Evidence from Clinical Trials

Psoriatic Arthritis

• In Phase 3 placebo-controlled trials, the incidence of hepatic events was higher in the SKYRIZI group (5.4%, 16.7 events per 100 patient-years) compared to placebo (3.9%, 12.6 events per 100 patient-years) 1.
• The most common hepatic events were ALT increased (SKYRIZI: 2.3% vs placebo: 1.7%), AST increased (SKYRIZI: 1.8% vs placebo: 1.3%), and GGT increased (SKYRIZI: 1.1% vs placebo: 0.7%) 1.
• Importantly, there were no serious hepatic events reported in these trials 1.

Plaque Psoriasis

• In the pooled analysis of 1,306 subjects treated with SKYRIZI 150 mg through Week 16, hepatic enzyme elevations were not specifically highlighted as a common adverse reaction (≥1% incidence) 1.
• Through 52 weeks of treatment, no new adverse reactions related to liver enzymes were identified beyond the initial 16-week period 1.

Crohn's Disease

• The FDA label for Skyrizi includes a specific warning about hepatotoxicity in the treatment of inflammatory bowel disease 1.
• In the induction and maintenance studies for Crohn's disease, hepatic enzyme elevations were monitored but not reported as common adverse reactions (>3% incidence) in the summary tables 1.

Clinical Significance and Management

Risk Assessment

• The liver enzyme elevations observed with Skyrizi are generally mild and transient, with no serious hepatic events reported in psoriatic arthritis trials 1.
• The pattern differs from other biologics where hepatotoxicity may be more pronounced; for example, tocilizumab shows ALT/AST elevations >3× ULN in 7.7%/3.6% of patients 2.

Monitoring Recommendations

• While the FDA label does not specify routine liver enzyme monitoring for psoriasis or psoriatic arthritis, baseline liver function tests should be obtained before initiating therapy, especially in patients with pre-existing liver disease 3.
• For patients with inflammatory bowel disease, more vigilant monitoring is warranted given the specific hepatotoxicity warning 1.
• If ALT increases to ≥5× ULN with normal bilirubin and no symptoms, repeat testing within 2-5 days and evaluate for competing etiologies 4.
• If ALT ≥8× ULN (regardless of bilirubin or symptoms), interrupt Skyrizi immediately and initiate close monitoring 4.
• If ALT ≥3× ULN with total bilirubin ≥2× baseline, interrupt Skyrizi immediately as this represents potential Hy's Law criteria 4.

Important Caveats

Distinguishing Drug Effect from Disease

• Elevated liver enzymes are frequently encountered in inflammatory bowel disease patients (36.4% in one cohort), and most elevations >3× ULN resolve spontaneously in 83% of cases 5.
• The use of concomitant immunomodulators is independently associated with liver enzyme abnormalities (OR 2.666) and may confound attribution to Skyrizi alone 5.

Patient-Specific Factors

• Pre-existing liver disease increases hepatotoxicity risk with any medication 3.
• Concomitant use of other hepatotoxic medications amplifies risk 3.
• Longer duration of biologic treatment is associated with increased likelihood of liver enzyme elevation 5.

Pattern Recognition

• ALT is more liver-specific than AST, which can be elevated from cardiac muscle, skeletal muscle, kidney, or red blood cell disorders 6.
• An AST:ALT ratio <1 is more characteristic of hepatocellular injury from medications or viral hepatitis, while AST:ALT >2 suggests alcoholic liver disease 7.
• The relatively short half-life of AST (18 hours) compared to ALT (36 hours) means that the ratio reflects the time course and aggressiveness of liver injury 7.