SUMMARY

• Summarized below are hepatic-related safety events in adult patients with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC).^1-6 
• A serious adverse reaction of drug-induced liver injury was reported in a patient with Crohn’s disease from the phase 2 GALAXI-1 trial following three doses of a higher than recommended induction regimen (1200 mg for three doses every 4 weeks [q4w]). Please see TREMFYA prescribing information for more details.^7,8

TREMFYA prescribing information

• A serious adverse reaction of drug-induced liver injury was reported in a patient with Crohn’s disease following three doses of a higher than recommended induction regimen.⁷
  • This patient had peak alanine aminotransferase (ALT) of 18x the upper limit of normal (ULN), aspartate aminotransferase (AST) of 11x ULN, and total bilirubin of 2.4x ULN. TREMFYA was subsequently discontinued, and the liver test abnormalities resolved following administration of corticosteroids. 
• In patients with Crohn’s disease or ulcerative colitis, evaluate liver enzymes and bilirubin at baseline, for at least 16 weeks of treatment, and periodically thereafter according to routine patient management.⁷ 
• Consider other treatment options in patients with evidence of acute liver disease or cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.⁷ 
• The efficacy and safety of TREMFYA was assessed in three randomized, double-blind, placebo-controlled trials (GALAXI program) that enrolled adult patients with moderately to severely active CD. Through 12 weeks of induction ALT ≥5x ULN was reported in 2/645 (0.3%) patients treated with intravenous TREMFYA 200 mg at Weeks 0, 4, and 8 and 0/211 patients treated with placebo. These elevations occurred without concomitant elevations in total bilirubin.⁷ 
• Through Week 48 in GRAVITI, a phase 3, randomized, double-blind, placebo-controlled trial that assessed subcutaneous (SC) TREMFYA for induction in Crohn’s disease, ALT ≥5x ULN was reported in 0/115 patients treated with SC TREMFYA 400 mg at Weeks 0, 4, and 8 followed by subcutaneous TREMFYA 100 mg every 8 weeks; 2/115 (1.7%) patients treated with SC TREMFYA 400 mg at Weeks 0, 4, and 8 followed by SC TREMFYA 200 mg every 4 weeks; and 0/117 patients treated with placebo. These elevations occurred without concomitant elevations in total bilirubin.⁷ 

CLINICAL DATA

GALAXI and GRAVITI– Crohn’s Disease

GALAXI

• Clinically important hepatic disorders were reported among patients in the TREMFYA groups, which were defined as hepatic disorder adverse events (AEs) reported as serious or events leading to discontinuation of the study agent.¹
• See Table: Occurrence of Clinically Important Hepatic Disorders in GALAXI 2 and 3 Pooled Results through Week 48.¹

GRAVITI

• Through week 48, adverse events of hepatic disorder were ≤5% and similar across treatment groups.⁵ 
  • No serious hepatic disorder adverse events were reported.
  • Most were liver test abnormalities that were resolved while patients were still receiving the study agent. The proportion of patients with alanine aminotransferase or aspartate aminotransferase of ≥5x ULN were low (placebo, 1 [0.9%]; TREMFYA, 3 [1.3%]).
  • No participant met criteria of Hy’s law.

QUASAR – Ulcerative Colitis

• The safety and efficacy of TREMFYA was evaluated through the phase 3, randomized, double-blind, placebo-controlled clinical trial program (QUASAR) in adult patients with moderately to severely active UC. Through 12 weeks of induction, the majority of hepatic disorder AEs were mild or moderate and none were considered serious or led to discontinuation of the study agent.^2,3,6
• Through 44 weeks of maintenance therapy, the proportion of participants with hepatic disorders were similar among treatment groups in the randomized safety analysis set. No events meeting Hy’s law were reported, and no hepatic disorder adverse events were serious AEs or led to discontinuation of the study intervention.^3,6 

Pooled Safety Analysis of Phase 2/3 Studies in Crohn's Disease and Ulcerative Colitis 

• Patients with moderately to severely active CD or UC through up to 1 year were included:⁴ 
  • UC: n=1514 from QUASAR induction study 1, 2 and the maintenance study
  • CD: n=1492 from GALAXI 1,2 and 3; GRAVITI (SC induction therapy with TREMFYA).
  • UC: VEGA study (Guselkumab plus golimumab combination therapy versus TREMFYA or golimumab monotherapy [VEGA]).
• TREMFYA studies were pooled for the induction period (GALAXI, GRAVITI, & QUASAR; Weeks 0-12 [VEGA excluded due to no PBO control]) and through 1 year (GALAXI, GRAVITI, QUASAR, & VEGA).
• In this pooled analysis, safety events were normalized to 100 patient-years (PY) of follow-up with corresponding confidence intervals.
• The rates of clinically important hepatic disorders through 1 year are reported in Table: Total Patient Years of Follow Up and Occurrence of Clinically Important Hepatic Disorders per 100 Patient Years. 

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 16 April 2025.