New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease

Aliment Pharmacol Ther. 2015 May;41(10):972-9. doi: 10.1111/apt.13159. Epub 2015 Mar 10.

Abstract

Background: Anti-tumour necrosis factor α (anti-TNF) agents have been implicated in drug-induced liver injury. There is minimal data on this occurrence in inflammatory bowel disease (IBD) patients.

Aim: To identify the characteristics of liver enzyme elevations following anti-TNF therapy initiation in IBD.

Methods: A retrospective cohort of patients initiating anti-TNF therapy were analysed for new onset alanine transaminase (ALT) elevation (≥60 U/L). We collected data on natural history, outcomes and patient characteristics compared with controls with persistent normal liver enzymes. Likelihood of causal association was assessed using the RUCAM score.

Results: From 1753 patients initiating an anti-TNF (1170 infliximab, 575 adalimumab, 8 certolizumab), 102 (6%) developed new onset ALT elevation. In 54 (53%), this could be linked to an alternate aetiology. Among those with idiopathic ALT elevations, the median time to ALT elevation from anti-TNF initiation was 18 weeks and median peak ALT was 96 U/L. Six underwent liver biopsy, all demonstrating hepatitis with autoimmune features. Compared to controls, cases were on a lower dose of infliximab (5.7 vs. 6.7 mg/kg, P = 0.02) but were otherwise similar in body mass index, sex and age. On follow-up, 34 continued the anti-TNF, 14 stopped therapy and 4 initiated steroids. Most (85%) normalised their LFTs after a median of 17 weeks including 28 (82%) of those who continued anti-TNF therapy. Ten patients were transitioned to a second anti-TNF without recurrence.

Conclusions: ALT elevations occurred in 6% of IBD patients initiating anti-TNF therapy. Most idiopathic elevations were mild, transient and resolved despite therapy continuation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adalimumab
  • Adult
  • Alanine Transaminase / metabolism
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biological Therapy / adverse effects
  • Biological Therapy / methods*
  • Certolizumab Pegol
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Chemical and Drug Induced Liver Injury / etiology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab
  • Liver Function Tests
  • Male
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fab Fragments
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Infliximab
  • Alanine Transaminase
  • Adalimumab
  • Certolizumab Pegol