Increased risk of developing Crohn's disease or ulcerative colitis in 17 018 patients while under treatment with anti-TNFα agents, particularly etanercept, for autoimmune diseases other than inflammatory bowel disease

Aliment Pharmacol Ther. 2019 Aug;50(3):289-294. doi: 10.1111/apt.15370. Epub 2019 Jul 2.

Abstract

Background: Anti-TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases.

Aim: To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti-TNFα agents for diseases other than inflammatory bowel disease (IBD) METHODS: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti-TNFα agents for non-IBD indications. Included were patients, who had diseases for which anti-TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti-TNFα.

Results: In total 17 018 individuals with autoimmune diseases were exposed to anti-TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4-2.8] and 2.0 [95% CI: 1.5-2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8-2.2] and 1.0 [95% CI:0.6-1.6], and for adalimumab 1.2 [95% CI: 0.8-1.8] and 0.6 [95% CI: 0.3-1.0].

Conclusions: Patients treated for autoimmune diseases with anti-TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / adverse effects
  • Adalimumab / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / epidemiology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / epidemiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Colitis, Ulcerative / chemically induced*
  • Colitis, Ulcerative / epidemiology*
  • Crohn Disease / chemically induced*
  • Crohn Disease / epidemiology*
  • Denmark / epidemiology
  • Etanercept / adverse effects*
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Infant, Newborn
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / epidemiology
  • Infliximab / adverse effects
  • Infliximab / therapeutic use
  • Male
  • Middle Aged
  • Registries
  • Risk Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept