Summary Safety Review - Tumour Necrosis Factor (TNF) alpha blockers (SIMPONI and CIMZIA) - Assessing the Potential Risk of Liver Inflammation (Autoimmune Hepatitis)

October 25, 2016

Product

Tumour necrosis factor (TNF) alpha blockers (Simponi and Cimzia)

Potential Safety Issue

Inflammation of the liver (Autoimmune Hepatitis)

Key Messages

  • Tumour Necrosis Factor (TNF) alpha blockers are a class of drugs used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis) and psoriasis.
  • Health Canada reviewed the risk of liver inflammation after 2 cases of serious liver inflammation linked with treatments using TNF alpha blockers were reported in a scientific publication. Health Canada’s review concluded that there may be a link between liver inflammation and treatment with TNF alpha blockers.
  • The Canadian product information for Simponi and Cimzia has been updated to better reflect the available evidence regarding the risk of inflammation of the liver.

Overview

Health Canada reviewed the link between TNF alpha blockers and liver inflammation following publication of 2 serious cases in the scientific literature, in which patients were treated with the TNF alpha blockers, Humira and Remicade. The Canadian product information for Humira, Remicade and Enbrel already stated liver inflammation as a very rare event that may lead to liver failure, but not for Simponi and Cimzia. Therefore, Health Canada assessed the risk of liver inflammation associated with use of all TNF alpha blockers using information provided by the manufacturer, cases published in scientific literature and cases of liver inflammation reported to the Canada Vigilance Database.

Use in Canada

  • TNF alpha blockers are immune system proteins (monoclonal antibodies) that block a specific protein (TNF alpha), resulting in a decrease of inflammation.
  • At the time of this review, five TNF alpha blockers were marketed in Canada:
    • Enbrel (etanercept): 2001
    • Remicade (infliximab): 2001
    • Humira (adalimumab): 2004
    • Cimzia (certolizumab pegol): 2009
    • Simponi (golimmab): 2009

Safety Review Findings

  • At the time of this review, 5 serious cases of liver inflammation were reported with Cimzia, of which 1 case was reported in the Canada Vigilance database. There were no cases of liver inflammation reported with the use of Simponi.
  • Of these 5 cases reported with Cimzia, the Canadian case and 2 non-Canadian cases were assessed as potentially linked to Cimzia. These 3 patients improved when they stopped using Cimzia.
  • For the remaining 2 cases, there was either not enough information to establish a link to Cimzia or there were other possible explanations for the liver inflammation.

Conclusions and Actions

  • Health Canada’s review found a possible link between the risk of liver inflammation and the use of TNF alpha blockers.
  • Following the completion of this safety review, the manufacturers of Cimzia and Simponi have updated the Canadian product information to include the risk of liver inflammation (autoimmune hepatitis).
  • Health Canada will continue to monitor adverse reaction information involving TNF alpha blockers, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.

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