Safety of drugs used for the treatment of Crohn’s disease

ABSTRACT

Introduction: Medications in treating Crohn’s disease (CD) have evolved over the last two decades, particularly with the use of biologic agents. There are, however, concerns about the safety and adverse events associated with these medications. The authors review the safety profile of immunosuppressive medications used in Crohn’s disease in adult patients.

Areas covered: The authors performed a literature search until October 2018 to examine safety data on thiopurines, methotrexate, anti-TNFα agents, vedolizumab and ustekinumab. The authors focused on ‘trial’ and ‘real-world’ data for the biologic agents. Safety in pregnancy and the elderly are also presented.

Expert opinion: Available data in CD suggest that immunosuppressive medications are relatively safe, although there are concerns about an elevated risk of serious infections, skin cancer and lymphoma particularly with thiopurines and anti-TNFα agents. Data on vedolizumab and ustekinumab suggest these newer biologic agents are well tolerated; however, longer term data in CD are required to identify risks with extended use. Apart from methotrexate, there appear to be no adverse congenital outcomes with exposure of drugs during pregnancy.

KEYWORDS:

• Adalimumab
• anti-TNFα
• Crohn’s disease
• inflammatory bowel disease
• infliximab
• methotrexate
• safety
• thiopurine
• ustekinumab
• vedolizumab

Article highlights

• Immunomodulators are important in the maintenance of remission in CD, however, there are concerns about lymphoma and NMSC adverse events

• Anti-TNFα agents are effective agents in CD, however, there are small but significant risks of infections, skin cancer and lymphoma in some studies

• Vedolizumab and ustekinumab are relatively safe medications in CD with the limited data available

• We suggest HIV serological testing prior to starting vedolizumab use, as the risk of PML will be higher if patients are HIV-positive

This box summarizes key points contained in the article.

Declaration of interest

V Kariyawasam does consultancy work for Janssen-Cilag Pty Limited and has grants from Takeda, Ferring, Abbvie and Shire. S Paramsothy does consultancy work for Janssen-Cilag Pty Limited and is a consultant to Finch Therapeutics, Inc. RW Leong has served on the advisory boards of AbbVie, Aspen, Celgene, Ferring, Hospira, Janssen, MSD, Pfizer and Takeda, and has received unrestricted research support from Shire, Janssen and NHMRC of Australia, and speakers honoraria from Emerge Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are an advisory board member of AbbVie and Janssen Canada. All other peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.