A safety assessment of anti-tumor necrosis factor alpha therapy for treatment of Crohn’s disease

ABSTRACT

Introduction: Anti-tumor necrosis factor-alpha (TNF-α) therapy has revolutionized the medical treatment of Crohn’s disease (CD). Nevertheless, anti-TNF-α therapy has been associated with serious adverse events (SAE) raising safety concerns. This review focuses on the safety profile of anti-TNF-α agents in CD.

Areas covered: We performed a literature search until August 2015 to collect safety data on infliximab, adalimumab and certolizumab pegol monotherapy or combined with immunomodulators (IMM). We have mainly focused on infections and malignancies. Safety in pregnancy, the elderly and children are also presented.

Expert opinion: Available data in CD suggest that anti-TNF-α monotherapy or in combination with IMM is relatively safe, although it may be associated with an elevated risk of serious infections, skin cancer and lymphoma. However, as this data derive mainly from cohort studies, post-marketing registries, and meta-analyses of RCTs, often characterized by inherited methodological weaknesses that may hinder their validity, data from large, statistically powered, prospective studies of sufficient follow up are required to define the actual risk of SAE during anti-TNF-α therapy in IBD. The role of therapeutic drug monitoring in predicting and preventing SAE awaits confirmation.

KEY WORDS:

• Anti-TNF-α therapy
• infliximab
• adalimumab
• certolizumab pegol
• Crohn’s disease
• infection
• malignancy
• safety
• mortality
• inflammatory bowel disease

Article highlights

• Safety of anti-TNF-α therapy in CD.

• Safety of anti-TNF-α combination therapy with IMM.

• Safety of anti-TNF-α therapy during pregnancy.

This box summarizes key points contained in the article.

Declaration of interest

K. Papamichael received a consultancy fee from MSD Hellas. G.J. Mantzaris received consultancy fees from OMEGA Pharma, Danon-Hellas, AbbVie, MSD and Takeda; lecture fees from OMEGA Pharma, Angelini, Ferring, AbbVie, MSD and Takeda; expert testimonies from AbbVie, OMEGA Pharma, MSD and Takeda; advisory fees from AbbVie, MSD and Takeda and financial support for research from Menarini, AbbVie, MSD. L. Peyrin-Biroulet received consulting fees from Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Therakos, Pharmacosmos, Pilège, BMS, UCB-pharma, Hospira, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, Pfizer, HAC-Pharma, Index Pharmaceuticals, lecture fees from Merck, Abbvie, Takeda, Janssen, Takeda, Ferring, Norgine, Tillots, Vifor, Therakos, Mitsubishi, HAC-pharma. 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