Optimizing biological therapy in Crohn’s disease

Abstract

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn’s disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn’s disease and identify strategies to optimize biological treatment.

KEYWORDS:

• adalimumab
• Crohn’s disease
• infliximab
• therapeutic drug level monitoring
• ulcerative colitis

Financial & competing interests disclosure

KB Gecse has served as an advisory board member for MSD, Abbvie, Hospira and Sandoz. KB Gecse has also served as a consultant for Hospira, Sandoz and Takeda and received speaker’s honoraria from AbbVie, MSD and Hospira. PL Lakatos has served as a speaker and/or advisory board member for AbbVie, EGIS, Hospira, MSD, Roche and Takeda and received unrestricted research grants from AbbVie, MSD and Hospira. 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.

Key issues

• Early biological therapy has become standard of care in Crohn’s disease (CD) patients where conventional treatment strategy failed.

• Unfortunately, primary and secondary loss of response occurs in a large proportion of CD patients over time.

• The definitions of loss of response are still not uniform and somewhat heterogeneous, including dose escalation or drug discontinuation, and incidence depends on the definition used (dose escalation in 23–46% and discontinuation in 5–13% at 12 months after the start of the therapy).

• Symptomatic patient assessment has become obsolete with objective tight monitoring, including frequent laboratory, endoscopic and imaging assessment.

• In addition, therapeutic drug monitoring has/will become the standard of care in CD patients with suspected loss of response, as it enables a more objective assessment of the underlying cause of the loss of response and an individualized, patient-centered decision making.

• Additional data are needed to enable to determine the optimal trough levels for adalimumab.

• A new class of biologicals is emerging in CD, and predictors of response, non-response, therapeutic drug monitoring and optimal positioning of these drugs in CD and IBD needs to be determined.