Optimization of biologic therapy in Crohn’s disease

ABSTRACT

Introduction: Crohn’s disease (CD) is a manifestation of inflammatory bowel disease (IBD), which can result in significant morbidity. Biologic therapy with anti-TNF medication has been effective in treating inflammation and reducing complications in CD. It is important for clinicians to have better knowledge of the various biologic therapies including mechanisms of action and optimization strategies.

Areas covered: The review describes optimization of biologic therapy in CD including different mechanisms of loss of response, therapeutic drug monitoring in CD, clinical implications and management strategies which utilize drug monitoring, and areas of future development and research in optimization of biologic therapy.

Expert opinion: Achieving adequate levels of the drug (antibody unbound) is one of the most important determinants of attaining clinical remission and mucosal healing. Drug level is also critical in determining if a patient requires combination therapy with an immunomodulator. Certain populations, including those with active perianal disease, may require higher serum levels to achieve healing or closure. Treat to target level is an algorithm that is not universally accepted and more data is need. Additionally, there are numerous assays that don’t always correlate, especially regarding measuring anti-drug antibodies.

KEYWORDS:

• Biologic therapy
• Crohn’s disease
• mucosal healing
• therapeutic drug monitoring

Article highlights

• Early initiation of therapy is critical to prevent the complications of Crohn’s including stricturing and penetrating complications.

• Achieving adequate levels of the drug (antibody unbound) is one of the most important determinants of attaining clinical remission and mucosal healing.

• Combination therapy with an immunomodulator may not be necessary if adequate drug levels can be achieved.

• In patients on combination therapy, the immunomodulator can be withdrawn as long as trough levels are therapeutic and sustained.

• There are numerous assays that don’t always correlate, especially with regard to measuring antidrug antibodies.

• There may be certain populations, such as those with active perianal disease who may require higher circulating drug levels

• Treating to a target level has thus far not been shown a difference in long-term clinical outcomes compared to usual care; however, it may be more cost effective.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript has not been funded.