Optimization of biologic therapy in Crohn’s disease

Abstract

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.

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

“…16 As such, "mucosal healing" is one of the most important factors predicting IBD remission in patients 13,17 and has been defined as an important future therapeutic focus in this context. [18][19][20][21] Furthermore, restoration of intestinal epithelial barrier function in IBD patients critically contributes to their improved outcomes. 4,21 In the complex interplay of all components contributing to intestinal barrier function, the intestinal epithelium is considered to play a critical role.…”

“…“Mucosal healing” is a term often used in the clinical setting to provide a macroscopic impression on the overall state of the mucosa including its intestinal barrier properties 16 . As such, “mucosal healing” is one of the most important factors predicting IBD remission in patients 13,17 and has been defined as an important future therapeutic focus in this context 18‐21 . Furthermore, restoration of intestinal epithelial barrier function in IBD patients critically contributes to their improved outcomes 4,21 …”

Optimizing biologic therapy in inflammatory bowel disease: a Delphi consensus in the United Arab Emirates

“…TDM has assumed even greater significance, given the loss of response that occurs with anti-TNF medications over a period of time. 5 TDM typically involves measuring the trough level of the drug along with the presence of anti-drug antibodies (ADAbs). Ideally, TDM assays should be drug tolerant, where quantitative trough and ADAbs levels are both reported.…”

“…4 However, approximatively 30% of patients do not respond to anti-TNF therapy and nearly 50% patients experience loss of response during treatment. 5 The latter are common clinical scenarios and paradoxically are not addressed in the commercial drug labels and available guidelines. There is therefore an urgent need for physicians to understand when and how to optimize biologic therapy, and this has been the focus of this systematic review and Delphi consensus.…”

Infliximab-Associated Hepatic Injury in Crohn’s Disease

“…Biologic therapy with anti-TNF medication has been effective in treating inflammation and reducing complications in CD 6 . Infliximab, adalimumab, and certolizumab have been shown to be effective as both induction and maintenance therapy in moderate to severe CD 7 .…”