Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

Abstract

Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes. Focusing on mucosal healing as the ultimate treatment goal, different drug concentration thresholds to achieve this outcome have been identified in the literature and are summarized in this review. For therapeutic drug monitoring to be successful in guiding clinical decision making, the used assay, the sampling time point, and the outcome that is aimed for should be taken into account when interpreting drug concentration thresholds. Awareness of these essential aspects among clinicians will improve the implementation of therapeutic drug monitoring and aid in making an evidence‐based decision.

A minimal physiologically based pharmacokinetic model to characterize colon TNF suppression and treatment effects of an anti-TNF monoclonal antibody in a mouse inflammatory bowel disease model

“…3 The treatment regimens for most of the approved biologics for IBD include an initial short-term, high-dose (or more frequently dosed) induction period followed by a long-term, low-dose maintenance period. 38 Infliximab is the first therapeutic protein approved for IBD treatment. For both CD and UC, the dosing regimen for infliximab is 5 mg/kg IV administration at Weeks 0, 2, and 6 (i.e., induction), then followed by 5 mg/kg every 8 weeks (i.e., maintenance).…”

“…Previous studies have demonstrated mucosal healing in patients with IBD treated with biological agents such as anti-TNF, anti-integrin, and anti‐interleukin agents, and mucosal healing has been associated with reduced inflammation. 38 , 39 Reduction in inflammation and mucosal healing are expected to result in less macromolecule distribution. Indeed, the reflection coefficient for colon in IBD mice was estimated to be significantly lower than that in the non-IBD mice (0.391 vs. 0.978), providing evidence that CNTO 5048 distribution to the IBD colon would be substantially lower when the inflammation is reduced.…”

The Future of Precision Medicine

“…Use of biologics in the treatment of inflammatory bowel disease is an emerging example. Van den Berghe et al 6 describe the advances in this field. They review the current evidence that supports the use of TDM in inflammatory bowel disease, showing that mucosal healing can be improved by acting upon serum concentrations of therapeutic antibodies against TNF, integrin, and interleukin-12/23.…”

Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

“…Existing clinical applications have confirmed that conventional drugs such as aminosalicylates, corticosteroids, and immunosuppressants were indeed effective in reducing colonic inflammation and achieving a certain duration of remission, but their effects in promoting intestinal mucosa healing was limited [10] . The unhealed mucosa facilitates the recurrent invasion of pathogenic factors, subsequently inducing IBD relapse [6,9,11–13] . In recent years, a large number of clinical studies have shown that mucosal healing and barrier function recovery are key endpoints of UC treatment, which can not only help reduce inflammation, promote epithelial repair, relieve clinical symptoms and prevent disease progression, but can also help avoid long‐term clinical need for steroids and reduce hospitalization and surgical excision rates [12,14,15] .…”

“…[10] The unhealed mucosa facilitates the recurrent invasion of pathogenic factors, subsequently inducing IBD relapse. [6,9,[11][12][13] In recent years, a large number of clinical studies have shown that mucosal healing and barrier function recovery are key endpoints of UC treatment, which can not only help reduce inflammation, promote epithelial repair, relieve clinical symptoms and prevent disease progression, but can also help avoid long-term clinical need for steroids and reduce hospitalization and surgical excision rates. [12,14,15] Therefore, promoting mucosal barrier repair is also an important approach for the treatment of UC.…”