Therapeutic Drug Monitoring in Perianal Fistulizing Crohn’s Disease

Abstract

Perianal fistulas are a common complication of Crohn’s disease (CD) that has, historically, been challenging to manage. Despite the strong available evidence that anti-tumor necrosis factor (anti-TNF) agents are useful in the treatment of perianal fistulizing Crohn’s disease (PFCD), a significant number of these patients do not respond to therapy. The use of therapeutic drug monitoring (TDM) in patients with CD receiving biologic agents has evolved and is currently positioned as an important tool to optimize and guide biologic treatment. Considering the treatment of PFCD can represent a challenge; identifying novel tools to improve the efficacy of current treatments is an important unmet need. Given its emerging role in other phenotypes of Crohn’s disease, the use of TDM could also offer an opportunity to enhance the effectiveness of available therapies and improve outcomes in the subset of patients with PFCD receiving biologics. Overall, there is mounting evidence that higher anti-TNF drug levels are associated with better rates of “fistula healing”. However, studies have been limited by their use of subjective outcomes and observational designs. Ultimately, further interventional, randomized controlled trials looking into the relationship between drug exposure and fistula outcomes are needed.

Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study

“…It has been suggested that patients with CD and perianal involvement would require higher drug levels to achieve improvement of the fistulous disease [ 20 , 21 ]. In our study, we observed that this subgroup of patients also achieved a significant increase in plasma levels of infliximab (pre-change 7.6 μg/dL vs. 20.27 μg/dL at 6 m) without observing clinical worsening (evaluated for clinical symptoms and pus discharge after digital pressure).…”

Challenges in Therapeutic Drug Monitoring: Optimizing Biological Treatments in Patients With Inflammatory Bowel Disease and Other Immune-Mediated Inflammatory Diseases

“…Optimal target concentrations of biologicals have yet to be established as these may depend on several aspects of treatment: timing of measurement (induction/maintenance); route of drug administration 67 , 68 ; desired therapeutic outcome 30 , 69 ; type of assay 70 , 71 ; and patient phenotype. 72 Numerous data from prospective studies and post hoc analyses of RCTs suggest a link between higher biological drug concentrations and the achievement of increasingly stringent therapeutic outcomes. 5 , 30 , 32 Cheifetz et al 32 have suggested therapeutic windows for biologicals during maintenance therapy of 5−10 μg/mL for infliximab, 8–12 μg/mL for adalimumab, 13–15 μg/mL for certolizumab pegol, 1–3 μg/mL for golimumab, 10–15 μg/mL for vedolizumab, and 1–3 μg/mL for ustekinumab.…”