Tissue penetration of anti-tumour necrosis factor therapy in perianal fistulising Crohn's disease: a proof-of-concept study
File(s)
Author(s)
Type
Journal Article
Abstract
Background
Perianal fistulising Crohn’s disease (pfCD) remains a therapeutic challenge, with a limited sustained response to biological therapy. Although higher serum anti-tumour necrosis factor (TNF) levels are associated with improved fistula healing, tissue pharmacokinetics in pfCD are poorly understood. This proof-of-concept study aimed to establish the feasibility of quantifying anti-TNF concentrations within fistula tissue and evaluate their relationship with serum levels and treatment outcomes.
Methods
Paired blood and fistula tract biopsies were obtained from 14 patients (infliximab, seven; adalimumab, seven) with active pfCD on established anti-TNF therapy (>14 weeks post-induction). The serum was processed by centrifugation within 8 h and stored at −80°C. Fistula tract biopsies were snap-frozen, homogenised, and extracted using an ELISA buffer proportional to tissue weight. Anti-TNF levels in the serum and tissue supernatants were quantified using standard and high-sensitivity ELISA assays, respectively.
Results
All patients had detectable anti-TNF concentrations in both serum and fistula tissues. Tissue and serum levels showed a moderate positive correlation (r = 0.45, P = 0.09), with a stronger and statistically significant association in the infliximab subgroup (r = 0.81, P = 0.01). Higher fistula-to-serum ratios, reflecting enhanced tissue penetration, tended towards improved clinical and radiological outcomes and lower perianal disease activity index scores, although the difference was not statistically significant.
Conclusion
Anti-TNF levels in perianal fistula tissue are measurable and correlated with serum concentrations, supporting a mechanistic link between systemic exposure and local drug penetration. These findings highlight the feasibility of tissue-level pharmacokinetic assessments and warrant validation in larger prospective cohorts.
Perianal fistulising Crohn’s disease (pfCD) remains a therapeutic challenge, with a limited sustained response to biological therapy. Although higher serum anti-tumour necrosis factor (TNF) levels are associated with improved fistula healing, tissue pharmacokinetics in pfCD are poorly understood. This proof-of-concept study aimed to establish the feasibility of quantifying anti-TNF concentrations within fistula tissue and evaluate their relationship with serum levels and treatment outcomes.
Methods
Paired blood and fistula tract biopsies were obtained from 14 patients (infliximab, seven; adalimumab, seven) with active pfCD on established anti-TNF therapy (>14 weeks post-induction). The serum was processed by centrifugation within 8 h and stored at −80°C. Fistula tract biopsies were snap-frozen, homogenised, and extracted using an ELISA buffer proportional to tissue weight. Anti-TNF levels in the serum and tissue supernatants were quantified using standard and high-sensitivity ELISA assays, respectively.
Results
All patients had detectable anti-TNF concentrations in both serum and fistula tissues. Tissue and serum levels showed a moderate positive correlation (r = 0.45, P = 0.09), with a stronger and statistically significant association in the infliximab subgroup (r = 0.81, P = 0.01). Higher fistula-to-serum ratios, reflecting enhanced tissue penetration, tended towards improved clinical and radiological outcomes and lower perianal disease activity index scores, although the difference was not statistically significant.
Conclusion
Anti-TNF levels in perianal fistula tissue are measurable and correlated with serum concentrations, supporting a mechanistic link between systemic exposure and local drug penetration. These findings highlight the feasibility of tissue-level pharmacokinetic assessments and warrant validation in larger prospective cohorts.
Date Issued
2026-08-01
Date Acceptance
2026-01-19
Citation
European Journal of Gastroenterology and Hepatology, 2026, 38 (8), pp.925-932
ISSN
0954-691X
Publisher
Lippincott, Williams & Wilkins
Start Page
925
End Page
932
Journal / Book Title
European Journal of Gastroenterology and Hepatology
Volume
38
Issue
8
Copyright Statement
© 2026 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons At tribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41784425
PII: 00042737-990000000-00667
Subjects
adalimumab
drug levels
infliximab
outcomes
perianal Crohn’s disease
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2026-02-24