| Title: |
Tissue penetration of anti-tumour necrosis factor therapy in perianal fistulising Crohn’s disease: a proof-of-concept study |
| Authors: |
Anandabaskaran, Sulak; Liu, Zhigang; Hanna, Luke; Lung, Phillip; Alexander, James L.; Powell, Nick; Connor, Susan J.; Tozer, Phil; Hart, Ailsa |
| Source: |
European Journal of Gastroenterology & Hepatology ; ISSN 0954-691X 1473-5687 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2026 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1097/meg.0000000000003169 |
| DOI: |
10.1097/MEG.0000000000003169 |
| Availability: |
https://doi.org/10.1097/meg.0000000000003169; https://journals.lww.com/10.1097/MEG.0000000000003169 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7A5D293E |
| Database: |
BASE |