Tissue penetration of anti-tumour necrosis factor therapy in perianal fistulising Crohn's disease: a proof-of-concept study

Sulak Anandabaskaran; Zhigang Liu; Luke Hanna; Phillip Lung; James L Alexander; Nick Powell; Susan J Connor; Phil Tozer; Ailsa Hart

doi:10.1097/MEG.0000000000003169

Tissue penetration of anti-tumour necrosis factor therapy in perianal fistulising Crohn's disease: a proof-of-concept study

Eur J Gastroenterol Hepatol. 2026 Feb 24. doi: 10.1097/MEG.0000000000003169. Online ahead of print.

Authors

Sulak Anandabaskaran^{1

2

3}, Zhigang Liu², Luke Hanna^{2

4}, Phillip Lung³, James L Alexander^{2

3

4

5}, Nick Powell², Susan J Connor^{6

7}, Phil Tozer^{3

4}, Ailsa Hart^{3

4}

Affiliations

¹ School of Clinical Medicine, University of New South Wales Faculty of Medicine, Sydney, New South Wales, Australia.
² Department of Metabolism, Digestion and Reproduction, Imperial College London.
³ Robin Phillips Fistula Research Unit, St Mark's the National Bowel Hospital, London.
⁴ Inflammatory Bowel Diseases Unit, St Mark's Hospital, Harrow.
⁵ Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK.
⁶ Department of Gastroenterology, Liverpool Hospital, Liverpool, New South Wales.
⁷ South West Sydney Clinical Campuses, UNSW Medicine & Health, UNSW Sydney, Sydney, Australia.

PMID: 41784425
DOI: 10.1097/MEG.0000000000003169

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.

Keywords: adalimumab; drug levels; infliximab; outcomes; perianal Crohn’s disease.