European journal of gastroenterology & hepatology · 2026
Tissue penetration of anti-tumour necrosis factor therapy in perianal fistulising Crohn's disease: a proof-of-concept study.
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Anandabaskaran Sulak, Liu Zhigang, Hanna Luke, Lung Phillip, Alexander James L, Powell Nick, Connor Susan J, Tozer Phil, Hart Ailsa
Аннотация
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.
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.