What is the evidence for anti‑TNF therapy as first‑line over surgical repair alone for reducing long‑term recurrence of perianal fistulas

What is known

- ECCO/UAE guidelines recommend anti-TNF (infliximab, optimized with an immunomodulator) as first-line medical therapy after adequate drainage — surgery is complementary, not the comparator. ^1–3 - Anti-TNF monotherapy has a high fistula recurrence rate once treatment is stopped after 1 year, and a meta-analysis found only ~34% of initial responders maintained long-term healing. ^1,4 - PISA-II RCT: short-term anti-TNF plus surgical closure achieved radiological healing more often than anti-TNF alone at 18 months; radiological healing predicted no recurrence. ^5,6 - Combination of biologic plus surgical intervention (e.g., seton) is associated with superior outcomes versus either modality alone in complex fistulizing CD. ³

What is unknown / caveats

- Only 4 studies, with conflicting findings, directly compared EUA+anti-TNF versus anti-TNF alone ⁴ - Recent data on benefit of seton placement before biologics is conflicting ³ - No retrieved trial pits anti-TNF against surgical repair alone as isolated first-line strategies — the comparisons are combination vs monotherapy - PISA-II was a patient-preference design, not fully randomised allocation - Long-term recurrence data beyond 18 months are limited - The question's premise — anti-TNF versus surgical repair alone — is not how the trial evidence is structured; the tested contrast is combined medical-surgical therapy versus anti-TNF alone.

## References

1. Garcia-Olmo D, Gilaberte I, Binek M, D Hoore AJL, Lindner D, Selvaggi F, Spinelli A, Panés J. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Dis Colon Rectum. 2022;65(5):713-720. PMID: 34890373.

2. Hanna LN, Munster LJ, Joshi S, Wendelien van der Bilt JD, Buskens CJ, Hart A, Tozer P, TOpClass C. Isolated perianal Crohn's disease: a systematic review and expert consensus proposing novel diagnostic criteria and management advice. Lancet Gastroenterol Hepatol. 2025;10(8):757-768. PMID: 40315877.

3. Al Awadhi S, Al Hassani A, El Ouali S, Alam MB, Azar C, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani RA, Quraishi MN. Second United Arab Emirates consensus guidance on the diagnosis and management of inflammatory bowel disease. World J Gastroenterol. 2025;31(35):109882. PMID: 41024766.

4. Chan M, Fung M, Chin Koon Siw K, Khanna R, de Buck van Overstraeten A, Sabri E, McCurdy JD. Examination Under Anesthesia May Not Be Universally Required Prior to Anti-TNF Therapy in Perianal Crohn's Disease: A Comparative Cohort Study. Inflamm Bowel Dis. 2023;29(5):763-770. PMID: 35815783.

5. Meima-van Praag EM, van Rijn KL, Wasmann KATGM, Snijder HJ, Stoker J, D'Haens GR, Gecse KB, Gerhards MF, Jansen JM, Dijkgraaf MGW, van der Bilt JDW, Mundt MW, Spinelli A, Danese S, Bemelman WA, Buskens CJ. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial. Lancet Gastroenterol Hepatol. 2022;7(7):617-626. PMID: 35427495.

6. Meima-van Praag EM, Becker MAJ, van Rijn KL, Wasmann KATGM, Stoker J, D'Haens GRAM, Ponsioen CY, Gecse KB, Dijkgraaf MGW, Spinelli A, Danese S, Bemelman WA, Buskens CJ. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial. EClinicalMedicine. 2023;61:102045. PMID: 37457118.

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_Draft — generated by the IBDology RAG and not yet clinician-reviewed. Answers are grounded in the retrieved literature listed above; a high faithfulness score means the answer matches its sources, not that the sources are correct._