{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:11:43Z","timestamp":1790079103252,"version":"4.0.1"},"reference-count":72,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Perianal fistulizing Crohn\u2019s disease (pfCD) represents one of the most challenging manifestations. Optimal management requires a multidisciplinary approach combining surgical drainage, appropriate imaging, and advanced medical therapies. While infliximab remains the first-line medical therapy, primary non-response or secondary loss of response occurs in many patients, which highlights the need for effective alternative treatments. This narrative review summarizes the current evidence regarding medical therapies beyond infliximab, including biologics, small molecules, and emerging therapeutic strategies. A literature search of PubMed, Embase, and Scopus was conducted up to February 2026 to identify studies evaluating medical treatments of pfCD. Current evidence suggests that ustekinumab and upadacitinib remain effective following anti-TNF failure, while vedolizumab demonstrates limited efficacy. Evidence supporting IL-23 inhibitors, including risankizumab and guselkumab, is limited but rapidly evolving, with ongoing prospective trials expected to clarify their role. Novel approaches such as advanced dual-targeted therapy, subcutaneous infliximab optimization, hyperbaric oxygen therapy, and exclusive enteral nutrition have also shown encouraging preliminary results in selected patients. However, most available data derive from post hoc analyses, retrospective cohorts, or small prospective studies, with considerable heterogeneity in outcome definitions and limited incorporation of standardized radiological endpoints. Future adequately powered randomized controlled trials using harmonized clinical and magnetic resonance imaging -based outcomes are essential to establish optimal treatment sequencing and improve long-term fistula healing. Until then, individualized multidisciplinary management remains fundamental to optimizing outcomes in patients with pfCD.<\/jats:p>","DOI":"10.3390\/jcm15187327","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medical Therapies Beyond Infliximab for Perianal Fistulizing Crohn\u2019s Disease: Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-1501","authenticated-orcid":false,"given":"Esteban","family":"Fuentes-Valenzuela","sequence":"first","affiliation":[{"name":"IBD Unit, Gastroenterology and Hepatology Department, Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Tarras\u00f3","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), IBD Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-5910","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Botella","sequence":"additional","affiliation":[{"name":"IBD Unit, Gastroenterology and Hepatology Department, Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-1511","authenticated-orcid":false,"given":"Pilar","family":"Nos","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), IBD Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vera","sequence":"additional","affiliation":[{"name":"IBD Unit, Gastroenterology and Hepatology Department, Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7360-7581","authenticated-orcid":false,"given":"Marisa","family":"Iborra","sequence":"additional","affiliation":[{"name":"Inflammatory Bowel Disease Research Group, Health Research Institute La Fe (IIS La Fe), IBD Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1093\/ibd\/izad195","article-title":"Management of Perianal Fistulizing Crohn\u2019s Disease","volume":"30","author":"Singh","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, Z., Cai, J., and Zhang, H. (2026). Cumulative risk of perianal Crohn\u2019s disease in population-based cohorts: A systematic review and meta-analysis of twenty-year follow-up. BMC Public Health, Online ahead of print.","DOI":"10.1186\/s12889-026-28041-5"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1463-1318.2011.02613.x","article-title":"Self-reported depressive symptoms and suicidal feelings in perianal Crohn\u2019s disease","volume":"14","author":"Mahadev","year":"2012","journal-title":"Color. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1093\/ecco-jcc\/jjad008","article-title":"Pathogenesis of Perianal Fistulising Crohn\u2019s Disease: Current Knowledge, Gaps in Understanding, and Future Research Directions","volume":"17","author":"Cao","year":"2023","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_5","first-page":"155","article-title":"Recommendations of the Crohn\u2019s Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn\u2019s disease","volume":"43","author":"Maroto","year":"2020","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1093\/ecco-jcc\/jjae091","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Medical Treatment","volume":"18","author":"Gordon","year":"2024","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1093\/ecco-jcc\/jjae089","article-title":"ECCO Guidelines on Therapeutics in Crohn\u2019s Disease: Surgical Treatment","volume":"18","author":"Adamina","year":"2024","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/S2468-1253(22)00007-3","article-title":"Classifying perianal fistulising Crohn\u2019s disease: An expert consensus to guide decision-making in daily practice and clinical trials","volume":"7","author":"Geldof","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1093\/ecco-jcc\/jjae056","article-title":"TOpCLASS Expert Consensus Classification of Perianal Fistulising Crohn\u2019s Disease: A Real-world Application in a Serial Fistula MRI Cohort","volume":"18","author":"Schroeder","year":"2024","journal-title":"J. Crohns Colitis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.cgh.2025.02.009","article-title":"Defining Radiological Healing in Perianal Fistulizing Crohn\u2019s Disease: A TOpClass Global Expert Delphi Consensus","volume":"24","author":"Anand","year":"2026","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13244-026-02260-1","article-title":"VALIDATE-PERIANAL: An international real-world multi-centre exploratory validation of the TOpClass definition of a radiologically healed fistula in perianal fistulising Crohn\u2019s disease","volume":"17","author":"Anand","year":"2026","journal-title":"Insights Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1056\/NEJM199905063401804","article-title":"Infliximab for the treatment of fistulas in patients with Crohn\u2019s disease","volume":"340","author":"Present","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1056\/NEJMoa030815","article-title":"Infliximab maintenance therapy for fistulizing Crohn\u2019s disease","volume":"350","author":"Sands","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.gastro.2006.11.041","article-title":"Adalimumab for Maintenance of Clinical Response and Remission in Patients with Crohn\u2019s Disease: The CHARM Trial","volume":"132","author":"Colombel","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1136\/gutjnl-2013-304488","article-title":"Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn\u2019s disease: A randomised, double-blind, placebo controlled trial (ADAFI)","volume":"63","author":"Dewint","year":"2014","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1365-2036.2010.04509.x","article-title":"Randomised clinical trial: Certolizumab pegol for fistulas in Crohn\u2019s disease\u2014Subgroup results from a placebo-controlled study","volume":"33","author":"Schreiber","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/ecco-jcc\/jjy019","article-title":"Efficacy of Vedolizumab in Fistulising Crohn\u2019s Disease: Exploratory Analyses of Data from GEMINI 2","volume":"12","author":"Feagan","year":"2018","journal-title":"J. Crohns Colitis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.cgh.2021.09.028","article-title":"Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn\u2019s Disease: ENTERPRISE Study","volume":"20","author":"Schwartz","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/apt.15665","article-title":"Vedolizumab for perianal Crohn\u2019s disease: A multicentre cohort study in 151 patients","volume":"51","author":"Bourrier","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wils, P., Nancey, S., Messmer, E., Bourreille, A., Buisson, A., Caillo, L., Vuitton, L., Altwegg, R., H\u00e9buterne, X., and Ernst, O. (2026). Ustekinumab for fistulising perianal Crohn\u2019s disease: A randomised placebo-controlled trial from the GETAID. Gut, Online ahead of print.","DOI":"10.1136\/gutjnl-2026-339158"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1093\/ecco-jcc\/jjae003","article-title":"Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn\u2019s Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial","volume":"18","author":"Reinisch","year":"2024","journal-title":"J. Crohns Colitis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cgh.2024.08.032","article-title":"Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn\u2019s Disease: A Post Hoc Analysis of 3 Phase 3 Trials","volume":"23","author":"Colombel","year":"2024","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1002\/ueg2.70059","article-title":"Effectiveness and Safety of Advanced Dual-Targeted Therapy in Refractory Perianal Crohn\u2019s Disease","volume":"13","author":"Fathallah","year":"2025","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ueg2.12189","article-title":"Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn\u2019s disease: Results of the HOT-TOPIC trial after 1-year follow-up","volume":"10","author":"Lansdorp","year":"2022","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_25","first-page":"522","article-title":"Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn\u2019s Disease and Ulcerative Colitis","volume":"47","year":"2024","journal-title":"Gastroenterol. Hepatol. (Engl. Ed.)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17562848251326471","DOI":"10.1177\/17562848251326471","article-title":"Switching from intravenous to subcutaneous infliximab is safe and feasible in patients with perianal Crohn\u2019s disease","volume":"18","author":"Wils","year":"2025","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_27","first-page":"1701","article-title":"Subcutaneous Infliximab for Perianal Crohn\u2019s Disease: The BioLap-Rem Multicenter Study From the GETAID","volume":"121","author":"Kirchgesner","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"jjae127","DOI":"10.1093\/ecco-jcc\/jjae127","article-title":"Subcutaneous Infliximab Cutoff Points in Patients with Inflammatory Bowel Disease: Data From the ENEIDA Registry","volume":"19","author":"Iborra","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.14309\/ajg.0000000000000810","article-title":"Ustekinumab for Perianal Crohn\u2019s Disease: The BioLAP Multicenter Study From the GETAID","volume":"115","author":"Kirchgesner","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1097\/MIB.0000000000000842","article-title":"Ustekinumab for the Treatment of Refractory Crohn\u2019s Disease: The Spanish Experience in a Large Multicentre Open-label Cohort","volume":"22","author":"Khorrami","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1111\/jgh.15390","article-title":"Real-world effectiveness and safety of ustekinumab for the treatment of Crohn\u2019s disease: The Scottish ustekinumab cohort","volume":"36","author":"Plevris","year":"2021","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1093\/ecco-jcc\/jjaa177","article-title":"Effectiveness And Safety Of Ustekinumab Intensification At 90 Mg Every Four Weeks In Crohn\u2019s Disease: A Multicenter Study","volume":"15","author":"Fumery","year":"2020","journal-title":"J. Crohns Colitis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/apt.15958","article-title":"Real-world long-term effectiveness of ustekinumab in Crohn\u2019s disease: Results from the ENEIDA registry","volume":"52","author":"Iborra","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yao, J., Zhang, H., Su, T., Peng, X., Zhao, J., Liu, T., Wang, W., Hu, P., Zhi, M., and Zhang, M. (2023). Ustekinumab Promotes Radiological Fistula Healing in Perianal Fistulizing Crohn\u2019s Disease: A Retrospective Real-World Analysis. J. Clin. Med., 12.","DOI":"10.3390\/jcm12030939"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, X., Yan, Y., Yi, J., Luo, D., Geng, J., Huang, H., Wang, J., Gu, Y., Yang, B., and Gong, Y. (2025). Ustekinumab trough concentrations predict clinical remission in perianal fistulizing crohn\u2019s disease: A real-world retrospective cohort study. BMC Gastroenterol., 25.","DOI":"10.1186\/s12876-025-04323-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/00365521.2020.1854848","article-title":"Efficacy of ustekinumab for active perianal fistulizing Crohn\u2019s disease: A systematic review and meta-analysis of the current literature","volume":"56","author":"Attauabi","year":"2021","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Devi, J., Patel, A., Quraishi, B., Dev, B., Tan, T., Kline, M., Chowla, N., Ramesh, P.R., Ballard, D.H., and Huang, L. (2026). Real-World Effectiveness of Upadacitinib for Perianal Crohn\u2019s Disease: A Multicenter Retrospective Study. Clin. Gastroenterol. Hepatol.","DOI":"10.1016\/j.cgh.2026.05.003"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/apt.70682","article-title":"One-Year Effectiveness of Upadacitinib in Perianal Crohn\u2019s Disease: A Real-World GETAID Study","volume":"64","author":"Richard","year":"2026","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10620-022-07582-w","article-title":"Upadacitinib Is Safe and Effective for Crohn\u2019s Disease: Real-World Data from a Tertiary Center","volume":"68","author":"Traboulsi","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1111\/apt.70073","article-title":"Effectiveness and Safety of Upadacitinib Induction Therapy for 223 Patients with Crohn\u2019s Disease: A GETAID Multicentre Cohort Study","volume":"61","author":"Richard","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.cgh.2023.03.001","article-title":"Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn\u2019s Disease: Prospective Real-World Experience","volume":"21","author":"Friedberg","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1093\/ibd\/izaf216","article-title":"Therapeutic Benefit of Upadacitinib in Severe Post-Proctectomy (Class 4) Perianal Crohn\u2019s Disease: A Three-Patient Case Series","volume":"32","author":"Hanna","year":"2025","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1007\/s12325-025-03328-y","article-title":"Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease","volume":"42","author":"Burmester","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Scaldaferri, F., Di Vincenzo, F., Aloi, M., Ascolani, M., Balestrieri, P., Bertani, L., Bezzio, C., Bodini, G., Bossa, F., and Calabrese, E. (2026). Multicenter Real-World Outcomes of Risankizumab in Crohn\u2019s Disease: The RESOLVE IG-IBD Study. Am. J. Gastroenterol., Online ahead of print.","DOI":"10.1093\/ecco-jcc\/jjaf231.1195"},{"key":"ref_45","unstructured":"(2026, February 23). Study Details|NCT05347095|A Study of Guselkumab in Participants with Fistulizing, Perianal Crohn\u2019s Disease|ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05347095."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1016\/S0140-6736(24)01762-8","article-title":"Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn\u2019s disease: A phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study","volume":"404","author":"Ferrante","year":"2024","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1016\/j.cgh.2026.01.049","article-title":"Mirikizumab Long-Term Efficacy and Safety in Patients with Crohn\u2019s Disease: Results From the VIVID-2 Open-Label Extension Trial","volume":"24","author":"Sands","year":"2026","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e361","DOI":"10.1016\/j.cgh.2021.03.034","article-title":"Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis","volume":"20","author":"Ahmed","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1007\/s10620-023-08060-7","article-title":"Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn\u2019s Perianal Fistulae","volume":"68","author":"Maas","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100697","DOI":"10.1016\/j.gastha.2025.100697","article-title":"Comparison Between Adalimumab and Infliximab in Perianal Crohn\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"4","author":"Aboursheid","year":"2025","journal-title":"Gastro Hep Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"jjaf099","DOI":"10.1093\/ecco-jcc\/jjaf099","article-title":"The effectiveness of second- and-third-line biologics in perianal Crohn\u2019s disease-a multicenter propensity score-matched study","volume":"19","author":"Shani","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1016\/j.dld.2024.05.009","article-title":"Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn\u2019s disease: The HEAL study from GETECCU","volume":"56","author":"Casanova","year":"2024","journal-title":"Dig. Liver Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Eldesouki, M.H., Rabea, E., Aldemerdash, M.A., Tageldin, O., Seminerio, J., Farraye, F.A., and Hashash, J.G. (2026). Comparison of Ustekinumab and Vedolizumab Effectiveness in Perianal Crohn\u2019s Disease: A Retrospective Propensity Matched Cohort Study. J. Clin. Gastroenterol., Online ahead of print.","DOI":"10.1097\/MCG.0000000000002398"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"52","DOI":"10.5217\/ir.2024.00168","article-title":"Comparative effectiveness of ustekinumab versus infliximab in the management of perianal fistulizing Crohn\u2019s disease: A retrospective study in China","volume":"24","author":"Chen","year":"2025","journal-title":"Intest. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hajjar, R., Bews, K.A., Alaoui, A.A., Khan, S., Gleason, L., Sanchez, E., Reynolds, I.S., Kane, S.V., Perry, W.R., and Mathis, K.L. (2025). Hyperbaric Oxygen Therapy in the Management of Refractory Perianal Crohn\u2019s Disease. J. Clin. Med., 14.","DOI":"10.3390\/jcm14196843"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1046\/j.1365-2036.2003.01793.x","article-title":"Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn\u2019s disease","volume":"18","author":"Dejaco","year":"2003","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0016-5085(03)00877-1","article-title":"Tacrolimus for the treatment of fistulas in patients with Crohn\u2019s disease: A randomized, placebo-controlled trial","volume":"125","author":"Sandborn","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ibd.20073","article-title":"Topical tacrolimus in the treatment of perianal Crohn\u2019s disease: Exploratory randomized controlled trial","volume":"13","author":"Hart","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/ncp.70135","article-title":"Exclusive enteral nutrition improves radiological outcomes in adults with perianal fistulizing Crohn\u2019s disease: A real-world retrospective cohort study","volume":"41","author":"Deng","year":"2026","journal-title":"Nutr. Clin. Pract."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"184","DOI":"10.5217\/ir.2019.00094","article-title":"Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn\u2019s disease: The Indian experience","volume":"18","author":"Sood","year":"2020","journal-title":"Intest. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1751-2980.2010.00434.x","article-title":"Exclusive enteral nutrition in the management of perianal Crohn\u2019s disease in children","volume":"11","author":"Wong","year":"2010","journal-title":"J. Dig. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/jpc.15184","article-title":"Exclusive enteral nutrition is effective and feasible as primary induction and re-induction therapy in Asian children with Crohn\u2019s disease","volume":"57","author":"Chan","year":"2021","journal-title":"J. Paediatr. Child Health"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.cgh.2021.07.053","article-title":"Higher Anti-tumor Necrosis Factor-\u03b1 Levels Correlate with Improved Radiologic Outcomes in Crohn\u2019s Perianal Fistulas","volume":"20","author":"Lee","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.3748\/wjg.v28.i23.2597","article-title":"Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn\u2019s disease","volume":"28","author":"Gu","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/MEG.0000000000001561","article-title":"Higher anti-tumor necrosis factor levels are associated with perianal fistula healing and fistula closure in Crohn\u2019s disease","volume":"32","author":"Plevris","year":"2020","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"s1","DOI":"10.1136\/gutjnl-2024-334395","article-title":"British Society of Gastroenterology guidelines on inflammatory bowel disease in adults: 2025","volume":"74","author":"Moran","year":"2025","journal-title":"Gut"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.14309\/ajg.0000000000003465","article-title":"ACG Clinical Guideline: Management of Crohn\u2019s Disease in Adults","volume":"120","author":"Lichtenstein","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s12664-025-01880-7","article-title":"Perianal fistulizing Crohn\u2019s disease: Clinical practice update from Colitis and Crohn\u2019s Foundation (India)","volume":"45","author":"Kumar","year":"2026","journal-title":"Indian J. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"He, M., Liang, H., Sun, L., and Fan, X. (2025). Efficacy and safety of IL-23 inhibitors in the treatment of moderate to severe ulcerative colitis: A meta-analysis based on randomized controlled trials. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1724448"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Jamal, F., Segun-Omosehin, T., Viggiano, T., Khan, H., Gonzalez, A.J., Thomas, G., Elmasry, S., and Malik, T.A. (2026). Advanced Medical Therapies for Perianal Fistulizing Crohn\u2019s Disease: A Systematic Review of Clinical, Radiological, Surgical, and Composite Outcomes. Pharmaceuticals, 19.","DOI":"10.3390\/ph19030417"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/ibd\/izac103","article-title":"Comparative Efficacy of Biologic Therapies for Inducing Response and Remission in Fistulizing Crohn\u2019s Disease: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials","volume":"29","author":"Shehab","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1016\/j.cgh.2025.11.005","article-title":"Recommendations to Standardize the Conduct of Clinical Trials Evaluating Novel Therapies for Perianal Fistulizing Crohn\u2019s Disease","volume":"24","author":"Hanzel","year":"2026","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:36:00Z","timestamp":1790076960000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":72,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187327"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187327","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}