{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:28Z","timestamp":1789106848073,"version":"build-2803163510"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor necrosis factor-\u03b1 inhibitors (anti-TNF-\u03b1) and mesenchymal stem cells (MSCs) have been proven to be effective for Perianal fistulizing Crohn\u2019s disease (PFCD). However, no head-to-head clinical trials have directly comparing these two therapies. Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of anti-TNF-\u03b1 and MSCs in PFCD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included randomized controlled trials (RCTs) evaluating anti-TNF-\u03b1 or MSCs against placebo (PBO) in PFCD patients. The primary efficacy outcomes were fistula remission and fistula response. The secondary outcome was clinical remission. Safety outcomes comprised adverse events and infections. Effect sizes were reported as odds ratios (ORs) with 95% credible intervals (CrIs). Treatment rankings were determined using the surface under the cumulative ranking curve (SUCRA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 15 RCTs involving 2, 475 patients were included. Compared with PBO, MSCs significantly improved fistula remission (OR\u00a0=\u00a05.33, 95% CrI: 2.19\u201319.03) and fistula response (OR\u00a0=\u00a04.76, 95% CrI: 1.78\u201320.37). Anti-TNF-\u03b1 also significantly increased fistula remission rates (OR\u00a0=\u00a02.19, 95% CrI: 1.01\u20134.54). SUCRA rankings placed MSCs first for both fistula remission (SUCRA\u00a0=\u00a00.97) and fistula response (SUCRA\u00a0=\u00a00.967). For clinical remission, anti-TNF-\u03b1 demonstrated superior efficacy (OR\u00a0=\u00a02.41, 95% CrI: 1.30\u20135.03) compared with MSCs (OR\u00a0=\u00a01.71, 95% CrI: 0.69\u20135.57) and PBO. Indirect comparisons revealed a non-significant trend favoring MSCs over anti-TNF-\u03b1 for fistula remission (OR\u00a0=\u00a02.44) and fistula response (OR\u00a0=\u00a02.55). Neither treatment showed statistically significant differences in adverse events or infections versus PBO, indicating favorable safety profiles for both.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In indirect comparisons, MSCs showed a numerically greater but not statistically significant effect on fistula healing compared with anti-TNF-\u03b1, whereas anti-TNF-\u03b1 was superior for clinical remission. Both treatments were generally safe. Given the indirect nature of these comparisons, direct head-to-head trials are needed to establish their comparative efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/recorddashboard<\/jats:ext-link>\n                      , identifier CRD42021283052.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1929235","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:29:51Z","timestamp":1789104591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of tumor necrosis factor-\u03b1 inhibitors and mesenchymal stem cells in the treatment of fistulizing Crohn\u2019s disease: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xue-Min","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Chun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liumei","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Wuzhou Red Cross Hospital","place":["Wuzhou, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiquan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4240\/wjgs.v17.i7.101767","article-title":"Epidemiology, treatment patterns, and associated risk factors in perianal fistulizing Crohn's disease: a systematic literature review","volume":"17","author":"Mckay","year":"2025","journal-title":"World J Gastrointest Surg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32362","article-title":"The natural history of fistulizing Crohn's disease in Olmsted County, 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