{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:07:14Z","timestamp":1777878434985,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Chronic Disease"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Steroid-refractory ulcerative colitis (SR-UC) is a severe form of ulcerative colitis (UC) that persists despite high-dose corticosteroid therapy. Management is challenging and often requires biologics, immunosuppressants or colectomy. Tacrolimus, a calcineurin inhibitor with immunomodulatory effects, has emerged as a potential alternative, though its efficacy, safety and long-term outcomes remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This systematic review evaluates the efficacy and safety of tacrolimus in SR-UC, compares it with anti-tumour necrosis factor (TNF) agents, and examines its role in patients with steroid-refractory ulcerative proctitis (SR-UP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed using the Oxford Centre for Evidence-Based Medicine framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources and methods:<\/jats:title>\n                    <jats:p>A comprehensive search of PubMed and Medline (1998\u20132025) identified studies reporting clinical remission, response rates, adverse effects and colectomy rates. Subgroup analyses compared oral tacrolimus with anti-TNF therapy and evaluated topical tacrolimus in SR-UP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Seventeen studies (658 patients) met the inclusion criteria. Tacrolimus demonstrated variable efficacy, with clinical remission rates of 9.4%\u201375.6% and response rates of 28.6%\u201389.6%. Adverse events, mainly neurotoxicity and nephrotoxicity, occurred in 16.7%\u201353.0% of cases, sometimes leading to treatment discontinuation. Colectomy rates ranged from 6.1% to 62%. No significant difference was observed between tacrolimus and anti-TNF agents in remission induction, though anti-TNFs had superior long-term outcomes. Topical tacrolimus showed promising efficacy in SR-UP (73.0%\u201375.0% remission) but was associated with high adverse event rates (45.0%\u201367.0%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Tacrolimus is a viable option for SR-UC, particularly in combination therapy, but its long-term efficacy remains uncertain. While it is comparable to anti-TNFs for short-term remission, high colectomy rates and adverse effects require careful monitoring. Topical tacrolimus shows promise for SR-UP but requires standardised dosing. Further large-scale trials are needed to optimise treatment strategies and evaluate long-term safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>The review has been registered with PROSPERO (CRD42023432827), the international prospective register of systematic reviews.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20406223251333570","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T02:34:02Z","timestamp":1749782042000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Systematic review: the use of tacrolimus in steroid-refractory ulcerative colitis"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2707-4591","authenticated-orcid":false,"given":"Vinay","family":"Jangra","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, Whipps Cross Hospital, Whipps Cross Road, London E11 1NR, UK"},{"name":"Queen Mary\u2019s University, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilsan","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delvene","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Andreani","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Hotouras","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.233"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-318484"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz180"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.5508"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.2.172"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.539_g.x"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S55458"},{"key":"e_1_3_5_9_2","first-page":"1","article-title":"Two decades of tacrolimus in renal transplant: basic science and clinical evidence","volume":"15","author":"Shrestha BM.","year":"2017","unstructured":"Shrestha BM. Two decades of tacrolimus in renal transplant: basic science and clinical evidence. Exp Clin Transplant 2017; 15: 1\u20139.","journal-title":"Exp Clin Transplant"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0282-2"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v12.i3.150"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2013.03.005"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.03010.x"},{"key":"e_1_3_5_14_2","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page MJ","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71.","journal-title":"BMJ"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-200209000-00002"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01662.x"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03764.x"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21853"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12118"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2013.03.008"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i6.1880"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.17235\/reed.2017.4899\/2017"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2017-100888"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i13.1603"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.02.027"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000493979"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgh3.12280"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3162595"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S143224"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68828-z"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2020-001699"}],"container-title":["Therapeutic Advances in Chronic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406223251333570","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20406223251333570","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406223251333570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:20:08Z","timestamp":1777591208000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20406223251333570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":30,"alternative-id":["10.1177\/20406223251333570"],"URL":"https:\/\/doi.org\/10.1177\/20406223251333570","relation":{},"ISSN":["2040-6223","2040-6231"],"issn-type":[{"value":"2040-6223","type":"print"},{"value":"2040-6231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,12]]},"article-number":"20406223251333570"}}