{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:37:03Z","timestamp":1785328623816,"version":"3.55.0"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Oral systemic corticosteroids have been used to induce remission in patients with active inflammatory bowel disease (IBD) for over 50\u00a0years; however, the wide array of adverse events (AEs) associated with these drugs prompted the development of steroid compounds with targeted delivery and low systemic bioavailability. This study assessed corticosteroids' comparative harm using network meta\u2010analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory authorities' websites and major conference proceedings, through March 2017. Randomized controlled trials that recruited adult IBD patients and compared oral systemic corticosteroids (prednisone\/prednisolone) or compounds\/formulations with low systemic bioavailability (budesonide, budesonide MMX, and beclomethasone dipropionate) with placebo, or against each other, were considered eligible for inclusion. Two reviewers independently extracted study data and outcomes, and rated each trial's risk\u2010of\u2010bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified and synthesized evidence from 31 trials including 5689 IBD patients. Budesonide MMX was associated with significantly fewer corticosteroid\u2010related AEs than oral systemic corticosteroids [odds ratio (OR): 0.25, 95% confidence interval (CI): 0.13\u20130.49] and beclomethasone (OR: 0.35, 95% CI: 0.13\u20131.00), but not significantly fewer AEs than budesonide (OR: 0.64, 95% CI: 0.37\u20131.11); it performed equally good with placebo. By contrast, the occurrence of serious AEs, and treatment discontinuations due to AEs, did not differ between the comparator treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Budesonide MMX is associated with fewer corticosteroid\u2010related AEs than its comparator steroid treatments for adult IBD patients. Further high\u2010quality research is warranted to illuminate the steroid drugs' comparative safety profiles.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13456","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:42:35Z","timestamp":1508719355000},"page":"239-251","source":"Crossref","is-referenced-by-count":44,"title":["Comparative safety of systemic and low\u2010bioavailability steroids in inflammatory bowel disease: Systematic review and network meta\u2010analysis"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6102-6579","authenticated-orcid":false,"given":"Stefanos","family":"Bonovas","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"IBD Center, Department of Gastroenterology Humanitas Clinical and Research Center  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios K.","family":"Nikolopoulos","sequence":"additional","affiliation":[{"name":"Medical School University of Cyprus  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Lytras","sequence":"additional","affiliation":[{"name":"Hellenic Center for Disease Control and Prevention  Athens Greece"},{"name":"Department of Experimental and Health Sciences Pompeu Fabra University  Barcelona Spain"},{"name":"Barcelona Institute for Global Health  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gionata","family":"Fiorino","sequence":"additional","affiliation":[{"name":"IBD Center, Department of Gastroenterology Humanitas Clinical and Research Center  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Peyrin\u2010Biroulet","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Gastroenterology and Inserm U954 University Hospital of Nancy, University of Lorraine  Vandoeuvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Danese","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"IBD Center, Department of Gastroenterology Humanitas Clinical and Research Center  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Oxford Textbook of Medicine","author":"Jewell DP","year":"2005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1102942"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2012.06.010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000338128"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2001.01060.x"},{"key":"e_1_2_8_7_1","first-page":"65","article-title":"Low bioavailability and traditional systemic steroids in IBD: can the former take over the latter?","volume":"22","author":"Fasci Spurio F","year":"2013","journal-title":"J Gastrointestin Liver Dis"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12712"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f2914"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7521.897"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1875"},{"key":"e_1_2_8_12_1","unstructured":"BonovasS NikolopoulosG LytrasT FiorinoG Peyrin\u2010BirouletL DaneseS.Comparative safety of systemic and low\u2010bioavailability corticosteroids in inflammatory bowel disease: a systematic review and network meta\u2010analysis of randomized controlled trials. PROSPERO2016: CRD42016038694. Available fromhttp:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.asp?ID=CRD42016038694"},{"key":"e_1_2_8_13_1","unstructured":"HigginsJPT GreenS editors.Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration;2011 version 5.0.1."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2011.04.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2011.01.011"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02799-9"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-0015-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X1501500403"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X1501500402"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076654"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X1101100206"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1045"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1761"},{"key":"e_1_2_8_26_1","first-page":"1185","article-title":"Software updates: st0156 2: multivariate random\u2010effects meta\u2010analysis","volume":"15","author":"White IR","year":"2015","journal-title":"Stata J"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1536867X0900900103"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099682"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.03.016"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys041"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1044"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3767"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(97)00049-8"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.57"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70254-9"},{"key":"e_1_2_8_36_1","first-page":"209","article-title":"Oral budesonide is as effective as oral prednisolone in active Crohn's disease","volume":"41","author":"Campieri M","year":"1997","journal-title":"The Global Budesonide Study Group. Gut"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.2.186"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199903000-00011"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1998.00285.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8536887"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199409293311303"},{"key":"e_1_2_8_42_1","first-page":"493","article-title":"Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease","volume":"42","author":"Gross V","year":"1998","journal-title":"The Budesonide Study Group. Gut"},{"key":"e_1_2_8_43_1","first-page":"905","article-title":"Oral pH\u2010modified release budesonide versus 6\u2010methylprednisolone in active Crohn's disease. German\/Austrian budesonide study group","volume":"8","author":"Gross V","year":"1996","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02338.x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70125-3"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.pm8964395"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.1.82"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(84)90409-8"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2010.12.001"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2002.01298.x"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199409293311304"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.08.003"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00662-7"},{"issue":"4","key":"e_1_2_8_54_1","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/0016-5085(79)90386-X","article-title":"National Cooperative Crohn's disease study: adverse reactions to study drugs","volume":"77","author":"Singleton JW","year":"1979","journal-title":"Gastroenterology"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2012.06.006"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304258"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05835.x"},{"key":"e_1_2_8_58_1","first-page":"PI29","article-title":"Beclomethasone dipropionate for the treatment of mild\u2010to\u2010moderate Crohn's disease: an open\u2010label, budesonide\u2010controlled, randomized study","volume":"12","author":"Tursi A","year":"2006","journal-title":"Med Sci Monit"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.114"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx032"},{"key":"e_1_2_8_61_1","unstructured":"Australian Government Department of Health and Aging Therapeutic Goods Administration.Australian public assessment report for budesonide; October 2012. Available fromhttps:\/\/www.tga.gov.au\/sites\/default\/files\/auspar\u2010budesonide\u2010121022\u20101.pdf"},{"key":"e_1_2_8_62_1","unstructured":"U.S. Food and Drug Administration Center for Drug Evaluation and Research.Drug approval package for Uceris (budesonide) 9 mg tablets Medical Review; January 2013. Available fromhttp:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2013\/203634Orig1s000MedR.pdf"},{"issue":"10","key":"e_1_2_8_63_1","first-page":"CD007698","article-title":"Oral budesonide for induction of remission in ulcerative colitis","author":"Sherlock ME","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjv101"},{"key":"e_1_2_8_65_1","first-page":"CD000296","article-title":"Budesonide for induction of remission in Crohn's disease","volume":"6","author":"Rezaie A","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"issue":"8","key":"e_1_2_8_66_1","first-page":"CD002913","article-title":"Budesonide for maintenance of remission in Crohn's disease","author":"Kuenzig ME","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.70"},{"issue":"4","key":"e_1_2_8_68_1","first-page":"CD006873","article-title":"Interventions for prevention of post\u2010operative recurrence of Crohn's disease","author":"Doherty G","year":"2009","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03891.x"},{"issue":"4","key":"e_1_2_8_70_1","first-page":"CD000301","article-title":"Corticosteroids for maintenance of remission in Crohn's disease","author":"Steinhart AH","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2000.00867.x"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.02.058"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13352"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T09:40:11Z","timestamp":1695894011000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":73,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/bcp.13456"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13456","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]}}}