{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:48:43Z","timestamp":1788364123878,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. Methods: Fourteen children (nine ulcerative colitis, one ulcerative colitis\/IBD-unspecified, four Crohn\u2019s disease) with a disease duration of 5.2 (8 months\u201314 years) years, initiated dual therapy at an age of 11.7 (3\u201317) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab\/adalimumab (VDZ + ADA), five (36%) with ustekinumab\/adalimumab (UST + ADA), and three (21%) with infliximab\/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. Results: A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC\/IBD-unspecified, 4 CD) on the PCDAI\/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 \u00b5g\/g (140\u201310,100) to 586 \u00b5g\/g (5\u20133410; p = 0.028) between baseline and 4 months. Conclusions: Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options<\/jats:p>","DOI":"10.3390\/children10010011","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T01:33:12Z","timestamp":1671672792000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dual Biologic Therapy in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Retrospective Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-9781","authenticated-orcid":false,"given":"Magdalena","family":"Wlaz\u0142o","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Meglicka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-1246","authenticated-orcid":false,"given":"Anna","family":"Wiernicka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4765-7849","authenticated-orcid":false,"given":"Marcin","family":"Osiecki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Kierku\u015b","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1097\/ACI.0000000000000486","article-title":"Very early onset IBD: Novel genetic etiologies","volume":"18","author":"Batura","year":"2018","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.5114\/ceji.2016.63131","article-title":"The relationship between the immune system and oral manifestations of inflammatory bowel disease: A review","volume":"41","author":"Vasovic","year":"2016","journal-title":"Cent.-Eur. J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/ibd.21493","article-title":"Pediatric modification of the Montreal classification for inflammatory bowel disease: The Paris classification","volume":"17","author":"Levine","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.crohns.2013.10.006","article-title":"Diferences in the management of pediatric and adult onset ulcerative colitis\u2014Lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis","volume":"8","author":"Ruemmele","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/j.1365-2036.2011.04857.x","article-title":"Diferences in phenotype and disease course in adult and paediatric infammatory bowel disease\u2014A population\u2014Bused study","volume":"34","author":"Jakobsen","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1038\/ajg.2009.177","article-title":"The natural history of pediatric ulcerative colitis: A population-based cohort study","volume":"104","author":"Dauchet","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/0016-5085(93)90883-E","article-title":"Growth failure in children with inflammatory bowel disease: A prospective study","volume":"105","author":"Motil","year":"1993","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00054725-199908000-00003","article-title":"Bone mineral density in children and young adults with Crohn\u2019s disease","volume":"5","author":"Semeao","year":"1999","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1007\/s10620-019-05486-w","article-title":"Early Response to Corticosteroid and Baseline C-Reactive Protein Predicts Outcomes in Children with Moderate to Severe Ulcerative Colitis","volume":"64","author":"Tan","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.cgh.2018.02.024","article-title":"Combining biologics in inflammatory bowel disease and other mediated inflammatory disorders","volume":"16","author":"Hirten","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/1574887113666180910120959","article-title":"A concise history of thiopurines for inflammatory bowel disease: From anecdotal reporting to treat-to-target algorithms","volume":"14","author":"Actis","year":"2019","journal-title":"Rev. Recent Clin. Trials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/ibd\/izaa279","article-title":"Takes two to make it right: Dual biological and small molecule therapy for treatment-refractory pediatric inflammatory bowel disease","volume":"27","author":"Geem","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17562848211006669","DOI":"10.1177\/17562848211006669","article-title":"Novel trends with biologics in inflammatory bowel disease: Sequential and combined approaches","volume":"14","author":"Privitera","year":"2021","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/MIB.0000000000000003","article-title":"A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease","volume":"20","author":"Vahabnezhad","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1053\/j.gastro.2012.04.046","article-title":"Safety and efficacy of adalimumab for moderate to severe Crohn\u2019s disease in children","volume":"143","author":"Hyams","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1093\/ibd\/izaa277","article-title":"Dual biologic and small-molecule therapies for the treatment of refractory pediatric inflammatory bowel disease","volume":"27","author":"Dolinger","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s40272-020-00396-1","article-title":"Combination of biological agents in moderate to severe pediatric inflammatory bowel disease: A case series and review of literature","volume":"22","author":"Rove","year":"2020","journal-title":"Pediatric Drugs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1097\/MEG.0000000000002203","article-title":"Dual biologic therapy with Vedolizumab and Ustekinumab for refractory Crohn\u2019s disease in children","volume":"34","author":"Howard","year":"2022","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.cgh.2020.02.017","article-title":"Combination biologic therapy in inflammatory bowel disease: Experience from a tertiary care center","volume":"19","author":"Kwapisz","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Huff-Hardy, K., Bedair, M., Vazquez, R., and Burstein, E. (2017). Efficacy of combination vedolizumab and ustekinumab for refractory Crohn\u2019s disease. Inflamm. Bowel Dis., 23.","DOI":"10.1097\/MIB.0000000000001232"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/00365521.2019.1597159","article-title":"Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: A systematic review with pool analysis","volume":"54","author":"Ribaldone","year":"2019","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1080\/00365521.2017.1304987","article-title":"Long-term effectiveness of vedolizumab in inflammatory bowel disease: A national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)","volume":"52","author":"Eriksson","year":"2017","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1046\/j.1365-2036.2001.01060.x","article-title":"Review article: The limitations of corticosteroid therapy in Crohn\u2019s disease","volume":"15","author":"Rutgeerts","year":"2001","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_24","first-page":"1386","article-title":"Predicting Endoscopic Crohn\u2019s Disease Activity Before and After Induction Therapy in Children: A Comprehensive Assessment of PCDAI, CRP, and Fecal Calprotectin","volume":"21","author":"Zubin","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1111\/apt.13197","article-title":"Systematic review: The financial burden of surgical complications in patients with ulcerative colitis","volume":"41","author":"Lindsay","year":"2015","journal-title":"Aliment Pharmacol Ther."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/1\/11\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:45:29Z","timestamp":1760147129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/10\/1\/11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["children10010011"],"URL":"https:\/\/doi.org\/10.3390\/children10010011","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,21]]}}}