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Subsequently, other humanized anti\u2010TNFs were developed and marketed, followed by antibodies to new targets including integrins (vedolizumab) and interleukin 12\/23 (ustekinumab). All these so\u2010called biologicals were shown in registrational trials to induce remission superior to placebo but consistently were effective in only a minority of patients. Even though in most trials only the responders were selected to continue on the respective medication for maintenance, many experienced a secondary loss of response and only a minority of usually &lt;25% of the initial cohort achieved long\u2010term (1 year) remission. In 'real life studies', the outcome was somewhat better, probably due to proper selection of patients and open, mostly retrospective study designs. A clear benefit of biologicals is apparent in otherwise treatment refractory patients, in extraintestinal manifestations and in Crohn\u00b4s disease (CD) with fistulizing complications. Biologicals achieve mucosal healing (MH) more often than corticosteroids or thiopurines, and MH is associated with improved prognosis. However, this does not justify escalating treatment until MH is reached since controlled trials proving this point of 'treat to target' are lacking both in ulcerative colitis and CD. Surgical rates have decreased with increasing use of biologicals, but disease progression has not been proven to improve. With the exception of opportunistic infections, serious adverse events are rare. In conclusion, biologicals have changed the scene considerably and expanded our armamentarium, but there is also a marketing hype fostering expectations without evidence.<\/jats:p>","DOI":"10.1111\/joim.13345","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T11:49:57Z","timestamp":1623757797000},"page":"806-825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Twenty\u2010five years of biologicals in IBD: What\u00b4s all the hype about?"],"prefix":"10.1111","volume":"290","author":[{"given":"Klaus R.","family":"Herrlinger","sequence":"first","affiliation":[{"name":"Asklepios Klinik Heidberg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-7387","authenticated-orcid":false,"given":"Eduard F.","family":"Stange","sequence":"additional","affiliation":[{"name":"University Hospital T\u00fcbingen  T\u00fcbingen 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