{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:59:18Z","timestamp":1773359958916,"version":"3.50.1"},"reference-count":46,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848015002"],"award-info":[{"award-number":["848015002"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,3,4]]},"published-print":{"date-parts":[[2020,5]]},"abstract":"\n Introduction<\/jats:title>\n Adalimumab is effective for maintenance of remission in patients with Crohn\u2019s disease (CD) at a dose of 40\u2009mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW).<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174\u2009CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10\u2009mg\/L, faecal calprotectin (FC) <150\u2009\u00b5g\/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 \u00b5g\/g, CRP\u226510 mg\/l, HBI\u22655. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences.<\/jats:p>\n <\/jats:sec>\n \n Trial registration numbers<\/jats:title>\n \n EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (\n NCT03172377<\/jats:ext-link>\n ); Dutch trial registry (NTRID6417).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-035326","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T06:29:37Z","timestamp":1590560977000},"page":"e035326","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Lengthening adalimumab dosing interval in quiescent Crohn\u2019s disease patients: protocol for the pragmatic randomised non-inferiority LADI 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Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A C","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Hoentjen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C J","family":"van der Woude","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on 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