Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: protocol for the pragmatic randomised non-inferiority LADI study. Issue 5 (26th May 2020)

• Record Type: Journal Article
• Authors: Smits, L J T; Pauwels, R W M; Kievit, W; de Jong, D J; de Vries, A C; Hoentjen, F; van der Woude, C J
• Other Names: author non-byline.; van Bodegraven A.A. author non-byline.; Bodelier A.G.L. author non-byline.; Boekema P.J. author non-byline.; de Boer N. author non-byline.; ter Borg P.C.J. author non-byline.; den Broeder A.A. author non-byline.; Gisbertz I.A.M author non-byline.; Hoentjen F author non-byline.; Jansen F.M author non-byline.; Jansen J author non-byline.; Jansen S.V. author non-byline.; de Jong D.J. author non-byline.; Kievit W. author non-byline.; van Linschoten R.C.A. author non-byline.; Löwenberg M author non-byline.; Lutgens M.W.M.D. author non-byline.; Mallant-Hent R.C. author non-byline.; van der Meulen A.E. author non-byline.; Oldenburg B. author non-byline.; Pauwels R.W.M. author non-byline.; Pierik M author non-byline.; Romberg-Camps M.J.L. author non-byline.; Römkens T.E.H. author non-byline.; Russel M.G.V.M. author non-byline.; Smits L.J.T. author non-byline.; Tan A.C.I.T.L. author non-byline.; Verhulst M.L. author non-byline.; de Vries A.C. author non-byline.; West R.L. author non-byline.; Wolfhagen F.H.J. author non-byline.; van der Woude C.J. author non-byline.;
• Is Part Of: BMJ open. Volume 10:Issue 5(2020)
• Publication Date: 2020-05-26
• Subjects: inflammatory bowel disease -- gastroenterology -- adverse events -- clinical trials -- health economics -- statistics & research methods; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2019-035326
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Adalimumab is effective for maintenance of remission in patients with Crohn's disease (CD) at a dose of 40 mg 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). Methods and analysis: 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 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/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 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness. Ethics and dissemination: 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. Trial registration numbers: EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377 ); Dutch trial registry (NTRID6417).