Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: Protocol for the pragmatic randomised non-inferiority LADI study
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).
|Keywords||adverse events, clinical trials, gastroenterology, health economics, inflammatory bowel disease, statistics & research methods|
|Persistent URL||dx.doi.org/10.1136/bmjopen-2019-035326, hdl.handle.net/1765/127547|
Smits, L.J.T. (L. J.T.), Pauwels, R.W.M. (R. W.M.), Kievit, W, De Jong, D.J, de Vries, A.C, Hoentjen, F, & Van Der Woude, C.J. (C. J.). (2020). Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: Protocol for the pragmatic randomised non-inferiority LADI study. BMJ Open, 10(5). doi:10.1136/bmjopen-2019-035326