BMJ Open (May 2020)

Lengthening adalimumab dosing interval in quiescent Crohn’s disease patients: protocol for the pragmatic randomised non-inferiority LADI study

  • ,
  • J Jansen,
  • L J T Smits,
  • R W M Pauwels,
  • W Kievit,
  • D J de Jong,
  • A C de Vries,
  • F Hoentjen,
  • C J van der Woude,
  • A.A. van Bodegraven,
  • A.G.L. Bodelier,
  • P.J. Boekema,
  • N. de Boer,
  • P.C.J. ter Borg,
  • A.A. den Broeder,
  • I.A.M Gisbertz,
  • F.M Jansen,
  • S.V. Jansen,
  • D.J. de Jong,
  • W. Kievit,
  • R.C.A. van Linschoten,
  • M Löwenberg,
  • M.W.M.D. Lutgens,
  • R.C. Mallant-Hent,
  • A.E. van der Meulen,
  • B. Oldenburg,
  • R.W.M. Pauwels,
  • M Pierik,
  • M.J.L. Romberg-Camps,
  • T.E.H. Römkens,
  • M.G.V.M. Russel,
  • L.J.T. Smits,
  • A.C.I.T.L. Tan,
  • M.L. Verhulst,
  • A.C. de Vries,
  • R.L. West,
  • F.H.J. Wolfhagen,
  • C.J. van der Woude

DOI
https://doi.org/10.1136/bmjopen-2019-035326
Journal volume & issue
Vol. 10, no. 5

Abstract

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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).