TY - JOUR
T1 - A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn’s Disease
T2 - Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial
AU - van Linschoten, Reinier C. A.
AU - Jansen, Fenna M.
AU - Pauwels, Renske W. M.
AU - Smits, Lisa J. T.
AU - Atsma, Femke
AU - Kievit, Wietske
AU - de Jong, Dirk J.
AU - de Vries, Annemarie C.
AU - Boekema, Paul J.
AU - West, Rachel L.
AU - Bodelier, Alexander G. L.
AU - Gisbertz, Ingrid A. M.
AU - Wolfhagen, Frank H. J.
AU - Römkens, Tessa E. H.
AU - Lutgens, Maurice W. M. D.
AU - van Bodegraven, Adriaan A.
AU - Oldenburg, Bas
AU - Pierik, Marieke J.
AU - Russel, Maurice G. V. M.
AU - de Boer, Nanne K.
AU - Mallant-Hent, Rosalie C.
AU - ter Borg, Pieter C. J.
AU - van der Meulen-de Jong, Andrea E.
AU - Jansen, Jeroen M.
AU - Jansen, Sita V.
AU - Tan, Adrianus C. I. T. L.
AU - van der Woude, C. Janneke
AU - Hoentjen, Frank
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6
Y1 - 2024/6
N2 - Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377.
AB - Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn’s disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377.
KW - Adalimumab
KW - Biologics
KW - Crohn’s disease
KW - Dose de-escalation
UR - https://www.scopus.com/pages/publications/85189886768
U2 - 10.1007/s10620-024-08410-z
DO - 10.1007/s10620-024-08410-z
M3 - Article
C2 - 38594435
SN - 0163-2116
VL - 69
SP - 2165
EP - 2174
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 6
ER -