A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn's Disease: Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial

被引：1

作者：

van Linschoten, Reinier C. A. ^{[1
,3
]}

Jansen, Fenna M. ^{[2
]}

Pauwels, Renske W. M. ^{[1
]}

Smits, Lisa J. T. ^{[2
]}

Atsma, Femke ^{[4
]}

Kievit, Wietske ^{[5
]}

de Jong, Dirk J. ^{[2
]}

de Vries, Annemarie C. ^{[1
]}

Boekema, Paul J. ^{[6
]}

West, Rachel L. ^{[3
]}

Bodelier, Alexander G. L. ^{[7
]}

Gisbertz, Ingrid A. M. ^{[8
]}

Wolfhagen, Frank H. J. ^{[9
]}

Romkens, Tessa E. H. ^{[10
]}

Lutgens, Maurice W. M. D. ^{[11
]}

van Bodegraven, Adriaan A. ^{[12
]}

Oldenburg, Bas ^{[13
]}

Pierik, Marieke J. ^{[14
]}

Russel, Maurice G. V. M. ^{[15
]}

de Boer, Nanne K. ^{[16
]}

Mallant-Hent, Rosalie C. ^{[17
]}

ter Borg, Pieter C. J. ^{[18
]}

van der Meulen-de Jong, Andrea E. ^{[19
]}

Jansen, Jeroen M. ^{[20
]}

Jansen, Sita V. ^{[21
]}

Tan, Adrianus C. I. T. L. ^{[22
]}

van der Woude, C. Janneke ^{[1
]}

Hoentjen, Frank ^{[2
,23
]}

机构：

[1] Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[2] Radboud Univ Nijmegen Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands

[3] Franciscus Gasthuis & Vlietland, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[4] Radboud Univ Nijmegen Med Ctr, Radboud Inst Hlth Sci, Sci Ctr Qual Healthcare, Nijmegen, Netherlands

[5] Radboud Univ Nijmegen Med Ctr, Radboud Inst Hlth Sci, Dept Hlth Evidence, Nijmegen, Netherlands

[6] Maxima Med Ctr, Dept Gastroenterol & Hepatol, Eindhoven, Netherlands

[7] Amphia Hosp, Dept Gastroenterol & Hepatol, Breda, Netherlands

[8] Bernhoven Hosp, Dept Gastroenterol & Hepatol, Uden, Netherlands

[9] Albert Schweitzer Hosp, Dept Gastroenterol & Hepatol, Dordrecht, Netherlands

[10] Jeroen Bosch Hosp, Dept Gastroenterol & Hepatol, Shertogenbosch, Netherlands

[11] Elisabeth Twee Steden Ziekenhuis, Dept Gastroenterol & Hepatol, Tilburg, Netherlands

[12] Zuyderland Med Ctr, Dept Gastroenterol Geriatr Internal & Intens Care, Sittard Geleen Heerlen, Netherlands

[13] UMC Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands

[14] Maastricht Univ, Med Ctr, Dept Gastroenterol & Hepatol, Maastricht, Netherlands

[15] Med Spectrum Twente, Dept Gastroenterol & Hepatol, Twente, Netherlands

[16] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam Gastroenterol Endocrinol Metab Res Inst, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[17] Flevoziekenhuis, Dept Gastroenterol & Hepatol, Almere, Netherlands

[18] Ikazia Hosp, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[19] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands

[20] OLVG, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[21] Reinier de Graaf Gasthuis Delft, Dept Gastroenterol & Hepatol, Delft, Netherlands

[22] CWZ Hosp, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands

[23] Univ Alberta, Dept Med, Div Gastroenterol, Zeidler Ledcor Ctr 2 20A, 8540-112 St NW, Edmonton, AB T6G 2P8, Canada

来源：

DIGESTIVE DISEASES AND SCIENCES | 2024年

关键词：

Adalimumab; Crohn's disease; Dose de-escalation; Biologics;

D O I：

10.1007/s10620-024-08410-z

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：2165 / 2174

页数：10