Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun;69(6):2165-2174.
doi: 10.1007/s10620-024-08410-z. Epub 2024 Apr 9.

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

Reinier C A van Linschoten #  1   2 , Fenna M Jansen  3 , Renske W M Pauwels  1 , Lisa J T Smits  3 , Femke Atsma  4 , Wietske Kievit  5 , Dirk J de Jong  3 , Annemarie C de Vries  1 , Paul J Boekema  6 , Rachel L West  2 , Alexander G L Bodelier  7 , Ingrid A M Gisbertz  8 , Frank H J Wolfhagen  9 , Tessa E H Römkens  10 , Maurice W M D Lutgens  11 , Adriaan A van Bodegraven  12 , Bas Oldenburg  13 , Marieke J Pierik  14 , Maurice G V M Russel  15 , Nanne K de Boer  16 , Rosalie C Mallant-Hent  17 , Pieter C J Ter Borg  18 , Andrea E van der Meulen-de Jong  19 , Jeroen M Jansen  20 , Sita V Jansen  21 , Adrianus C I T L Tan  22 , C Janneke van der Woude #  1 , Frank Hoentjen #  23   24 ; LADI study group, the Dutch Initiative on Crohn, Colitis (ICC)
Affiliations

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

Reinier C A van Linschoten et al. Dig Dis Sci. 2024 Jun.

Abstract

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.

Keywords: Adalimumab; Biologics; Crohn’s disease; Dose de-escalation.

PubMed Disclaimer

Conflict of interest statement

FMJ has received a research grant from ZonMW. DJdJ has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Galapagos and held leadership roles in the Dutch Initiative on Crohn and Colitis and the IBD workgroup of the Dutch Gastroenterology Society. ACdV has received research grants from Takeda, Janssen and Pfizer. RLW has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ferring, Pfizer, Galapagos, AbbVie and Janssen. TEHR payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie and has participated in the advisory board for Galapagos. MWMDL has received a grant for podcasts from Pfizer, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Jansen-Cilag and Galapagos, participated in advisory boards of BMS and Galapagos, and held leadership roles in the Elisabeth Twee Steden Ziekenhuis. AAvB has received research grants from Pfizer, Teva and ZonMW, consulting fees from Ferring, Galapagos, AbbVie and BMS, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ferring, Galapagos and Janssen, support for attending meetings from Janssen, and held leadership roles in committees of the Dutch Gastroenterology Society and National Federation of Medical Specialists. BO has received research grants from Galapagos, Takeda, Ferring and Celltrion, has received consulting fees from AbbVie, Galapagos, Pfizer, Ferring, Takeda and Janssen, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Takeda, Galapagos, AbbVie and Ferring and was chairman of the IBD committee of the Dutch Association of Gastroenterology (NVMDL). MJP has received consulting fees from Takeda, Janssen, Galapagos and AbbVie and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Janssen. NKdB has served as a speaker for AbbVie, Takeda and MSD. He has served as consultant and principal investigator for Takeda and TEVA. He has received research grants from Dr. Falk, Takeda, TEVA and MLDS. All outside the submitted work.RMH has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ITS and is a member of the national IBD committee of the Dutch Association for Gastroenterology and Hepatology. AEvdMdJ has received research grants from Galapagos, nestle, Cablon and Norgine, has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Galapagos, Tramedico and Janssen-Cilag, and has participated in an advisory board for Ferring. CJvdW has received funding for the present study from ZonMW, has received research grants from ZonMW, Falk and Pfizer, has received consulting fees from Janssen, Galapagos, and Pfizer, has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Ferring and AbbVie and had leadership roles in the European Crohn’s & Colitis organisation, United European Gastroenterology council and the Dutch Association for Gastroenterology (NVGE). FH has received funding for the present study from ZonMW, has received research grants from Janssen, AbbVie, Pfizer and Takeda, and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Janssen, Takeda and Pfizer. RCAvL, RWMP, LJTS, FA, WK, PJB, AGLB, IAMG, FHJW, MGVMR, PCJtB, JMJ, SVJ, ACIATLT has nothing to disclose.

Figures

Fig. 1
Fig. 1
Apparent area under the receiver operating characteristic curves for the models predicting successful adalimumab interval increase. AUC Area under the receiver operating characteristic curve
Fig. 2
Fig. 2
Apparent calibration curves for the models predicting successful adalimumab interval increase
Fig. 3
Fig. 3
Optimism-corrected decision curves for the models predicting successful adalimumab (ADA) interval increase
See this image and copyright information in PMC

References

    1. Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut. 2007;56:1232–1239. doi: 10.1136/gut.2006.106781. - DOI - PMC - PubMed
    1. Singh S, Facciorusso A, Dulai PS, Jairath V, Sandborn WJ. Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2020;18:69–81.e3. doi: 10.1016/j.cgh.2019.02.044. - DOI - PMC - PubMed
    1. van Linschoten RCA, Visser E, Niehot CD, van der Woude CJ, et al. Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents. Aliment Pharmacol Ther. 2021;54:234–248. doi: 10.1111/apt.16445. - DOI - PMC - PubMed
    1. van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, et al. Increased versus conventional adalimumab dose interval for patients with Crohn’s disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. The Lancet Gastroenterology & Hepatology. 2023 doi: 10.1016/S2468-1253(22)00434-4. - DOI - PubMed
    1. Steyerberg EW, Eijkemans MJ, Harrell FE, Habbema DF. Prognostic Modeling with Logistic Regression Analysis In Search of a Sensible Strategy in Small Data Sets. Med Decis Making. 2001;21:45–56. doi: 10.1177/0272989X0102100106. - DOI - PubMed

Publication types

Associated data