P2544 - Model-Informed Dosing Interval Extension of Infliximab in Patients With Inflammatory Bowel Diseases: Six Months Interim Analysis of the MODIFI Trial

Award: Presidential Poster Award

Zhigang Wang, MSc, PharmD¹, Ine De Greef, MS, MD¹, Wannee Kantasiripitak, MS, PhD¹, Sebastian G. Wicha, PhD², Sophie Tops, PhD¹, Melissa Nigro, MS³, An Outtier, PhD³, Debby Thomas, PhD¹, Séverine Vermeire, MD, PhD⁴, Marc Ferrante, MD, PhD³, Erwin Dreesen, PharmD; PhD^1
1Katholieke Universiteit Leuven, Leuven, Vlaams-Brabant, Belgium; ²Universität Hamburg, Hamburg, Hamburg, Germany; ³University Hospitals, Leuven, Vlaams-Brabant, Belgium; ⁴University Hospitals Leuven, Leuven, Vlaams-Brabant, Belgium

Introduction: Extending the infliximab (IFX) infusion interval has been attempted in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who sustained treatment response following an earlier interval shortening. We aimed to compare IFX interval extension based on therapeutic drug monitoring (TDM) with interval extension guided by a model-informed precision dosing (MIPD) software tool in patients with CD and UC.

Methods: MODIFI is a monocentric, open-label, historically controlled Phase 4 trial (NCT04982172). Eligible patients with steroid-free clinical and biological remission (two-item patient-reported outcome [PRO2] ≤1 for UC and ≤8 for CD, and C-reactive protein [CRP] < 5 mg/L and fecal calprotectin [FC] < 250 mg/kg) on less than 8-weekly IFX infusion schedules underwent interval extension to every eight weeks, guided by TDM (historical control) or MIPD targeting an IFX trough concentration (C_min) of 5 mg/L with ≥80% probability of target attainment (prospective intervention). The primary endpoint of relapse-free survival was evaluated at each study visit over 52 weeks. IFX concentrations were measured right before every infusion. Bayesian forecasting was performed using the TDMx Infliximab module (www.TDMx.eu).




Results: The study enrolled 23 adult patients in the TDM arm (12 CD, 11 UC) and 31 in the MIPD arm (20 CD, 11 UC). In total, 61% (n=14/23) and 61% (n=19/31) of patients in the TDM and MIPD arms, respectively, remained relapse-free until six months after IFX interval extension (Figure 1A).

The median 8-weekly IFX dose per kg bodyweight at screening was significantly higher in the MIPD arm (11.7 [interquartile range IQR 6.8–14.9] mg/kg) than in the TDM arm (6.7 [IQR 6.1–8.4] mg/kg) (p < 0.050). The median IFX C_min at baseline was significantly higher in the MIPD arm (9.2 [6.3–13.7] mg/L) than in the TDM arm (5.7 [4.2–9.1] mg/L) (p < 0.010). Following a single model-informed dose at baseline, the IFX C_min immediately decreased to median 5.9 mg/L [IQR 4.4–7.5 mg/L] with 65% of patients >5 mg/L (Figure 1B). MIPD resulted a high classification accuracy of 83% at the C_min target of 5 mg/L (the number of true positive and true negative predictions divided by the total number of predictions)

The median 8-weekly dose over six months was not significantly different between the MIPD and TDM arms (8.5 mg/kg [IQR 6.0–10.4] and 7.5 mg/kg [IQR 7.4–8.5], respectively).

Discussion: MIPD was equally effective as TDM to guide IFX interval extension in patients with CD and UC.



Disclosures:


Zhigang Wang, MSc, PharmD¹, Ine De Greef, MS, MD¹, Wannee Kantasiripitak, MS, PhD¹, Sebastian G. Wicha, PhD², Sophie Tops, PhD¹, Melissa Nigro, MS³, An Outtier, PhD³, Debby Thomas, PhD¹, Séverine Vermeire, MD, PhD⁴, Marc Ferrante, MD, PhD³, Erwin Dreesen, PharmD; PhD¹. P2544 - Model-Informed Dosing Interval Extension of Infliximab in Patients With Inflammatory Bowel Diseases: Six Months Interim Analysis of the MODIFI Trial, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.