P1064 Association of subcutaneous infliximab CT-P13 serum levels and therapeutic outcomes in patients affected by Inflammatory Bowel Disease: A retrospective international multicentric study
Authors: Centritto A , Samaan M , Ward M , Van Wees J , Outtier A , Ferrante M , Novak G , Šubic Ž , Papamichail K , Irving P M ,   spECTRUM
Published: January 2025

Abstract

Background
The association between therapeutic outcomes and serum levels associated with the use of subcutaneous (SC) IFX CT-P13 in patients with inflammatory bowel disease [IBD] has been poorly studied. We aimed to define SC-IFX thresholds associated with therapeutic outcomes.

Methods
Patients receiving SC-IFX who had at least one therapeutic drug monitoring [TDM] were enrolled. Therapeutic outcomes were assessed as follows: clinical remission [HBI &lt;5, SCCAI ≤2]; fecal calprotectin [FCAL] remission [&lt;250 mg/g]; C-reactive protein [CRP] remission [CRP &lt;5 mg/L]; deep remission [clinical + biomarker remission]. Chi-squared test for trend was used to analyze serum levels quartile data.

Results
177 patients [54% male; 67% Crohn’s disease; Weight ≥ 80 kg 51%; 7% active smoker; 39% on immunosuppressants [IMM]; 9% on steroids; 26% with previous biologic exposure] from 4 centres had a total of 263 TDM measurements. Of these, were available 242 concurrent clinical measurement, 244 CRP and 152 FCAL.Median duration of SC treatment at time of TDM was 24 months (4-135). Proportion of patients achieving outcomes is described in table 1. The median IFX serum level was significantly higher in patients with clinical remission as well as in those with clinical and CRP remission (Figure 1), compared with patients who did not reach these targets. Conversely, there was no significant difference for the FCAL, clinical and FCAL, clinical and CRP and FCAL outcomes. In univariate analysis of factors associated with clinical remission (p&lt;0.1) were sex, concomitant IMM, concomitant steroids, and previous biologic exposure and were included in a multivariate analysis in which only concomitant IMM showed remained significant [OR 0,1796 CI 95% 0,028-0,633]. Quartile analysis showed better outcome on higher drug levels for clinical remission, but not for other outcomes. Based on the ROC analysis and the Youden index, the cut-off levels for the therapeutic outcomes were respectively: clinical remission 12.85 mg/ml [sensitivity 0.85, specificity 0.5]; FCAL remission 11.8 mg/ml [sensitivity 0.82, specificity 0.32]; clinical and CRP remission 14.55 mg/ml [sensitivity 0.77, specificity 0.44]; clinical and FCAL remission 12.05 mg/ml [sensitivity 0.85, specificity 0.35]; clinical, CRP and FCAL remission12.05 mg/ml [sensitivity 0.85, specificity 0.33].

Conclusion
An association between drug levels and clinical outcomes was identified in patients with IBD treated with SC IFX. Clinical remission was associated with a level of 12.8 mg/ml but the association between higher drug levels and deeper remission that has been described previously was not seen.

References
Roblin X, Nancey S, Papamichael K, et al. Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(5):679-685. doi:10.1093/ecco-jcc/jjad188
Iborra M, Caballol B, Garrido A, et al. Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry. J Crohns Colitis. Published online August 22, 2024. doi:10.1093/ecco-jcc/jjae127