P0523 Comparative analysis of two ELISA methods for measuring serum ustekinumab levels in Inflammatory Bowel Disease ¿Is interchangeability feasible?
Authors: Dueñas-Prieto L , Cabrera-Marante Ó , Algara M , Alfocea-Molina Á , Rafael de la Cruz D , Garcinuño S , Masedo Á , Yela C , López F , Olmedo C , Casis B , Gonzalez Lama MD- PhD Y 
Published: January 2025

Background

Ustekinumab (UTK) is a recently introduced biologic therapy for inflammatory bowel disease (IBD), and consequently, the clinical use of UTK trough concentrations is less standardized compared to other biologic therapies. Therefore, accurate measurement of serum UTK levels is essential for adjusting treatment efficacy. The objective of the present study is to compare two enzyme-linked immunosorbent assay (ELISA) methods to evaluate their correlation, concordance, and systematic bias, given the variability between methods.

Methods

The study assessed the correlation and the agreement between two different methods available for UTK measurement. Thirty-six blood samples from different patients, which had a previous diagnosis of IBD, were analyzed. All patients were recruited from September to November 2024 from the autoimmunity laboratory of the Hospital Universitario 12 de Octubre, Madrid. Serum UTK levels were measured using the two ELISA techniques: IDKmonitor® ELISA assay (Immundiagnostik AG; Bensheim, Germany) (T1) and the alternative Promonitor® ELISA assay (Grifols; Barcelona, Spain) (T2). Measurements were further categorized into therapeutic ranges for response classification: non-responders (0–1 µg/mL), clinical response (1–4.5 µg/mL), and endoscopic response (&gt;4.5 µg/mL).

Results

A strong linear correlation was observed between the two methods (Pearson’s r = 0.9693, p &lt; 0.0001, R² = 0.9395), confirming a proportional relationship despite systematic differences. Lin’s concordance coefficient was moderate-to-good (0.7025), indicating agreement despite systematic differences. Bland-Altman analysis revealed a mean difference of 2.79, with increasing variability at higher concentrations, consistent with proportional error. Passing-Bablok regression revealed a systematic bias, indicating an overestimation by the Promonitor-Grifols ELISA: the slope was 1.4342 (95% CI: 1.2530–1.6387) and the intercept 1.2591 (95% CI: 0.7591–1.8309). Considering these results, a linear regression adjustment was conducted. Categorization into therapeutic ranges revealed poor concordance between the methods (Kappa index = 0.28), suggesting that systematic errors substantially affect clinical interpretation. T2 consistently assigned higher therapeutic ranges, potentially impacting treatment decisions.

Conclusion

While the two ELISA methods show strong correlation, moderate concordance and significant systematic biases limit their interchangeability. Adjustment strategies should be adopted to harmonize results and ensure reliable therapeutic decisions in IBD management.

References

- Kwon Y, Kang B, Kim ES, Choe YH, Kim MJ. Comparison of Ustekinumab Trough Concentrations Measured by 2 ELISA Kits and Evaluation of Clinical Response in Crohn’s Disease. Ther Drug Monit. 2022;44(4):535-542. doi:10.1097/FTD.0000000000000976

- Rodríguez-Moranta F, Argüelles-Arias F, Hinojosa Del Val J, et al. Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU). Gastroenterol Hepatol. 2024;47(5):522-552. doi:10.1016/j.gastrohep.2024.01.007