Development and Validation of an Interleukin-6 Nomogram to Predict
Primary Non-response to Infliximab in Crohn’s Disease Patients: From
Bedside to Bioinformatics.
Background: The primary nonresponse (PNR) rate of Infliximab (IFX)
varies from 20% to 46% for the treatment of Crohn’s disease (CD).
Detected PNR reduces the improper use of specific treatments. To date,
there is hardly any knowledge regarding early markers of PNR. The aim of
this study was to evaluate the role of Interleukin-6 (IL-6) as an early
predictor of PNR of IFX for the treatment of CD. Methods: We enrolled
322 bio-naïve patients diagnosed with CD from January 2016 to May 2020.
Primary response was determined at week 14. Multivariable logistic
regression was used to construct prediction models. The discrimination,
calibration and clinical validity of the models in the validation cohort
were assessed by area under the curve (AUC), calibration and decision
curves analyses. GEO data were analyzed to identify potential mechanisms
of IL-6 in IFX therapy for CD. Results: PNR occurred in 31.06% (100 of
322) patients who were assessable at week 14. IL-6 levels significantly
decreased after IFX therapy (P < 0.001). The validation model
containing IL-6 presented enhanced discrimination with an AUC of 0.908
and high calibration. Decision curve analysis (DCA) indicated that the
model added extra predictive value. GEO data confirmed the IL-6 levels
were increased in the PNR group and IL-6-related differently expressed
genes (DEGs) were enriched in the inflammatory response. Conclusion: We
concluded that IL-6 may be used as a predictive factor to assess the
risk of PNR to IFX therapy.