Predictive value of the combination of infliximab trough levels and C reactive protein in secondary loss of response to infliximab after induced remission

Abstract

Objective To evaluate the role of infliximab trough levels (IFX-TL) and C reactive protein (CRP) concentration in prediction secondary loss of response (LOR) to infliximab (IFX) in patients with Crohn′s disease (CD) during IFX maintenance therapy since 14 weeks after induced treatment. Methods From November 2015 to October 2016, 43 CD patients received IFX treatment were enrolled. IFX was initially given at zero, two, and six weeks at 5 mg/kg as induced therapy, and then the same dose was given every eight weeks as long-term maintenance treatment. Serum IFX-TL and CRP concentration were measured at 14th week after the first IFX injection. The disease activity of CD was assessed by the Harvey-Braddshaw index. According to the follow-up results, the enrolled patients were divided into LOR group and continuous response group, and then the differences in IFX-TL and CRP concentrations at the 14th week after induced therapy were compared between two groups. Mann-Whitney U test and receiver operating characteristic (ROC) curve were performed for statistical analysis. Results After a median 54 weeks of follow-up, 18 (41.9%) of 43 CD patients achieved a sustained response to IFX therapy, while 11 patients (25.6%) were LOR to IFX therapy. At the 14th week after induced therapy, serum IFX-TL of LOR group was 2.30 μg/mL (0.52 μg/mL, 2.92 μg/mL), which was lower than that of continuous response group (5.10 μg/mL (3.54 μg/mL, 9.34 μg/mL)), and the difference was statistically significant (Z=-3.236, P=0.001). The CRP concentration of LOR group was 3.10 mg/L (0.38 mg/L, 21.70 mg/L), which was higher than that of continuous response group (0.51 mg/L (0.27 mg/L, 1.50 mg/L)), and the difference was statistically significant (Z=-1.732, P=0.015). The results of ROC curve analysis indicated that at 14th week after induced therapy the area under curve (AUC) value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864 (95% confidence interval (CI) 0.728 to 0.999), sensitivities were 83.3% and 81.8%, specificities were 94.4% and 54.5%, cut-off values of accuracies were 3.115 μg/mL and 5.93 mg/L. Conclusion IFX-TL 5.93 mg/L at 14th week since IFX induced therapy might be used as effective predictors of LOR in CD patients during maintenance therapy. Key words: Crohn disease; C reactive protein; Infliximab, trough levels; Loss of response