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P361 Laboratory criteria of infliximab therapy inefficiency in children with IBD

A. Potapov*1, T. Radigina2, S. Petrichuk2, D. Gerasimova2, A. Illarionov1,3, A. Anushenko1, T. Erlikh-Fox4

1National Medical Research Center for Children's Health, Gastroenterology and Hepatology, Moscow, Russian Federation, 2National Medical Research Center for Children's Health, Laboratory of Experimental Immunology and Virology, Moscow, Russian Federation, 3Sechenov First Moscow State Medical University, Department of Peliatrics and Rheumatology, Moscow, Russian Federation, 4National Medical Research Center for Children's Health, Cytochemical Research Center, Moscow, Russian Federation

Background

Our aim was to identify the value of the laboratory criteria such as residual level of infliximab (IFX) in blood, antibodies to IFX and circulating cytokine levels in the prognosis of the effectiveness of the therapy in children with IBD.

Methods

Were included in the study 75 children with IBD (31 patients with UC and 44 patients with CD) aged 4–18 years who were treated with IFX. Clinical response was evaluated according PUCAI (UC) and PCDIA (CD) scores. Blood samples were taken 8 weeks after the last infusion of IFX. Residual levels of IFX (Q-IFX) in serum and IFX antibodies (ATI) were assessed by enzyme immunoassay using Shikari Q-INFLIXI, Q-ATI (Turkey) kits. The cytokine levels were measured by multiplex analysis using HumanThl7 MagneticBead Panel (MilliplexMapKit, Germany). Evaluation of the statistical significance was performed using nonparametric Mann–Whitney test and ROC-analysis.

Results

There were observed increase in the inflammatory activity according to PUCAI and PCDIA scores (p = 0.000) in children with the loss of response to IFX. In patients with the loss of the effect to IFX (Group 1) there was a significant decrease Q-IFX compared with a group of children with persistent positive effect (Group 2) in both diseases CD (p = 0.002) and UC (p = 0.019). ROC analysis showed that the cut-off level for patients with UC is 2.55 μg/ml (AUC = 0.813; sensitivity (Se) 64%, specificity (Sp) 92%), and for children with CD 2.21 μg/ml (AUC=0.813; Se 79%, Sp 78%). In the examined patients, IFX antibodies were detected in 17% cases, and the fast formation of IFX antibodies were associated to the younger age of children (R = 0.58). In one patient with a persistent positive effect for 5 years of therapy, the values of Q-IFX were in the range from 4.9 to 9.4 μg/ml in the absence of IFX antibodies. Cytokine analysis revealed significant differences between examined groups in the level of proinflammatory cytokines: IL-23, IL-27, IL-22, INF-γ, TNFα. ROC analysis revealed good quality TNFα as the separation model, the cut-off level was 13.4 pg/ml (AUC = 0.843; Se = 77%, Sp = 79%).

Conclusion

The reduction of the Q-IFX in children with UC below 2.55 μg/ml and in children with CD below 2.21 μg/ml, leads to the decrease of the therapy effect and can adduct to the exacerbation of the disease. These findings correlate with the results obtained in adults (>2 µg/ml, C. Moore et al., 2016). TNFα level (>13.4 pg/ml) can serve as the laboratory criterion of loss of effect from IFX. Elevated levels of proinflammatory cytokines correlates with the lower Q-IFX and loss of the therapy effect.