Biomarkers to predict the efficacy of Infliximab in the Patients with Inflammatory Bowel Disease

抄録

Background : Infliximab (IFX) is one of therapeutic antibodies targeting to tumor necrosis factor alpha (TNF). It is commonly used against autoimmune disorders such as inflammatory bowel disease (IBD) including Crohn's disease and Ulcerative colitis. However, the production of anti-drug antibodies (ADAs) due to its immunogenicity is one of the problems in the clinical use of IFX. ADA binds to IFX to decrease blood concentration of IFX, and causes the loss of response. In this study, we examined serum levels of IFX, TNF and ADA against IFX in IBD patients to identify the biomarkers predicting the efficacy of IFX.

Methods : Eighty-eight Japanese patients with IBD at Kyoto University Hospital were enrolled in this study. Serum IFX levels were determined by LC-MS/MS (LCMS-8040, Shimadzu) with nano-surface and molecular-orientation limited (nSMOL) proteolysis . Serum TNF and ADA were detected by the Enzyme Linked Immunosolvent Assay (R&D Systems and Somru Bioscience, respectively).

Results : A large variation was observed in serum concentrations of IFX among the patients. ADAs were detected in 6 patients whose IFX levels were extremely low. Some of the patients with lower IFX levels exhibited higher CRP levels. TNF was also detected in most patients, and some patients with higher TNF levels exhibited higher CRP levels. We classified the patients into four groups; (1) IFX-high & TNF-high, (2) IFX-low & TNF-high, (3) IFX-high & TNF-low and (4) IFX-low & TNF-low. IFX-high & TNF-low group showed favorable outcomes by the IFX therapy, compared with the patients in other three groups.

Conclusions : IFX and TNF levels in the blood would be a good marker to represent the efficacy of IFX treatment. Monitoring of IFX levels is useful to obtain optimal treatment strategies for each patient with IBD.