Clinical and genetic factors associated with clinical relapse during anti-tumor necrosis factor therapy in Japanese patients with Crohn’s disease

Abstract

Background: Little is known about clinical and genetic factors that predict the long-term response of anti-TNF therapy are limited in Japanese patients with Crohn’s disease (CD). Methods: Association between clinical factors and cumulative clinical relapse-free rates were investigated in 464 patients with CD (373 anti-TNF naïve and 91 anti-TNF switch patients). A genome-wide association study (GWAS) was performed using Cox proportional hazards model. Genotype data of 5,657,947 SNPs from 275 anti-TNF naïve patients were used for GWAS. Results: Lower serum albumin level, perianal disease, and younger age at disease onset were identified as risk factors for earlier clinical relapse in the anti-TNF naïve group (hazard ratio: HR = 1.76, 1.43, and 1.36; P = 0.00029, 0.044, and 0.045, respectively). Previous intestinal resection was associated with clinical relapse in the anti-TNF switch group (HR = 0.42; P = 0.0075). In the GWAS, rs12613485, which is located between RFX8 and MAP4K4, showed the strongest association with relapse (HR = 2.44; P = 3.42E-7). Pathway analysis indicated the association of the TGF-β signaling pathway (P = 3.06E-4). Conclusions: We identified several reasonable clinical factors and candidate genetic factors associated with early relapse during anti-TNF treatments in Japanese CD patients.