Does HLA-DQA1*05 carriage have a greater impact on the outcome of infliximab therapy for isolated small-bowel Crohn's disease?

Abstract

Carriage of HLA-DQA1*05 is thought to increase the formation of anti-tumour necrosis factor alpha (TNF-α) antibodies, reducing the drug efficacy in Crohn's disease (CD) patients. However, little data are currently available for small-bowel Crohn's disease (SB-CD). A specific assessment of the impact of HLA-DQA1*05 on the clinical response to treatment with infliximab (IFX), a TNF-α antagonists, in SB-CD patients is necessary. We conducted a single-center retrospective study that included 106 SB-CD patients treated with IFX. The serum samples were collected for antibodies to infliximab (ATI) testing and HLA-DQA1*05 genotyping. Double-balloon enteroscopy (DBE) was performed following the IFX treatment, with endoscopic outcomes evaluated using the partial simple endoscopic score for CD (pSES-CD), whereas the clinical response was assessed with the Crohn's disease activity index (CDAI). Multivariate logistic regression and multivariate COX regression analyses were employed to analyze the correlation of the HLA-DQA1*05 genotypes with other clinical variables. In this study, 30.2% of SB-CD patients carried the HLA-DQA1*05 allele, which significantly increased their risk of ATI generation (odds ratio [OR]=2.337, p=.043), but it was not associated with the clinical response to IFX and drug persistence (OR=2.356, p=.145; OR=0.457, p=.249). The endoscopic remission rates were 40.6% (13/32) and 55.4% (41/74) in HLA-DQA1*05 carriers and non-carriers, respectively. HLA-DQA1*05 was not associated with endoscopic remission (OR=0.684, p=.414). The HLA-DQA1*05 variant is identified as a significant risk factor of ATI formation in Chinese patients with SB-CD, but is not associated with the clinical response of IFX treatment and endoscopic remission of SB lesions.