Influence of HLADQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring: A Retrospective Cohort Study

Abstract

Background Carriers of the human leucocyte antigen variant HLADQA1*05 (rs2097432) are at risk of developing antibodies against infliximab and adalimumab with reduced tumor necrosis factor (TNF) antagonist persistence. The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed. Methods We conducted a retrospective single-center cohort study including patients with inflammatory bowel disease starting anti-TNF therapy between January 2017 and March 2021. Proactive therapeutic drug monitoring was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, followed by dose optimization. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis. Results A total of 112 patients were included, 52 (46.4%) HLA-DQA1*05 carriers, with a median follow-up of 73.9 (interquartile range, 35.4-133.1) weeks. Combination therapy with thiopurines was more frequent among HLA-DQA1*05 noncarriers (28 [46.7%] vs 12 [23.1%]; P = .01). Clinical remission rates at week 14 (77.9% vs 73.9%; P = .69) and 56 (73.2% vs 68.4%; P = .64) were similar between HLA-DQA1*05 noncarriers and carriers. Drug persistence was higher among HLA-DQA1*05 carriers (hazard ratio [HR], 0.32; 95% confidence interval, 0.14-0.71; P = .01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (HR, 4; 95% confidence interval, 1.7-9.7) as a risk factor and HLA-DQA1*05 carriers (HR, 0.31; 95% confidence interval, 0.12–0.81) as a protective factor of treatment cessation. Conclusion In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not associate a higher risk of treatment cessation nor worse clinical outcomes.

A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

“…This suggests that PTDM may overcome the anticipated reduction in treatment survival expected in HLA-DQA1*05 carriers. In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not appear to be associated with a higher risk of treatment cessation or worse clinical outcomes [348].…”

A Review of Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Combination Therapy

“…In a post hoc analysis of the precision infliximab trial, HLA-DQA1*05 carriage was not associated with ADA formation or higher drug durability [68]. Another single-center retrospective cohort suggests that carriers of this genotypic variant under a proactive TDM strategy are not associated with a higher risk of treatment cessation or worse clinical outcomes [69]. Proactive TDM may be a better predictor of immunogenicity, but larger prospective studies are needed to confirm this.…”