HLA-DQA1*05 risk variant carriage does not affect the development of antidrug antibodies (ADA) in patients with inflammatory bowel disease (IBD) receiving infliximab, according to a study in Gastroenterology.

Researchers sought to determine whether the HLADQA1*05 variant affects immunogenicity when a proactive, dose-optimization strategy is used during induction of infliximab. The prospective Precision IFX trial (ClinicalTrials.gov Identifier: NCT02624037) used a dashboard-guided dosing strategy, which would recommend a dose and interval schedule to allow for achievement of a prespecified target trough concentrations.

The participants (N=186; median age, 17 years; 52% men; 81% White) had active IBD, were scheduled for induction infliximab treatment, and were evaluated for 12 months or until drug withdrawal. The primary outcome was the proportion of patients prescribed accelerated dosing at infusion 3 or 4 based on a priori trough concentrations. Secondary outcomes included ADA development and infliximab durability.


Continue Reading

The post-hoc analysis of Precision IFX was conducted in participants from the Personalising Anti-TNF Therapy in Crohn Disease study with use of the RiskImmune test (Prometheus Laboratories). Analyses were performed per protocol for the entire cohort and in participants beginning infliximab monotherapy (n=159).

The proportion of participants (90% on monotherapy) with immunogenicity was low, with 12% (23/186) having ADA by 1 year and 83% (19/23) occurring with a nontherapeutic drug concentration. HLA-DQA1*05 variant carriage in the full cohort was 46%. Risk variant carriage was not associated with immunogenicity (P =.50), with 9/23 (39%) participants with the risk variant having ADA vs 14/23 (61%) without the variant.

In addition, 10 patients discontinued infliximab due to a high level of ADA, and 50% of these were risk variant carriers (P =.78). Hispanic ethnicity was the only demographic variable associated with immunogenicity (P =.02).

The rates of ADA formation and infliximab durability were not significantly different between carriers and noncarriers. The rate of ADA formation was significantly faster in participants who did not achieve the target level, but durability was not different between these groups in a comparison of those who did and did not achieve the infusion 3 target trough level.

Cox proportional hazard analysis showed that achievement of the target trough level at infusion 3 was associated (achieving target level hazard ratio [HR], 5.0; 95% CI, 1.8-13.7) with the rate of immunogenicity. HLA variant carriage (noncarrier HR, 0.7; 95% CI, 0.3-2.0) did not significantly affect the immunogenicity rate when accounting for achievement of infusion 3 trough level. Additionally, ADA levels were not significantly different between those who had the risk variant and those who did not have the variant (P =.12). These findings were consistent in participants receiving infliximab monotherapy.

“While our study is limited by its post-hoc design and one year follow-up, it warrants further investigation into the impact of risk variant carriage in the setting of early proactive dose optimization,” the investigators stated.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Spencer EA, Stachelski J, Dervieux T, Dubinsky MC. Failure to achieve target drug concentrations during induction and not HLA-DQA1*05 carriage is associated with anti-drug antibody formation in patients with inflammatory bowel disease. Gastroenterol. Published online January 10, 2022. doi: 10.1053/j.gastro.2022.01.009