Journal Article

PMO-41 Incorporating HLADQA105 in pre-biologic screening in IBD patients initiating biologic therapies

Stamp, Katie, Myers, Sally, Turnbull, Jack, Ramachandran, Sankaranarayanan, Sebastian, Shaji, Pattinson, Alison, Whitehead, Emma, Talbot, Alison, Gonzalez, Haidee Aleman

2021

Overview

IntroductionThe PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available.AimTo evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomesMethodsWe prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at 6 and 12 months. Secondary outcomes were steroid free remission at 6 and 12 months, use concomitant immunosuppression and proportion needing dose escalation.ResultsSeventy-six patients were included in analysis (UC= 32, CD=43, IBD-U =1). HLADQA1*05 was positive in 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in 44% of the whole cohort and in 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in 8 patients and secondary loss of response in 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in 10 (15.6%) patients with 7 out of 10 positive for HLADQA1*05. However, only 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at 6 months was recorded in 77.1% and 78% respectively. There was no significant difference in drug persistence rates at 6 months and 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure 2). Steroid free remission at 6 and 12 months was also similar irrespective of the variant status (Figure 3)Abstract PMO-41 Figure 1Initial Theraphy choiceAbstract PMO-41 Figure 2Treatment presistance with initial theraphy strategyAbstract PMO-41 Figure 3Steroid free remissionConclusionsChoice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: Biomarkers / Colitis / Crohn's disease / Histocompatibility antigen HLA / Immunogenicity / Immunosuppression / Induction therapy / Infliximab / Monoclonal antibodies / Patients / Remission / Remission (Medicine) / Steroids / Tumor necrosis factor-TNF / Tumor necrosis factor-α