P90 Tailoring the need for combination immunosuppressive therapy in IBD patients initiating anti-TNF agents using pre-biologic HLA-DQA1*05 screening: a prospective study

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Introduction Combination therapy using thiopurines or methotrexate is recommended to reduce the risk of immunogenicity in IBD patients treated with anti TNF agents. The PANTS study reported the association of HLA DQA1*05 carriage with development of anti-drug antibodies to anti TNFs in patients with Crohn`s disease. Since 2020, we have incorporated determination of HLA status in the pre-biologic screening of IBD patients. We aimed to evaluate persistence at 6 and 12 months in patients stratified to receive mono or combo therapy with anti TNFs Methods A prospective database of all IBD patients starting biologics was interrogated to select patients initiating on anti TNF agents. We excluded patients Crohn`s disease perianal fistula who had specific indication for combo therapy, patients with acute severe UC receiving accelerated induction those who were already on imunomodulators prior to initiation of anti TNF agents. Data was collected on demographics, disease characteristics, HLA DQA1*05 status, drugs levels and antidrug antibody status at week 6, week 14 and at least one time point during a 1 year maintenance period. The primary outcome was drug persistence at 12 months. Results One hundred and fifty six patients were initiated on anti TNFs during the study period. HLA DQA1*05 was positive in 59 (37.8%) of patients. These patients received combination therapy (Infliximab + thiopurines in 42, Infliximab plus methotrexate in 9, adalimumab plus azathioprine 6, Adalimumab plus methotrexate in 2). All patients negative for HLADQA1805 received monotherapy with infliximab (78) or adalimumab (19). Primary non response was identified in 30 patients (overall 19%, Monotherapy 17(17.5%), combo therapy 13 (22% ) and were switched to a non anti TNF agent Further 9% of patients had dose escalation due to suboptimal drug levels and partial response among whom 6 patients were switched to another class. Eleven patients stopped anti TNFs (4 and 7 in mono and combo therapy group respectively) due to intolerance and five patients discontinued immunomodulators in the combo therapy due to adverse effects. Anti-drug antibodies was detected at week 6 in 2 patients in the monotherapy group and 3 patients in combo therapy group (p=NS). There was no difference in rates of antidrug antibody development during maintenance period between the two groups. One hundred and twelve patients remained on anti TNFs across both groups at 12 months follow up. The overall drug persistence rates was similar in the mono and combination therapy group (66.1% vs 72.2%, p=NS). Conclusions HLA DQA1*05 status incorporated anti TNF treatment strategy may alleviate the need for combination therapy in IBD patients with no impact on development of anti-drug antibodies and drug persistence. A biomarker stratified randomised trial is recommended.

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