P682 Development of anti-ustekinumab antibodies is an independent factor associated to loss of response to ustekinumab therapy in IBD patients

Abstract

Abstract Background Monitoring of antibodies (ADA) under ustekinumab therapy in routine practice is not recommended in IBD patients. Aim of study to investigate the relationship between ADA detected by a drug-tolerant assay and loss of response to therapy in a cohort of IBD patients treated with ustekinumab. Methods This was a retrospective study enrolling consecutively all adult patients with moderate to severe active IBD and having a follow up period of at least 2 years after ustekinumab induction. Loss of clinical response was defined as CDAI > 220 or HBI > 4 for CD and partial Mayo subscore > 3 for UC associated with the decision to modify disease management or treatment. Results Ninety patients were included (78 CD and 12 UC, mean age 37 years). Median levels of anti-ustekinumab antibodies (AUA) were significantly higher in patients with LOR compared with those in responder patients (15.2 µg/mL-eq CI (7.9-21.5) and 4.7 µg/mL-eq CI (2.1-10.5), respectively; p=0.04). The area under the ROC curve (AUROC) for AUA in predicting LOR was 0.76. The optimal cut-off point capable to accurately identify patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80 % and specificity of 85 %. In multivariate analysis, serum AUA ≥ 9.5 µg/mL-eq (HR=0.84), prior vedolizumab exposition (HR=0.78) and azathioprine (HR=3.78) exposures were the only independent factors associated with subsequent clinical response to ustekinumab therapy. Table 1 : univariate and multivariate analysis to isolate factors associtaed with subsequent clinical response to ustekinumab therapy Conclusion In our real-life cohort, AUA was identified as an independent predictor of LOR and subsequent drug failure to treatment