P640 Role of vedolizumab trough levels in predicting clinical response in Inflammatory Bowel Disease: a multicentre prospective study

Abstract

Abstract Background Medical treatment of Inflammatory Bowel Diseases (IBD) has developed aiming at a target-therapy using molecular-targeted drugs, such as vedolizumab (VDZ), recommended in moderate to severe forms of IBD refractory to conventional therapy. Considering the low rate of clinical remission after 12 months of treatment (about 30%) and its cost, it is important to identify predictors of clinical efficacy: therapeutic drug monitoring (TDM) based on measuring VDZ trough levels (TL) and circulating neutralizing antibodies could be useful in this setting. This prospective study aims at evaluating the association between VDZ TLs at week 24 and clinical and biochemical disease activity at the same timepoint and at week 52, in order to identify if these levels can predict 12-months clinical remission Methods The study has included patients who started VDZ treatment from 2016 to 2022 at two IBD centres (Turin and Pisa). Patients were monitored through clinical scores (HBI and PMS) and laboratory tests (haemoglobin, CRP, faecal calprotectin) at the beginning of treatment, at 6, at 12-months; TDM has been performed at month 6; response to the treatment and clinical remission have been defined according to IOIBD criteria after 6 and 12 months Results All of 40 patients included (16 CD, 24 UC) have undergone a follow-up at month 6, while only 35 have been to an annual evaluation. At the beginning of treatment the clinical disease activity was moderate (HBI mean 7.5; PMS mean 4.9), it became mild at the second timepoint (HBI mean 3.5; PMS mean 2.5) and was found to be mild or in remission after a year (HBI mean 3.6; PMS mean 1.5). The response rate (77%) and clinical remission rate (63%) at 6 and 12-months have been steady over time. TDM has found a mean of VDZ TLs of 79.3 μg/ml (SD 51.3) and no anti-VDZ antibodies. 12-months clinical remission has been tested through logistic regression in order to identify predictive factors: it was inversely proportional to PMS (OR 0.47; p 0.02) and abnormal CRP levels (OR 0.24; p 0.04) at 6-months and directly associated with haemoglobin concentration at 0 (OR 2.14; p 0.04) and 6-months (OR 1.86; p 0.02). As to TDM, VDZ TLs at the second timepoint were positive predictors of symptoms remission at the next timepoint (OR 1.02; p 0.03): higher concentrations at 43.1 μg/ml were associated with clinical remission (AUC 0.69; p 0.03) and were positively correlated with laboratory tests, such as haemoglobin (r 0.36; p 0.03) Conclusion Response to VDZ at the end of the year can be predicted after the first 6 months with clinical evaluation and laboratory tests, as well as TDM: lower PMS, higher haemoglobin, quiescent inflammatory biomarkers together with higher VDZ TLs allow to identify who will achieve clinical remission.