Real-world Endoscopic and Histological Outcomes Are Correlated with Ustekinumab Exposure in Patients with Ulcerative Colitis

Background Histo-endoscopic outcomes are being proposed as new treatment targets in ulcerative colitis [UC]. Little is known about the pharmacokinetic-pharmacodynnamic [PK-PD] relationship of ustekinumab [UST] in UC patients or whether serum UST concentrations reflect tissue drug exposure. We aimed to study UST serum concentrations and their relation to tissue exposure and drug effectiveness in a real-world setting. Methods A total of 42 UC patients starting UST were prospectively followed by clinical, endoscopic and histological assessments at Week 16. Histological remission was defined as Nancy Histology Index of 0. Analogous to the UNIFI programme, histo-endoscopic mucosal improvement was defined as a combination of histological improvement [Geboes <= 3.1] and endoscopic improvement [MES <= 1]. Paired trough serum samples and colonic mucosal biopsies were collected for UST levels measurement. Results After 16 weeks [IQR 15.8-16.4] of therapy, histological remission and histo-endoscopic mucosal improvement were observed in 19 [45%] and 18 [43%] patients, respectively. Patients who achieved these outcomes had higher serum UST levels than those who did not. Patients with shorter disease duration and clinical response at Week 8 had higher odds to achieve histological remission. UST concentrations from paired serum and biopsy samples revealed a strong positive correlation [r = 0.88, p < 0.001], in both inflamed and uninflamed tissue. Conclusions In this real-world cohort of refractory UC patients initiating UST, more than a third of the patients achieved histological remission. A drug exposure-response relationship was observed for histo-endoscopic outcomes, with no added value of measuring tissue exposure given the strong correlation with serum exposure.