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Real-world endoscopic and histologic 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 PK-PD relationship of ustekinumab (UST) in UC patients, and whether serum UST concentrations reflect tissue drug exposure. We aimed to study UST serum concentrations and its relation to tissue exposure and drug effectiveness in a real-world setting.


METHODS
Forty-two UC patients starting UST were prospectively followed by clinical, endoscopic and histological assessments at week 16. Histologic remission was defined as Nancy histology index of 0. Analogous to the UNIFI program, histo-endoscopic mucosal improvement was defined as a combination of histologic improvement (Geboes ≤3.1) and endoscopic improvement (MES ≤1). Paired trough serum sample and colonic mucosal biopsies were collected for UST levels measurement.


RESULTS
After 16 weeks [IQR 15.8 - 16.4] of therapy, histologic 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 didn't. Patients with shorter disease duration and clinical response at week 8 had higher odds to achieve histologic remission. UST concentrations from paired serum and biopsy samples revealed a strong positive correlation (r = 0.88, p < 0.001), both in inflamed and uninflamed tissue.


CONCLUSION
In this real-word cohort of refractory UC patients initiating UST, more than a third of the patients achieved histologic 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.