A disease model predicting placebo response and remission status of patients with ulcerative colitis using modified...

The Mayo Clinical Score is used in clinical trials to describe the clinical status of patients with ulcerative colitis (UC). It comprises four subscores: rectal bleeding (RB), stool frequency (SF), physician's global assessment, and endoscopy (ENDO). According to recent US Food and Drug Administration guidelines (Ulcerative colitis: developing drugs for treatment, Guidance Document, https://www.fda.gov/regulatory-information/s. 2022), clinical response and remission should be based on modified Mayo Score (mMS) relying on RB, SF, and ENDO. Typically, ENDO is performed at the beginning and end of each phase, whereas RB and SF are more frequently available. Item response theory (IRT) models allow the shared information to be used for prediction of all subscores at each observation time; therefore, it leverages information from RB and SF to predict ENDO. A UC disease IRT model was developed based on four etrolizumab phase III studies to describe the longitudinal mMS subscores, placebo response, and remission at the end of induction and maintenance. For each subscore, a bounded integer model was developed. The placebo response was characterized by a mono-exponential function acting on all mMS subscores similarly. The final model reliably predicted longitudinal mMS data. In addition, remission was well-predicted by the model, with only 5% overprediction at the end of induction and 3% underprediction at the end of maintenance. External evaluation of the final model using placebo arms from five different studies indicated adequate performance for both longitudinal mMS subscores and remission status. These results suggest utility of the current disease model for informed decision making in UC clinical development, such as assisting future clinical trial designs and evaluations.