Muna J. Tahir, PhD1, Saeid Shahraz, MD, PhD2, Pravin Kamble, PhD3, Song Wang, PhD3, Peter Nagy, MD4 1ICON Plc., South San Francisco, CA; 2ICON Plc., South San Francisco, CA, USA; Tufts Medical Center, Boston, MA; 3Takeda, Cambridge, MA; 4Takeda, Zurich, Zurich, Switzerland
Introduction: The Ulcerative Colitis Electronic Diary (UC e-diary) is a novel, validated, 5-item patient-reported measure assessing the severity of signs and symptoms of UC, including bowel movement, rectal bleeding, diarrhea, urgency, and abdominal pain. This analysis aimed to define and validate the remission threshold of the UC e-diary as a clinical endpoint in patients with moderate-to-severe UC.
Methods: We employed a discriminant model to define a clinical remission threshold for the UC e-diary using data from 2 Phase 3 trials (NCT03259334 and NCT03259308) of patients with UC randomized to receive 1 of 3 treatments in a 2:2:1 ratio (ontamalimub 25mg or 75mg or placebo) (N=657). Using receiver operating characteristic (ROC) curves, we characterized the discriminant model’s ability to distinguish between patients who achieved clinical remission from those who did not. The gold standard for reaching the threshold was a Mayo stool frequency score of 0 or 1 with ≥1-point change from baseline, a rectal bleeding severity score of 0, and a modified endoscopic score of 0 or 1 at week 12. The UC e-diary threshold was the point on the ROC curve that maximized the product of sensitivity and specificity.
Results: The ROC curve (Figure 1) demonstrated that the area under the curve for the discriminant model was 0.82. This value indicates minimal patient misclassification vs the gold standard and represents the reliability of the UC e-diary to identify patients who achieved clinical remission vs those who did not. According to the maximal product of sensitivity and specificity cutpoint, patient-reported clinical remission was 0.7, corresponding to a sensitivity of 74% and specificity of 80%.
Discussion: A UC e-diary value of 0.7 indicated clinical remission. This patient-reported cut-off distinguished patients who met clinical remission criteria using various Mayo score components from those who did not. This UC e-diary threshold could aid in interpreting outcomes of clinical trials in UC and clinical practice.
Figure: Figure 1. ROC curve for the discriminant model to classify the remission threshold
Muna J. Tahir, PhD1, Saeid Shahraz, MD, PhD2, Pravin Kamble, PhD3, Song Wang, PhD3, Peter Nagy, MD4. P2634 - Clinical Remission Using the Patient-Reported Ulcerative Colitis Electronic Diary (UC e-Diary) in Adults With Moderate-to-Severe Ulcerative Colitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.