S1587 Baseline Characteristics Associated With Probability of Remission and Greater Absolute Benefit of Treatment With Afimkibart (RO7790121/RG6631)

Introduction: In the phase IIb TUSCANY-2 study (NCT04090411), afimkibart (RO7790121/RG6631), an anti-TL1A antibody, had a clinically meaningful effect in patients (pts) with moderate to severe ulcerative colitis. We report post hoc analyses of the relationship between baseline clinical characteristics and Week 14 (W14) efficacy in pts enrolled in TUSCANY-2. Methods: Pts were randomized to receive subcutaneous afimkibart 50 mg, 150 mg, 450 mg or placebo (PBO) monthly during induction. In this analysis, afimkibart doses were pooled; the endpoint was clinical remission by modified Mayo score (mMS; defined as stool frequency subscore = 0/1; rectal bleeding subscore = 0; and endoscopic subscore = 0/1) at W14. Investigation of patient-specific treatment effects was guided by the risk modeling approach from the Predictive Approaches to Treatment effect Heterogeneity statement. We developed a regularized logistic regression model to predict the probability of W14 remission using baseline mMS, C-reactive protein (CRP), serum albumin, Robart’s Histopathology Index (RHI), number of failed advanced therapy classes, corticosteroid use, disease extent, disease duration, age and sex. The model was used to separate patients by baseline clinical characteristics to interrogate variation in treatment effects. Results: Overall, 32.5% of pts achieved clinical remission by mMS at W14 in the afimkibart arm (65/200; 90% CI 27.3–38.1) vs 13.3% (6/45; 90% CI 7.1–23.8) with PBO (treatment Δ 19.2%; 90% CI 7.6–27.9). Based on calibrated predictions from the multivariate model, all pts (PBO and afimkibart arms) had a 2–76% probability of W14 remission at baseline. On the clinically meaningful absolute scale, the treatment Δ in the top 50% of pts with a higher baseline probability of remission (27–76%) was 28.5% (90% CI 8–42; 45.2% afimkibart vs 16.7% PBO), vs a treatment Δ of 7.6% (90% CI –7–18; 18.8% afimkibart vs 11.1% PBO) in pts with a lower baseline probability of remission (2–27%). Lower baseline CRP, lower RHI and higher serum albumin contributed to a greater probability of remission and absolute benefit with afimkibart. Conclusion: This analysis demonstrates how precision medicine approaches that simultaneously account for diverse baseline characteristics may improve interpretation of positive inflammatory bowel disease (IBD) clinical trial results. Integrating genetic and novel biomarkers with clinical features could help to better predict outcomes for pts with IBD.