S1446 Does Mild Endoscopic Disease Drive Persistent Symptoms in Crohn’s Disease? A Repeated Measures Analysis

Introduction: Persistent gastrointestinal (GI) symptoms despite mucosal healing are common in Crohn’s disease (CD) but remain poorly understood. Although the treat-to-target (T2T) strategy emphasizes endoscopic remission, many patients continue to report symptoms even when inflammation is absent or mild. We aimed to evaluate whether mild inflammation independently contributes to symptoms and to identify predictors of symptom severity in a longitudinal cohort. Methods: We analyzed 303 colonoscopy scores from 239 patients enrolled in the SPARC IBD study at tertiary center. Patients were selected if they had quiescent or mild endoscopic CD based on the Simple Endoscopic Score (SES-CD ≤6). GI symptoms included abdominal pain, urgency, increased stool frequency, liquid stool consistency, and blood in stool, and were further classified as moderate-to-severe when appropriate. Generalized estimating equations (GEE) with a logit link and robust variance estimates were used to study associations between SES-CD category (Quiescent 0-2 vs Mild 3-6) and symptom severity, adjusting for sex, stricturing/fistulizing phenotype (B2/B3), perianal disease (PAD), upper GI involvement (UGI), and extraintestinal manifestations (EIMs). Results: Mild inflammation (SES-CD 3–6) was not associated with any GI symptom, including moderate-severe abdominal pain (OR 0.95, P = 0.896), urgency (OR 1.14, P = 0.677), stool frequency (OR 0.92, P = 0.852), blood in stool (OR 1.00, P = 0.990), or liquid stools (OR 0.91, P = 0.762). No significant association was found when repeating the model for segmental ileitis, colitis, or proctitis. Other covariates including PAD, EIMs, UGI involvement, and stricturing/fistulizing phenotype were not associated with persistent symptoms. In contrast, female sex (52.1% of cohort and 51.9% of SES-CD 3-6) was independently associated with any abdominal pain (OR 2.48 [1.42–4.32], P = 0.001), any stool frequency increase (OR 2.30, [1.32–4.01], P = 0.003), any urgency (OR 2.69 [1.51–4.76], P < 0.001), moderate-severe urgency (OR 2.22 [1.19–4.15], P = 0.012), and blood in stool (OR 2.06, 95% CI: 1.05–4.08, P = 0.037). Conclusion: In this well-characterized prospective cohort, mild mucosal inflammation was not a driver of GI symptoms. Instead, female sex was a consistent predictor of persistence and severity of symptoms. These findings suggest that, beyond mucosal healing, individualized symptom evaluation, particularly in women, may be essential to improving quality of life of patients with Crohn’s disease.