The Impact of Endoscopic Healing on Disease-Related Outcomes in Patients with Ulcerative Proctitis

Introduction: The role of endoscopic healing (EH) in ulcerative proctitis (UP) is unclear. The long-term treatment goal in ulcerative colitis (UC) is achieving symptomatic resolution and EH, which has been associated with a reduced risk of colectomy. UP is a limited form of UC involving only the rectum and, unlike extensive/left-sided UC, has not been associated with elevated colorectal cancer risk. Therefore, achieving EH as compared to clinical remission in UP represents an uncertain therapeutic target. Methods: This study assessed the impact of EH on outcomes in UP patients. This was a single-center, retrospective cohort study including patients aged ≥ 18 with a UP diagnosis based on clinical/endoscopic criteria. Patients had ≥2 endoscopies, with the first showing active disease (Mayo endoscopy score [(MES) of 1, 2, or 3]) and ≥1 month to the follow-up scope. EH was defined as an MES of 0 or 1 at the second scope. Descriptive statistics were used for baseline characteristics. The relationship of EH to IBD-related outcomes was assessed using univariate analysis (Pearson's Chi-squared test; Fisher's exact test; Welch Two Sample t-test) and those independently associated with EH were identified using logistic regression analysis (odds ratio, 95% confidence interval). Results: Among 200 UP patients, 109 patients (54.5%) achieved EH. The median time from baseline to follow-up was 15 months (IQR: 6, 31). EH was associated with fewer IBD-related ED visits (EH: 8.3%, no EH: 21%) or hospitalizations (5.5% vs 18%) and fewer GI visits per follow-up year (mean: 1.47 [SD: 1.40], vs 2.96 [2.52]) after the follow-up scope. Patients with EH were less likely to have iron deficiency anemia (IDA; 23% vs 41%), iron infusion (10% vs 25%), C. difficile infection (0.9% vs 6.6%), or to initiate a new biologic after relapse (15% vs 33%). Patients with EH had a greater time to clinical relapse (650 days [730] vs 270 days [416]) (P=0.008). Patients with EH had reduced odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73) or hospitalization (0.26 [0.09, 0.67]), and 64% lower odds of biologic initiation after relapse (0.36 [0.13, 0.95]), adjusting for index MES score (Table 1). Conclusion: UP patients with EH had less IBD-related healthcare utilization, fewer IBD-related complications, and were less likely to escalate to biologics after relapse than patients without EH. Using a treatment target of EH may be desirable in UP given its potential utility in preventing disease-related complications and improving long-term outcomes. Table 1 - Characteristic Overall, N=2001 Mucosal healing, N=1091 No mucosal healing, N=911 P-value2 IBD complication 0.4 Multiple complications 60 (30%) 31 (28%) 29 (32%) No complications 67 (34%) 41 (38%) 26 (29%) Clinical relapse (n=167) 98 (59%) 47 (53%) 51 (65%) 0.14 Dysplasia 5 (2.5%) 3 (2.8%) 2 (2.2%) >0.99 CRC 0 (0%) 0 (0%) 0 (0%) Colectomy 8 (4.0%) 2 (1.8%) 6 (6.6%) 0.14 IBD-related ED visit 28 (14%) 9 (8.3%) 19 (21%) 0.01 IBD-related hospitalization 22 (11%) 6 (5.5%) 16 (18%) 0.007 Recent ESR (mm/h)3 (n=101) 0.13 Mean (SD) 12 (11) 10 (11) 13 (11) Range 0, 52 0, 51 1, 52 Recent CRP (mg/dL)3 (n=94) 0.28 Mean (SD) 2.54 (17.94) 0.51 (0.52) 4.11 (23.86) Range 0.01, 174.30 0.01, 2.89 0.01, 174.39 Recent calprotectin (mcg/g)3 (n=38) 0.24 Mean (SD) 275 (408) 196 (369) 355 (440) Range 4, 1250 4, 1250 11, 1144 GI Visits per follow-up year < 0 .001 Mean (SD) 2.17 (2.13) 1.47 (1.40) 2.96 (2.52) Range 0.10, 10.84 0.10, 6.28 0.16, 10.84 IDA 62 (31%) 25 (23%) 37 (41%) 0.007 Iron infusion 34 (17%) 11 (10%) 23 (25%) 0.004 C. Difficile infection 7 (3.5%) 1 (0.9%) 6 (6.6%) 0.048 Extra-intestinal manifestations, after 2nd scope 84 (42%) 48 (44%) 36 (40%) 0.52 Extra-intestinal manifestations, after 2nd scope - type 0.49 Multiple sites 10 (5.0%) 5 (4.6%) 5 (5.5%) No sites 116 (58%) 61 (56%) 55 (60%) Arthritis/arthralgias 69 (34%) 39 (36%) 30 (33%) 0.68 Uveitis 5 (2.5%) 1 (0.9%) 4 (4.4%) 0.18 Rash 10 (5.0%) 7 (6.4%) 3 (3.3%) 0.35 PSC 0 (0%) 0 (0%) 0 (0%) Oral ulcers 11 (5.5%) 6 (5.5) 5 (5.5) >0.99 Biologic initiation after relapse (n=98) 24 (24%) 7 (15%) 17 (33%) 0.034 Biologic initiation after relapse - type (n=24) 0.75 Anti-TNF 9 (38%) 4 (57%) 5 (29%) Clinical Trial 1 (4.2%) 0 (0%) 1 (5.9%) JAK inhibitor 1 (4.2%) 0 (0%) 1 (5.9%) Anti-IL-12/23 3 (12%) 0 (0%) 3 (18%) Anti-integrin 10 (42%) 3 (43%) 7 (41%) 1n (%) 2 Pearson's Chi-squared Test; Welch 2 Sample t-Test; Fisher's Exact Test 3 'Recent' was Defined as Within 3 Months Before or After the Time of the Second Scope CRC: colorectal cancer ED: emergency department IBD: inflammatory bowel disease GI: gastroenterology IDA: iron deficiency anemia EIMs: extra-intestinal manifestations.