Introduction
The impact of achieving endoscopic remission in ulcerative proctitis (UP) is unclear. The preferred long-term treatment goal in ulcerative colitis (UC) is achieving both the symptomatic resolution and endoscopic remission (ER),1 which has been associated with reduced risk of complications, including colectomy.2,3 UP is an anatomically limited form of UC, involving only the rectum. Unlike in extensive or left-sided UC, UP has not been associated with elevated colorectal cancer risk. Therefore, the achievement of endoscopic healing as compared to clinical remission in UP represents an uncertain therapeutic target.4
Aims & Methods
This study assessed the impact of achieving EH on subsequent outcomes in UP patients. This was a single-center retrospective cohort study including patients aged ≥ 18 with a confirmed diagnosis of UP based on clinical and endoscopic criteria. Included patients had at least two endoscopies and active endoscopic disease (Mayo endoscopy score [(MES) of 1, 2, or 3]) at the first (baseline) endoscopy. EH was defined as an MES of 0 or 1 at the second (follow-up) procedure. A minimum time of 1 month between scopes was required for inclusion. 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 we identified those independently associated with EH using multivariable logistic regression analysis (odds ratio with 95% confidence interval).
Results
Among 200 UP patients with baseline endoscopic activity, 109 patients (54.5%) achieved EH at follow-up. The median time from baseline to follow-up was 15 months (IQR: 6, 31). EH at follow-up was significantly associated with fewer IBD-related ED visits (healing: 8.3%, no healing: 21%) or hospitalizations (5.5% vs 18%) and fewer GI visits (mean: 8 [SD: 9], vs 17 [22]) after the second 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 also had a greater time to clinical relapse (650 days [730] vs 270 days [416]). In multivariable analysis, patients with mucosal healing had 68% lower odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73), 74% lower odds of IBD-related hospitalization (0.26 [0.09, 0.67]), and 64% lower odds of biologic initiation after relapse (0.36 [0.13, 0.95]) compared to patients with no mucosal healing, adjusting for the index MES score.
| Overall, N = 2001
| Healing, N = 1091
| No healing, N = 911
| P-value2
|
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
|
Total Number of GI Visits,
mean (SD)
| 12 (17)
| 8 (9)
| 17 (22)
| <0.001
|
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
|
Biologic Initiation After Relapse (n=98)
| 24 (24%)
| 7 (15%) | 17 (33%)
| 0.034
|
1 n (%)
2 Pearson's Chi-squared test; Welch Two Sample t-test; Fisher's exact test
Conclusion
UP patients with endoscopic healing had less IBD-related healthcare utilization (ED visits, hospitalizations, GI visits), fewer IBD-related complications (IDA, iron infusion, C. difficile infection), and were less likely to escalate to biologics after relapse. Our findings suggest that using a treatment target of endoscopic healing is desirable in UP and shed light on its potential utility in preventing disease-related complications and improving long-term outcomes.
References
1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Off J Am Coll Gastroenterol ACG. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233
2. Colombel JF, Rutgeerts P, Reinisch W, et al. Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis. Gastroenterology. 2011;141(4):1194-1201. doi:10.1053/j.gastro.2011.06.054
3. Impact of mucosal healing on long‐term outcomes in ulcerative colitis treated with infliximab: a multicenter experience - Laharie - 2013 - Alimentary Pharmacology & Therapeutics - Wiley Online Library. Accessed September 24, 2022. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12289
4. Zhou Q, Shen ZF, Wu B sheng, et al. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2019;2019:1-11. doi:10.1155/2019/5363261
Disclosure
E.L., A.A.: no conflicts of interest to disclose
R.B.: Consulting/Speaker: Janssen, Abbvie, Bristol Myers Squibb, Prometheus Laboratories, Pfizer, Takeda
R.L.: Consulting/Speaking Fees: Pfizer, Enzymetrics, Ancilia Biosciences. Grant Support: National Institute of Health (NIH)
E.S.: Consulting/Speaking Fees: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Grant Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech, Seres Therapeutics, Celgen. R.B.: Consulting: Prometheus
D.L.: Consulting/Speaking Fees: Abbvie, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, Janssen, Palatin, Pfizer, Prometheus Biosciences, Takeda; Grants: Abbvie, Janssen, Takeda