Introduction

Ulcerative proctitis (UP) is associated with disabling symptoms such as diarrhea, hematochezia and bowel urgency¹. Adequate therapy is crucial for symptom control and may reduce the risk of proximal disease extension. Although prior studies have explored risk factors for disease progression, they are limited by small sample sizes and have conflicting results^2,3.

Aims & Methods

We aimed to (1) assess the incidence and (2) identify risk factors for disease progression in newly diagnosed UP patients. We included all patients diagnosed with UP (inflammation ≤15 cm beyond the anal verge) between January 2000 and January 2024 in a large, non-academic hospital in the Netherlands. Data were collected from diagnosis until the end of follow-up. Disease progression was defined as endoscopic extension of UP (Montreal E1) to either left-sided (E2) or pancolitis (E3). To avoid overestimating the risk of disease progression, we used a Fine & Gray (F&G) regression model to account for patients in long-term remission who had no in-hospital follow-up. Patients who were referred back to primary care and/or had no in-hospital follow-up for ≥2 years were considered in long-term remission, which was used as a competing event in the F&G model. The cumulative incidence of disease progression was calculated at 1-, 5- and 10-years follow-up and compared to the progression rates of traditional Kaplan-Meier survival estimates.

Results

In total, 486 UP patients were included; 283 (58%) were female and median age at diagnosis was 39 years (IQR 29-53). 371 (76%) patients were in clinical remission at last follow-up. Of those, 291 (78%) were treated with topical and/or oral 5-aminosalicylates (5-ASA) and/or topical steroids; 202 (54%) required only topical and/or oral 5-ASA. 50 (10%) patients had refractory UP and required treatment with immunosuppressants or advanced therapies. During a median follow-up of 6.2 years (IQR 2.1-12.2), disease progression occurred in 112 patients (23%), of whom 80 (16%) progressed to E2 and 32 (6.6%) to E3. Median time to progression was 57 months (IQR 22-103). The cumulative incidence of disease progression was 2.8% (95% CI 1.4-4.4%) at 1 year, 13.2% (95% CI 9.9-16.4%) at 5 years and 23.9% (95% CI 19.4-28.4%) at 10 years after diagnosis and would have been overestimated with traditional Kaplan-Meier analysis (5.1% [95% CI 1.9-8.1%] at 1 year, 24.6% [95% CI 14.9-33.3%] at 5 years and 46.3% [95% CI 30.3-58.6%] at 10 years). F&G analyses demonstrated that age <18 years at diagnosis (HR 2.61, p=0.009) and the absence of steroid-free remission at 3 months (HR 1.97, p=0.005) were significant predictors for disease progression (Table 1).

Conclusion

In this large cohort of newly diagnosed UP patients, the 10-year cumulative incidence of disease progression was 23.9%. Most patients responded well to conventional treatment, as 60% reached clinical remission with only topical and/or oral 5-ASA and/or topical steroids. Absence of steroid-free remission at 3 months and age <18 at diagnosis were significant predictors for disease progression. Better prediction of disease progression could help identify high-risk patients who may benefit from tailored monitoring strategies, as well as low-risk patients that may be suitable for referral back to primary care.

References

1. Meucci G, Vecchi M, Astegiano M, et al. The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII). Am J Gastroenterol. 2000;95(2):469-473
2. Huguet JM, Ferrer-Barceló L, Suárez P, et al. Endoscopic progression of ulcerative proctitis to proximal disease. Can we identify predictors of progression?. Scand J Gastroenterol. 2018;53(10-11):1286-1290.
3. Walsh E, Chah YW, Chin SM, et al. Clinical Predictors and Natural History of Disease Extension in Patients with Ulcerative Proctitis. Inflamm Bowel Dis. 2017;23(11):2035-2041.
4. Andersen PK, Geskus RB, de Witte T, Putter H. Competing risks in epidemiology: possibilities and pitfalls. Int J Epidemiol. 2012;41(3):861-870.

Disclosure

RJBP, JH, RAJP, REAvD and AGLB have nothing to disclose. LAAPD has served on advisory boards for Abbvie, Janssen, Galapagos, and Pfizer, and has received independent research funding from Pfizer. ACdV has has served on advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos and has received unrestricted research grants from Takeda, Janssen, and Pfizer.