Introduction
Recently, endoscopic healing (EH) has been recognized as a long term treatment goal for ulcerative colitis (UC)1. It has been demonstrated that UC does not often remain limited to the mucosa but affects all layers of the bowel2. Intestinal ultrasound (IUS) is a useful tool to assess transmural disease in UC3.
Aims & Methods
We performed a retrospective study on UC patients in remission and on stable maintenance treatment with EH (endoscopic Mayo score of ≤ 1) who had an IUS performed between 2 weeks before and 6 months after endoscopic evaluation and had clinical follow up data available for at least 6 months. Patients were identified from 4 prospective cohorts (January 1, 2017 up till December 31, 2023). Clinical follow up data were analysed from date of endoscopy till December 31, 2023.
Transmural healing (TH) measured with IUS was defined as bowel wall thickness(BWT) ≤ 3mm and modified Limberg Doppler score of ≤ 1 on all colonic segments except for rectum. Histology data (healing defined as absence of granulocytes) was also obtained.
Primary outcome was occurrence of any UC related event: documented relapse, initiation of corticosteroids, intensification/change of medical therapy, hospitalization and/or surgery. Patients were censored at first event and time to event analyses with Cox regression was used to determine the association between TH, EH, histological healing and UC related event.
Results
There were 48 patients available for the current analysis. Baseline characteristics are shown in Table 1. The mean duration of follow up was 38.1±13.1 months. Primary outcome occurred in 18/48 patients (37.5%; TH=5, no TH=13). All patients had a clinical relapse as the first UC related event. Subsequently, 4 patients were initiated with corticosteroids, 13 patients had intensification/change of medical therapy and 1 patient had a colectomy. The mean time to event was numerically shorter in patients without TH than in those with TH (67.9±46.4 weeks vs 92.4±61.2 weeks; p=0.370)
Univariate Cox regression showed that TH (HR 0.17, 95% CI 0.06-0.48), endoscopic Mayo score of 0 (HR 0.52, 95% 0.18-1.48) and histological healing (n = 31, HR 0.96, 95% CI 0.26-3.59) were associated with absence of UC related event. However, in multivariate analysis adjusting for age, gender, duration of disease and number of previous biologics and anti-TNF exposure, only TH remained a significant factor (p=0.025) associated with event-free long term outcome. Similar results were observed in analysis involving BWT ≤ 3mm with modified Limberg Doppler score 0.
| Characteristic | Transmural Healing (n=30) | Non Transmural Healing (n=18) | Overall (n=48) | p value
|
| Gender (male, %) | 15 (50.0) | 8 (44.4) | 23 (47.9) | 0.71
|
| Duration of disease (years, median, IQR) | 8.6 (3.2, 11.7) | 7.6 (4.1, 16.7) | 7.9 (3.6, 17.1) | 0.77
|
| Age at baseline (years, median, IQR) | 33 (27, 46) | 42 (27, 55) | 38 (27, 50) | 0.37
|
| C-Reactive Protein (mg/L, median, IQR) | 0.6 (0.3, 0.9) | 1.3 (0.4, 4.4) | 0.7 (0.3, 9.0) | 0.22
|
Number of prior biologics used (%)
0
1
2
≥ 3 |
12 (40.0)
8 (26.7)
5 (16.7)
5 (16.7) |
1 (0)
9 (50.0)
5 (27.8)
3 (16.7) |
13 (27.1)
17 (35.4)
10 (20.1)
8 (16.7) | 0.09
|
Previous anti-TNF use (%)
Yes
No |
16 (53.3)
14 (46.7) |
14 (77.8)
4 (22.2) |
30 (62.5)
18 (37.5) | 0.09
|
Current Medications (%)
5-Aminosalicylate
Thiopurines / Methotrexate
Anti-TNF (Infliximab / Adalimumab)
Vedolizumab
Ustekinumab
Jak Inhibitors |
7 (23.3)
2 (6.7)
7 (23.3)
7 (23.3)
0 (0)
13 (43.3) |
5 (27.8)
1 (5.6)
4 (22.2)
0 (0)
2 (11.1)
11 (61.1) |
12 (25.0)
3 (6.3)
11 (22.9)
7 (14.6)
2 (4.2)
24 ((50.0) | 0.88
|
UC Extent (Montreal classification) (%)
E1 Ulcerative proctitis
E2 Left-sided UC
E3 Pancolitis |
2 (6.7)
12 (40.0)
16 (53.3) |
2 (11.1)
6 (33.3)
10 (55.6) |
4 (8.3)
18 (37.5)
26 (54.2) | 0.82
|
Endoscopic Mayo Score (%)
0
1 |
12 (40.0)
18 (60.0) |
6 (33.3)
12 (66.7) |
18 (37.5)
30 (62.5) | 0.64
|
Conclusion
TH is an independent predictor of favorable long-term outcome for UC patients with EH. This novel finding is currently undergoing validation in larger cohorts.
References
1. Turner, Dan et al. “STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.” Gastroenterology vol. 160,5 (2021): 1570-1583. doi:10.1053/j.gastro.2020.12.031
2. Maaser, Christian et al. “Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis: results from the TRUST&UC study.” Gut vol. 69,9 (2020): 1629-1636. doi:10.1136/gutjnl-2019-319451
3. Ilvemark, Johan F K F et al. “Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement.” Journal of Crohn's & colitis vol. 16,4 (2022): 554-580. doi:10.1093/ecco-jcc/jjab173
Disclosure
Chong-Teik Lim: None.
Christoph Teichert: None.
Maarten Pruijt: None.
Floris de Voogd: received speaker or honoraria fees from AbbVie, Janssen, Galapagos, Pfizer and Takeda.
Geert D’Haens: received research grants from Abbvie, Alimentiv, BMS, J&J, Pfizer, Takeda; consulting fees from Abbvie, Agomab, Alimentiv, AstraZeneca, AMT, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Index Pharmaceuticals, Kaleido, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Progenity, Protagonist, and Ventyx; speaker’s fees from Abbvie, Arena, Boehringer Ingelheim, Celltrion, Galapagos, Gilead, Pfizer, BMS, and Takeda; data monitoring board: Galapagos, AstraZeneca, Seres Health.
Krisztina Gecse: received grants from Pfizer Inc, Celltrion, and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis, and Takeda; and speaker’s honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts.