Introduction

The impact of increased advanced therapy prescribing on colectomy rates in ulcerative colitis (UC) to date are conflicting. We have previously demonstrated a decrease in the rates of colectomy over time from 2005 to 2018.¹ The influence of the expanding number of available therapies for UC on colectomy rates is unknown.

Aims & Methods

We aimed to describe prescribing trends of all available advanced therapies for UC in the Lothian IBD cohort up until the end of 2023 along with the corresponding colectomy rates. We identified all patients who started an advanced therapy for UC, and all patients who underwent colectomy for UC in the Lothian population from January 1st, 2005, to December 31st, 2023. Incidence and prevalence data of UC in Lothian was obtained from the rigorously validated Lothian IBD Registry.² Prescribing and colectomy rates are presented as a proportion of the prevalent population. Linear and segmental regression analyses were used to identify the annual percentage change and temporal trends in colectomy rates.

Results

From 2005 to 2023, 509 patients with ulcerative colitis underwent colectomy. The median age at colectomy was 42 years old (IQR 29-56). The median time from diagnosis to colectomy was 2.6 years (IQR 0.4-9.7). Colectomy rates per 100 UC patients were 1.47 in 2005, 1.53 in 2010, 0.68 in 2015, and 0.22 in 2023. 68% of colectomies (346/509) were performed for acute severe UC, of which 34% were within 90 days of diagnosis. 3.5% (18/509) of colectomies were for cancer (n=11) or dysplasia (n=7).
Over the same time period 615 patients received at least one advanced therapy for UC. The median age at first advanced therapy was 40 years old (IQR 28-54). New advanced therapy prescriptions per 100 UC patients increased from 0.67 in 2005, to 0.37 in 2010, 1.01 in 2015, 3.21 in 2020, and 5.15 in 2023. Persistence rates on first line therapy were highest with vedolizumab, followed by infliximab. By the end of 2023, 43% (n=265), 20% (n=121), 9% (n=54), and 3% (n=21), of the 615 patients had received a second, third, fourth, and fifth line of advanced therapy respectively.

Conclusion

The incidence of colectomy for ulcerative colitis has substantially decreased over time and correlates with an increased use, and number of available advanced therapies. However, correlation cannot ascribe causation.

References

1. Jenkinson PW, Plevris N, Lyons M, Grant R, Fulforth J, Kirkwood K, Arnott ID, Wilson D, Watson AJM, Jones GR, Lees CW. Analysis of colectomy rates for ulcerative colitis in pre- and postbiological eras in Lothian, Scotland. Colorectal Dis. 2021 May;23(5):1175-1183. doi: 10.1111/codi.15491. Epub 2021 Feb 17. PMID: 33350054.
2. Jones GR, Lyons M, Plevris N, Jenkinson PW, Bisset C, Burgess C, Din S, Fulforth J, Henderson P, Ho GT, Kirkwood K, Noble C, Shand AG, Wilson DC, Arnott ID, Lees CW. IBD prevalence in Lothian, Scotland, derived by capture-recapture methodology. Gut. 2019 Nov;68(11):1953-1960. doi: 10.1136/gutjnl-2019-318936. Epub 2019 Jul 11. PMID: 31300515; PMCID: PMC6839733.

Disclosure

ATE, NCC, PWJ, SO, NG and GRJ have no disclosures. BG has served as consultant to Galapagos and Abbvie and as speaker for Abbvie, Janssen, Takeda, Pfizer and Galapagos. NP has served as a speaker for Janssen, Takeda and Pfizer. IDA has received speaking/consutlting fees for Abbvie, Takeda, Dr Falk, Ferring, BMS, Lilley, Galapagos/Alphasigma and Vifor. CWL has acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, Galapagos, Eli Lilly, Bristol Myers Squibb, B.I., Sandoz, Novartis, GSK, Gilead, ViforPharma, Dr Falk, and Iterative Health; he has received speaking fees and travel support from Pfizer, Janssen, Abbvie, Eli Lilly, Galapagos, MSD, Takeda, Shire, Ferring, Hospira and Dr Falk.

Introduction

Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic naïve patients. We aimed to compare the efficacy, safety and persistence of tofacitinib and vedolizumab as the first advanced treatment for patients with UC.

Aims & Methods

Patients who received either tofacitinib or vedolizumab as their first advanced therapy for UC via the NHS Lothian health board were included. Patients aged 65 years or older were excluded. We used inverse probability of treatment weighting (IPTW). The probability of treatment assignment was calculated via logistic regression using age, gender, IBD duration, Montreal extent, CRP, concomitant corticosteroids, and partial Mayo score at drug commencement. Missing data for these variables were imputed using multivariate imputation by chained equations. Confounder-adjusted survival curves were created using Kaplan-Meier estimates weighted via IPTW. The Pepe and Fleming test was used to compare survival curves.

Results

We included 158 patients of whom 81 (51.2%) received vedolizumab and 77 (48.7%) tofacitinib. Median follow-up for patients on vedolizumab was 3.1 (1.6-4.8) years and for tofacitinib 1.5 (0.34-2.3) years. The cohort was 59.3% male with a median age of 41.1 years (31.5-51.8) and disease duration of 6.21 years (2.56-13.5). At drug commencement there were no differences in steroid prescription, partial Mayo score, CRP or faecal calprotectin.
Vedolizumab persistence was superior to tofacitinib (p=0.005). Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. At week 12, steroid free clinical remission was more frequent in the vedolizumab group (69% vs 51.4%, p=0.030), Table 1.There were no differences in the frequency of adverse events (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). However, adverse events resulting in temporary discontinuation of the drug occurred in 1 (1.2%) vedolizumab versus 11 (14.3%) tofacitinib, p=0.013.

Conclusion

We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bio-naïve UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy in UC.

Disclosure

Beatriz Gros has served as consultant to Galapagos and Abbvie and as speaker for Abbvie, Jansen, Takeda, Pfizer and Galapagos. Nikolas Plevris has served as a speaker for Janssen, Takeda and Pfizer. Professor Charlie Lees has acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, Galapagos, Bristol Myers Squibb, B.I., Sandoz, Novartis, GSK, Gilead, ViforPharma, Dr Falk, Trellus Health and Iterative Scopes; he has received speaking fees and travel support from Pfizer, Janssen, Abbvie, Galapagos, MSD, Takeda, Shire, Ferring, Hospira and Dr Falk. Gareth-Rhys Jones has served as a speaker for Takeda, Janssen, Abbvie, Fresnius and Ferring.

Introduction

The incidence of Ulcerative Colitis (UC) in the England has changed little over the last fifteen years (1,2). Medical and surgical management however has transformed during that period. Our aim was to investigate whether colectomy rates and 90-day mortality following surgery have changed in the last two decades.

Aims & Methods

This was a population-based cohort study using computerized health records from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics data. An incident cohort was defined as patients with a new diagnosis of UC between 2005-2020.
Time to first colectomy was calculated from diagnosis date. Cumulative incidence of colectomy and 90-day mortality was calculated using life tables. Colectomy rates following UC diagnosis were calculated annually for each year between 2005 and 2020 using the denominator of total person time contributing to that year. Rates were modelled using Poisson regression analysis. Cox regression was used to model the risk of surgery and 90-day mortality rates and the effect of gender, socioeconomic status and region. Analysis was performed using StataMP 18.

Results

46,730 patients had an incident diagnosis of UC, 49.33% (23,055/46730) were female. 5.72% (2672/46730) underwent colectomy. The one year risk of colectomy was 2.32% (95% CI 2.19-2.47%), with a 5-year risk of 4.92% (95% CI 4.72-5.13%) and 10-year risk of 6.47% (95% CI 6.22-6.73%). 90-day mortality for emergency and elective colectomy was 3.54% (95% CI 2.73-4.58%) and 1.44% (95% CI 0.92-2.25%) respectively.
Total colectomy rate fell from 17.15 per 1000 person-years in 2005 to 5.96 per 1000 person years in 2020 (IRR 0.35, 95% CI 0.27-0.45). Elective colectomy rates fell from 6.78 per 1000 person-years in 2005 to 2.75 per 1000 person-years in 2020, (IRR 0.41, 95% CI 0.27-0.60). Emergency colectomy rates fell from 10.37 per 1000 person-years in 2005 to 3.21 per 1000 person-years in 2020 (IRR 0.31, 95% CI 0.22-0.43).
Females were 30% less likely to undergo colectomy (HR 0.70, 95% CI 0.65-0.75). There was a statistically significant difference in risk of colectomy by region with London, South East, East of England and North West having lower colectomy rates than West Midlands and the North East. There was no significant difference between gender, region or socioeconomic status for 90-day mortality.

Conclusion

There has been a significant reduction in both elective and emergency colectomy rates between 2005-2020. There was gender and regional variation in risk of colectomy. Further work may attempt to correlate these findings with prescription rates of particular medications to elicit a cause for these findings.

References

1. King D, Reulen RC, Thomas T, Chandan JS, Thayakaran R, Subramanian A, et al. Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000-2018. Aliment Pharmacol Ther. 2020;(December 2019):1–13.
2. Freeman K, Ryan R, Parsons N, Taylor-Phillips S, Willis BH, Clarke A. The incidence and prevalence of inflammatory bowel disease in UK primary care: a retrospective cohort study of the IQVIA Medical Research Database. BMC Gastroenterol [Internet]. 2021;21(1):1–7. Available from: https://doi.org/10.1186/s12876-021-01716-6

Introduction

Despite new therapeutic strategies, substantial proportion of patients with ulcerative colitis (UC) undergo colectomy at some point. Restorative proctocolectomy with ileal pouch ano anastomosis (IPAA) is regarded as intervention of choice in these patients. However, the disease conversion to Crohn´s disease (CD) is reported in up to one third of these patients who necessitate immune suppressive treatment after IPAA. Considering the life-long need for immune suppressive therapy in these patients, ileo-rectal anastomosis (IRA) would represent a good alternative to IPAA in this specific group of patients. Todate, no data are available to predict the UC-CD conversion. One of the possibility to reduce the risk of performing IPAA in patients developing CD in pouch is to use the modified two-stage proctocolectomy approach and identify patients who develop CD endoscopically between colectomy and the restoration of continuity.

Aims & Methods

The aim of the present study was to assess the UC-CD conversion rate identified prior IPAA via ileoscopy.
All patients with UC operated in one tertiary IBD center between 2016 and 2021 were identified in medical records. The main outcome was CD detected at ileoscopy between the first stage operation, i.e. total colectomy with terminal ileostomy and the restoration of continuity either via IPAA or IRA. The ileoscopy was performed between three to six months after colectomy. The secondary outcome was the rate of conversion to CD after IPAA or IRA.

Results

Sixty patients underwent total colectomy (mean age 41 years, range 22-77; 62% were men); seven patients were lost to follow-up, finally the data from 53 patients were analysed. The majority of these patients (36 - 68%) underwent colectomy for therapy resistent chronically active UC, 9 (17%) patients for acute severe UC, 2 patients had benign colonic stenosis, 5 had high-grade dysplasia or colorectal cancer detected at surveillance colonoscopy and one patient had extensive pseudopolyposis.
All resection specimen were reviewed and no histopathological features of CD were found. Three out of the 53 (6%) ileoscopically assessed patients prior IPAA or IRA were diagnosed with CD in prestomal terminal ileum. During the further follow-up, additional 4 patients developped CD, two after IPAA, one with definitive ileostomy in prestomal ileum and one in neoterminal ileum after IRA.
In total 7 out of 53 patients in this cohort developped CD (13%). Using the two stage approach with ileoscopy between colectomy and restoration of continuity, three out of these seven patients with CD convertion in this cohort were detected prior the decision on the type of second-stage operation.

Conclusion

The conversion from ulcerative colitis to Crohn`s disease occurs in a significant proportion of IBD patients after colectomy. Ileoscopy performed between the two stages of restorative proctolectomy is helpfull in detecting these patients and guiding the decision on the type of surgical intervention to restore continuity.

Disclosure

Nothing to disclose.

Introduction

Acute severe ulcerative colitis (ASUC) is a medical emergency requiring hospitalisation. Overtime, there has been an increasing number of biologic and non-biologic treatment options available to induce and maintain disease remission. A previous study found no significant difference in length of stay or colectomy rates for those on biologic or small molecule therapy prior to admission compared to those who were not on advanced ulcerative colitis (UC) therapies, but found they had higher rates of surgical consultation and 90-day readmission rates.¹ We aimed to evaluate the preadmission medications patients were receiving at time of ASUC presentation, and to determine whether maintenance biologic and small molecule therapy had an effect on patient outcomes, including need for rescue therapy, colectomy, total parental nutrition (TPN), length of stay (LOS), readmission rates and mortality.

Aims & Methods

A retrospective review was conducted on all ASUC presentations to a quaternary Sydney hospital over a 10-year period. A modified Truelove and Witts’ criteria was used to define ASUC.Data was collected on preadmission UC medications, including aminosalicylates, thiopurines, steroids and advanced UC therapies, including biologics and small molecule inhibitors. Outcomes assessed included need for biologic rescue therapy, colectomy, TPN, length of stay, 30- and 90-day readmission rates, and 30- and 90-day mortality rate.

Results

A total of 172 ASUC presentations were identified. Of these, 143 presentations (83%) were patients with existing diagnosis of UC. Pre-admission medications in these patients included aminosalicylates (62%, n=89), thiopurines (25%, n=36), steroids (61%, n=87), biologics (17%, n=25), and small molecule inhibitors (2%, n=3). Patients taking aminosalicylates as maintenance therapy had significantly lower rates of need for rescue therapy (32% vs 51%, p=0.015). Patients on aminosalicylates-only had lower rates of 90-day readmission compared to those on both aminosalicylates and additional advanced UC therapies (0% vs 31%, p=0.007). There was no significant difference in need for rescue therapy for those on other maintenance therapies. Patients who presented on prednisolone <20 mg/d had a significantly higher rate of 90-day readmission compared to those on a dose ≥20mg (47% vs 13%, p=0.004). Those on biologic maintenance therapy had significantly higher rates of TPN use, colectomy, 90-day readmission, 30-and 90-day mortality and mean length of stay (Table 1). Patients on small molecule inhibitors had a shorter length of stay (7±1 vs 11±9.2 days, p=0.001), but no difference in other treatment outcomes.

Conclusion

Patients with pre-existing diagnosis of UC on maintenance biologic therapy who presented with ASUC were more likely to require TPN, colectomy, 90-day readmission, 30-and 90-day mortality and longer length of stay. Patients on aminosalicylates-only had lower rates of 90-day readmission. Our study findings may reflect that patients on advanced outpatient UC therapies have a more severe phenotype translating to a more severe ASUC admission course. More research is needed to predict such markers of severity.

References

1. Sabrie, N., Jogendran, M., Jogendran, R. & Targownik, L.E. Outcomes of patients admitted with acute, severe ulcerative colitis on biologic therapy: a retrospective analysis from a tertiary referral hospital. Journal of the Canadian Association of Gastroenterology 7, 306-311 (2024).