The Natural History after Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Population-Based Cohort Study from the United States

Abstract

Background:

There are limited data regarding the natural history after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1-, 3-, 5- and 10-years: the incidence of pouchitis, Crohn’s-like disease of the pouch (CLDP), use of advanced therapies after IPAA, and pouch failure requiring excision in a network of electronic health records (EHRs).

Methods:

We performed a retrospective cohort study in TriNetX, a research network of EHRs. In addition to evaluating incidence rates, we also sought to identify factors associated with pouchitis and advanced therapy use within 5 years of IPAA after 1:1 propensity score matching (PSM), expressed as adjusted Hazard Ratios (aHRs).

Results:

Among 1,331 patients who underwent colectomy with IPAA for UC, the incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA. After PSM, nicotine dependence (aHR 1.61, 95% CI 1.19–2.18) and anti-TNF therapy (aHR 1.33, 95% CI 1.13–1.56) and vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06–1.96) were associated with an increased risk of pouchitis in the first 5 years after IPAA. The incidence of CLDP increased to 10.3% within 10 years of IPAA while pouch failure increased to 4.1%. The incidence of advanced therapy use peaked at 14.4% at 10 years after IPAA.

Conclusions:

The incidence of inflammatory conditions of the pouch remains high in the current era, with 14% of patients requiring advanced therapies after IPAA.

INTRODUCTION

Although ileal pouch-anal anastomosis (IPAA) has been established as the most common restorative surgery among patients with ulcerative colitis (UC) who require a proctocolectomy, many questions remain regarding the natural history after IPAA. In particular, the epidemiology of inflammatory disorders of the pouch and the subsequent need for re-initiation of advanced therapies among the general population of patients undergoing IPAA surgery in the United States (US) remains poorly defined. Recent efforts to evaluate the epidemiology of pouchitis in administrative claims have led to more generalizable estimates of the burden of pouchitis within the first 2 years after IPAA in the US.¹ However, there is a need for improved understanding of later outcomes such as chronic inflammatory conditions of the pouch and need for advanced therapies in generalizable populations as well. Patients with recurrent pouchitis and/or chronic inflammatory conditions of the pouch have demonstrated a significant burden of disease, both as individual patients and on the healthcare system in terms of cost and healthcare utilization.^{1, 2} Thus an improved understanding of the natural history after IPAA and potential factors associated with a complicated disease course remains an unmet need at this time.

Traditionally, much of our understanding of the epidemiology of pouch-related disorders has been generated from single-center or selected populations from inflammatory bowel disease centers of excellence.^3–6 In recent years, new methods for the identification of patients with pouchitis in administrative claims⁷ have allowed for larger, more generalizable estimates of the epidemiology and burden of pouchitis and pouch-related disorders in the US^{1, 2} as well as in other large data sources such as the Danish health registers.⁸ These efforts, along with an increased emphasis on standardized approaches to the evaluation of patients after IPAA,^9–12 have led to an increased emphasis on early, accurate, and standardized detection of inflammatory conditions of the pouch and generalizable assessments of the natural history after IPAA surgery that can improve patient-centered care.

Given this background, we sought to evaluate the natural history after IPAA surgery in the modern era in the US using a multi-institutional research network of over 80 million patients. In particular, our objectives were to analyze the incidence of pouchitis and Crohn’s-like disease of the pouch (CLDP) along with the use of advanced therapies after IPAA and the rate of pouch failure requiring excision of IPAA. We also sought to evaluate other specific adverse outcomes after IPAA, including the rate of certain malignancies.

METHODS

Data Source

We performed a retrospective cohort study utilizing the global federated research network known as TriNetX (Cambridge, MA, USA). TriNetX provides real-time access to de-identified electronic health records (EHRs), involving more than 85 million patients from 56 health care organizations (HCOs) in the US and has been described in prior studies of pouchitis.¹³ The de-identification process is performed at a network-level and attested through a formal determination by a qualified expert as defined in the HIPAA Privacy Rule. Coded clinical variables are derived directly from EHRs while non-structured data can also be retrieved through a built-in natural language processing system that extracts variables from clinical documents. Robust quality assurance is achieved at the time of extraction from EHRs before inclusion in the database. Finally, to further protect patient health information, the interface only provides aggregate counts and statistical summaries, ensuring that the data remain de-identified at all levels of data retrieval and dissemination.

Study Participants and Cohorts

We performed a real-time search and analysis of the US Collaborative Network in the TriNetX platform, evaluating patients age 18 years and older who underwent IPAA surgery between January 1, 2010 and December 31, 2022. We first identified patients with UC using International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes for UC (K51*) plus RxNorm codes for at least one UC-related medication (mesalamine, sulfasalazine, balsalazide, olsalazine, azathioprine, mercaptopurine, methotrexate, adalimumab, golimumab, infliximab, vedolizumab, ustekinumab and tofacitinib). These definitions and the TriNetX database have previously been used in the evaluation of patients with IBD^{13, 14} with complex case definitions for IBD demonstrating high specificity and positive predictive value.¹⁵ Patients undergoing proctocolectomy with IPAA were identified using Current Procedural Terminology (CPT) codes (Supplemental Table 1). The final stage of surgery was defined as a CPT code for an IPAA or CPT code for an ileostomy takedown following CPT code for total abdominal colectomy or total proctocolectomy (with or without IPAA at the time of initial colectomy).

Outcomes

The principal objectives of this study were to identify 4 key outcomes in the natural history after IPAA within 1-, 3-, 5- and 10-years. The primary outcome was to define the incidence of pouchitis. Secondary outcomes including defining the incidence of: CLDP, use of advanced therapies after IPAA, and pouch failure requiring excision. Since patients could have undergone IPAA surgery at any point during the study period, we created separate sub-cohorts to ensure all patients had adequate follow up for the period of interest. Patients with pouchitis were identified using a previously validated case-finding definition for use in administrative claims data^{1, 7} as summarized in the Supplemental Methods. Patients who developed CLDP were identified by at least two ICD-10-CM codes for CD (K50*). The database allows temporal relationships to be established between two variables of interest within a cohort. This functionality was utilized to ensure that the diagnosis of CD occurred for the first time after IPAA. Patients who required advanced therapies were identified using RxNorm codes for infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib or upadacitinib (Supplemental Table 2). Pouch failure was defined by the CPT code for excision of ileoanal reservoir with ileostomy (45136).

Secondary outcomes

The secondary objectives of the study were to identify factors associated with the development of pouchitis and advanced therapy use at 5 years after IPAA. Potential variables analyzed in these objectives were chosen given their prior association (presence or absence) with pouchitis. These include age of IPAA surgery¹⁶ (divided into age <40 and ≥ 40), sex,¹⁷ nicotine dependence,^18–21 primary sclerosing cholangitis (PSC),²² obesity,²³ pre-colectomy use of anti-tumor necrosis factor alpha (anti-TNF) therapy,^{1, 24} and colectomy during inpatient admission for UC (inpatient colectomy).²⁵ Given the association of anti-TNF use and risk of pouchitis, we also analyzed vedolizumab use prior to colectomy. We were unable to analyze predictors of CLDP due to requiring two or more ICD-10 CM codes during outcome assessment which is not feasible in the database for such analysis. We were also unable to analyze variables associated with pouch failure due to the low number of events (pouch failure). Additional secondary outcomes were to identify the incidence of specific malignancies within the 10 years after IPAA, including rectal cancer, small intestinal cancer, lymphoma/leukemia, melanoma and non-melanoma skin cancers (NMSC).

Statistical analysis

Baseline demographics and clinical characteristics are presented with means, standard deviations (SDs), and proportions. One-to-one (1:1) propensity score matching was performed in the two sub-cohorts for the variable of interest to balance the other covariates which included the following: age of pouch surgery, sex, race, primary sclerosing cholangitis, nicotine dependence, obesity, colectomy setting and anti-TNF exposure pre-colectomy. TriNetX platform utilizes input matrices of the user-identified covariates to conduct logistic regression analysis to obtain propensity scores for all individual subjects. The propensity scores generated are used to match patients using greedy nearest-neighbor algorithms with a caliper width of 0.1 pooled standard deviations. TriNetX randomizes the order of rows to eliminate bias resulting from nearest-neighbor algorithms. All Cox proportional hazard models satisfied the proportional hazard assumption. Hazard ratios and its associated confidence intervals, together with the test for proportionality were calculated using R’s survival package. The numbers are validated by comparing them with output from SAS version 9.4 (SAS Institute, Cary, NC, USA). After propensity score matching, the risk of each outcome was calculated and expressed as adjusted hazard ratios (aHR) with 95% confidence intervals (CIs). Two-sided p-values <0.05 were considered statistically significant. All other statistical analyses were conducted using the TriNetX software using the browser-based real-time analytics feature, TriNetx Live (TriNetX LLC, Cambridge, MA).

RESULTS

We identified 1,331 patients who underwent a colectomy with IPAA for UC during the study period. The mean age at the time of pouch surgery was 38.9 years (SD 15.5) with 737 patients (57%) being male (Table 1). Among the entire population, 89 (7%) had a diagnosis of PSC prior to colectomy and 65% had used at least one advanced therapy prior to colectomy, with infliximab (37%) being the most common advanced therapy utilized prior to colectomy. The proportion of patients with 1, 3, 5, and 10-years of follow up is depicted in Supplemental Table 3.

Table 1.

Demographics and clinical characteristics of patients undergoing colectomy with ileal pouch-anal anastomosis during study period

	Patients with IPAA N=1331
	mean	SD
Age at UC diagnosis	36.8	15.6
Age at pouch surgery	38.9	15.5
	n	%
Male sex	737	57
Race and/or ethnicity
White	1011	79
African American	70	5
Asian	35	3
Hispanic or Latino	135	11
Comorbid diseases
Primary sclerosing cholangitis	89	7
Hypertension	354	28
Hyperlipidemia	258	20
Diabetes mellitus	146	11
Ischemic heart disease	134	10
Chronic lower respiratory diseases	242	19
Obesity	30	11
Nicotine dependence	165	13
Alcohol use disorder	43	3
UC-related medications prior to colectomy #
Infliximab	477	37
Adalimumab	307	24
Golimumab	39	3
Vedolizumab	232	18
Ustekinumab	74	6
Tofacitinib	103	8
Azathioprine	329	26
Mercaptopurine	151	12
Methotrexate	131	10

Ileal pouch-anal anastomosis (IPAA); Ulcerative colitis (UC)

^#Patient could have been on more than one medication

Incidence and predictors of pouchitis

The incidence of pouchitis increased from 58% in the first year after IPAA to 72% at 10 years after IPAA (Figure 1). The 3- and 5-year incidence rates of pouchitis were 67% and 72% respectively. After propensity score matching, nicotine dependence was associated with an increased risk of pouchitis in the first 5 years after IPAA (aHR 1.61, 95% CI 1.19–2.18) as was use of anti-TNF therapy prior to colectomy for UC (aHR 1.33, 95% CI 1.13–1.56) and use of vedolizumab prior to colectomy (aHR 1.44, 95% CI 1.06–1.96). In this analysis, age, sex, a history of PSC, and colectomy during an inpatient admission for UC were not significantly associated with the development of pouchitis (Table 2).

Figure 1.

Cumulative incidence of pouch-related disorders in the first 10 years after ileal pouch-anal anastomosis, stratified by pouch-related disorder

Table 2.

Evaluation of factors associated with pouchitis after ileal pouch anal anastomosis after one-to-one propensity score matching

Variable	N (%)	aHR	95% CI	Log rank p value
Age <40	280 (68.6%)	1.01	0.85–1.19	0.90
Age ≥ 40	278 (68.1%)
Female sex	285 (68.3%)	0.95	0.81–1.12	0.56
Male sex	294 (70.5%)
Nicotine dependence	97 (82.2%)	1.61	1.19–2.18	0.001
No nicotine dependence	76 (64.4%)
Primary sclerosing cholangitis	48 (78.6%)	0.89	0.60–1.33	0.59
No Primary sclerosing cholangitis	48 (78.6%)
Obesity	189 (71.3%)	1.04	0.84–1.27	0.69
No obesity	184 (69.4%)
anti-TNF use pre-colectomy	320 (75.4%)	1.33	1.13–1.56	0.0004
No anti-TNF use pre-colectomy	286 (67.4%)
Vedolizumab use pre-colectomy	89 (79.4%)	1.44	1.06–1.96	0.01
No vedolizumab use pre-colectomy	75 (66.9%)
Inpatient colectomy	182 (72.5%)	1.08	0.88–1.33	0.43
Outpatient colectomy	173 (68.9%)

adjusted hazard ratio (aHR), anti-tumor necrosis factor (anti-TNF), confidence interval (CI)

Incidence and outcomes of advanced therapy use

The incidence of advanced therapy use increased from 4.0% in the first year after IPAA to 9.1% in the first 3 years after IPAA. This incidence continued to increase to 11.8% by 5 years after IPAA, ultimately reaching 14.4% of patients in the first 10 years after IPAA. After propensity score matching, patients less than age 40 at the time of IPAA surgery were more likely to be prescribed advanced therapies after IPAA (aHR 1.68, 95% CI 1.12–2.53) as was nicotine dependence (aHR 2.94, 1.38–6.28, Table 3). Additionally, patients with obesity were more likely to require advanced therapies after IPAA (aHR 1.80, 95% CI 1.04–3.11). When examining the individual advanced therapies utilized, anti-TNF therapies were the predominant therapies utilized at each time point examined (Table 4), with 76% of patients who had utilized an advanced therapy after IPAA in the first 10 years being prescribed at least one anti-TNF therapy. However, the proportion of patients prescribed vedolizumab and/or ustekinumab over the 10-year follow up period also increased, peaking at 24% and 29% of patients prescribed an advanced therapy respectively.

Table 3.

Evaluation of factors associated with advanced therapy use after ileal pouch anal anastomosis after one-to-one propensity score matching

Variable	N (%)	aHR	95% CI	Log rank p value
Age <40	60 (14.7%)	1.68	1.12–2.53	0.01
Age ≥ 40	38 (9.3%)
Female sex	59 (14.1%)	1.01	0.70–1.46	0.94
Male sex	55 (13.1%)
Nicotine dependence	26 (22.0%)	2.94	1.38–6.28	0.003
No nicotine dependence	10 (8.4%)
PSC	11 (18.0%)	0.99	0.42–2.35	0.99
No PSC	10 (16.3%)
Obesity	37 (15.3%)	1.80	1.04–3.11	0.03
No obesity	20 (8.2%)
Pre-colectomy anti-TNF use	65 (15.3%)	1.34	0.93–1.94	0.11
Pre-colectomy no anti-TNF use	50 (11.7%)
Vedolizumab use pre-colectomy	18 (16%)	1.04	0.53–2.02	0.89
No vedolizumab use pre-colectomy	17 (15.1%)
Inpatient colectomy	48 (19.1%)	1.35	0.87–2.08	0.17
Outpatient colectomy	36 (14.3%)

adjusted hazard ratio (aHR), anti-tumor necrosis factor (anti-TNF), confidence interval (CI), primary sclerosing cholangitis (PSC)

Table 4.

Distribution of advanced therapy use at 1-, 3-, 5-, and 10-years after ileal pouch-anal anastomosis surgery. Each time period of outcome assessment is a separate sub-cohort

Advanced therapy	1 year (n=55 [4%])	3 years (n=103 [9.1%])#	5 years (n=102 [11.8%])#	10 years (n=42 [14.4%])#
anti-TNF	31 (56.3%)	74 (71.8%)	72 (70.5%)	32 (76.1%)
Vedolizumab	12 (21.8%)	14 (13.5%)	18 (17.6%)	10 (23.8%)
Ustekinumab	11 (20%)	26 (25.2%)	29 (28.4%)	12 (28.5%)
JAK-inhibitor	<10	<10	<10	<10

Anti-tumor necrosis factor alpha (anti-TNF), janus kinase (JAK)

^#Patients could have been on more than one advanced therapy over the time period

Incidence of Crohn’s-like disease of the pouch and pouch failure

The incidence of CLDP at 1-, 3-, 5-, and 10- years after IPAA was 2.9%, 6.2%, 8.6%, and 10.3% respectively. The incidence of pouch failure increased from 1.15% at 1 year after IPAA to 4.1% at 10 years after IPAA (1.2%, 1.8%, 2.2% and 4.1% at 1-, 3-, 5-, and 10-years after IPAA respectively).

Incidence of malignancy after IPAA

When examining the incidence rates of malignancy after IPAA, the overall incidence of rectal cancer at 10 years after IPAA was 1.4% while the incidence of small intestinal cancer was 0.7%. The incidence of lymphoma or leukemia was 0.9% during the study period. Finally, the incidence of melanoma at 10 years after IPAA was 0.7%, while the incidence of non-melanoma skin cancer was 0.8%.

DISCUSSION

In this analysis of a large, geographically-representative database of over 1,300 patients undergoing IPAA for UC, we have provided a new longitudinal evaluation of the natural history after IPAA in the US, with an emphasis on clinically-relevant outcomes in the modern treatment era. Given recent indications that the incidence of pouchitis is increasing,⁸ our findings demonstrating advanced therapy use patterns that are similar to pre-colectomy use in patients with UC in other evaluations of administrative claims^{26, 27} may prompt consideration of the burden of disease demonstrated by patients with inflammatory disorders of the pouch. Additionally, our 10-year estimates of CLDP are similar to accepted incidence rates of CLDP,^{9, 10} perhaps indicating a continued unmet need for earlier identification of at-risk patients and potential early intervention for those patients at greatest risk for chronic inflammatory conditions of the pouch and pouch failure.

In our evaluation, over half of patients developed intermittent pouchitis within the first year after IPAA, with that rate increasing to >70% by 5 and 10 years postoperatively. In longitudinal, single-center studies from the US, >75% of patients will develop pouchitis with long-term follow up.⁴ However, the early identification of patients at risk for the development of pouchitis remains an unmet need given that patients developing pouchitis in the first year after IPAA have demonstrated an increased risk for chronic inflammatory conditions of the pouch.^{28, 29} In our evaluation, anti-TNF use pre-colectomy was associated with an increased risk for pouchitis, a finding which has previously been demonstrated in multiple studies to date.^{1, 24} Whether anti-TNF therapy modulates the ileal environment prior to colectomy with IPAA or is a marker of more severe disease at the time of colectomy remains an ongoing discussion,³⁰ however other studies have indicated that the number of biologics prior to colectomy and a colectomy for ASUC are associated with an increased risk for pouchitis.²⁵ In our evaluation, vedolizumab was also associated with an increased risk for pouchitis, however emergent colectomy in the inpatient setting was not associated with an increased risk for pouchitis after propensity score matching and adjusting for the other factors in our model.

Although smoking and nicotine dependence is traditionally poorly coded in administrative claims,³¹ patients who were diagnosed with nicotine dependence during the study period were at increased risk for pouchitis. Smoking has previously been identified as a potential risk factor for pouchitis, although this remains a somewhat questionable association.^{18, 19} Given the inability to definitively delineate current smokers from former smokers and the amount of active smoking among current smokers, the relationship between nicotine dependence and pouchitis likely warrants continued exploration in prospective studies.

Our understanding of the individual patient’s risk for CLDP at the time of colectomy remains a critical knowledge gap in pre-IPAA counseling. Although individual clinical and serologic factors have been linked to future development of CLDP,^32–34 many of these are not clinically actionable at this time. In this study, we did not have access to serologic data prior to IPAA. Additionally, due to the structure of the TriNetX data, we relied on ICD-10-CM coding for a diagnosis of CLDP rather than the more accepted clinical criteria of pre-pouch ileitis, stricturing disease, or the presence of a fistula.^{9, 10} Despite this limitation, our 10-year incidence rate of CLDP is similar to a recent systematic review and meta-analysis of all population-based studies¹⁰ and thus further adds to this literature base.

Given these concerns regarding the potential development of inflammatory conditions of the pouch, understanding the burden of disease as it relates to continued use of advanced therapies after IPAA was a critical objective of this study. We demonstrated increased use of advanced therapies over time, including both anti-TNF therapies and novel biologic therapies. Given that anti-TNF use pre-colectomy has been demonstrated as a risk factor for pouchitis,^{1, 24} the recycling of biologic therapies (as compared to the use of novel biologic therapies) after IPAA has increasingly been a topic of interest. In a single-center study, Kayal and colleagues demonstrated that recycling therapy with anti-TNF was associated with a decreased odds of clinical remission for chronic inflammatory conditions of the pouch,³⁵ although older studies have demonstrated no significant differences in these practices.³⁶ The recent EARNEST study comparing vedolizumab to placebo in the treatment of chronic pouchitis provides further evidence for the use of advanced therapies in this setting,³⁷ as do prospective evaluations from A Prospective Registry for the Study of Outcomes of Pouchitis and Pouch-Related Disorders (PROP-RD)^{38, 39} and other open-label or observational studies.^40–42 This improved understanding of the therapeutic landscape after IPAA may be beneficial to many stakeholders, including patients and providers participating in shared-decision making as well as payors and future researchers.

The rates of malignancy after IPAA have generated significant discussion in recent years, particularly when considering the appropriate surveillance approach for potentially high-risk individuals such as those with PSC and those who have undergone colectomy for dysplasia or colorectal cancer.⁴³ In a recent single-center evaluation of patients with PSC undergoing subtotal colectomy vs. IPAA, only 1 patient (1% of IPAA population) developed neoplasia of the rectal cuff,⁴⁴ with a similar proportion developing neoplasia in a larger evaluation of all patients with an IPAA.⁴⁵ In earlier evaluations from the Swedish National Patient Register⁴⁶ and the Cleveland Clinic,⁴⁷ rates of rectal cancer after IPAA were even lower. Placing our evaluations of rectal cancer after IPAA into these context would indicate that current recommended surveillance protocols are likely adequate,⁴⁸ although we did not have the same granularity as single-center evaluations.

Strengths of this study include the large sample size, long follow-up period allowing for an assessment of the progression of phenotypes after the first 2 years after IPAA surgery, and the geographically representative nature of the TriNetX database. Our study does have limitations. This was not an inception cohort, and thus individuals contributed differing amounts of time to the incidence analyses, with longer follow-up times potentially increasing the potential for development of inflammatory complications of the pouch and offering the potential for over-estimation of these incidences among patients contributing longer follow-up time. Additionally, changes in pre-colectomy and post-IPAA care over time may have influenced outcomes. Although over 85 million patients are represented, if an individual left a participating healthcare system or health plan following IPAA surgery, there is potential for loss to follow up and under-representation in the outcomes of interest. While this would bias to the null, this may also be non-differential as a patient with normal pouch function could also experience loss to follow up in the same scenario. The case-finding definitions for pouchitis have been validated, however our analyses rely on clinical coding and case-finding definitions, and thus do not include endoscopic or disease activity evaluations that are available in other more granular assessments after IPAA. This is particularly true when considering patients with CLDP, where a diagnostic code for CD may also represent a change in diagnosis that occurred at the time of colectomy (based on clinical or pathologic appearance) or more proximal small intestinal or upper gastrointestinal tract inflammation. Similarly, our clinical characteristics used in propensity score matching are derived from a retrospective database and are subject to misclassification. Additionally, patients who request pouch excision for lifestyle preferences rather than refractory disease would be misclassified. Finally, although our objective was to evaluate the use of advanced therapies after IPAA, we recognize that the indication for advanced therapy may overlap with other immune-mediated conditions outside of pouch-related disorders, in a minority of cases.

In conclusion, in a large, geographically representative database, we have provided modern estimates of the natural history after IPAA in the US. These include new estimates of the burden of pouchitis and CLDP, as well as the utilization of advanced therapies after IPAA. These data should provide multiple stakeholders with an updated evaluation of the natural history after IPAA and prompt continued evaluation of opportunities for early intervention to improve outcomes after IPAA.

STUDY HIGHLIGHTS.

WHAT IS KNOWN

• Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA)

• Other inflammatory conditions of the pouch create a burden for individual patients, but studies of the natural history and burden on the healthcare system are lacking

WHAT IS NEW HERE

• We analyzed outcomes in a geographically-representative database of over 1,300 patients undergoing IPAA for ulcerative colitis in the United States

• Approximately 14% of patients will utilize advanced therapies for inflammatory conditions of the pouch in the first 10 years after IPAA

• Nicotine dependence, obesity, and younger age at the time of IPAA were associated with an increased risk for advanced therapy use after IPAA

• The incidence of Crohn’s-like disease of the pouch increased to 10% within 10 years of IPAA while pouch failure increased to 4%