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Ileal pouch-anal anastomosis (IPAA), sometimes known as J-pouch surgery, is a procedure performed in patients with ulcerative colitis (UC), often for those whose treatment has not responded to medication.¹ Though common, the procedure is not without complications. For example, as many as 80% of patients with UC who underwent IPAA have been reported to develop pouchitis symptoms at some point after the surgery, with 17% developing chronic symptoms.² Other issues include pouch failure, the development of Crohn鈥檚-like disease of the pouch (CLDP), or even the need for advanced anti-inflammatory treatment.³

Until recently, research focusing on pouch-related disorders has been limited to small study population sample sizes.³ However, efforts have been made to standardize evaluation for patients post IPAA to improve patient care, and identification of patients has become easier with improved case-finding definitions using administrative claims data.4 However, data on the natural history after IPAA surgery are still lacking.³

To that end, researchers from the University of North Carolina at Chapel Hill investigated health outcomes of UC patients who underwent IPAA surgery and their use of advanced immunosuppressive therapies to manage pouchitis symptoms, including antitumor necrosis factor (anti-TNF) therapy use, within 10 years of the procedure to gain insight into the circumstances surrounding inflammatory conditions of the pouch.^2,3 Data were gathered from a multi-institutional research network of >80 million patients. Out of the database, researchers identified 1331 patients to include in the study.³

Incidence of pouch-related complications increased, but malignancy rates remained low 

This retrospective study evaluated data of adult patients previously diagnosed with UC who underwent an IPAA procedure between 2010 and 2022. The researchers sought to define the incidence of pouchitis within 1, 3, 5, and 10 years of the procedure as well as identify risk factors associated with development of pouchitis. What they found was that the incidence of pouchitis increased over time, beginning with 58% in the first year, 67% in the third year, and 72% in the fifth and tenth years.³

A small subset (n=89) of patients received a primary sclerosing cholangitis (PSC) diagnosis prior to their colectomy. While some would consider this group of patients as high-risk for post-operative complications, the researchers did not find significant associations between a prior PSC diagnosis and development of pouchitis. Furthermore, although overall cancer rates in post-IPAA patients are unknown, and surveillance guidelines remain loose, this study found that at 10 years post-IPAA, the overall incidences of rectal cancer and small intestinal cancer were 1.4% and 0.7%, respectively. The incidences of other cancers calculated included lymphoma or leukemia, melanoma, and nonmelanoma skin cancers, which were 0.9%, 0.7%, and 0.8%, respectively.³

Other complications stemming from IPAA, as noted above, included CLDP and pouch failure. In this population, it was found that the incidence of both CLDP and pouch failure increased slightly over the 10-year follow-up period³:

Incidence of CLDP

• 1-year: 2.9%
• 3-year: 6.2%
• 5-year: 8.6%
• 10-year: 10.3%

Incidence of pouch failure

• 1-year: 1.2%
• 3-year: 1.8%
• 5-year: 2.2%
• 10-year: 4.1%

Prior use of anti-TNF therapy may increase the need for advanced therapies after IPAA

The study explored a patient鈥檚 history prior to their colectomy and IPAA and their use of advanced therapy after the procedures. The average UC patient was diagnosed at age 36.8 years (SD, 15.6), while the average age for IPAA surgery was 38.9 (SD, 15.5). The data showed that patients under 40 years were more likely to be prescribed advanced therapy after their IPAA procedure (adjusted hazard ratio [aHR], 1.68; 95% confidence interval [CI], 1.12-2.53). Among patients who required advanced therapy after IPAA, 65% had also used at least 1 advanced therapy prior to colectomy, with infliximab (37%), an anti-TNF agent, being the most common. Researchers also identified other factors that could increase a patient鈥檚 chance of requiring advanced therapies, including nicotine dependence (aHR, 2.94; 95% CI, 1.38-6.28) and obesity (aHR, 1.80; 95% CI, 1.04-3.11).³

Advanced therapy use within the first year after IPAA was 4.0%, but it increased to 9.1% after 3 years and continued to increase to 11.8% after 5 years and 14.4% after 10 years. Advanced immunosuppressive therapies, such as anti-TNF agents and JAK inhibitors, are often prescribed to patients who develop pouch-related complications. In this population, anti-TNF therapy was the most commonly prescribed (76.1% at 10 years after IPAA), followed by vedolizumab (23.8%), ustekinumab (28.5%), and JAK inhibitors (n, <10).³

Research we need going forward 

This study identified patients on a database using various ICD-10-CM (International Classification of Disease, Tenth Revision, Clinical Modification) codes. While identification of UC patients only requires 1 code, K51*, identifying predictors of CLDP diagnoses required 2 or more ICD-10-CM codes, which is not feasible on the database, limiting the parameters of patients鈥� natural history prior to IPAA. Moreover, because the patients were not part of an inception cohort, the lack of uniformity in time to diagnosis and follow-up appointments could contribute to unmeasurable discrepancies, leading to overestimation of malignancy rate incidences and increasing potential for pouchitis development. 

The researchers noted, 鈥淭he 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.鈥� Post-IPAA complications can be devastating as they pose significant financial burdens on patients, thus identifying at-risk individuals and improving early interventions are essential.³

Published: December 27, 2024