Clinical Update on the Prevention and Management of Postoperative Crohn's Disease Recurrence.

PURPOSE OF REVIEW: Despite advances in therapeutics, a significant portion of patients with Crohn's disease still require surgical management. In this article, we present updates to the natural history, prognostication and postoperative monitoring, and novel therapeutics in the prevention and treatment of postoperative Crohn's disease recurrence. RECENT FINDINGS: Clinical risk factors have been associated with higher rates of postoperative recurrence (POR), and in recent studies demonstrate an increased cumulative risk with presence of additional risk factors. Additional novel clinical, histologic, and "-omic" risk factors for recurrence have recently been elucidated, including the role of the mesentery on recurrence and perioperative intraabdominal septic complications. High-risk patients benefit most from medical prophylaxis, including anti-TNF with or without immunomodulator therapy to prevent recurrence. New biologics such as vedolizumab and ustekinumab have emerging evidence in the use of prophylaxis, especially with recent REPREVIO trial data. Non-invasive disease monitoring, such as cross-sectional enterography, intestinal ultrasound, and fecal calprotectin, have been validated against ileocolonoscopy. Recent advances in the prediction, prevention, and monitoring algorithms of postoperative Crohn's disease may be leading to a reduction in postoperative recurrence. Ongoing trials will help determine optimal monitoring and management strategies for this at-risk population.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

BACKGROUND: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). METHODS: We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. RESULTS: Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). CONCLUSION: Development of EIPD was not associated with number or type of preoperative advanced therapies.

Real-World Surgical and Endoscopic Recurrence Based on Risk Profiles and Prophylaxis Utilization in Postoperative Crohn's Disease.

BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.

Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn's Disease Recurrence.

GOALS: Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis. BACKGROUND: Postoperative biologic prophylaxis reduces postoperative Crohn's disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated. STUDY: Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy. RESULTS: Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation. CONCLUSION: In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.

Anastomotic Configuration and Temporary Diverting Ileostomy Do Not Increase Risk of Anastomotic Stricture in Postoperative Crohn's Disease.

INTRODUCTION: Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. METHODS: A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. RESULTS: A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. DISCUSSION: AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Mild neoterminal ileal post-operative recurrence of Crohn's disease conveys higher risk for severe endoscopic disease progression than isolated anastomotic lesions.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease. METHODS: Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence. RESULTS: One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P < 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P < 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86). CONCLUSION: Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Mesenteric Excision and Exclusion for Ileocolic Crohn's Disease: Feasibility and Safety of an Innovative, Combined Surgical Approach With Extended Mesenteric Excision and Kono-S Anastomosis.

INTRODUCTION: Ileocolic resection for Crohn's disease traditionally does not include a high ligation of the ileocolic pedicle, and most commonly is performed with a stapled side-to-side ileocolic anastomosis. The mesentery has recently been implicated in the pathophysiology of Crohn's disease. Two techniques have been developed and are associated with reduced postoperative recurrence: the Kono-S anastomosis that excludes diseased mesentery and extended mesenteric excision that resects diseased mesentery. We aimed to assess the technical feasibility and safety of a novel combination of techniques: mesenteric excision and exclusion. TECHNIQUES: This initial report is a single-center descriptive study of consecutive adults who underwent mesenteric excision and exclusion for primary or recurrent ileocolic Crohn's disease from September 2020 to June 2021. Medication exposure and endoscopic balloon dilation before surgery were recorded. Phenotype was classified using the Montreal Classification. Thirty-day outcomes were reported. A video of the mesenteric excision and exclusion including the Kono-S anastomosis is presented. RESULTS: Twenty-two patients with ileocolic Crohn's disease underwent mesenteric excision and exclusion: 100% had strictures, 59% had fistulas, 81% were on biologics, and 27% had previous ileocolic resection(s). Seventy-two percent underwent laparoscopic procedures, a mesenteric defect was closed in 86%, omental flaps were fashioned in 77%, and 3 patients were diverted. Median operative time was 175 minutes. Median postoperative stay was 4 days. At 30 days, there were 2 readmissions for reintervention: 1 seton placement and 1 percutaneous drainage of a sterile collection. There were no cases of intra-abdominal sepsis or anastomotic leak. CONCLUSIONS: Mesenteric excision and exclusion represents an innovative, progressive, and promising approach that appears to be highly feasible and safe. Further study is warranted to determine if mesenteric excision and exclusion is associated with reduced postoperative recurrence of ileocolic Crohn's disease.

Pouch Function Over Time and With Advancing Age.

BACKGROUND: No long-term pouch studies have included follow-up >30 years or an analysis in patients >80 years old. OBJECTIVE: This study aimed to investigate pouch function and pouch failure in patients with a pouch in situ >30 years and in patients >80 years old. DESIGN: This is a retrospective review. SETTING: This study was conducted at an IBD referral center. PATIENTS: Adult patients with ulcerative colitis who underwent an IPAA between 1983 and 1990 were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were pouch function and pouch failure rates. METHODS: Data collection included diagnosis, age at IPAA, indication for IPAA, medications at IPAA, pathology at the time of IPAA, postoperative morbidity, functional outcomes, quality of life, pouch excision or ileostomy and indication, and date of last follow-up. All living patients were contacted in April 2020 to retrieve functional data and pouch failure rates. RESULTS: A total of 566 patients had a pouch constructed between 1983 and 1990; of the 145 at most recent contact, 75 had their pouch in situ ≥30 years and 14 were ≥80 years old. Mean age at diagnosis was 25.8 years (10.6 SD), age at surgery was 34.7 years (11.3 SD), and age at last follow-up was 60.5 years (13.2 SD). At a median of 30 years (IQR, 21-32), 145 patients responded to the functional survey. Significantly increased rates of urgency (always, mostly, sometimes: 71.5% vs 23.5%) and seepage during the day (71.4% vs 22.4%) were observed in patients ≥80 years. In patients ≥80 years with a pouch in situ ≥30 years, urgency and incontinence were sometimes experienced by nearly 50% and pouch failure occurred in one third of patients. The overall rate of pouch failure was 19.4% (n = 110) at a median follow-up of 15 years; risk factors were female sex, 3-stage approach, and pelvic sepsis. LIMITATIONS: A retrospective database was used. CONCLUSION: Patients with IPAA maintain good pouch function even after 30 years and in patients over the age of 80 years. Pouch function declines with time and failure rates increase over time. See Video Abstract at http://links.lww.com/DCR/B684.Función De La Bolsa Ileal En El Tiempo Y En Pacientes De Edad Avanzada. ANTECEDENTES: No se han efectuado estudios en pacientes con bolsa a largo plazo que incluyan un seguimiento por treinta años o más y en pacientes mayores de 80 años. OBJETIVO: Investigar la funcionalidad o la falla de la bolsa en pacientes bolsa in situ por mas de treinta años y en pacientes mayors de 80 años. DISEO: Revisión retrospective. ESCENARIO: Centro de referencia de Enfermedad Inflamatoria Intestinal. PACIENTES: Pacientes adultos con diagnóstico de colitis ulcerative sometidos a anastomosis bolsa ileal anal (IPAA) entre 1983 y 1990. PRINCIPALES PARAMETROS DE RESULTADOS: Indices de efectividad y disfunción de la bolsa ileal. METODOS: Recopilación de la información incluyendo diagnóstico, edad del procedimiento (IPAA), indicaciones para IPAA, medicamentos para IPAA, patología en el transcurso del IPAA, morbilidad postoperatoria, resultados funcionales, calidad de vida, excisión de la bolsa o ileostomía y su indicación y fecha de seguimiento mas reciente. Se contactaron a todos los pacientes vivos en abril de 202 para recuperar la información de los índices de funcionalidad o disfunción de la bolsa. RESULTADOS: Se les construyó una bolsa a un total de 566 pacientes entre 1983 y 1990; de los 145 mas recientemente contactados, 75 permanecían con su bolsa in situ ≥ 30 años y 14 eran mayores de 80 años. La edad media en el momento de diagnóstico fue de 25.8 años (con desviación estándar de 10.6, sd), edad al momento de la cirugía fue de 34.7 años (11.3sd), y la edad en el último seguimiento de 60.5 años (13.2,sd). A una media de 30 años (IQR: 21,32), 145 pacientes respondieron al cuestionario de funcionalidad. En pacientes mayores de 80 años se observaron tasas aumentadas de urgencia (siempre, la mayor parte de las veces, algunas veces: 71.5% vs 23.5%) y fuga durante el día (71.4% versus 22.4%). En pacientes mayores de 80 años con una bolsa in situ durante 30 años o más, experimentaron urgencia e incontinencia en cerca del 50% y disfunción de la bolsa en un tercio de los pacientes. La tasa global de fallo de la bolsa fue de 19.4% (n = 110) en un seguimiento a 15 años; los factores de riesgo asociados fueron: sexo femenino, abordaje de tres tiempos y sepsis pélvica. LIMITACIONES: Información retrospective. CONCLUSIONES: Los pacientes con IPAA continúan con una función adecuada de la bolsa aún después de 30 años de efectuada así como en pacientes mayores de 80 años. La funcionalidad de la bolsa disminuye con el tiempo y las tasa de falla aumentan de igual forma con el tiempo. Consulte Video Resumen en http://links.lww.com/DCR/B684. (Traducción- Dr. Miguel Esquivel-Herrera).

Medical therapies for postoperative Crohn's disease.

Postoperative recurrence of Crohn's disease is common and requires a multidisciplinary approach between surgeons and gastroenterologists in the perioperative and postoperative period to improve outcomes in this patient population. Endoscopic recurrence precedes clinical and surgical recurrence and endoscopic monitoring is crucial to guide postoperative management. Risk stratification of patients is recommended to guide early prophylactic management, and follow-up endoscopic monitoring can guide intensification of therapy. This review summarizes evidence behind postoperative recurrence rates, disease monitoring techniques, nonbiologic and biologic therapies available to prevent and treat postoperative recurrence, risk factors associated with recurrence, and postoperative management strategies guided by endoscopic monitoring.

Hypoalbuminaemia, Not Biologic Exposure, Is Associated with Postoperative Complications in Crohn's Disease Patients Undergoing Ileocolic Resection.

BACKGROUND: There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. METHODS: Crohn's disease patients who underwent ileocolic resection over 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. RESULTS: A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [p = 0.21], vedolizumab [p = 0.17], or ustekinumab [p = 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albumin < 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). CONCLUSIONS: In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.

The burden of cost in inflammatory bowel disease: a medical economic perspective.

PURPOSE OF REVIEW: The cost of care for inflammatory bowel disease (IBD) has nearly doubled over the last two decades. With evolving treatment paradigms utilizing costly but efficacious biologic agents earlier and more often, the cost burden is only expected to worsen. The purpose of this review is to explore the current economic landscape and drivers of IBD healthcare costs along with potential mechanisms for improving value and cost-effectiveness of IBD care. RECENT FINDINGS: The prevalence of IBD continues to rapidly expand with costs following suit. As compensation models change, the medical community is more incentivized than ever to develop cost reduction strategies including incorporation of high-value care measures, cooperative data aggregation, and technological solutions, with many of these interventions demonstrating promising results. SUMMARY: IBD is an expensive chronic disease with payments only expected to rise. In light of this financial conundrum, new practice models, such as the IBD specialty medical home and remote telemedicine, are being tested with an emphasis on cost reduction. Many of these strategies are demonstrating improved patient outcomes while also curbing expenses. These early successes set the stage for continued cooperation, collaboration, and growth in value-based management of IBD.

The Burden of Cost in Inflammatory Bowel Disease: A Medical Economic Perspective and the Future of Value-Based Care.

PURPOSE OF REVIEW: To examine the quantifiable economic impact of inflammatory bowel disease (IBD), key cost drivers and determinants, and the impact of value-based care in IBD. Finally, we prognosticate on future directions and opportunities on healthcare economics in IBD. RECENT FINDINGS: New value-based initiatives, technologically driven interventions, and quality improvement programs have demonstrated reductions in healthcare utilization and enhanced patient outcomes, and several have realized cost of care reductions. IBD is a costly, chronic illness with unbalanced spending by a small proportion of individuals. Pharmaceutical costs are overtaking inpatient expenses as the primary cost driver. Value-based care initiatives including the IBD medical home, remote monitoring platforms such as myIBDcoach and Project Sonar, and learning healthcare networks exemplified by ImproveCareNow have all demonstrated successes in improving care quality, patient outcomes, and reduced healthcare spending in some populations. The future of value-based care in IBD is bright, with ample opportunities for model refinement, collaboration, and growth.

The Cost of Crohn's Disease: Varied Health Care Expenditure Patterns Across Distinct Disease Trajectories.

BACKGROUND: Patients with Crohn's disease (CD) encompass a heterogeneous disease spectrum, with variable health care utilization and expenditure patterns. Lémann Index (LI) is a metric that quantifies cumulative bowel damage and has shown utility in delineating distinct disease phenotypes. We aimed to characterize the financial burden from all medical care in CD cohort in relation to the variations in LI-based disease phenotypes. METHODS: CD patients with 5-year (y) follow-up from a prospective registry were included. LI was calculated from first (LI1) and last (LI2) clinical encounters. Change in score (LI2-LI1) or Delta LI (DLI) was used for association analysis with health care expenditures. RESULTS: A total of 243 patients with CD formed the study population (median age, 44 years; 58% women; median disease duration 12 years). DLI was used to define disease trajectories: DLI <0 (indicating improving bowel damage); DLI = 0 (stable); DLI >0 (worsening); which comprised 15.6%, 30.9%, and 53.5% of the cohort, respectively. Patients with DLI >0 had significantly higher CD-related surgeries, health care utilization, medication (steroids and biologics) use as well as higher median 5 years total and stratified charges compared with the other groups. Total 5-year expenditure was $56 million; 67% of which was related to hospitalization. Total expense showed independent positive correlation with LI2 (P = 0.001) and DLI (P = 0.001), and negative correlation with age (P = 0.029) and 5-year quality of life score (P = 0.024). CONCLUSIONS: The financial burden of CD is significantly associated with worsening bowel damage. Further research should focus on the prediction and management of the costliest/sickest patients with CD.