A Clinical Prediction Model for Early Colectomy in Patients With Severe Ulcerative Colitis Treated With Tacrolimus

Natural History of Severe Ulcerative Colitis in a Community-Based Health Plan

Inflammatory Bowel Disease Clinical

Background and AimSeveral studies have identified postinduction therapy predictors of long‐term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC.MethodsNinety‐five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5‐aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti‐Tumor Necrosis Factor (TNF)‐α antibodies], and laboratory data (hemoglobin, albumin, C‐reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P < 0.05 was considered significant.ResultsAll clinical parameters were not significant predictors of colectomy. Among laboratory parameters, the serum albumin level on admission was a significant independent predictor of colectomy (odds ratio: 6.097, 95% confidence interval: 1.8310–20.3047). Receiver operating characteristic curves were plotted for the serum albumin levels of the 95 patients at admission. The cut‐off value of serum albumin was 2.45 g/dL.ConclusionsWhen the serum albumin level of UC patients at admission is below 2.45 g/dL, we should consider presenting the option of surgical treatment to patients.

Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX. Patients and methods: Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the “Tor Vergata University” hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy. Results: A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level <3 g/dL and colonic dilation >5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08–22.8, and OR 8.5, 95% CI: 1.23–58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor. Conclusions: A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX.

Calcineurin inhibitors (CNIs) such as cyclosporine A (CSA) and tacrolimus (FK506) are often used as a second-line drug for steroid-refractory or steroid-dependent patients with ulcerative colitis (UC). The aim of the present study was to determine the prognostic factors for early colectomy. A total of 85 hospitalized patients with UC (CSA, 50 patients; FK506, 35 patients) were enrolled. Colectomy carried out within 60 days of starting CNI therapy was defined as 'early colectomy'. To assess the prognostic factors affecting early colectomy, clinical practical variables, including the Onodera-prognostic nutritional index (O-PNI): 10xAlb+0.005× (total lymphocyte count), were analyzed. The results demonstrated that the significant factors predicting early colectomy were i) disease severity, ii) immunomodulator-naïve history, iii) lower serum hematocrit, iv) lower serum albumin and v) lower O-PNI. In addition, the significant factors predicting overall colectomy were as follows: i) C7-HRP positivity and ii) >10,000 mg of prednisolone used prior to the initiation of CNI treatment. The combination of hematocrit and O-PNI enhanced the prediction of early colectomy. Clinical variables such as hematocrit and O-PNI were the significant factors predicting colectomy. These results may be used as a guide to predict the outcome of patients with UC in clinical settings.

Severity of Primary Sclerosing Cholangitis and Ulcerative Colitis: Does Liver Transplantation Protect Against Colectomy?

Incidence of Colectomy During Long-term Follow-up After Cyclosporine-Induced Remission of Severe Ulcerative Colitis

The risk of colectomy in patients with ulcerative colitis (UC) has decreased since the 20th century. Our aim was to determine the colectomy risk of newly diagnosed Finnish UC patients and compare the risk of the prebiological and biological era. We used the registry of the Social Insurance Institution of Finland to find newly diagnosed UC patients, and colectomies were collected from the Finnish Institute for Health and Welfare. The patients were stratified according to the year of UC diagnosis into 3 groups: 2000-2005 (prebiological), 2006-2012, and 2013-2020. We identified 32108 UC patients and 2195 colectomies performed on them. The 1-, 5-, and 10-year cumulative colectomy risk was 1.0%, 4.7%, and 7.3%, respectively. The risks declined with the incidence rate ratio (IRR) 0.98 (95% CI, 0.96-0.99), IRR 0.97 (CI, 0.96-0.98), and IRR 0.97 (CI, 0.96-0.99), respectively. Men and the pediatric group had higher risk of surgery (IRR 1.25, CI, 1.15-1.37 and IRR 1.69, CI, 1.51-1.89). Colectomy risks were lower in the last study era (IRR 0.757, CI, 0.574-0.997 in 1-year and IRR 0.70, CI, 0.61-0.82 in 5-year risk), and the 10-year risk was also decreased in the second era (IRR 0.87, CI, 0.78-0.97) compared to the prebiological era. The pediatric population had lower risk of surgery only in the last era, whereas the risk among the elderly remained constant. The risk of colectomy in UC patients has decreased in the 21st century.

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment

The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. Multiple electronic databases were searched systematically through July 2014 for studies reporting the risk of colectomy in patients with UC with CMV stratified by treatment with antiviral agents. Colectomy rates were assessed for the overall cohort and stratified by corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95% confidence intervals, using random-effects model, and used Grading of Recommendations Assessment, Development, and Evaluation criteria to appraise the quality of evidence. Fifteen observational studies (333 patients with UC with CMV, 43.2% treated with antiviral agents) were identified, of which 8 stratified patients according to CS-refractory disease (55.4% treated with antiviral agents). Antiviral therapy resulted in a significantly lower risk of colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95% confidence interval, 0.08-0.49; I = 0%) but not in the overall population of patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65). The quality evidence was low. The results were stable when restricting the analysis to patients with a tissue diagnosis of CMV and studies that defined CS-refractory disease as a failure to respond to intravenous CS. Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS. Further prospective trials are required to confirm these findings.

Background Up to 15% of patients with ulcerative colitis (UC) do not respond to medical therapies and ultimately require colectomy for disease control. Baseline endoscopic severity and failure to achieve endoscopic healing, as defined by a Mayo Endoscopic Subscore (MES) ≤ 1, following therapy have been associated with an increased risk of colectomy. Intestinal ultrasound severity, as defined by a Milan ultrasound criteria (MUC) score &amp;gt; 6.2, has been associated with an increased risk of colectomy. The aim of this study is to evaluate and compare MES and MUC in predicting the need for colectomy in patients with UC. Methods This is a double-center prospective observational cohort study. All consecutive adult UC patients between January 2016 and January 2020 requiring colonoscopy received intestinal ultrasound within 20 ± 12 days in a blinded fashion. Colectomies were evaluated during the follow-up. Univariable and multivariable Cox regression analyses were used to identify variables independently associated with colectomy risk. ROC analysis was used to compare baseline MES and MUC scores' performances in predicting colectomy. Results A total of 141 patients were enrolled (Table 1). Overall 13 patients underwent colectomy during 256.41 person-years of observation time. At baseline, patients requiring colectomy had increased mean values of MUC as compared to patients not undergoing surgery (6.84 ± 2.49 vs 10 ± 1.9, p &amp;lt;0.001). At univariate analysis, MES (HR: 3.15, 95% CI:1.18 – 8.37, p = 0.02) and MUC (HR: 1.48, 95% CI:1.19 – 1.76, p &amp;lt;0.001) were associated with colectomy risk. At multivariable analysis, MUC but not MES was associated with colectomy risk (HR: 1.46, 95% CI: 1.06 – 2.02, p 0.02). As compared with MES, MUC score demonstrated a higher AUROC (0.83, 95% CI: 0.75 – 0.92 vs 0.71 95% CI: 0.62 – 0.80) and better performance for assessing the need for colectomy (p = 0.02) (Figure 1). The optimal MUC score cutoff for predicting colectomy, as assessed by the Youden index, was 7.72, with a sensitivity and specificity of 1 and 0.6, respectively. Conclusion Ultrasound severity, as assessed by the MUC score, is superior to endoscopic severity in predicting the need for colectomy in patients with UC. A baseline MUC score of &amp;lt; 7.72 may rule out colectomy risk in UC patients.

Despite progress in medical treatment for ulcerative colitis, a considerable fraction of ulcerative colitis patients undergo colectomy. We analyzed the clinical variables of ulcerative colitis patients and determined the risk factors and indications for colectomy. The clinical records of 981 consecutive Japanese patients with ulcerative colitis were reviewed both retrospectively and prospectively. Of 981 patients with ulcerative colitis, 85 patients underwent colectomy. Multivariate analysis indicated that male gender (risk ratio, 2.16; 95 percent confidence interval, 1.37-3.42), onset year during and after 2000 (risk ratio, 2.85; 95 percent confidence interval, 1.31-6.22), severe disease activity (risk ratio, 2; 95 percent confidence interval, 1.15-3.48), corticosteroid resistance (risk ratio, 7.05; 95 percent confidence interval, 4.29-11.59), and complications because of corticosteroid administration (risk ratio, 3.55; 95 percent confidence interval, 2.08-6.06) were significant risk factors for colectomy. In patients with disease duration of more than five years, only corticosteroid resistance and complications because of corticosteroid were significant risk factors for colectomy. When we stratified indications for colectomy for the 85 cases via patient disease duration, massive hemorrhage was a relatively frequent cause of colectomy in patients with a disease duration of less than five years (P = 0.091). On the other hand, colon dysplasia or cancer was a major cause for colectomy in patients with a disease duration of more than ten years (P = 0.0001). In ulcerative colitis patients, the risk factors and indications for colectomy were different according to the patient's clinical background. Our findings may help to predict patients with ulcerative colitis who have a high risk for colectomy.

Background Acute severe ulcerative colitis (ASUC) is a life-threatening condition which requires quick decision making and urgent treatment. To facilitate this process, it is essential to identify patients at a high risk of emergency colectomy. The aim of this study is to identify predictors for emergency colectomy in patients with ASUC. Methods A retrospective study of 121 patients admitted with ASUC to a single gastroenterology centre between 2010 and 2020 was performed. Clinical and demographic data, laboratory and endoscopic examinations results were analysed as potential predictors of colectomy. Albumin and C-reactive protein (CRP) levels were recorded at baseline and at the 3rd day after intravenous steroids (IVS) initiation. Results 119 patients initially received IVS, while 2 patients with suspected intestinal perforation underwent emergency colectomy on the first day. 64 (53%) were women, with a median age of all patients of 33 (IQR 27-49) yrs. 15 (12.4%) patients admitted with ASUC underwent colectomy, while mortality rate during hospitalization was 1.7%. During the entire follow-up period, with a median duration of 46.5 months (23-88.25), colectomy was performed in 19 (15.7%) patients. Overall, in the study group, colectomy rate at 1 month, 3 months and 2 years were 12.4%, 12.4%, and 14.0%, respectively. Assessing further outcomes after colectomy, during the follow-up period, 13 (68.4%) achieved clinical remission, 1 died during the operation, and 5 (26.3%) patients still have an active course of the disease requiring immunosuppressive treatment. When comparing patients in the colectomy group (n=13) with patients who avoided colectomy during this hospitalization (n=105), no significant differences were found in age, sex, duration of illness, body mass index, endoscopic activity, the use of prednisolone or azathioprine prior to admission or previous treatment with biologics. The presence of cytomegalovirus and Clostridium difficile infection was also not associated with a higher risk of colectomy. Significant differences between the groups were found comparing the laboratory findings: the strongest predictor of colectomy was the CRP/albumin ratio at day 3 after IVS initiation (median value was 1.26 (0,81-3,26) in colectomy group vs. 0,64 (0,25-1,36) in non-colectomy group, p&amp;lt;0.001). The difference was also observed when comparing albumin (median 26 (24-28) vs. 29 (27-32), p=0.012) and CRP (median 33 (25-83) vs. 16 (8-37), p=0.003) levels separately on the 3rd day, while at baseline there was no significant differences in laboratory findings. Conclusion A low serum albumin level, higher CRP and CRP/albumin ratio are predictive factors of emergency colectomy in ASUC patients.

Ulcerative Colitis Care Pathway

BACKGROUND Acute severe ulcerative colitis (ASUC) is a life-threatening presentation of ulcerative colitis requiring prompt treatment. The Oxford (Travis) Index, developed in 1996, is the most widely used scoring system for identifying patients at risk of failing steroid therapy and requiring colectomy or second-line medical therapy in patients with ASUC. The Oxford Index, which was developed based on a retrospective case series of 48 patients, demonstrated that a stool frequency &amp;gt;8 bowel movements (BMs) per day or a stool frequency of 3-8 BMs per day in combination with a C-reactive protein (CRP) &amp;gt; 45 mg/L after 72 hours of corticosteroid treatment was associated with an 85% chance of requiring colectomy. Using an absolute CRP cutoff, as in the case of the Oxford Index, does not accurately consider the heterogeneity in admission CRPs and rate of improvement that exist among ASUC patients. We aim to determine the optimal timepoint and threshold of CRP for identifying patients with ASUC at risk for colectomy. METHODS We performed a cohort study of adult patients hospitalized with ASUC between 01/2014 – 04/2024 at a single academic hospital. Latent class analysis was employed to identify distinct patient subgroups based on admission CRP levels. Univariable logistic regression was used to identify associations between 90-day colectomy and absolute CRP value and rate of CRP change from Day 0 to Day 3. Model performance was assessed using area under the receiver operator characteristic (auROC) curve. RESULTS Between 01/2014 – 04/2024, 880 patients were admitted with ASUC. Latent class analysis identified 4 distinct CRP subgroups: CRP non-producers (admission CRP &amp;lt; 1.0mg/dL; n=162), CRP Low (admission CRP 1.0 to 3.3mg/dL; n=321), CRP Intermediate (admission CRP 3.4 to 9.4; n=221), and CRP High (admission CRP ≥ 9.5mg/dL; n=176) Table 1 provides demographic and outcome data. Figure 1 provides longitudinal CRP trend according to admission CRP subgroup and 90-day colectomy status. Our analysis demonstrated that only an absolute Day 3 CRP [Odds Ratio (OR) 1.07; 95% confidence interval (CI) 1.02 to 1.13; p =0.008; auROC 0.684] and Day 0 to Day 3 rate of CRP change (OR 1.16; 95% CI 1.02 to 1.34; p =0.29; auROC 0.62) was associated with 90-day colectomy in the High CRP group. Absolute CRP and Day 0 to Day 3 rate of CRP change was not associated with 90-day colectomy in the Low CRP or Intermediate CRP subgroup. CONCLUSION Absolute day 3 CRP value and Day 0 to Day 3 rate of CRP change were identified as a significant predictor of 90-day colectomy in patients with ASUC in the High CRP subgroup; No association between CRP and 90-day colectomy were observed in the Low or High CRP subgroups. These data suggest that using an absolute CRP cutoff to determine the risk of requiring colectomy or second-line therapy may not be appropriate for all patients with ASUC. Table 1: Demographic Characteristics and Clinical Outcomes Stratified by Admission C-reactive Protein Subgroup Figure 1: Longitudinal CRP Value and Trend on Each Day of Admission