Real-World Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis.

Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2-8 and weeks 24-48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

Real-world effectiveness of ustekinumab for patients with ulcerative colitis: a systematic review and meta-analysis.

Ustekinumab has recently been approved for the treatment of ulcerative colitis (UC) based on data from clinical trials. However, the effectiveness of ustekinumab in patients with UC in a real-world setting remains unclear. Hence, in this meta-analysis, we aimed to evaluate the effectiveness of ustekinumab in a real-world setting and to investigate the predictors of its effectiveness. A comprehensive literature search was performed to examine the effectiveness of ustekinumab in UC patients admitted between January 2019 and December 2021. Data on clinical remission, response, and corticosteroid-free clinical remission rates were extracted, pooled, and analyzed. Meta-regression analysis was performed to investigate the source of heterogeneity and the impact of moderators on the outcomes of interest. A total of 14 eligible studies were identified. The pooled clinical remission rate was 55.0% at week 8, 36.1% at week 16, 46.6% at month 6, and 38.6% at month 12. The meta-regression analysis showed that prior use of anti-tumor necrosis factor (TNF) agents and vedolizumab and the publication style were significant moderators. Additionally, out of 258 patients, there were 28 adverse events (AEs) (10.9%). The effectiveness of ustekinumab in real-world patients with UC was consistent with the results clinical trials. Moreover, previous treatment with anti-TNF agents and vedolizumab might have affected the effectiveness of ustekinumab.

The role of early video capsule endoscopy in the diagnosis and prognosis of obscure gastrointestinal bleeding: A multi-center propensity score matching study.

BACKGROUND AND AIM: Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients. METHODS: A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14 days of bleeding (early group, n = 678) to patients that did not (late group, n = 319) via 1:1 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1 year between these groups before and after PSM. RESULTS: Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P = 0.001) and with a significantly lower incidence of rebleeding within 1 year following treatment (24.7% vs 36.7%, P = 0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P = 0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P = 0.007, respectively) was found to be linked with a higher rate of positive findings. CONCLUSION: Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.

Systematic review and meta-analysis of the diagnostic and therapeutic yield of small bowel endoscopy in patients with overt small bowel bleeding.

BACKGROUND: Small bowel endoscopy, including small bowel capsule endoscopy (SBCE) and balloon-assisted endoscopy (BAE), is useful for small bowel bleeding (SBB) assessment. However, the specific management strategy for overt SBB is not well established. This meta-analysis aimed to evaluate the pooled diagnostic yields (DYs) and therapeutic yields (TYs) of small bowel endoscopy in overt SBB and to determine the optimal endoscopy timing. METHODS: A comprehensive literature search was performed of studies examining the DY and/or TY of small bowel endoscopy in overt SBB. Data on the DY, TY, and timing of small bowel endoscopy were extracted, pooled, and analyzed. The pooled DY and TY of small bowel endoscopy for patients with overt SBB were calculated. Meta-regression and subgroup analysis were performed. RESULTS: Twenty-two studies were included. The pooled DY was 65.2% and 74.0% for SBCE and BAE, respectively. The pooled TY of SBCE and BAE was 55.9% and 35.8%, respectively. A meta-regression model showed that the timing of endoscopy was significantly associated with the DY of BAE and the TY of SBCE and BAE. CONCLUSIONS: Small bowel capsule endoscopy and BAE would be useful diagnostic and therapeutic modalities in overt SBB. According to the subgroup analysis, in which the TY seemed to be higher within 2 days after bleeding for SBCE and BAE, the optimal timing of endoscopy would be within 2 days.

Nomogram-based prediction of rebleeding in small bowel bleeding patients: the 'PRSBB' score.

Small bowel capsule endoscopy (SBCE) and balloon-assisted endoscopy (BAE) have revolutionized the diagnosis and treatment of small bowel bleeding (SBB), allowing access to the small bowel and identification of specific bleeding lesions. However, some patients experience rebleeding after small bowel investigation, and there are no definitive algorithms for determining the most appropriate follow-up strategy in SBB patients. We developed and validated a nomogram that can predict rebleeding risk and be used to develop a risk-stratified follow-up strategy in SBB patients. A retrospective study was performed using data from 401 SBB patients who underwent SBCE at Nagoya University Hospital. We developed and internally validated a predictive model for rebleeding in the form of a nomogram using Cox regression models and a bootstrap resampling procedure. Optimal risk factors were selected according to the least absolute shrinkage and selection operator (LASSO). The LASSO method identified 8 independent predictors of rebleeding that could be assessed to obtain a 'predicting rebleeding in SBB', or 'PRSBB' score: age, sex, SBB type, transfusion requirement, cardiovascular disease, liver cirrhosis, SBCE findings, and treatment. The c-statistic for the predictive model was 0.681. In conclusion, our PRSBB score can help clinicians devise appropriate follow-up plans.

Risk factors for rebleeding and risk-based follow-up of obscure gastrointestinal bleeding after its initial diagnosis.

Capsule endoscopy (CE) and double-balloon endoscopy (DBE) have revolutionized the diagnosis and treatment of obscure gastrointestinal bleeding (OGIB). Although CE and DBE provide access to the small bowel and OGIB can be effectively treated by the identification of specific bleeding lesions, some patients experience rebleeding after small bowel investigation. There are no definite algorithms to determine the best follow-up period for patients with OGIB. The purpose of this study was to investigate the long-term outcomes and risk factors for rebleeding and to develop a follow-up strategy for patients with overt OGIB. Among 386 patients who underwent CE for OGIB at Nagoya University Hospital between June 2004 and December 2015, 318 patients with overt OGIB were enrolled in this retrospective study. The clinical characteristics and risk factors for rebleeding were analyzed, and a predictive model for the same was developed. Rebleeding occurred in 45 patients (14.2%) during a median follow-up period of 16.8 months. Multivariable regression analysis identified the following factors as significant independent predictors of rebleeding:vascular lesions seen during CE, transfusion requirement, and patients aged ≥60 years. The predictive model for rebleeding was developed using these factors to identify patients who had a high risk of rebleeding and to provide useful information to physicians in clinical practice. The C-statistic of the predictive model was 0.698. A risk-based approach to follow-up patients with OGIB can help clinicians determine a follow-up period for patients after small bowel investigation.

Development and validation of a new scoring system to determine the necessity of small-bowel endoscopy in obscure gastrointestinal bleeding.

BACKGROUND: Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established. AIMS: We aimed to develop a new scoring system that predicts the necessity of DBE in OGIB. METHODS: A retrospective study was performed in 330 patients who underwent SBCE for OGIB at Nagoya University Hospital. The enrolled patients were randomly assigned to either a development or a validation dataset. The former was used to construct a prediction scoring system to assess the necessity of DBE using independent predictors selected by logistic regression. The diagnostic yield of the prediction model was assessed using the validation dataset. RESULTS: Multivariate logistic regression analysis of the development dataset identified OGIB type, blood transfusion, and SBCE findings as independent predictors of the necessity of DBE. A prediction score gave an area under the receiver operating characteristics curve of 0.77. The sensitivity, specificity, positive predictive value, and negative predictive value at a cutoff ≥2.5 points were 72.5%, 74.6%, 72.6%, and 74.5%, respectively. CONCLUSION: Our scoring system may aid clinicians in deciding when to recommend DBE for patients with OGIB.