A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Efficacy and safety of biosimilar infliximab in bio-naïve patients with Crohn's disease.

BACKGROUND AND STUDY AIMS: The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease. PATIENTS AND METHODS: This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration. RESULTS: The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups. CONCLUSION: The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.

Differences Between Patients with Heartburn Refractory to Vonoprazan and Those Refractory to Proton Pump Inhibitors.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn. METHODS: This study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance-pH (MII-pH) testing with vonoprazan/PPI discontinuation. Patients' backgrounds, symptom scores from four questionnaires, MII-pH results and high-resolution manometry results were compared between the two groups. RESULTS: The vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII-pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII-pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0-0.3]). CONCLUSION: Patients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn.

Characteristics of factors contributing to follow-up for suspect delayed bleeding after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Delayed bleeding (DB) is a major adverse event associated with colorectal endoscopic submucosal dissection (ESD) that sometimes causes difficulties in making decisions regarding endoscopic hemostasis. This study identified the factors that contribute to follow-up without endoscopic hemostasis when DB is suspected after colorectal ESD. METHODS: In total, 583 patients (603 tumors) who underwent ESD or hybrid ESD for colorectal tumors at Chiba University Hospital between June 2009 and January 2022 were retrospectively registered. Of these, 141 cases (141 tumors) with DB; with hematochezia or hemoglobin decrease ≥2 g/dL after colorectal ESD were analyzed. The DB group was divided into the Hemostasis group (H group; endoscopic hemostasis performed) and no-Hemostasis group (no-H group; no endoscopy performed, or endoscopy performed but no hemostasis performed after hematochezia or hemoglobin decrease). Univariate and multivariate logistic regression analyses were performed to assess the factors contributing to follow-up. RESULTS: Thirty-one patients with 31 tumors were categorized into the H group, while 110 patients with 110 tumors were in the no-H group. Multivariate regression analysis revealed that date from ESD to first hematochezia ≤Day 3 (odds ratio [OR] 4.55, 95% confidence interval [CI] 1.44-14.33; p = 0.010) and bleeding duration ≤1 day (OR 3.35, 95% CI 1.35-8.34; p = 0.009) contributed to follow-up. CONCLUSIONS: In cases of DB after colorectal ESD, a bleeding duration ≤1 day or date from ESD to first hematochezia ≤Day 3 may contribute to follow-up observation without endoscopic hemostasis.

Severe ulcerative colitis induced by COVID-19 vaccination.

A 37-year-old woman developed severe colitis with diffuse mucosal erythema and ulcerations throughout the entire colon after the 3rd vaccination of COVID-19. Stool culture was negative, and the pathological findings showed increased lymphoplasmacytic and neutrophilic infiltration in the colonic lamina propria, which were consistent with ulcerative colitis. After the treatment with anti-tumor necrosis factor-α agent, the ulceration markedly improved with development of severe colonic stenosis, which was successfully dilated with endoscopic balloon dilation. In case of COVID-19 vaccination, it should be noted that vaccination could be a trigger for the onset of UC.

Differences in mucosal permeability among patients with ulcerative colitis classified based on the colonic location and disease activity.

BACKGROUND: s: Factors affecting mucosal permeability (MP) in ulcerative colitis (UC) are largely unknown. We aimed to investigate the difference in MP among patients with UC classified according to the colonic locations and to evaluate the correlations between local MP and endoscopic or histological activity of UC. METHODS: The transepithelial electrical resistance (TER), which is inversely proportional to permeability, of tissue samples from the mucosa of the ascending colon, descending colon, and rectum of patients with UC and healthy individuals (HI) was measured by using the Ussing chamber. TERs were compared between patients with UC and HI, and evaluated according to colonic locations and disease activity of UC. RESULTS: Thirty-eight patients with UC and 12 HI were included in this study. Both in HI and patients with UC, MP tends to be higher in the anal side. TER in the ascending colon was significantly lower in patients with UC than in HI (45.3 ± 9.0 Ω × cm2 vs. 53.5 ± 9.7 Ω × cm2, p = 0.01). The increased permeability in UC was observed also in the descending colon, only when the inflammation involved the location. A significant correlation between TER and endoscopic activity was found in the rectum only (r = -0.49, p = 0.002). There were no significant correlations between TERs and UC histology. CONCLUSIONS: The MP in the colon differs according to the colonic location. The ascending colon among patients with UC showed disease-specific changes in MP, whereas the MP is increased in proportion to the endoscopic activity in the rectum.

Utility of prophylactic clipping after colorectal cold snare polypectomy in patients on oral antithrombotic agents.

BACKGROUND AND AIMS: There is no consensus on the effectiveness of prophylactic clipping after colonic cold snare polypectomy (CSP). This study aimed to evaluate the utility of prophylactic clipping in preventing delayed bleeding (DB) after colorectal CSP in patients on antithrombotic agents. METHODS: We retrospectively recruited consecutive patients on antithrombotic agents who underwent colorectal CSP in Chiba University Hospital. The DB rate was compared between patients with and without prophylactic clipping. RESULTS: The study included 133 patients (422 polyps) requiring prophylactic clipping and 85 patients (282 polyps) not requiring prophylactic clipping. There were no significant differences in DB and hematochezia rates between the groups. By weighted logistic regression analysis, the odds ratio of hematochezia was 0.557 (95% confidence interval, 0.225-1.378; P = .205) in patients without clipping compared to those with clipping. CONCLUSIONS: Prophylactic clipping may not be necessary to prevent DB after colorectal CSP in patients on antithrombotic agents.

Risk factors of unintentional piecemeal resection in endoscopic mucosal resection for colorectal polyps ≥ 10 mm.

This study aimed to investigate the lesion and endoscopist factors associated with unintentional endoscopic piecemeal mucosal resection (uniEPMR) of colorectal lesions ≥ 10 mm. uniEPMR was defined from the medical record as anything other than a preoperatively planned EPMR. Factors leading to uniEPMR were identified by retrospective univariate and multivariate analyses of lesions ≥ 10 mm (adenoma including sessile serrated lesion and carcinoma) that were treated with endoscopic mucosal resection (EMR) at three hospitals. Additionally, a questionnaire survey was conducted to determine the number of cases treated by each endoscopist. A learning curve (LC) was created for each lesion size based on the number of experienced cases and the percentage of uniEPMR. Of 2557 lesions, 327 lesions underwent uniEPMR. The recurrence rate of uniEPMR was 2.8%. Multivariate analysis showed that lesion diameter ≥ 30 mm (odds ratio 11.83, 95% confidence interval 6.80-20.60, p < 0.0001) was the most associated risk factor leading to uniEPMR. In the LC analysis, the proportion of uniEPMR decreased for lesion sizes of 10-19 mm until 160 cases. The proportion of uniEPMR decreased with the number of experienced cases in the 20-29 mm range, while there was no correlation between the number of experienced cases and the proportion of uniEPMR ≥ 30 mm. These results suggest that 160 cases seem to be the minimum number of cases needed to be proficient in en bloc EMR. Additionally, while lesion sizes of 10-29 mm are considered suitable for EMR, lesion sizes ≥ 30 mm are not applicable for en bloc EMR from the perspective of both lesion and endoscopist factors.

Investigation of risk factors for metachronous recurrence in patients with early gastric adenocarcinoma by miRNA-mRNA integral profiling.

The mechanism of metachronous recurrence (MR) after performing endoscopic treatment for early gastric adenocarcinoma (GAC) and eradicating Helicobacter pylori (H. pylori) is unknown. To elucidate the mechanism and risk factors of MR, we analyzed gene expression at multiple locations of the gastric mucosa. We selected each five patients with MR and without MR (control), after early GAC treatment and eradication of H. pylori. Mucosal tissue was collected from four sites in the stomach of each patient as biopsy specimens for mRNA sequencing, gene set enrichment analysis, and microRNA (miRNA) sequencing. We also performed correlation analysis and target prediction on pathways. As a result, endoscopically, the MR group had more intestinal metaplasia and enlarged folds. A total of 384 mRNAs presented changes in expression and 31 gene sets were enriched in the MR group. Immune-related pathways were enriched in the entire stomach, and the IFN-α response had the highest enrichment score. Additionally, 32 miRNAs revealed changes in their expression. Correlation analysis and target prediction with genes in the gene set of IFN-α response revealed that 10 miRNA-mRNA pairs presented a significant correlation. Immune-related pathways with miRNAs in the gastric mucosa after H. pylori eradication may be a risk factor for MR.

Outcomes for Underwater Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection of 21-30-mm Colorectal Polyps: A Feasible Study.

BACKGROUND AND AIMS: This randomized controlled trial (RCT) was designed to evaluate the short-term outcomes of underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) of 21-30 mm colonic polyps. METHOD: We conducted a single-center RCT. Patients diagnosed with suspected colorectal intramucosal carcinoma (21-30 mm and adaptable for both UEMR and ESD) were randomly assigned to the UEMR and ESD groups at a 1:1 ratio. The primary endpoint was the R0 resection rate. We independently performed one-sample tests against the set threshold for each treatment. The significance level was set at p = 0.224. RESULT: Eleven polyps each in the UEMR and ESD groups, respectively, were analyzed. The R0 resection rate (%) was 36 (95% confidence interval 11-69) and 100 (72-100) for UEMR and ESD, respectively, with a significant difference between the two groups (p = 0.002). The p-value against the set threshold for UEMR was 0.743, whereas that for ESD was < 0.001 (one-sample binomial test). The en bloc resection rates (%) were 82 (48-97) and 100 (72-100) for UEMR and ESD, respectively; however, no significant difference was observed (p = 0.167). The mean treatment time (min) was significantly shorter in the UEMR group (8 ± 6) than in the ESD group (48 ± 29) (p = 0.001). CONCLUSION: ESD could achieve a high R0 resection rate, while the en bloc resection rate was comparable between the two treatment techniques with less burden on patients undergoing UEMR for 21-30-mm colorectal polyps. CLINICAL TRIAL REGISTRATION: The study was registered at the Japan Registry of Clinical Trial as jRCT1030210015 and jRCT1030210177.

Treatment strategy changes for inflammatory bowel diseases in biologic era: results from a multicenter cohort in Japan, Far East 1000.

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation.

Carcinogenic potential in regenerated mucosa after endoscopic resection of esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Little is known about genetic mutations in the regenerated mucosa (RM) after endoscopic resection (ER) of esophageal carcinoma. Thus, this study investigates the status of genetic variation in RM after ER of esophageal squamous cell carcinoma (ESCC). METHODS: The study cohort included 19 patients with ESCC. We used an esophageal carcinoma panel to identify target sequences for squamous cell carcinoma (SCC), background mucosa (BM), and RM after ER of ESCC. We used OncoKB to check whether each mutation was a putative driver. RESULTS: We identified 77 mutations of 32 genes in SCC, 133 mutations of 34 genes in BM, and 100 mutations of 29 genes in RM. Putative driver mutations were identified in 20 mutations in 14 cases in SCC, 16 mutations in 10 cases in BM, and 7 mutations in 11 cases in RM. The rate of putative driver mutations to total mutations was significantly lower in RM (26% in SCC vs 12% in BM vs 7% in RM, P = 0.009). Additionally, the rate of cases with TP53 putative driver mutations was significantly lower in RM (63% in SCC vs 37% in BM vs 16% in RM, P = 0.011). The percentage of putative driver mutations and the percentage of cases with a putative driver of TP53 were significantly lower in RM. CONCLUSION: Esophageal RM after ER of ESCC could have a lower risk of carcinogenesis.

Clinical Features Focusing on Extraintestinal Manifestations in Japanese Patients with Inflammatory Bowel Diseases: Far East 1000.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) can develop extraintestinal manifestations (EIMs) during the disease course, which sometimes impact their quality of life. OBJECTIVES: This study aimed to clarify the prevalence and types of EIMs using a hospital-based IBD cohort in Japan. METHODS: A patient cohort with IBD was established in 2019, as participated by 15 hospitals in Chiba Prefecture of Japan. Using this cohort, the prevalence and types of EIMs, which are defined based on previous reports and the Japanese guidelines, were investigated. RESULTS: This cohort enrolled 728 patients, including 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). Of these patients with IBD, 10.0% were identified with one or more EIMs (57 (10.5%) with UC and 16 (8.6%) with CD). Arthropathy and arthritis were the most common EIM in 23 (4.2%) patients with UC, followed by primary sclerosing cholangitis (PSC) (2.6%). Arthropathy and arthritis were also the most common in patients with CD, but no cases of PSC were observed. EIMs were more frequently observed in patients with IBD treated by specialists than in those treated by non-specialists (12.7% vs. 5.5%, p = 0.011). The incidence of EIMs in patients with IBD was not significantly different over time. CONCLUSIONS: The prevalence and types of EIMs in our hospital-based cohort in Japan did not significantly differ from those reported in previous or Western studies. However, the incidence might be underestimated due to the limited ability of non-IBD specialists to discover and describe EIMs in patients with IBD.

Utility of a super-soft hood for esophageal endoscopic submucosal dissection below an esophageal stricture.

Video 1Use of a super-soft hood (Space Adjuster; TOP, Tokyo, Japan) for esophageal endoscopic submucosal dissection below an esophageal stricture.

Validity of pathological diagnosis for early colorectal cancer in genetic background.

BACKGROUND: This study aimed to investigate the validity of pathological diagnosis of early CRC (E-CRC) from the genetic background by comparing data of E-CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD-CRC). METHODS: TCGA data on AD-CRC were studied in silico, whereas by next-generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E-CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell-cycle-signaling pathways was compared among CRA, E-CRC, and AD-CRC. RESULTS: The study included 22 CRA and 30 E-CRC lesions from the Chiba University Hospital and 212 AD-CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell-cycle-signaling pathways, E-CRC was comparable to AD-CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E-CRC. CONCLUSIONS: In conclusion, the definition of E-CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD-CRC. Based on the main pathway, it seemed reasonable to classify E-CRC as adenocarcinoma. The pathological diagnosis of E-CRC according to Japanese definition seemed to be valid from a genetic point of view.

Long-term course of gastric submucosal tumors: growth speed and size-increasing factors.

BACKGROUND AND AIMS: Gastric submucosal tumors (SMTs) are treated or monitored according to GI stromal tumor guidelines, but the adequacy of the guidelines has not been thoroughly examined. We investigated the long-term course of gastric SMTs to determine the validity of guideline-based follow-up methods and the factors contributing to their size increase. METHODS: This study included gastric SMTs diagnosed as GI mesenchymal tumors (GIMTs) by using EUS and followed up with EUS. The percentage and speed of GIMT enlargement and factors associated with the enlargement were investigated by using the Cox proportional hazards model. RESULTS: From January 1994 to May 2022, a total of 925 gastric SMTs were evaluated with EGD, and 231 SMTs were diagnosed as GIMTs. Of the 231 GIMTs, 145 were examined by EUS more than twice and were followed up for >6 months. The mean ± standard deviation follow-up period was 5.20 ± 4.04 years (range, 0.5-17.3 years), with 39 (26.9%) of 145 GIMTs increasing in size with a mean doubling time of 3.60 ± 3.37 years. A multivariate analysis of factors influencing tumor growth revealed that irregular extraluminal borders were an increasing factor (hazard ratio, 3.65; 95% confidence interval, 1.26-10.52), initial tumor size ≤9.5 mm (hazard ratio, .23; 95% confidence interval, 0.07-0.77) was a nonincreasing factor, and GIMTs with calcification (n = 13) did not increase in size. CONCLUSIONS: Tumor growth in gastric GIMTs <9.5 mm in diameter and/or with calcification is rare. Follow-up intervals for these lesions could be extended.

Clinical effects and emerging issues of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma from Japanese real-world practice.

BACKGROUND: Although the efficacy of atezolizumab has been demonstrated in randomized controlled trials, its long-term efficacy and association with adverse events in real-world practice are unknown. This study was designed to shed light on these issues. METHODS: In this multicenter retrospective study, data were collected from patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab in seven institutions in Japan. The authors focused on the efficacy and adverse events related to vascular endothelial growth factor (VEGF) inhibition. RESULTS: A total of 123 patients were enrolled in this study. The median progression-free survival (PFS) for the first-line treatment group was 8.0 months (95% confidence interval [CI], 6.1-9.9), whereas the median PFS for the second- or later-line treatment group was 4.1 months (95% CI, 2.6-5.7), which was significantly worse than that of the first-line treatment group (p = .005). Twenty-seven patients had interrupted bevacizumab treatment. Proteinuria accounted for the largest proportion of bevacizumab treatment interruptions. The cumulative incidence rate of bevacizumab interruption due to anti-VEGF-related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus than in those without (p = .026). The landmark analysis showed that patients experienced bevacizumab interruption by 24 weeks from treatment initiation had poorer PFS than those who did not (p = .013). CONCLUSIONS: The PFS of atezolizumab plus bevacizumab as first-line treatment mostly replicates that of a global phase 3 trial. Interrupted bevacizumab treatment was more common in patients with hypertension and/or diabetes mellitus, which may be associated with worsening long-term PFS. PLAIN LANGUAGE SUMMARY: Atezolizumab plus bevacizumab has been the standard front line systemic therapy for advanced hepatocellular carcinoma. With the growing incidence of fatty liver due to metabolic syndrome as a background liver disease for hepatocellular carcinoma, the rate of comorbid hypertension and diabetes mellitus has been increasing accordingly. The present study demonstrated the cumulative incidence rate of bevacizumab interruption due to anti-VEGF-related adverse events was significantly higher in patients with hypertension and/or diabetes mellitus. The landmark analysis clarified that interruption of bevacizumab might be a risk of impaired efficacy of atezolizumab plus bevacizumab over the long term in patients with advanced hepatocellular carcinoma.

Long-term vonoprazan administration causes gastric fundic gland-type hyperplastic polyps and chronic bleeding.

A patient experienced gastric fundic gland-type hyperplastic polyps, consisting of foveolar epithelium and parietal cells, complicated with chronic bleeding due to long-term treatment with vonoprazan. The patient had progressive anemia, probably caused by bleeding from the polyps. After switching from vonoprazan to a histamine-2 (H2) receptor antagonist, the polyps markedly shrank and the anemia improved. Vonoprazan can produce reversible hyperplastic polyps and anemia. In case of anemia in patients receiving long-term vonoprazan, it is important to consider drug cessation or change to an H2 blocker.

The long-term effect of biologics in patients with ulcerative colitis emerging from a large Japanese cohort.

To gain a better understanding of the effects of biologics, we evaluated clinical outcomes in patients with moderate to severe exacerbations of ulcerative colitis (UC). This retrospective, multicenter study retrieved the entire clinical courses of UC patients who began treatments between 2004 and 2018. All exacerbations and clinical parameters, including treatment details for exacerbations and both remission and re-exacerbation dates, were identified during the observation period. Two different endpoints, the cumulative incidence rates of surgical resection and re-exacerbation, were evaluated separately in moderate to severe exacerbation events. Among 1401 patients, 1626 exacerbation events were determined according to a partial Mayo score (remission: < 2, mild: 2-4, moderate: 5-7, and severe: > 7). During the observation period, as administration rates of biologics increased, both surgical resection and hospitalization rates decreased, for 959 moderate to severe exacerbation events. We confirmed that biologics significantly reduced the cumulative re-exacerbation rate in moderate to severe exacerbation events during the study period compared with suboptimal therapies (a 0.507-fold decreased risk according to COX regression analysis, P < 0.001). However, they had not enough impact in reducing the cumulative incidence rate of surgical resection in moderate to severe exacerbation events that were corticosteroid-refractory or dependent (a 0.878-fold decreased risk according to COX regression analysis, P = 0.606). Biologics may improve remission duration, but these agents had no significant impact in reducing the risk of surgical resection in moderate to severe active UC.