Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis.

Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.

Late-onset Rupture of the Intrahepatic Pseudoaneurysm Developed by Endoscopic Ultrasonography-guided Hepaticogastrostomy: A Case Report and Literature Review.

Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) has emerged as an alternative drainage technique for patients with malignant biliary obstruction. However, few reports have discussed the occurrence of late-onset rupture of hepatic artery pseudoaneurysms following EUS-HGS. A recently available drill dilator equipped with a long screw segment was used in the dilation step of EUS-HGS. We highlight the potential concern that this long screw segment may increase the risk of damage to the hepatic artery, leading to late-onset life-threatening rupture of a pseudoaneurysm.

Impact of a Time-Related Benchmark on the Adenoma Detection Rate in Surveillance Colonoscopy: A STROBE Statement-Oriented Cross-Sectional Cohort Study.

BACKGROUND/AIMS: Colorectal adenomas are precursor lesions of globally increasing colorectal cancer. Hence, a high adenoma detection rate in colonoscopy is pivotal. We investigated the clinical impact of stratified colonoscopy observation time combined with observation time/intubation time ratio on the detection of colorectal adenomas. MATERIALS AND METHODS: We conducted a single-center retrospective study including 369 consecutive patients who underwent colonoscopy following fecal immunochemical tests between May 2021 and April 2022. The primary outcome measure was the impact of the stratified observation time and observation time/ intubation time ratio (category 1: <6.0 minutes and <1.0, category 2: <6.0 minutes and ≥1.0, category 3: ≥6.0 minutes and <1.0, and category 4: ≥6.0 minutes and ≥1.0) on adenoma detection rate. RESULTS: Cecum intubation was obtained in 367 patients (99.5%). Adenomas were detected in 226 patients (61.2%). From the univariate analysis, age ≥53 years, habitual alcohol intake, colonoscopy attachment (+), and observation time with observation time/intubation time ratio categories 3 and 4 were determined as significant factors for adenoma detection rate. From the logistic regression analysis, age ≥ 53 years (odds ratio: 4.86, 95% CI: 2.25-10.52), habitual alcohol intake (odds ratio: 2.26, 95% CI: 1.33-3.82), category 3 (odds ratio: 3.66, 95% CI: 1.81-7.45), and category 4 (odds ratio: 5.60, 95% CI: 2.92-10.73) were significant factors for adenoma detection rate. CONCLUSION: We propose the observation time with observation time/intubation time ratio combined benchmark (with categories' thresholds based on observation time >6 minutes and scope withdrawal time exceeding intubation time [observation time/intubation time ratio > 1]) as a novel colonoscopy quality indicator. These findings represent an important educational message for endoscopists.

Reovirus combined with a STING agonist enhances anti-tumor immunity in a mouse model of colorectal cancer.

Reovirus, a naturally occurring oncolytic virus, initiates the lysis of tumor cells while simultaneously releasing tumor antigens or proapoptotic cytokines in the tumor microenvironment to augment anticancer immunity. However, reovirus has developed a strategy to evade antiviral immunity via its inhibitory effect on interferon production, which negatively affects the induction of antitumor immune responses. The mammalian adaptor protein Stimulator of Interferon Genes (STING) was identified as a key regulator that orchestrates immune responses by sensing cytosolic DNA derived from pathogens or tumors, resulting in the production of type I interferon. Recent studies reported the role of STING in innate immune responses to RNA viruses leading to the restriction of RNA virus replication. In the current study, we found that reovirus had a reciprocal reaction with a STING agonist regarding type I interferon responses in vitro; however, we found that the combination of reovirus and STING agonist enhanced anti-tumor immunity by enhancing cytotoxic T cell trafficking into tumors, leading to significant tumor regression and survival benefit in a syngeneic colorectal cancer model. Our data indicate the combination of reovirus and a STING agonist to enhance inflammation in the tumor microenvironment might be a strategy to improve oncolytic reovirus immunotherapy.

Trajectory analyses to identify persistently low responders to COVID-19 vaccination in patients with inflammatory bowel disease: a prospective multicentre controlled study, J-COMBAT.

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.

Potential Risk of Misjudgment in the Decision-making Process Based on the 2018 Tokyo Guidelines in Older Patients with Acute Cholecystitis.

Objective The 2018 Tokyo Guidelines (TG18) were published to facilitate the decision-making processes (DMP), including the diagnosis and operation of acute cholecystitis (AC). However, only a few guidelines consider older adults. This study evaluated the DMP based on the TG18, focusing on older patients with AC. Methods This was a single-armed, single-center retrospective study. The primary outcome measure was the "undiagnosable" AC rate, and the secondary outcome measure was the degree of concordance of "unfit for surgery" decisions. Patients Two hundred and nine patients with AC. Results Sixty (28.7%) of 209 patients with AC were "undiagnosable" on admission based on the TG18 criteria. The numbers and rate of "undiagnosable" AC in patients ≤59, 60-79, and ≥80 years old were 4 (10.0%), 20 (24.4%), and 36 (41.4%), respectively (p<0.001). The multiple logistic regression analysis following the univariate analysis revealed that age >73 years old was the most significant risk factor for undiagnosable AC [p=0.006, odds ratio (OR): 3.06, 95% confidence interval (CI): 1.38-6.81]. Female sex (p=0.033, OR: 2.09, 95% CI: 1.06-4.09) and severe AC (p=0.049, OR: 2.97, 95% CI: 1.01-8.76) were also significant risk factors for undiagnosable AC. The number of cases unfit for surgery based on the Charlson Comorbidity Index and American Society of Anesthesiologists physical status was 90 (43.1%) and 75 (35.9%), respectively. The κ value between these 2 indicators revealed a minimal concordance of 0.33 (95% CI: 0.20-0.47). Conclusion The DMP based on the TG18 potentially harbors a misjudgment risk, especially in older patients with AC (UMIN000047715).

A Transanal Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy for an Intrapelvic Tumor Diagnosed as Recurrence of a Smooth Muscle Tumor of Uncertain Malignant Potential Following Uterine Morcellation.

A transoral endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a well-established tissue-sampling method. However, performing a transanal EUS-FNAB remains challenging. Uterine morcellation has emerged as a minimally invasive approach for benign tumor treatment. However, uterine myomas are heterogeneous and include malignant and indeterminate malignant cells. We herein report a rare case of intrapelvic tumor diagnosed by a transanal EUS-FNAB as a recurrence of smooth muscle tumors of uncertain malignant potential following uterine morcellation. Physicians should be aware that a previous uterine myoma resected under morcellation has the possibility of intra-abdominal recurrence. A transanal EUS-FNAB is a practical option for making a pathological diagnosis.

Acute Promyelocytic Leukemia in a Patient With Chronic Continuous Type of Crohn's Disease.

Chronic inflammation can induce leukemogenic mutations in hematopoietic stem cells (HSCs). We report a case of acute promyelocytic leukemia (APL) in a patient with chronic continuous type of Crohn's disease. The patient had been diagnosed with Crohn's disease at the age of 28 years and had received conventional treatments with biologics, but not azathioprine. At the age of 51, he was diagnosed with APL with ider(17). Long-term exposure to chronic continuous inflammation from Crohn's disease might be a factor inducing genomic instability in HSCs, which lead to the subsequent development of APL. APL is a rare hematological manifestation that required attention in Crohn's disease patients.

Relationship between gene mutations and clinicopathological features in nonampullary duodenal epithelial tumors.

BACKGROUND: Molecular features of nonampullary duodenal epithelial tumors (NADETs) remain unclear. AIM: The aim of this study is to determine the association between the genetic features and clinicopathological findings of NADETs. METHODS: In total, 75 NADETs were enrolled in this study, and was performed targeted DNA sequencing of the GNAS, KRAS, TP53, and APC genes. Histological grade was classified as category 3 or category 4/5 according to the Vienna classification, and the immunophenotype was categorized as the gastric phenotype (G type), gastrointestinal phenotype (GI type), or the intestinal phenotype (I type). RESULTS: The prevalence of GNAS and KRAS mutations was significantly higher in the G type than in the GI/I type (GNAS, P = 0.027; KRAS, P = 0.005). In contrast, the frequency of TP53 mutations was significantly higher in the GI/I type than in the G type (P = 0.049). Notably, APC mutations, excluding c.4479 G>A which was synonymous mutation, were more frequently identified in category 4/5 tumors than in category 3 tumors (50% vs. 24.5%; P = 0.039). CONCLUSION: G-type NADETs harbored frequent GNAS and KRAS mutations, whereas TP53 mutations are common in NADETs with intestinal features. APC mutations were significantly associated with high-grade neoplasia and invasive carcinoma.

5-aminolaevulinic acid (5-ALA) accumulates in GIST-T1 cells and photodynamic diagnosis using 5-ALA identifies gastrointestinal stromal tumors (GISTs) in xenograft tumor models.

Gastrointestinal stromal tumor (GIST) diagnosis using conventional gastrointestinal endoscopy is difficult because such malignancies cannot be distinguished from other types of submucosal tumors. Photodynamic diagnosis (PDD) is based on the preferential uptake of photosensitizers by tumor tissues and its detection by fluorescence emission upon laser excitation. In this study, we investigated whether PDD using 5-aminolevulinic acid (5-ALA), a standard photosensitizer used worldwide, could be used for GIST diagnosis. 5-ALA is metabolized to endogenous fluorescent protoporphyrin IX (PpIX). We examined the accumulation of PpIX in GIST-T1 cells using flow cytometry and immunofluorescent staining. Furthermore, we established GIST-T1 xenograft mouse models and examined PpIX accumulation in the resultant tumors. PpIX accumulated in GIST-T1 cells and was localized mainly to lysosomes. PpIX accumulation was also observed in murine xenograft tumors. Moreover, tumor and normal tissues could be distinctly identified by relative PpIX fluorescence. Thus, our results demonstrated that PDD with 5-ALA has substantial clinical potential for GIST diagnosis.

Relationship between Immunophenotype and Clinicopathological Findings for Superficial Nonampullary Duodenal Epithelial Tumor.

INTRODUCTION: The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. MATERIALS AND METHODS: A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. RESULTS: Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (p = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (p < 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, p = 0.043). CONCLUSION: Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.

Evidence-based diagnosis and clinical practice guidelines for intestinal Behçet's disease 2020 edited by Intractable Diseases, the Health and Labour Sciences Research Grants.

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.

Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). METHODS: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japan, from March 2015 to March 2017. We collected data on fecal biomarkers, endoscopic severities, and other clinical indices from Cohort 1 (n = 427) and assessed the diagnostic accuracy of FCP measurement and FIT results in determining clinical severity, based on Mayo score, and endoscopic remission, based on Mayo endoscopic sub-score (MES) or UC endoscopic index of severity. We also followed 452 patients in clinical remission from UC (Cohort 2) for 12 months and evaluated the associations of FCP levels and FIT results with clinical recurrence. RESULTS: The levels of FCP and FIT each correlated with the MES and UC endoscopic index of severity. There were no significant differences in the areas under the curve of FCP vs FIT in distinguishing patients with MES≤1 from those with MES≥2 (P = .394) or in distinguishing patients with MES=0 from those with MES≥1 (P = .178). Among 405 patients in clinical remission at baseline, 38 (9.4%) had UC recurrences within 3 months and 90 (22.2%) had recurrences within 12 months. FCP≥146 mg/kg (hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.80-8.33) and FIT≥77 ng/mL (HR, 2.92; 95% CI, 1.76-4.83) were independently associated with clinical recurrence within 12 months. UC recurred within 12 months in 69% of patients with levels of FCP≥146 mg/kg and FIT ≥77 ng/mL; this value was significantly higher than the rate of recurrence in patients with levels of FCP≥146 mg/kg and FIT <77 ng/mL (31.5%, P < .001) or patients with levels of FCP<146 mg/kg and FIT ≥77 ng/mL (30.0%, P < .001). CONCLUSION: In a nationwide study of patients with UC in Japan, we found that the level of FCP and FIT could each identify patients with endoscopic markers of disease severity (MES≥2). The combination of FCP and FIT results can identify patients in remission who are at risk for disease recurrence. Clinical Trials Registry no: UMIN000017650 (http://www.umin.ac.jp/ctr/).

Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study.

BACKGROUND: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS: This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS: A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS: The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

Antitumor Effect of a Novel Photodynamic Therapy With Acetylated Glucose-conjugated Chlorin for Gastrointestinal Cancers.

BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion. MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC50 was calculated as well as its accumulation in cancer cells was examined by flow cytometry. Confocal microscopy was used to observe the intracellular localization of AcN003HP. The excretion and antitumor effects of AcN003HP were also evaluated in vivo. RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects. CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.

The efficacy of maintenance therapy after remission induction with tacrolimus in ulcerative colitis with and without previous tumor necrosis factor-α inhibitor.

BACKGROUND AND AIM: Tacrolimus (TAC) is an important therapeutic option for remission induction in patients with refractory ulcerative colitis (UC). However, there is little evidence available on long-term outcomes and maintenance treatments after TAC therapy, especially in cases with previous tumor necrosis factor-α (TNF-α) inhibitor therapy. METHODS: Long-term outcomes and remission induction after TAC treatment were retrospectively examined in refractory UC patients with and without previous TNF-α inhibitor therapy. RESULTS: The mean disease activity index and the endoscopic activity index scores decreased significantly during the 12-week treatment after TAC therapy in both groups, showing a significantly greater decrease in the group without TNF-α inhibitor therapy than in the group with previous TNF-α inhibitor therapy. One year or more after TAC therapy, TNF-α inhibitor and/or azathioprine was used as maintenance therapy in most cases in the group without previous TNF-α inhibitor treatment, while azathioprine was primarily used in the group with previous TNF-α inhibitor treatment. Colectomy was performed in 45.5% (5/11) and 15.6% (7/45) of the groups with and without previous TNF-α inhibitor therapy, respectively, and the group without previous TNF-α inhibitor treatment had a better colectomy-free rate than the group with previous TNF-α inhibitor treatment after TAC therapy on Kaplan-Meier analysis. CONCLUSIONS: TAC is effective for remission induction in refractory UC patients with and without previous TNF-α inhibitor treatment. Maintenance medication after TAC therapy is an issue for the future, especially in UC cases with previous TNF-α inhibitor treatment failure.

Adalimumab Dose-Escalation Therapy Is Effective in Refractory Crohn's Disease Patients with Loss of Response to Adalimumab, Especially in Cases without Previous Infliximab Treatment.

BACKGROUND/AIMS: Adalimumab dose escalation is one of the most important options in refractory Crohn's disease patients with loss of response to adalimumab. The goal of this study was to evaluate the effectiveness of adalimumab dose escalation in Crohn's disease patients with loss of response to adalimumab, since there are few reports of adalimumab dose escalation, especially in East Asia. METHODS: The clinical response to adalimumab dose escalation in Crohn's disease patients with loss of response to adalimumab was evaluated retrospectively, using the Crohn's disease activity index score, serum C-reactive protein levels, and endoscopic analyses. RESULTS: Of the 203 Crohn's disease patients treated with anti-tumor necrosis factor, 14 refractory Crohn's disease patients with loss of response to adalimumab received adalimumab dose-escalation therapy. The C-reactive protein level was significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in the whole group, although there were no significant reductions of Crohn's disease activity index scores. Both Crohn's disease activity index scores and C-reactive protein levels were significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in patients without previous infliximab treatment, although C-reactive protein levels were positive in all cases with previous infliximab exposure at weeks 12 and 52. Endoscopic mucosal healing was achieved with adalimumab dose escalation in 2 cases without previous infliximab treatment. CONCLUSIONS: Adalimumab dose-escalation therapy is effective in refractory Crohn's disease patients with loss of response to adalimumab, especially in cases without previous infliximab treatment.

Real-world efficacy of adalimumab and infliximab for refractory intestinal Behçet's disease.

BACKGROUND: Anti-tumor necrosis factor-α agents are important for managing refractory intestinal Behçet's disease. Few studies have reported the efficacy of anti-tumor necrosis factor-α monoclonal antibodies for intestinal Behçet's disease due to its rarity. AIMS: The aim was to examine the efficacy of anti-tumor necrosis factor-α antibodies for intestinal Behçet's disease in real-world practice. METHODS: This was a retrospective review of medical records at 4 hospitals in Japan. Global gastrointestinal symptom and endoscopic assessment scores were analyzed in intestinal Behçet's disease patients given anti-tumor necrosis factor-α agents at 3 and 12 months after the start of therapy. RESULTS: Of 53 intestinal Behçet's disease patients, 22 received anti-tumor necrosis factor-α monoclonal antibody treatment. At the first line, 14 were given adalimumab, and 8 were given infliximab. After 3 and 12 months of treatment, 7 and 11 patients showed complete response of gastrointestinal symptom scores, respectively, and 5 and 9 showed complete remission of the endoscopic assessment score, respectively. Three patients switched anti-tumor necrosis factor-α agents. CONCLUSION: Anti-tumor necrosis factor-α monoclonal antibodies are effective for refractory intestinal Behçet's disease in real-world situations. Switching anti-tumor necrosis factor-α agents may be useful for failure of first-line anti-tumor necrosis factor-α therapy in some refractory cases.