Kazuo Ohtsuka

Real-world data on the effectiveness of risankizumab as induction therapy for ustekinumab-refractory ulcerative colitis

Yasuharu Maeda, Shin-ei Kudo, Takanori Kuroki, Yurie Kawabata, Katsuro Ichimasa, Masashi Misawa, Noriyuki Ogata, Kazuo Ohtsuka. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl260078

Indolent T‐cell lymphoma of the gastrointestinal tract (iTCL‐GI) is a relatively newly recognized disease entity. iTCL‐GI was first proposed by Perry et al. in 2013, before it was formally incorporated as a distinct disease category in the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors: Lymphoid Neoplasms in 2022. Although the prognosis of iTCL‐GI is generally favorable, some cases may present with malignant transformation or severe clinical manifestations. Herein, we describe a case of iTCL‐GI with a poor clinical outcome. An 85‐year‐old female presented with chronic diarrhea and weight loss. Esophagogastroduodenoscopy and colonoscopy performed at the referring clinic were nondiagnostic, and the patient was referred to our institution. Balloon‐assisted enteroscopy revealed multiple ulcerative lesions in the distal ileum, which were eventually diagnosed as iTCL‐GI based on the biopsy findings. Palliative care was provided in accordance with the patient's preferences. Her gastrointestinal symptoms progressed rapidly, and she died 5 months after symptom onset. In this report, we discuss how balloon‐assisted enteroscopy can be useful in the diagnosis of iTCL‐GI, as well as a review of the literature on potential risk factors for poor clinical outcomes, including the presence of ulcers on endoscopy.

Background/Aims: Tofacitinib and upadacitinib are small-molecule compounds that inhibit the Janus kinase pathway for the treatment of refractory ulcerative colitis. Only a few reports have compared the efficacy and safety of these 2 drugs in real-world practice. We aimed to show our real-world evidence of these drugs and compare the efficacy and safety profiles in the treatment of ulcerative colitis. Methods: This study is a single-center retrospective analysis. Patients treated with tofacitinib or upadacitinib at our hospital between June 2018 and January 2024 who were monitored for 24 weeks were included. The primary outcome was steroid-free clinical remission at 24 weeks. Secondary outcomes were response and remission rates at each time point, time series changes in partial Mayo scores and laboratory results, treatment survival at 24 weeks, and the incidence of adverse events. Results: A total of 68 patients treated with tofacitinib and 34 patients treated with upadacitinib were included. Steroid-free clinical remission rate at 24 weeks was significantly higher in upadacitinib-treated patients than in tofacitinibtreated patients (64.7% vs. 38.2%). The response rates in upadacitinib-treated patients exceeded 60% after 8 weeks of treatment through to 24 weeks, and the rates were higher than those in tofacitinib-treated patients. The incidences of adverse events were 79.4% in upadacitinib-treated patients and 38.2% in tofacitinib-treated patients. The most common adverse event was acne for upadacitinib. Conclusions: Upadacitinib was more effective than tofacitinib in inducing remission in ulcerative colitis patients. The incidence of adverse events was significantly higher with upadacitinib than tofacitinib.

Advanced endoscopy and artificial intelligence-enabled vascular healing for ulcerative colitis: promising frontiers or mere mirage?

Background/Aims: The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. Methods: A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Results: Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Conclusions: Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

Background/Aims: Endoscopic activity confirmed by enteroscopy is associated with poor clinical outcome in Crohn’s disease (CD). We investigated which of the existing biomarkers best reflects endoscopic activity in CD patients including the small bowel, and whether their combined use can improve accuracy.Methods: One hundred and four consecutive patients with ileal and ileocolonic type CD who underwent balloon-assisted enteroscopy (BAE) from October 2021 to August 2022 were enrolled, with clinical and laboratory data prospectively collected and analyzed.Results: Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.Conclusions: The biomarkers LRG, fecal calprotectin, and fecal hemoglobin can serve as noninvasive and accurate tools for assessing activity in CD patients confirmed by BAE, especially when used in combination.

A 30-year-old female patient presented with monthly episodes of severe intermittent upper abdominal pain, especially after consuming fatty meals. Over a period of 5 years, she visited the emergency department 21 times due to the intensity of the pain. Although the pain appeared consistent with biliary pain, both blood and imaging tests showed no abnormalities. Despite not meeting the Rome IV criteria, we suspected sphincter of Oddi dysfunction (SOD). To further investigate, we conducted hepatobiliary scintigraphy (HBS), which revealed a clear delay in bile excretion. With the patient’s informed consent, we performed endoscopic sphincterotomy (EST) and as of 10 months later, there have been no recurrences. This case demonstrates an instance of SOD that could not be diagnosed using the Rome IV criteria alone but was successfully identified through HBS. It underscores the possibility of hidden cases of SOD among patients who regularly experience severe epigastric pain, where routine blood or imaging tests may not provide a diagnosis. HBS may be a useful non-invasive test in confirming the presence of previously undiagnosed SOD. As SOD can be easily treated with EST, updating the current diagnostic criteria to include such types of SOD should be considered in the future.