Real-World Data on the Effectiveness and Safety of Filgotinib for Ulcerative Colitis in Japanese Patients: A Single-Center Experience.

Introduction Filgotinib is a JAK-1 selective inhibitor approved for ulcerative colitis (UC) treatment in Japan. Its effectiveness has been confirmed but remains unknown in actual clinical practice. Therefore, we aimed to evaluate the effectiveness and safety of filgotinib and identify suitable patients in the Japanese population. Methods We retrospectively reviewed the background, clinical course, and laboratory data of patients treated with filgotinib 200 mg for UC between May 2022 and December 2023. Results The median observation period for the 25 patients was 232 days (interquartile ranges (IQR) 102-405). The median age of the patients was 43 years (IQR 29-55), disease duration was nine years (IQR 2-12), and 36% (9/25) of patients were biologic or small molecule naïve. The median patient-reported outcome (PRO2) and partial Mayo (pMayo) scores at agent initiation were 3 (IQR 1-4) and 4.5 (IQR 3-6), respectively. The PRO2 and pMayo scores improved significantly two weeks after treatment initiation (p < 0.05). Clinical remission rates at 24 weeks after treatment initiation were 60% (15/25) for PRO2 ≤ 1 and 52% (13/25) for pMayo ≤ 1. The Mayo endoscopic subscore significantly improved after filgotinib initiation (p=0.04), and the endoscopic remission rate was 47% (8/17). At 24 weeks, patients in clinical remission, compared to those not in remission, had significantly lower baseline PRO2 and pMayo scores and longer disease duration (p=0.03, p=0.03, and p=0.04, respectively). The filgotinib persistence rate was 68% (17/25), with no discontinuation because of adverse events. Patients who continued treatment had significantly lower PRO2, pMayo scores, and blood neutrophil counts at initiation than those who discontinued (p=0.02, p=0.03, and p=0.02, respectively). Conclusion Filgotinib appears to be effective and safe in Japanese patients with UC. Effectiveness and persistence were high in patients whose PRO2 and pMayo scores were low at the time of treatment initiation.

A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Multiple ulcerative colitis-associated aseptic abscesses successfully treated with infliximab: a case report.

Aseptic abscesses are rare extraintestinal manifestations of inflammatory bowel disease. Herein, we present the case of a 69-year-old female patient with ulcerative colitis in whom multiple aseptic abscesses were successfully treated with infliximab. Aseptic abscesses associated with ulcerative colitis are difficult to differentiate from infectious abscesses. In the present case, we reached a diagnosis of aseptic abscesses associated with ulcerative colitis as antibiotics were ineffective and repeated Gram stains and cultures of blood and abscess were negative. Aseptic abscesses are commonly found in the spleen, lymph nodes, liver, and skin; however, in the present case, the periosteum was the major site. Prednisolone is often effective for aseptic abscesses; however, the present patient was initially treated with a combination of 40 mg/day of prednisolone and granulocyte and monocyte adsorption apheresis, with inadequate effect. Infliximab was administered as the patient was steroid-resistant, with strong effect. Subsequently, infliximab treatment has been continued, with no recurrence after 2 years. However, as there have been reports of cases of recurrence even after remission with treatment, careful follow-up in the future is therefore necessary.

Molecular and functional characterization of flavin-containing monooxygenases in pigs, dogs, and cats.

Flavin-containing monooxygenases (FMOs) are drug-oxygenating enzymes that are present in the human genome as FMO1-5 and FMO6P. Among pig, dog, and cat FMOs, pig and dog FMO1 and FMO3 have been partly characterized, but other FMOs have not been systematically identified. In this study, orthologous FMO cDNAs were isolated from pig, dog, and cat livers and evaluated by sequence and phylogenetic analyses, tissue expression, and catalytic function. The amino acid sequences of pig, dog, and cat FMO1-5 shared high sequence identities (83-89%) with human FMO1-5 and were closely clustered in a phylogenetic tree. The gene structure and genomic organization of FMO1-5 were conserved across these species. Dog and pig FMO6P contained insertions of 1 and 83 bases, respectively, and are possibly pseudogenes similar to human FMO6P. Among the tissue types analyzed, pig FMO1 mRNA was abundant in liver, kidney, and lung; dog FMO3, FMO2, and FMO5 mRNAs were abundant in liver, lung, and kidney, respectively; cat FMO1 and FMO3 mRNAs were abundant in kidney and liver, respectively. Recombinant pig and dog FMO1-5 and cat FMO1-6 all mediated benzydamine and trimethylamine N-oxygenations and methyl p-tolyl sulfoxide S-oxygenation. The selective human FMO3 substrate trimethylamine was predominantly metabolized by pig FMO1, dog FMO3, and cat FMO3. Cat FMO6 was also active toward trimethylamine. These results suggest some similarities in the drug-metabolizing capabilities of FMO3 in dogs, cats, and humans and that dog and cat FMO3 generally have molecular and functional characteristics similar to human FMO3, being the major FMO in human liver.