Masaki Kato ¹, Masaki Yamashita ¹, Shigeki Kojima ², Mitsuto Tsukui ¹, Yoshihiko Iijima ¹, Kenichi Araki ¹, Jun Ishida ¹, Takumi Komatsu ¹, Yusuke Nakamoto ¹, Akiyo Kawashima ¹, Maki Konno ¹, Hirofumi Kiyokawa ¹, Yoshinori Sato ¹, Tsutomu Sakurada ², Tadateru Maehata ¹, Hiroshi Yasuda ¹, Keisuke Tateishi ¹

Medicine (Baltimore). 2025 Aug 1;104(31):e43389. doi: 10.1097/MD.0000000000043389.

5-Aminosalicylate (5-ASA) intolerance complicates ulcerative colitis (UC) management, often necessitating alternative treatment approaches. Granulocyte and monocyte adsorptive apheresis (GMA) has been recognized as a safe treatment option for patients with UC who are refractory or intolerant to conventional drugs, including steroids; however, its effectiveness and safety in patients with 5-ASA intolerance remain unclear. This study aimed to investigate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. We conducted a retrospective observational study to evaluate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. Eighty-five patients with UC who underwent GMA were assessed, including 21 with 5-ASA intolerance and 64 with 5-ASA tolerance. This study compared the patient characteristics, treatment outcomes, concomitant drugs, and adverse events between the 2 groups. The remission rate was 28.6% (6/21) in the 5-ASA-intolerant group and 31.3% (20/64) in the 5-ASA-tolerant group, with no significant difference between the groups (P = .967). Both groups showed significant reductions in the dose of oral prednisolone and Lichtiger clinical activity index scores following the GMA. Our study suggests that GMA is equally effective and safe in 5-ASA-intolerant and 5-ASA-tolerant patients, offering an alternative treatment option in this challenging clinical scenario.

Eytan Wine, Marina Aloi, Stephanie Van Biervliet, Jiri Bronsky, Javier Martín di Carpi, Marco Gasparetto, Laura Gianolio, Hannah Gordon, Iva Hojsak, Alexandra S. Hudson, Séamus Hussey, Johan van Limbergen, Erasmo Miele, Lorenzo Norsa, Ola Olén, Gianluca Pellino, Patrick van Rheenen, Lissy de Ridder, Richard K. Russell, Dror S. Shouval, Eunice Trindade, Dan Turner, David C. Wilson, Anat Yerushalmy Feler, Amit Assa

J Pediatr Gastroenterol Nutr. 2025; 1-51. doi:10.1002/jpn3.70097

Objectives

Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points.

Methods

These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate.

Results

Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more ‘traditional’ UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines.

GMA has a good safety profile, especially in difficult-to-treat and paediatric settings^. GMA also requires central venous access but may still be considered in children with UC who do not respond or lose response to conventional treatments, but more studies are needed before formal recommendations can be made.

Conclusions

These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

Vaios Svolos, Hannah Gordon ¹, Miranda C E Lomer ², Marina Aloi ^3 4, Aaron Bancil ⁵, Alice S Day ⁶, Andrew S Day ⁷, Jessica A Fitzpatrick ⁸, Konstantinos Gerasimidis ⁹, Konstantinos Gkikas ⁹, Lihi Godny ¹⁰, Charlotte R H Hedin ^11 12, Konstantinos Katsanos ¹³, Neeraj Narula ¹⁴, Richard K Russell ¹⁵, Chen Sarbagili-Shabat ^16 17, Jonathan P Segal ^18 19, Rotem Sigall-Boneh ^20 21, Harry Sokol ²², Catherine L Wall ²³, Kevin Whelan ², Eytan Wine ²⁴, Henit Yanai ^25 26, Richard Hansen, Emma P Halmos ²⁷

J Crohns Colitis. 2025 Jul 12:jjaf122. doi: 10.1093/ecco-jcc/jjaf122. Online ahead of print.

curcumin & qing dai statements: 16.1, 16.2, 16.3

Documento de posicionamiento de geteccu sobre fragilidad, edad avanzada y enfermedad inflamatoria intestinal

Míriam Mañosa ^a, Margalida Calafat ^a, Esther Francia ^b, Francesc Riba ^c, Francisco Mesonero ^d, Cristina Suárez ^e, Santiago García-López ^f, Francisco Losfablos ^g, Xavier Calvet ^hi, Eugeni Domènech ^ai, Ana Gutiérrez Casbas ^j, Ingrid Ordás ^k, Luis Menchén ^l, Francisco Rodríguez-Moranta ^m, Yamile Zabana ⁿ

Gastroenterología y Hepatología, 2025, 502529, ISSN 0210-5705, https://doi.org/10.1016/j.gastrohep.2025.502529.

Resumen

La fragilidad es un estado de vulnerabilidad caracterizado por una disminución de la reserva fisiológica y la capacidad de respuesta ante el estrés, lo que aumenta el riesgo de complicaciones, efectos adversos a los tratamientos y al deterioro funcional. La valoración de la fragilidad permite determinar la edad biológica de los pacientes, más allá de su edad cronológica, proporcionando una visión más precisa de su estado de salud y necesidades asistenciales. La proporción de adultos de edad avanzada con EII se halla en aumento de forma paralela al envejecimiento de la población general y se estima que, en la próxima década, más de un tercio de los pacientes con EII superarán los 60 años. Esta población puede sufrir las complicaciones derivadas de la propia EII desarrolladas previamente a la vez que es particularmente susceptible a desarrollar efectos secundarios del tratamiento, lo que hace imprescindible su evaluación integral con el fin de identificar aquellos más vulnerables. A la fragilidad se unen otros síndromes geriátricos como la comorbilidad y la polifarmacia que pueden interferir de forma notable con el manejo y el curso de la EII, condicionando la estrategia terapéutica y el pronóstico.

Objetivo

En este contexto, la evaluación geriátrica integral debe ser sistemática en los pacientes de edad avanzada con EII, con el objetivo de detectar déficits funcionales e implementar intervenciones específicas de apoyo nutricional, rehabilitación funcional y atención psicológica para optimizar su evolución. Este documento de posicionamiento pretende establecer recomendaciones al respecto basadas en la evidencia disponible.

Conclusiones

La incorporación sistemática de la valoración geriátrica integral en el manejo de personas mayores con EII representa una estrategia esencial para mejorar los resultados clínicos, adaptar los tratamientos a la capacidad funcional del paciente y favorecer un enfoque verdaderamente centrado en la persona.

Recomendamos valorar el uso de GMA en los pacientes frágiles o de edad avanzada con EII corticodependientes por su seguridad.

En los pacientes con EII de edad avanzada o en situación de fragilidad, donde el riesgo de efectos adversos por inmunosupresores y corticoides es mayor, la GMA puede representar una opción terapéutica segura. Esta estrategia permite controlar la inflamación sin incrementar significativamente el riesgo de infecciones o neoplasias. Disponemos de datos que han demostrado que la GMA puede inducir remisión clínica en un porcentaje considerable de pacientes mayores con CU moderada o grave, con un perfil de seguridad favorable y sin eventos adversos graves, incluso en presencia de múltiples comorbilidades

Nobuhiro Ueno ^1 2, Yu Kobayashi ³, Aki Sakatani ², Tatsuya Dokoshi ³, Keitaro Takahashi ³, Katsuyoshi Ando ³, Shin Kashima ³, Kentaro Moriichi ³, Hiroki Tanabe ³, Yuki Kamikokura ⁴, Mishie Tanino ⁴, Mikihiro Fujiya ² 

J Clin Apher. 2025 Jun;40(3):e70030. doi: 10.1002/jca.70030.

Ulcerative colitis (UC) is a chronic inflammatory condition requiring lifelong management, with anti-tumor necrosis factor α (anti-TNF-α) agents often used for refractory cases. However, secondary loss of response (LOR) to these agents, due to anti-drug antibodies, poses a significant therapeutic challenge. This report describes a case where granulocyte and monocyte adsorptive apheresis (GMA) maintenance therapy successfully restored the efficacy of an anti-TNF-α agent in a 26-year-old male with active UC experiencing LOR to infliximab. Following GMA induction therapy and continued infliximab administration, clinical symptoms improved, fecal calprotectin levels decreased, and clinical remission was achieved. Long-term maintenance with GMA enabled sustained clinical remission, with mucosal healing observed one year post-therapy. This case suggests that GMA maintenance therapy may serve as a novel therapeutic approach for patients with active UC experiencing LOR to anti-TNF-α agents. However, further studies are warranted to elucidate the underlying mechanisms and validate its efficacy.

Yuko Higashi ^1 2, Atsuko Ibusuki ¹, Tomoko Fukushige ¹, Ryoko Sagara ¹, Risako Yonezawa ¹, Natsumi Terada ¹, Hisao Kawahira ¹, Kimiko Kazumura ³, Takuro Kanekura ¹

Ther Apher Dial. 2025 Aug;29(4):702-706. doi: 10.1111/1744-9987.70043. Epub 2025 May 25.

Introduction: Activated neutrophils play a crucial role in the development of neutrophilic dermatoses, including pustular psoriasis. Adsorptive granulocyte and monocyte apheresis (GMA) is an effective treatment for skin disorders. Although previous basic research has demonstrated neutrophil activation, no efficient method exists to assess it in clinical settings.

Methods: We measured neutrophil activity in patients with GPP who underwent GMA therapy using the FLP-H4200, a newly developed neutrophil activity evaluation system. Blood samples were collected before the first and after the fifth GMA session.

Results: In Case 1, which responded to GMA, the neutrophil activation value decreased from 118 603 to 26 234, reaching the normal range. In Case 2, the response to GMA was poor, and the neutrophil activation value decreased from 140 623 to 76 780, which remained significantly above the normal level.

Conclusion: These results suggest that the neutrophil activity evaluation system may be useful for assessing disease severity and therapeutic efficacy.

Yukari Okubo ¹, Ryuhei Okuyama ², Shinichi Imafuku ³, Yayoi Tada ⁴, Keiichi Yamanaka ⁵, Kazumitsu Sugiura ⁶, Yukie Yamaguchi ⁷, Masahito Yasuda ⁸, Wataru Sakamoto ⁹, Morihisa Saitoh ⁹, Akimichi Morita ¹⁰; Study Investigators

Dermatol Ther (Heidelb). . 2025 Jul;15(7):1883-1899. doi: 10.1007/s13555-025-01429-8. Epub 2025 May 19.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan.

Methods: Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed.

Results: The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare).

Conclusion: In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.

Miki Urushiyama ¹, Kunio Tarasawa ², Rintaro Moroi ¹, Hideya Iwaki ¹, Yusuke Hoshi ³, Hiroshi Nagai ¹, Yusuke Shimoyama ¹, Takeo Naito ¹, Fumihiko Kakuta ³, Hisashi Shiga ¹, Shin Hamada ¹, Yoichi Kakuta ¹, Kiyohide Fushimi ⁴, Yoshitaka Kinouchi ¹, Daiki Abukawa ³, Kenji Fujimori ², Atsushi Masamune ¹

JGH Open. . 2025 May 14;9(5):e70175. doi: 10.1002/jgh3.70175. eCollection 2025 May.

Aims: This study aimed to investigate the trends in pediatric inflammatory bowel diseases (IBD) management in Japan over the past decade.

Methods: We retrospectively analyzed data from Japan’s nationwide database from 2012 to 2022. Patients aged ≤ 15 years diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) were included. Trends in the use of biologics, capsule endoscopy, total parenteral nutrition (TPN), elemental diets, surgery, and granulocyte and monocyte apheresis (GMA) were examined using the Cochrane-Armitage and Jonckheere-Terpstra trend tests.

Results: Among the 8037 and 6153 pediatric UC and CD admissions, respectively, the use of biologics increased significantly (CD: from 46.0% to 53.6%; UC: from 15.0% to 33.0%, p < 0.0001). The use of capsule endoscopy in pediatric patients with CD increased markedly from 6.6% to 16.7% (p < 0.0001), whereas TPN use decreased from 8.4% to 3.0% (p < 0.0001). Surgery rates for patients with CD remained at approximately 5%, whereas those for patients with UC decreased (from 3.7% to 1.7%, p = 0.002). Elemental diets for pediatric patients with CD increased (from 54.4% to 66.2%, p < 0.0001). The use of GMA decreased significantly in patients with UC (from 12.1% to 2.7%, p < 0.0001).

Conclusion: The use of biologics and capsule endoscopy has increased in pediatric patients with IBD, whereas the use of more invasive treatments has decreased. These trends suggest a shift toward less invasive and more targeted therapeutic strategies in managing pediatric patients with IBD in Japan.

Anas Zaher ¹, Maria Julia Moura Nascimento Santos ², Hassan Elsaygh ³, Stephen J Peterson ¹, Carolina Colli Cruz ², Anusha Shirwaikar Thomas ², Yinghong Wang ²

Expert Opin Drug Saf. 2025 Apr 21:1-10. doi: 10.1080/14740338.2025.2496431. Online ahead of print.

Introduction: This review discusses the epidemiology, pathophysiology, and factors associated with refractory immune-mediated diarrhea and colitis (r-IMDC), emphasizing tailored treatment strategies.

Areas covered: The current literature on r-IMDC was reviewed using PubMed (2015-2025), focusing on clinical trials, meta-analyses, and case reports relevant to its management.

Expert opinion: Effectively managing r-IMDC is crucial for balancing toxicities and antitumor response. Available second and third-line management options for r-IMDC cases must be carefully evaluated. Future perspectives include development of standardized protocols beyond second-line therapies and predictive biomarkers to enable personalized treatment.

• ICIs are essential in cancer therapy but often cause IMDC, with up to 41% of patients developing steroid-refractory cases.
• Current guideline-recommended second-line therapies, such as infliximab and vedolizumab, fail in 11% of IMDC cases, underscoring the need for third-line interventions.
• Emerging therapies, including Janus kinase inhibitors, fecal microbiota transplantation, and interleukin-targeting agents, show promise for r-IMDC management. Also gma, IVIG.
• Personalized management strategies, incorporating gut microbiota modulation and targeted immune suppression, could improve outcomes in refractory colitis.
• Effective management of r-IMDC is critical for reducing prolonged immunosuppression, minimizing cancer treatment interruptions, and improving patient quality of life.

Satoshi Tanida ^1 2, Naoto Imura ², Shun Sasoh ², Yoshimasa Kubota ², Tesshin Ban ², Tomoaki Ando ², Makoto Nakamura ², Takashi Joh ²

J Clin Med Res  2025 Apr;17(4):240-246. doi: 10.14740/jocmr6188. Epub 2025 Apr 5.

Case 1 involved a 34-year-old woman who had been diagnosed with Crohn’s disease (CD) at 30 years old. After deciding to discontinue CD treatment, she was diagnosed with moderate flare-up of CD based on disease activity and endoscopic findings. Inadequate response was seen 7 days after starting oral prednisolone (PSL) at 30 mg/day, so combination therapy was started with intensive granulocyte and monocyte adsorptive apheresis (GMA) plus upadacitinib (UPA) at 45 mg/day. Twelve weeks after starting this combination therapy, clinical remission and endoscopic and histological improvements of the inflamed mucosa were achieved with no adverse events. Case 2 involved a 26-year-old man who had been diagnosed with CD at 13 years old. He was diagnosed with severe flare-up of CD based on disease activity and endoscopic findings due to loss of response to double doses of infliximab (IFX). Combination therapy was started with intensive GMA plus UPA at 45 mg/day. Twelve weeks after starting this therapy, clinical remission and endoscopic and histological improvements of the inflamed mucosa were achieved with no adverse events. The combination of intensive GMA plus UPA appears to have provided an effective therapeutic option for refractory CD in a patient with a 4-year history of CD and refractoriness to systemic corticosteroids, and in another patient with a 13-year history of CD and loss of response to IFX.