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.

Johannes Hasskamp ¹, Christian Meinhardt ², Petrease H Patton ³, Antje Timmer ¹

Cochrane Database Syst Rev.2025 Feb 27;2(2):CD000478. doi: 10.1002/14651858.CD000478.pub5.

Background: Maintenance of remission is essential in inflammatory bowel disease (IBD) in terms of disease course and long-term prognosis. The thiopurines azathioprine and 6-mercaptopurine have longstanding merit in ulcerative colitis, but more therapeutic options have been developed. This review is an update and extension of a review last published in 2016.

Objectives: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine in monotherapy or combined therapy regimens compared to placebo or active controls for the maintenance of remission in ulcerative colitis.

Search methods: We searched Cochrane Central Register of Controlled Trials (until May 2023), ClinicalTrials.gov (until May 2023), Embase (until August 2022), MEDLINE (until May 2023), and WHO ICTRP (until May 2023). We checked reference lists of the included studies and, if needed, contacted the authors to request more data or information.

Main results: We included 10 studies in the review, including 468 adult participants with ulcerative colitis. The risk of bias across these was low for most outcomes, but we considered some outcomes to have some concerns or high risk of bias due to insufficient information on concealment of allocation and outcome measurement. Based on five placebo-controlled studies, azathioprine or 6-mercaptopurine may reduce the risk of failing to maintain remission. In the thiopurine group, 45% (64/143) of participants failed to maintain remission compared to 67% (96/143) of participants receiving placebo (RR 0.66, 95% confidence interval (CI) 0.54 to 0.82; 5 studies, 286 participants; low-certainty evidence). Three studies reported withdrawals due to adverse events. Among participants on azathioprine, 4% (3/80) withdrew due to adverse events compared to 0% (0/82) of placebo participants (RD 0.04, 95% CI -0.02 to 0.09; 3 studies, 162 participants; low-certainty evidence). The evidence is of low certainty when comparing 6-mercaptopurine to 5-aminosalicylate. Based on one three-armed trial, 27% (3/11) of 6-mercaptopurine participants failed to maintain remission compared to 100% (2/2) of 5-aminosalicylate participants (RR 0.35, 95% CI 0.13 to 0.97; 1 study, 13 participants; low-certainty evidence). This trial also involved an induction phase; we only included the results for participants in remission. The single trial comparing 6-mercaptopurine to 5-aminosalicylate did not report separate data on adverse events and withdrawals due to adverse events for the subgroup with successful induction of remission, so we could not analyze these outcomes for this comparison.

Authors’ conclusions: Low-certainty evidence suggests that azathioprine or 6-mercaptopurine therapy may be more effective than placebo for the maintenance of remission in ulcerative colitis. More research is needed to evaluate the value of therapeutic drug monitoring and the effects of various treatment modalities on long-term safety.

Tomotaka Tanaka ¹, Daiki Hirano ¹, Syohei Ishimaru ¹, Keiko Arataki ¹

Cureus 2025 Jan 18;17(1):e77641. doi: 10.7759/cureus.77641. eCollection 2025 Jan.

We report the case of a 37-year-old male patient diagnosed with moderate left-sided ulcerative colitis (UC). Initial therapy with 5-aminosalicylic acid (5-ASA) was terminated within days due to exacerbation of symptoms, leading to a diagnosis of 5-ASA intolerance. Although induction of remission was achieved with prednisolone, the patient developed steroid dependency. Treatment with vedolizumab and ustekinumab subsequently failed to achieve clinical or endoscopic improvement. Intensive granulocyte and monocyte apheresis (GMA) was introduced, successfully inducing remission. However, during maintenance therapy with GMA, the patient experienced a relapse. Initiation of golimumab yielded suboptimal results, necessitating a combination therapy involving prednisolone and reintensified intensive GMA. This multimodal approach successfully achieved remission induction and maintenance. This case highlights the potential utility of intensive GMA in combination with golimumab and prednisolone for the management of refractory UC, particularly in patients with 5-ASA intolerance and failure of multiple biologic agents. A brief review of the relevant literature is included.

Francisco José Fernández-Pérez ¹, Nuria Fernández-Moreno ², Estela Soria-López ², Francisco Javier Rodriguez-González ², Francisco José Fernández-Galeote ³, Ana Lifante-Oliva ⁴, Concepción Ruíz-Hernández ⁴, Elisabeth Escalante-Quijaite ⁴, Francisco Rivas-Ruiz ⁵

Gastroenterol Hepatol. 2024 Nov;47(9):502196. doi: 10.1016/j.gastrohep.2024.502196. Epub 2024 May 6. (Article in Spanish)

Introduction: Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn’s disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission.

Patients and method: Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions.

Results: We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD.

Conclusions: GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.

Maki Setake ¹, Ryosaku Tomiyama ¹, Tomoya Kuda ², Kanetaka Maeshiro ³, Akira Hokama ⁴

Rev Esp Enferm Dig. 2024 Oct 4. doi: 10.17235/reed.2024.10795/2024. 

A 17-year-old man with ulcerative colitis (UC) presented to our hospital with neck pain and fever after vomiting. On examination, a snowflake sensation was noted in the neck. A chest radiograph showed extensive subcutaneous emphysema in the chest. CT scans showed extensive subcutaneous emphysema in the neck, shoulders and axilla, as well as pneumomediastinum and pneumothorax. A diagnosis of pneumomediastinum with exacerbation of UC was made, and he was fasted and treated with antibiotics. Intensive granulocyte and monocyte adsorption apheresis (GMA) was started for exacerbation of UC. His symptoms and the radiological findings of pneumomediastinum improved. He remained in remission on azathioprine. UC is a chronic inflammatory bowel disease (IBD) associated with extraintestinal manifestations (EIM). Very few cases have been complicated by pneumomediastinum. The increase in alveolar pressure due to vomiting and systemic inflammation-related pleural or esophageal damage may cause pneumomediastinum in this case. Prevention of progression to mediastinitis and treatment of exacerbated UC are contradictory. GMA was successful because it was not an immunosuppressive therapy. Our case highlights that rare EIM may complicate exacerbation of UC.

Maria-Bernadette Madel ¹, Lidia Ibáñez ¹, Thomas Ciucci ², Julia Halper ¹, Antoine Boutin ¹, Ghada Beldi ¹, Alice C Lavanant ³, Henri-Jean Garchon ⁴, Matthieu Rouleau ¹, Christopher G Mueller ³, Laurent Peyrin-Biroulet ⁵, David Moulin ⁶, Claudine Blin-Wakkach ⁷, Abdelilah Wakkach ⁸

Mucosal Immunol.. 2025 Feb;18(1):90-104. doi: 10.1016/j.mucimm.2024.09.005. Epub 2024 Sep 26.

Inflammatory bowel disease (IBD) is characterized by very severe intestinal inflammation associated with extra-intestinal manifestations. One of the most critical ones is bone destruction, which remains a major cause of morbidity and a risk factor for osteopenia and osteoporosis in IBD patients. In various mouse models of IBD, we and other have demonstrated concomitant bone loss due to a significant increase in osteoclast activity. Besides bone resorption, osteoclasts are known to control hematopoietic niches in vivo and modulate inflammatory responses in vitro, suggesting they may participate in chronic inflammation in vivo. Here, using different models of colitis, we showed that osteoclast inhibition significantly reduced disease severity and that induction of osteoclast differentiation by RANKL contributed to disease worsening. Our results demonstrate a direct link between osteoclast activity and myeloid cell accumulation in the intestine during colitis. RNAseq analysis of osteoclasts from colitic mice revealed overexpression of genes involved in the remodeling of hematopoietic stem cell niches. We also demonstrated that osteoclasts induced hematopoietic progenitor proliferation accompanied by a myeloid skewing in the early phases of colitis, which was confirmed in a model of RANKL-induced osteoclastogenesis. Mechanistically, inhibition of TNF-α reduced the induction of myeloid skewing by OCL both in vitro and in vivo. Lastly, we observed that osteoclastic activity and the proportion of myeloid cells in the blood are positively correlated in patients with Crohn’s disease. Collectively, our results shed light on a new role of osteoclasts in colitis in vivo, demonstrating they exert their colitogenic activity through an early action on hematopoiesis, leading to an increase in myelopoiesis sustaining gut inflammation.