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

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.

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.

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.

Walter Jauregui ¹, Yozahandy A Abarca ², Yasmin Ahmadi ³, Vaishnavi B Menon ⁴, Daniela A Zumárraga ⁵, Maria Camila Rojas Gomez ⁶, Aleeza Basri ⁷, Rohitha S Madala ⁸, Peter Girgis ⁹, Zahra Nazir ¹⁰

Cureus. 2024 Sep 3;16(9):e68569. doi: 10.7759/cureus.68569. eCollection 2024 Sep.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

in CD Moderate to severe Oral corticosteroids. Consider enteral nutritional therapy. TNF inhibitors are recommended to be considered for steroid-dependent or refractory patients. If pharmacotherapy or nutrition therapy is ineffective or unable to adapt, the combination with granulocyte monocyte apheresis (GMA) can be considered.

I Rodríguez-Lago, D Ginard, R J Díaz Molina, M Vicuña, E Domenech, M Abanades, O Moralejo Lozano, G Bastida, A D Sánchez Capilla, E Iglesias, F Rancel-Medina, M D M Blasco, M Bosca-Watts, M Calvo Iñiguez, C Herrera deGuisé, E Leo, A Viejo Almanzor, V Hernández Ramirez, C Suárez Ferrer, L Quilez Pérez, M Muñoz, F Fernández Pérez, J M Huguet, P Fradejas, C López Ramos, A M Fuentes Coronel, C Reygosa Castro, N Rull Murillo, P Zapico, J L Cabriada
Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1011, doi.org=10.1093/ecco-jcc/jjad212.0641

Background
The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn’s disease (CD) patients who were underrepresented in CT is still limited.

Methods
GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of patients and their management and outcome 4 weeks after GMA treatment.

Results
A total of 95 evaluable patients were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of patients had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 patients (10.6%) with CD, all had B1, and 3 patients had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of patients had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of patients received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 patients reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed.

Conclusion
Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory patients with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of patients were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.

A Morant-Domínguez , B Vera-Santana , A Hernández-Camba , L Ramos , I Alonso-Abreu , N Hernández Álvarez-Buylla , M Vela , M Hernández-Guerra , A Laura , I Ferraz-Amaro , M Carrillo Palau

Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i870,  https://doi.org/10.1093/ecco-jcc/jjad212.0556

Background: Ulcerative colitis (CU) and Crohn’s disease (CD) are described as inflammatory bowel diseases (IBD). Emerging as potential blood-based inflammatory biomarkers in various chronic diseases are the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIRI, calculated as neutrophils × monocytes/lymphocytes). In this work we aim to analyze if these hematological composite scores differ between IBD patients and healthy controls, and whether they are related to disease activity.

Methods: A total of 197 IBD patients, 130 with CD and 67 with CU, and 208 age- and sex-matched healthy controls were recruited. NLR, MLR, PLR, and SIRI were calculated. Multivariable linear regression analysis was performed to study whether these scores differ between patients and controls and how they related to IBD activity scores.

Results: After multivariable analysis adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls (table 1). C-reactive protein and SIRI and NLR correlated in patients with IBD. Nevertheless, fecal calprotectin was not related to none of these blood scores. Besides, disease activity parameters were not associated with any of the composite blood-based scores in both patients with CD and CU.

Conclusion: NLR and PLR, independently, are heightened in IBD patients in contrast to controls. However, SIRI and MLR do not share this distinction. Surprisingly, none of the four hematological scores displayed correlations with disease activity in either CD or UC patients.

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Farah Yasmin ¹, Hala Najeeb ¹, Unaiza Naeem ¹, Abdul Moeed ¹, Thoyaja Koritala ², Salim Surani ^3 4

World J Clin Cases  2022 Jul 26;10(21):7195-7208. doi: 10.12998/wjcc.v10.i21.7195.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn’s Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA’s conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

https://pubmed.ncbi.nlm.nih.gov/36158031/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353887/