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Farkas B, Ivány E, Bálint A, Bacsur P, Molnár T, Farkas K. Diagnostic and Therapeutic Challenges in Severe Peristomal Pyoderma Gangrenosum. Inflamm Bowel Dis 2025; 31:885-886. [PMID: 39028852 DOI: 10.1093/ibd/izae167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Indexed: 07/21/2024]
Abstract
Lay Summary
In this case of a young female, ulcerations around the ileostoma appeared after colectomy and were thought to be due to surgical site infection. Given inadequate treatment, an extensive defect of the abdominal wall developed. Peristomal pyoderma gangrenosum was diagnosed, for which ustekinumab was given successfully.
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Affiliation(s)
- Bernadett Farkas
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Emese Ivány
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Anita Bálint
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Peter Bacsur
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Tamás Molnár
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
| | - Klaudia Farkas
- Center for Gastroenterology, Department of Internal Medicine, University of Szeged, Szeged, Hungary
- HCEMM-USZ Translational Colorectal Research Group, University of Szeged, Szeged, Hungary
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2
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Yang YJ, Jeon SR. Metabolic musculoskeletal disorders in patients with inflammatory bowel disease. Korean J Intern Med 2025; 40:181-195. [PMID: 40102707 PMCID: PMC11938716 DOI: 10.3904/kjim.2024.359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/13/2024] [Accepted: 11/14/2024] [Indexed: 03/20/2025] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder that affects not only the gastrointestinal tract but also extraintestinal organs, leading to various extraintestinal manifestations and complications. Among these, musculoskeletal disorders such as osteoporosis, sarcopenia, and axial and peripheral spondyloarthritis are the most commonly observed. These conditions arise from complex mechanisms, including chronic inflammation, malnutrition, gut dysbiosis, and glucocorticoid use, all of which contribute to reduced bone density, muscle loss, and joint inflammation. Osteoporosis and sarcopenia may co-occur as osteosarcopenia, a condition that heightens the risk of fractures, impairs physical performance, and diminishes quality of life, particularly in elderly patients with IBD. Holistic management strategies, including lifestyle modifications, calcium, and vitamin D supplementation, resistance training, and pharmacological interventions, are essential for mitigating the impact of these conditions. Spondyloarthritis, which affects both axial and peripheral joints, further complicates disease management and significantly compromises joint health. Timely diagnosis and appropriate medical interventions, such as administration of nonsteroidal anti-inflammatory drugs and biologics, are critical for preventing chronic joint damage and disability. Moreover, a multidisciplinary approach that addresses both metabolic and inflammatory aspects is essential for optimizing physical function and improving treatment outcomes in patients who have IBD with musculoskeletal involvement.
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Affiliation(s)
- Young Joo Yang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon,
Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon,
Korea
| | - Seong Ran Jeon
- Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul,
Korea
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3
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Moriya K, Nagamatsu S, Nishio Y, Komeda Y, Kikukawa S, Matsuura K, Matsuo H, Uejima M, Kitagawa T, Nakamura F. Efficacy of Serum BDNF for the Evaluation of Depressive Neurological Symptoms in Patients with Refractory Ulcerative Colitis. J Clin Med 2025; 14:874. [PMID: 39941545 PMCID: PMC11818054 DOI: 10.3390/jcm14030874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment (p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) (p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker.
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Affiliation(s)
- Kei Moriya
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Shinsaku Nagamatsu
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Yuya Nishio
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Yusuke Komeda
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Shoma Kikukawa
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Kyohei Matsuura
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Hideki Matsuo
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (S.N.); (Y.N.); (Y.K.); (S.K.); (K.M.); (H.M.)
| | - Masakazu Uejima
- Department of Endocrinology and Metabolism, Nara Prefecture General Medical Center, Nara 630-8581, Japan;
| | - Takamichi Kitagawa
- Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (T.K.); (F.N.)
| | - Fumihiko Nakamura
- Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (T.K.); (F.N.)
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Isaacs KL, Sayed CJ. Nonmalignant Dermatologic Disorders in Inflammatory Bowel Disease. Am J Gastroenterol 2025; 120:115-124. [PMID: 39466220 DOI: 10.14309/ajg.0000000000003155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 10/17/2024] [Indexed: 10/29/2024]
Abstract
Inflammatory bowel disease (IBD) is associated with extraintestinal manifestations that can affect multiple body systems. Extraintestinal manifestations (EIMSs) are seen in up to 50% of patients with IBD. Skin involvement is particularly common occurring in up to 15%-20% of patients. Skin reactivity presents in multiple forms with unique pathology. Therapy for IBD also may affect the skin directly through inflammatory processes or indirectly because of skin infections. This review will concentrate on the most common nonmalignant dermatologic conditions associated with IBD with a focus on prevalence, diagnostic approaches, and management strategies.
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Affiliation(s)
- Kim L Isaacs
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Christopher J Sayed
- Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA
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5
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Falloon K, Forney M, Husni ME, Feagan B, Rieder F. Diagnosis and Management of Inflammatory Bowel Disease-Associated Spondyloarthritis. Am J Gastroenterol 2025; 120:106-114. [PMID: 39360937 DOI: 10.14309/ajg.0000000000003092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 09/16/2024] [Indexed: 10/19/2024]
Abstract
Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is common but remains poorly understood. In this review article, we aimed to provide guidance regarding the diagnosis and management of this condition. For diagnosis of IBD-associated peripheral SpA (IBD-pSpA), we recommend collaboration with rheumatology for incorporation of clinical symptoms, physical examination findings, joint imaging if applicable, and available diagnostic criteria. For the management of IBD-pSpA, we first recommend assessment and treatment of underlying luminal IBD disease activity. We provide guidance regarding positioning of advanced therapies for IBD in patients with IBD-pSpA based on the limited available literature. For diagnosis of IBD-associated axial SpA, we recommend rheumatology referral to make the diagnosis based on incorporation of symptoms, laboratory data, imaging findings (sacroiliitis), and available diagnostic criteria. For the management of axial SpA, we recommend comanagement with rheumatology and use of either antitumor necrosis factor agents or Janus kinase inhibitors, when applicable.
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Affiliation(s)
- Katherine Falloon
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Michael Forney
- Department of Musculoskeletal Radiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - M Elaine Husni
- Department of Rheumatologic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Brian Feagan
- Alimentiv, London, Ontario, Canada
- Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
- Cleveland Clinic Program for Global Translational Inflammatory Bowel Disease (GRID-IBD), Cleveland Clinic, Cleveland, Ohio, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
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6
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Sanz Segura P, Gomollón F, Casas D, Iborra M, Vela M, Fernández-Clotet A, Muñoz R, García de la Filia I, García Prada M, Ferrer Rosique JÁ, García MJ, de Francisco R, Arias L, Barrio J, Guerra I, Ponferrada Á, Gisbert JP, Carrillo-Palau M, Calvet X, Márquez-Mosquera L, Gros B, Cañete F, Monfort D, Madrigal Domínguez RE, Roncero Ó, Laredo V, Montoro M, Muñoz C, López-Cauce B, Lorente R, Fuentes Coronel A, Vega P, Martín D, Peña E, Varela P, Olivares S, Pajares R, Lucendo AJ, Sesé E, Botella Mateu B, Nos P, Domènech E, García-López S. Psoriasis induced by antiTNF therapy in inflammatory bowel disease: Therapeutic management and evolution of both diseases in a nationwide cohort study. Dig Liver Dis 2024; 56:2060-2068. [PMID: 38876834 DOI: 10.1016/j.dld.2024.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 06/16/2024]
Abstract
BACKGROUND some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible. AIMS to assess the management of antiTNF-IP in IBD, and its impact in both diseases. METHODS patients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks. RESULTS 234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse. CONCLUSION skin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies.
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Affiliation(s)
| | - Fernando Gomollón
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Instituto de Investigación Sanitaria (ISS) Aragón, Zaragoza, Spain
| | - Diego Casas
- Instituto de Investigación Sanitaria (ISS) Aragón, Zaragoza, Spain; Gastroenterology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Marisa Iborra
- Gastroenterology Department, Hospital Universitario La Fe, Valencia, Spain
| | - Milagros Vela
- Gastroenterology Department, Hospital Universitario Ntra. Sra. de Candelaria, Santa Cruz de Tenerife, Spain
| | - Agnès Fernández-Clotet
- Gastroenterology Department, Hospital Clinic de Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd). Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Roser Muñoz
- Gastroenterology Department, Hospital General Universitario Dr. Balmis, Alicante, Spain
| | | | - María García Prada
- Gastroenterology Department, Complejo Asistencial Universitario de León, Spain
| | | | - María José García
- Gastroenterology and Hepatology Department, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - Ruth de Francisco
- Gastroenterology Department, Hospital Universitario Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Lara Arias
- Gastroenterology Department, Hospital Universitario de Burgos, Burgos, Spain
| | - Jesús Barrio
- Gastroenterology Department, Hospital Universitario Río Hortega. Gerencia Regional de Salud de Castilla y León (SACYL). Valladolid, Spain
| | - Iván Guerra
- Gastroenterology Department, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Ángel Ponferrada
- Gastroenterology Department, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Marta Carrillo-Palau
- Gastroenterology Department, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
| | - Xavier Calvet
- Servei d'Aparell Digestiu. Parc Taulí, Hospital Universitari. Institutd'Investigació i Innovació Parc Taulí(I3PT-CERCA). Universitat Autònoma de Barcelona. Sabadell, Spain. Centro de Investigación Biomédica En Red de enfermedades hepáticas y digestivas (CIBERehd). Instituto de Salud Carlos III. Madrid, Spain
| | - Lucía Márquez-Mosquera
- Servei de Digestiu, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Beatriz Gros
- Gastroenterology Department, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Fiorella Cañete
- Gastroenterology Department, Hospital Universitari Germans Trials i Pujol and CIBERehd, Badalona, Barcelona, Spain
| | - David Monfort
- Gastroenterology Department, Consorci Sanitari de Terrassa, Spain
| | | | - Óscar Roncero
- Gastroenterology Department, Hospital General La Mancha Centro, Ciudad Real, Spain
| | - Viviana Laredo
- Gastroenterology Department, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Miguel Montoro
- Gastroenterology Department, Hospital San Jorge, Huesca, Spain
| | - Carmen Muñoz
- Gastroenterology Department, Hospital de Basurto, Bilbao, Spain
| | - Beatriz López-Cauce
- Gastroenterology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Rufo Lorente
- Gastroenterology Department, Hospital General de Ciudad Real, Ciudad Real, Spain
| | - Ana Fuentes Coronel
- Gastroenterology Department, Hospital Virgen de La Concha, Complejo Asistencial de Zamora, Zamora, Spain
| | - Pablo Vega
- Gastroenterology Department, Complejo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Dolores Martín
- Gastroenterology Department, Hospital Universitario La Paz, Madrid, Spain
| | - Elena Peña
- Gastroenterology Department, Hospital Royo Villanova, Zaragoza, Spain
| | - Pilar Varela
- Gastroenterology Department, Hospital Universitario de Cabueñes, Gijón, Spain
| | | | - Ramón Pajares
- Gastroenterology Department, Hospital Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain
| | - Alfredo J Lucendo
- Gastroenterology Department, Hospital General de Tomelloso, IIS-IP, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM) and CIBEREHD Ciudad Real, Spain
| | - Eva Sesé
- Gastroenterology Department, Hospital Universitario Arnau de Vilanova de Lleida, Spain
| | - Belén Botella Mateu
- Gastroenterology Department, Hospital Universitario Infanta Cristina, Madrid, Spain
| | - Pilar Nos
- Gastroenterology Department, Hospital Universitario La Fe, Valencia, Spain
| | - Eugeni Domènech
- Gastroenterology Department, Hospital Universitari Germans Trials i Pujol and CIBERehd, Badalona, Barcelona, Spain
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Fanizzi F, Allocca M, Fiorino G, Zilli A, Furfaro F, Parigi TL, Peyrin-Biroulet L, Danese S, D’Amico F. Raising the bar in ulcerative colitis management. Therap Adv Gastroenterol 2024; 17:17562848241273066. [PMID: 39600566 PMCID: PMC11589388 DOI: 10.1177/17562848241273066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/17/2024] [Indexed: 11/29/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by growing incidence and prevalence around the world in the last few decades. The range of available existing treatment and strategies for its management is being implemented. Given the introduction of newly developed molecules and the lack of specific guidelines, drug positioning may represent a tough clinical challenge. UC management is mostly medical, and it has been shifting toward a more personalized approach with the aim to create a tailored strategy depending on the patient's profile. A treat-to target strategy seems to be the best approach to reach disease control as it allows to carry out therapeutic choices based on objective and specific parameters: histological, ultrasonographic, and molecular targets may add to the already used clinical, endoscopic, and biochemical targets. In addition, dual-targeted therapy has emerged as an attractive therapeutic strategy for patients not achieving remission. This review aims to provide an overview of the available strategies to raise the bar in UC.
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Affiliation(s)
- Fabrizio Fanizzi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Mariangela Allocca
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Gionata Fiorino
- Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, Rome, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Federica Furfaro
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Tommaso Lorenzo Parigi
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privé Ambroise Paré—Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Via Olgettina 60, Milan 20132, Italy
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Holmer AK, Hudesman D. Positioning Crohn's Disease Therapies in the Era of Small Molecules and Combination Therapies. Curr Gastroenterol Rep 2024; 26:263-272. [PMID: 38970743 DOI: 10.1007/s11894-024-00937-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 07/08/2024]
Affiliation(s)
- Ariela K Holmer
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38Th Street, 23Rd Floor, New York, NY, 10016, USA
| | - David Hudesman
- Inflammatory Bowel Disease Center, Division of Gastroenterology, NYU Langone Health, 240 East 38Th Street, 23Rd Floor, New York, NY, 10016, USA.
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9
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Hong SM, Moon W. [Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti-interleukins]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 84:65-81. [PMID: 39176462 DOI: 10.4166/kjg.2024.076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 08/13/2024] [Accepted: 08/13/2024] [Indexed: 08/24/2024]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gastrointestinal tract. The introduction of biologics, particularly anti-interleukin (IL) agents, has revolutionized IBD treatment. This review summarizes the role of ILs in IBD pathophysiology and describes the efficacy and positioning of anti-IL therapies. We discuss the functions of key ILs in IBD and their potential as therapeutic targets. The review then discusses anti-IL therapies, focusing primarily on ustekinumab (anti-IL-12/23), risankizumab (anti-IL-23), and mirikizumab (anti-IL-23). Clinical trial data demonstrate their efficacy in inducing and maintaining remission in Crohn's disease and ulcerative colitis. The safety profiles of these agents are generally favorable. However, long-term safety data for newer agents are still limited. The review also briefly discusses emerging therapies such as guselkumab and brazikumab. Network meta-analyses suggest that anti-IL therapies perform well compared to other biological agents. These agents may be considered first- or second-line therapies for many patients, especially those with comorbidities or safety concerns. Anti-IL therapies represent a significant advancement in IBD treatment, offering effective and relatively safe options for patients with moderate to severe disease.
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Affiliation(s)
- Seung Min Hong
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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10
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Faggiani I, Fanizza J, D’Amico F, Allocca M, Zilli A, Parigi TL, Barchi A, Danese S, Furfaro F. Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment. Biomedicines 2024; 12:1839. [PMID: 39200303 PMCID: PMC11351332 DOI: 10.3390/biomedicines12081839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/02/2024] [Accepted: 08/09/2024] [Indexed: 09/02/2024] Open
Abstract
The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn's disease and ulcerative colitis.
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Affiliation(s)
- Ilaria Faggiani
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alberto Barchi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (I.F.); (J.F.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.); (F.F.)
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11
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Larson C, Munir N, Rao P, Farkash E, Kathuria P, Romain D, Berinstein J. Crohn's Disease Associated With IgA Nephropathy Effectively Treated With the Interleukin-23 Inhibitor Risankizumab. ACG Case Rep J 2024; 11:e01437. [PMID: 39021716 PMCID: PMC11254109 DOI: 10.14309/crj.0000000000001437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 06/14/2024] [Indexed: 07/20/2024] Open
Abstract
Extraintestinal manifestations (EIMs) are common in inflammatory bowel disease (IBD). Renal EIMs, including immunoglobulin A nephropathy (IgAN), are relatively rare. EIMs are important to consider when developing a treatment plan for IBD. Studies differ on whether IBD disease activity correlates with IgAN disease activity. Published guidance on effective therapies for IBD-associated IgAN is limited. This case report suggests that risankizumab, an effective therapy for Crohn's disease, may also be effective in treating Crohn's disease-associated IgAN.
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Affiliation(s)
- Charlotte Larson
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | | | - Panduranga Rao
- Department of Nephrology, University of Michigan, Ann Arbor, MI
| | - Evan Farkash
- Department of Pathology, University of Michigan, Ann Arbor, MI
| | - Priya Kathuria
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Dustin Romain
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
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12
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Tímár ÁE, Párniczky A, Budai KA, Hernádfői MV, Kasznár E, Varga P, Hegyi P, Váncsa S, Tóth R, Veres DS, Garami M, Müller KE. Beyond the Gut: A Systematic Review and Meta-analysis of Advanced Therapies for Inflammatory Bowel Disease-associated Extraintestinal Manifestations. J Crohns Colitis 2024; 18:851-863. [PMID: 38189533 PMCID: PMC11147804 DOI: 10.1093/ecco-jcc/jjae002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 12/19/2023] [Accepted: 01/07/2024] [Indexed: 01/09/2024]
Abstract
BACKGROUND AND AIMS Extraintestinal manifestations are frequent in patients with inflammatory bowel disease and have a negative impact on quality of life. Currently, however, there is no evidence available to determine which drug should be recommended for these patients beyond anti-tumour necrosis factor [anti-TNF] treatment. We aimed to analyse the frequency of new extraintestinal manifestations and the behaviour of pre-existing extraintestinal manifestations during advanced therapy. METHODS We conducted a systematic search on November 15, 2022, and enrolled randomized controlled trials, cohorts, and case series reporting the occurrence and behaviour of extraintestinal manifestations in patients with inflammatory bowel disease receiving advanced therapy [non-TNF inhibitor biologicals and JAK inhibitors]. Proportions of new, recurring, worsening, and improving extraintestinal manifestations were calculated with 95% confidence intervals [CIs]. The risk of bias was assessed with the QUIPS tool. RESULTS Altogether, 61 studies comprising 13,806 patients reported eligible data on extraintestinal manifestations. The overall proportion of new extraintestinal manifestations was 8% [95% CI, 6-12%] during advanced therapy. There was no significant difference between the frequency of new extraintestinal manifestations during vedolizumab and ustekinumab therapy [11%, 95% CI, 8-15% vs 6%, 95% CI, 3-11%, p = 0.166]. The improvement of pre-existing manifestations was comparable between vedolizumab- and ustekinumab-treated patients, except for joint involvement [42%, 95% CI, 32-53% vs 54%, 95% CI, 42-65%, p = 0.029]. CONCLUSION The proportion of new extraintestinal manifestations was low during advanced therapy. Furthermore, the improvement of pre-existing manifestations was comparable between advanced therapies, except for pre-existing joint manifestations.
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Affiliation(s)
- Ágnes Eszter Tímár
- Heim Pál National Pediatric Institute, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Párniczky
- Heim Pál National Pediatric Institute, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Kinga Anna Budai
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary
| | - Márk Viktor Hernádfői
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Bethesda Children’s Hospital, Budapest, Hungary
| | - Emese Kasznár
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Péter Varga
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Réka Tóth
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Dániel Sándor Veres
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | - Miklós Garami
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Katalin Eszter Müller
- Heim Pál National Pediatric Institute, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Family Care Methodology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
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13
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Shen B, Yao Q, Scherl EJ. Management of Primary Sclerosing Cholangitis and Extraintestinal Disorders in Patients With Ileal Pouches: A Systematic Review. Dis Colon Rectum 2024; 67:S106-S114. [PMID: 38411984 DOI: 10.1097/dcr.0000000000003231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
BACKGROUND Restorative proctocolectomy with IPAA improves the quality of life in patients with ulcerative colitis by the removal of diseased large bowel and preservation of the natural route of defecation. Although the surgery may improve preexisting extraintestinal manifestations in the joints, skin, and eyes, extraintestinal manifestations, particularly primary sclerosing cholangitis, can persist after colectomy. OBJECTIVES A systematic review of diagnosis and treatment of liver, joint, skin, and eye manifestations in patients with restorative proctocolectomy and IPAA for ulcerative colitis. DATA SOURCES PubMed, Google Scholar, and Cochrane database. STUDY SELECTION Relevant articles on primary sclerosing cholangitis and extraintestinal manifestations in ileal pouches published between January 2001 and July 2023 in English were included on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INTERVENTION Diagnosis and treatment of primary sclerosing cholangitis and extraintestinal manifestations in patients with restorative proctocolectomy and IPAA were included. MAIN OUTCOME MEASURES Association between primary sclerosing cholangitis, extraintestinal manifestations, and inflammatory disorders of the pouch and their management. RESULTS Primary sclerosing cholangitis and extraintestinal manifestations are associated with pouchitis, particularly chronic pouchitis. Primary sclerosing cholangitis is associated with chronic pouchitis, enteritis, and possible pouch neoplasia. However, the disease severity and course of primary sclerosing cholangitis and pouchitis do not appear to be parallel. Despite the fact that oral vancomycin or budesonide have been used to treat primary sclerosing cholangitis-associated pouchitis, their impact on the disease course of primary sclerosing cholangitis is not known. Biological therapy for chronic inflammatory disorders of the pouch may also be beneficial for the concurrent extraintestinal manifestations of the joints, skin, and eyes. However, studies on the correlation between the severity of inflammatory pouch disorders and the severity of joint, skin, and eye diseases are lacking. LIMITATIONS This is a qualitative, not quantitative, review of case series and case reports. CONCLUSIONS Primary sclerosing cholangitis and extraintestinal manifestations of the joints, skin, and eyes appear to be associated with inflammatory disorders of the ileal pouch. Although the treatment of pouchitis does not seem to affect the disease course of primary sclerosing cholangitis, effective therapy of inflammatory pouch disorders, particularly with biologics, likely benefits concurrent disorders of the joints, skin, and eyes. See video from the symposium .
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Affiliation(s)
- Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/NewYork Presbyterian Hospital, New York, New York
| | - QingPing Yao
- Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, New York
| | - Ellen J Scherl
- Division of Gastroenterology and Hepatology, Department of Medicine, New York-Presbyterian/Weill Cornell Medical Center, New York, New York
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14
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Patel PV, Zhang A, Bhasuran B, Ravindranath VG, Heyman MB, Verstraete SG, Butte AJ, Rosen MJ, Rudrapatna VA. Real-world effectiveness of ustekinumab and vedolizumab in TNF-exposed pediatric patients with ulcerative colitis. J Pediatr Gastroenterol Nutr 2024; 78:1126-1134. [PMID: 38482890 PMCID: PMC11065561 DOI: 10.1002/jpn3.12169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 12/09/2023] [Accepted: 12/19/2023] [Indexed: 03/24/2024]
Abstract
OBJECTIVES Vedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC. METHODS We performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk. RESULTS Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness. CONCLUSIONS UST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.
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Affiliation(s)
- Perseus V. Patel
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Amy Zhang
- Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, California, USA
| | - Balu Bhasuran
- Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA
| | - Vignesh G. Ravindranath
- Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA
| | - Melvin B. Heyman
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
| | - Sofia G. Verstraete
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
| | - Atul J. Butte
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
- Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, California, USA
| | - Michael J. Rosen
- Division of Pediatric Gastroenterology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Vivek A. Rudrapatna
- Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA
- Department of Medicine, Division of Gastroenterology, University of California San Francisco, San Francisco, California, USA
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15
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Mukhtar MS, Mosli MH. Selecting first-line advanced therapy for ulcerative colitis: A clinical application of personalized medicine. Saudi J Gastroenterol 2024; 30:126-137. [PMID: 38597333 PMCID: PMC11198921 DOI: 10.4103/sjg.sjg_427_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/03/2024] [Accepted: 03/13/2024] [Indexed: 04/11/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease that affects the colon, leading to symptoms of bloody diarrhea, abdominal cramps, and urgency. The treatment of UC has evolved over the past few decades from locally active anti-inflammatory compounds to more selective therapies that target specific arrays of the immune system. The challenge of selecting the first advanced therapy became apparent in this rapidly expanding landscape of medications. No current investigational tools, such as genetic, immunologic, or biological markers, can guide the identification of the safest and most effective therapeutic option for each patient. Hence, physicians must carefully assess patient/disease characteristics and match them with the most suitable drug through a clinically driven assessment. In this paper, we outline patient and drug characteristics that play a role in selecting first-line advanced therapies for UC and propose an algorithm for selection.
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Affiliation(s)
- Mariam S. Mukhtar
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mahmoud H. Mosli
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
- Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
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16
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Macaluso FS, Caprioli F, Benedan L, Bezzio C, Caporali R, Cauli A, Chimenti MS, Ciccia F, D'Angelo S, Fantini MC, Festa S, Iannone F, Lubrano E, Mariani P, Papi C, Provenzano G, Pugliese D, Rispo A, Saibeni S, Salvarani C, Variola A, Zenga M, Armuzzi A, Orlando A, Gerli R. The management of patients with inflammatory bowel disease-associated spondyloarthritis: Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and Italian Society of Rheumatology (SIR) recommendations based on a pseudo-Delphi consensus. Autoimmun Rev 2024; 23:103533. [PMID: 38521214 DOI: 10.1016/j.autrev.2024.103533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 03/20/2024] [Accepted: 03/20/2024] [Indexed: 03/25/2024]
Abstract
Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA.
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Affiliation(s)
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan, Italy; Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy.
| | - Laura Benedan
- Bicocca-Applied Statistics Center, Department of Economics, Management and Statistics, University of Milano-Bicocca, Milano, Italy
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Roberto Caporali
- Rheumatology Unit, Department of Clinical and Community Sciences, University of Milan, ASST Gaetano Pini-CTO, Milan, Italy
| | - Alberto Cauli
- Rheumatology Unit, Department of Medicine and Public Health, AOU and University of Cagliari, Cagliari, Italy
| | - Maria Sole Chimenti
- Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Italy
| | - Francesco Ciccia
- Department of Precision Medicine, Division of Rheumatology, Università della Campania L. Vanvitelli, Naples, Italy
| | - Salvatore D'Angelo
- Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Potenza, Italy
| | - Massimo Claudio Fantini
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy; Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy
| | | | | | - Ennio Lubrano
- Dipartimento di Medicina e Scienze della Salute, Università degli Studi del Molise, Campobasso, Italy
| | - Paolo Mariani
- Bicocca-Applied Statistics Center, Department of Economics, Management and Statistics, University of Milano-Bicocca, Milano, Italy
| | | | | | - Daniela Pugliese
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; IBD Unit, CEMAD, Digestive Diseases Center, Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Antonio Rispo
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University "Federico II" of Naples, Naples, Italy
| | - Simone Saibeni
- IBD Center, Gastroenterology Unit, Rho Hospital ASST Rhodense, Italy
| | - Carlo Salvarani
- Azienda USL-IRCCS di Reggio Emilia e Università di Modena e Reggio Emilia, Italy
| | | | - Mariangela Zenga
- Bicocca-Applied Statistics Center, Department of Economics, Management and Statistics, University of Milano-Bicocca, Milano, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | | | - Roberto Gerli
- Rheumatology Unit, Department of Medicine & Surgery, University of Perugia, Italy
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17
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Manrai M, Jha AA, Dawra S, Pachisia AV. Biologics, Small Molecules and More in Inflammatory Bowel Disease: The Present and the Future. FUTURE PHARMACOLOGY 2024; 4:279-316. [DOI: 10.3390/futurepharmacol4010017] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2024]
Abstract
Inflammatory bowel disease (IBD) is a group of heterogeneous chronic inflammatory diseases of the gut presenting with intestinal and extraintestinal manifestations. Most cases fit in predominantly two types, namely, ulcerative colitis and Crohn’s disease. The incidence of IBD has been increasing steadily in the past three decades. Focused research has resulted in many therapeutic options. Biologics (derived from humans or animals) and small molecules have emerged as the cornerstone in the management of IBD and have become widely available. Currently, monoclonal antibodies against tumor necrosis factor-alpha (infliximab, adalimumab, certolizumab, and golimumab), integrins (vedolizumab and natalizumab), and interleukin (IL)-12 and IL-23 antagonists (ustekinumab), along with small molecules (tofacitinib), are approved for use. This article summarizes various aspects of these drugs, like clinical pharmacology, indications for use in IBD, safety in pregnancy and lactation, and the adverse effects profile based on the studies leading to their approval. This review also focuses on the recent advances and future perspectives specific to biologics in IBD.
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Affiliation(s)
- Manish Manrai
- Department of Gastroenterology, Command Hospital, Lucknow Pin 226002, Uttar Pradesh, India
| | - Atul Abhishek Jha
- Department of Gastroenterology, Command Hospital, Lucknow Pin 226002, Uttar Pradesh, India
| | - Saurabh Dawra
- Department of Gastroenterology, Command Hospital, Pune Pin 411040, Maharashtra, India
| | - Aditya Vikram Pachisia
- Department of Gastroenterology, Command Hospital, Bengaluru Pin 560007, Karnataka, India
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18
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Mocci G, Tursi A, Onidi FM, Usai-Satta P, Pes GM, Dore MP. Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms. J Clin Med 2024; 13:1519. [PMID: 38592377 PMCID: PMC10933994 DOI: 10.3390/jcm13051519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/04/2024] [Accepted: 03/05/2024] [Indexed: 04/10/2024] Open
Abstract
Inflammatory bowel diseases, comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of 'real-world' data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.
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Affiliation(s)
- Giammarco Mocci
- Division of Gastroenterology, “Brotzu” Hospital, 09124 Cagliari, Italy; (G.M.); (F.M.O.); (P.U.-S.)
| | - Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, 76123 Andria, Italy;
- Department of Medical and Surgical Sciences, School of Medicine, Catholic University, 00168 Rome, Italy
| | - Francesca Maria Onidi
- Division of Gastroenterology, “Brotzu” Hospital, 09124 Cagliari, Italy; (G.M.); (F.M.O.); (P.U.-S.)
| | - Paolo Usai-Satta
- Division of Gastroenterology, “Brotzu” Hospital, 09124 Cagliari, Italy; (G.M.); (F.M.O.); (P.U.-S.)
| | - Giovanni Mario Pes
- Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy;
| | - Maria Pina Dore
- Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy;
- Baylor College of Medicine, One Baylor Plaza Blvd., Houston, TX 77030, USA
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19
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Zhang W, Zhong G, Ren X, Li M. Research progress of Ustekinumab in the treatment of inflammatory bowel disease. Front Immunol 2024; 15:1322054. [PMID: 38455044 PMCID: PMC10917885 DOI: 10.3389/fimmu.2024.1322054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 02/05/2024] [Indexed: 03/09/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal disorder with elusive etiology. Interleukin-12 (IL-12) and IL-23 have emerged as key proinflammatory mediators/cytokines in IBD pathogenesis. Ustekinumab (UST), targeting IL-12 and IL-23, has demonstrated promising efficacy and safety in the treatment of IBD. Recently, UST has become increasingly favored as a potential first-line treatment option. This review delineates UST's mechanism of action, its clinical applications in IBD, including the response rates, strategies for dose optimization for case of partial or lost response, and potential adverse events. This review aims to offer a comprehensive understanding of UST's role as a therapeutic option in IBD management.
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Affiliation(s)
| | | | - Xingxing Ren
- Inflammatory Bowel Disease Research Center, Department of Gastroenterology, Guangdong Province Key Laboratory of Major Obstetric Disease, Province Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Mingsong Li
- Inflammatory Bowel Disease Research Center, Department of Gastroenterology, Guangdong Province Key Laboratory of Major Obstetric Disease, Province Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
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Gonzalez Diaz I, Gutierrez Riart M, Martin-Arranz MD, Plasencia Rodriguez C, Suarez Ferrer C. Incidence and Course of Joint Inflammation Associated with Inflammatory Bowel Disease in Patients Undergoing Treatment with Vedolizumab/Ustekinumab: The VEDUSTAR Study. J Clin Med 2024; 13:1076. [PMID: 38398390 PMCID: PMC10889195 DOI: 10.3390/jcm13041076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/10/2024] [Accepted: 02/11/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND The role of ustekinumab (UST) and vedolizumab (VDZ) in the extraintestinal joint manifestations of inflammatory bowel disease (IBD) remain unclear, and most existing studies are retrospective. The aim of this prospective study was to analyze the incidence of new-onset joint disease or the worsening of pre-existing IBD-associated joint disease in patients treated with UST and VDZ. METHODS The study population comprised IBD patients with previous spondyloarthritis (SpA) or new-onset arthropathy undergoing treatment with VDZ or UST. RESULTS Eighty patients were referred to rheumatology because of previous SpA or onset of symptoms. Most patients (90%) were anti-TNF experienced. Two patients with previous SpA (2/22; 9%) experienced a flare-up (one with UST and one with VDZ), and two patients with VDZ developed SpA during follow-up (2/58; 3%). Only one of these four patients did not have gastrointestinal symptoms, and VDZ was discontinued because of joint symptoms. The other three patients had concomitant intestinal activity, and treatment was not discontinued. CONCLUSION Our experience shows that treatment with UST and VDZ did not worsen joint disease in patients with SpA. Most remained stable or improved. In addition, poor control of IBD in patients with joint flare-ups could be the main cause of worsening SpA.
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Affiliation(s)
- Irene Gonzalez Diaz
- Gastroenterology Department, La Paz University Hospital, 28046 Madrid, Spain;
| | - Mariana Gutierrez Riart
- Rheumatology Department, La Paz University Hospital, 28046 Madrid, Spain; (M.G.R.); (C.P.R.)
| | - Maria Dolores Martin-Arranz
- Gastroenterology Department, La Paz University Hospital, 28046 Madrid, Spain;
- Hospital La Paz Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain
- Faculty of Medicine, Universidad Autónoma, 28046 Madrid, Spain
| | | | - Cristina Suarez Ferrer
- Gastroenterology Department, La Paz University Hospital, 28046 Madrid, Spain;
- Hospital La Paz Institute for Health Research, La Paz University Hospital, 28046 Madrid, Spain
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21
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Gordon H, Burisch J, Ellul P, Karmiris K, Katsanos K, Allocca M, Bamias G, Barreiro-de Acosta M, Braithwaite T, Greuter T, Harwood C, Juillerat P, Lobaton T, Müller-Ladner U, Noor N, Pellino G, Savarino E, Schramm C, Soriano A, Michael Stein J, Uzzan M, van Rheenen PF, Vavricka SR, Vecchi M, Zuily S, Kucharzik T. ECCO Guidelines on Extraintestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2024; 18:1-37. [PMID: 37351850 DOI: 10.1093/ecco-jcc/jjad108] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Indexed: 06/24/2023]
Affiliation(s)
- Hannah Gordon
- Department of Gastroenterology, Barts Health NHS Trust, London, Centre for Immunobiology, Blizard Institute, Faculty of Medicine, Barts & The London Medical School, Queen Mary University of London, UK
| | - Johan Burisch
- Gastrounit, medical division, Hvidovre Hospital, University of Copenhagen, Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | | | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, University and Medical School of Ioannina, Ioannina, Greece
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Giorgos Bamias
- GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Manuel Barreiro-de Acosta
- University Hospital Santiago De Compostela CHUS, Department of Gastroenterology - IBD Unit, Santiago De Compostela, Spain
| | - Tasanee Braithwaite
- School of Immunology and Microbiology, King's College London, The Medical Eye Unit, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, GZO - Zurich Regional Health Center, Wetzikon, Division of Gastroenterology and Hepatology, University Hospital Lausanne - CHUV, Lausanne, Switzerland; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Catherine Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London; Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland; Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Justus Liebig University Giessen, Bad Nauheim, Germany
| | - Nurulamin Noor
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Gianluca Pellino
- Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB, Barcelona, Spain; Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, Italy
| | - Christoph Schramm
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alessandra Soriano
- Gastroenterology Division and IBD Center, Internal Medicine Department, Azienda Unità Sanitaria Locale - IRCCS, 42122 Reggio Emilia, Italy
| | - Jürgen Michael Stein
- Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt/Main, Germany
| | - Mathieu Uzzan
- Department of Gastroenterology, Hôpital Henri Mondor, APHP, Créteil, France
| | - Patrick F van Rheenen
- Department of Paediatric Gastroenterology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Maurizio Vecchi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stephane Zuily
- Vascular Medicine Division and French Referral Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France
| | - Torsten Kucharzik
- Department of Gastroenterology, Lüneburg Hospital, University of Münster, Lüneburg, Germany
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González-Lama Y, Ricart E, Carpio D, Bastida G, Ceballos D, Ginard D, Marin-Jimenez I, Menchen L, Muñoz F. Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus. BMJ Open Gastroenterol 2024; 11:e001246. [PMID: 38267072 PMCID: PMC10870792 DOI: 10.1136/bmjgast-2023-001246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 10/24/2023] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Despite research, there are still controversial areas in the management of Crohn's disease (CD). OBJECTIVE To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD. METHODS Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process. RESULTS Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator. CONCLUSION This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD.
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Affiliation(s)
- Yago González-Lama
- Gastroenterology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Elena Ricart
- Gastroenterology Department, CIBEREHD, Madrid, Spain
| | - Daniel Carpio
- Gastroenterology Department, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
| | | | - Daniel Ceballos
- Gastroenterology Department, Hospital Universitario Doctor Negrin, Las Palmas de Gran Canaria, Spain
| | - Daniel Ginard
- Gastroenterology Department, Hospital Universitario Son Espases, Palma, Spain
| | | | - Luis Menchen
- Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Fernando Muñoz
- Gastroenterology Department, Hospital Universitario de Salamanca, Salamanca, Spain
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Gordon H, Wichmann K, Lewis A, Sanders T, Wildemann M, Hoti I, Hornsby E, Kok KB, Silver A, Lindsay JO, Stagg AJ. Human Intestinal Dendritic Cells Can Overcome Retinoic Acid Signaling to Generate Proinflammatory CD4 T Cells with Both Gut and Skin Homing Properties. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2024; 212:96-106. [PMID: 37955427 DOI: 10.4049/jimmunol.2300340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 09/18/2023] [Indexed: 11/14/2023]
Abstract
Retinoic acid, produced by intestinal dendritic cells (DCs), promotes T cell trafficking to the intestinal mucosa by upregulating α4β7 integrin and inhibiting the generation of cutaneous leukocyte Ag (CLA) required for skin entry. In the present study, we report that activation of human naive CD4 T cells in an APC-free system generates cells expressing α4β7 alone; in contrast, activation by intestinal DCs that produce retinoic acid and induce high levels of α4β7 also results in CLA expression, generating CLA+α4β7+ "dual tropic" cells, with both gut and skin trafficking potential, that also express high levels of α4β1 integrin. DC generation of CLA+α4β7+ T cells is associated with upregulation of FUT7, a fucosyltransferase involved in CLA generation; requires cell contact; and is enhanced by IL-12/IL-23. The blood CD4+ T cell population contains CLA+α4β7+ cells, which are significantly enriched for cells capable of IFN-γ, IL-17, and TNF-α production compared with conventional CLA-α4β7+ cells. Dual tropic lymphocytes are increased in intestinal tissue from patients with Crohn's disease, and single-cell RNA-sequencing analysis identifies a transcriptionally distinct cluster of FUT7-expressing cells present only in inflamed tissue; expression of genes associated with cell proliferation suggests that these cells are undergoing local activation. The expression of multiple trafficking molecules by CLA+α4β7+ T cells can enable their recruitment by alternative pathways to both skin and gut; they may contribute to both intestinal and cutaneous manifestations of inflammatory bowel disease.
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Affiliation(s)
- Hannah Gordon
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Katherine Wichmann
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Amy Lewis
- Centre for Genomics and Child Health, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Theodore Sanders
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Martha Wildemann
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Inva Hoti
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - Eve Hornsby
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - K Bel Kok
- Department of Gastroenterology, Barts Health NHS Trust, London, United Kingdom
| | - Andrew Silver
- Centre for Genomics and Child Health, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
| | - James O Lindsay
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
- Department of Gastroenterology, Barts Health NHS Trust, London, United Kingdom
| | - Andrew J Stagg
- Centre for Immunobiology, Blizard Institute, Faculty of Medicine and dentistry, Barts and The London Medical School, Queen Mary University of London, London, United Kingdom
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da Silva Júnior RT, Apolonio JS, de Souza Nascimento JO, da Costa BT, Malheiro LH, Silva Luz M, de Carvalho LS, da Silva Santos C, Freire de Melo F. Crohn's disease and clinical management today: How it does? World J Methodol 2023; 13:399-413. [PMID: 38229938 PMCID: PMC10789097 DOI: 10.5662/wjm.v13.i5.399] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/11/2023] [Accepted: 10/25/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's Disease (CD) is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature. Its etiology results from the interaction between genetic, enviromental and microbial factors. Regarding pathophysiology, it involves high levels of interleukin (IL)-12, IL-17, and Th1 profile, along with loss of tolerance mechanisms, an increase in pro-inflammatory interleukins, beyond the possibility to affect any part of the gastrointestinal tract. Its symptoms include abdominal pain, chronic diarrhea, weight loss, anorexia, and fatigue, as well as blood in the stool or rectum. Additionally, conditions comprising musculoskeletal, cutaneous, ocular, hepatic, and hematological alterations may be associated with this scenario and extra-intestinal presentation, such as erythema nodosum, anterior uveitis, osteoporosis, and arthritis can also occur. Today, clinical history, exams as fecal calprotectin, ileocolonocopy, and capsule endoscopy can be performed in the diagnosis investigation, along with treatments to induce and maintain remission. In this sense, anti-inflammatory drugs, such as corticosteroids, immunomodulators, and biological agents, as well as surgery and non-pharmacological interventions plays a role in its therapy. The aim of this review is to bring more current evidence to clinical management of CD, as well as to briefly discuss aspects of its pathophysiology, surveillance, and associated disorders.
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Affiliation(s)
| | - Jonathan Santos Apolonio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Bruna Teixeira da Costa
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Luciano Hasimoto Malheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Lorena Sousa de Carvalho
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Cleiton da Silva Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Grova M, Vitello A, Mannino M, Casà A, Renna S, Macaluso FS, Orlando A. Role of ustekinumab in treatment of ulcerative colitis: a narrative review. Immunotherapy 2023; 15:1539-1552. [PMID: 38018475 DOI: 10.2217/imt-2023-0106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 10/12/2023] [Indexed: 11/30/2023] Open
Abstract
The therapeutic armamentarium for gastroenterologists in treating ulcerative colitis (UC) has been rapidly growing since the introduction of monoclonal antibodies directed against anti-TNFs. Ustekinumab is a monoclonal antibody binding the shared p40 subunit of IL-12 and IL-23, and the inhibition of these two cytokines, implicated in host response to microbial pathogens, has demonstrated clinical efficacy in different immune-mediated diseases, including moderate-to-severe UC. This narrative review summarizes the newest clinical evidence regarding the efficacy, effectiveness and safety of ustekinumab in moderate-to-severe UC, including specific situations (pregnancy, breastfeeding, elderly/pediatric populations, extraintestinal manifestations, acute severe UC, pouchitis and dual biological therapy). Finally, positioning is discussed in light of the existing evidence.
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Affiliation(s)
- Mauro Grova
- Digestive Endoscopy Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
| | - Alessandro Vitello
- Gastroenterology & Endoscopy Unit, S. Elia-Raimondi Hospital, Caltanissetta, 93100, Italy
| | - Mariella Mannino
- Inflammatory Bowel Disease Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
| | - Angelo Casà
- Inflammatory Bowel Disease Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
| | - Sara Renna
- Inflammatory Bowel Disease Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
| | - Fabio Salvatore Macaluso
- Inflammatory Bowel Disease Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
| | - Ambrogio Orlando
- Inflammatory Bowel Disease Unit, Department of Medicine, "Villa Sofia-Cervello" Hospital, Palermo, 90100, Italy
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Lutz M, Caldera F, Schroeder K, Gazis D, Crawford JM, Long MD, Barnes EL. Prevalence of Immunomodulator Use as Combination Therapy With Vedolizumab or Ustekinumab in Inflammatory Bowel Disease. Clin Transl Gastroenterol 2023; 14:e00620. [PMID: 37450671 PMCID: PMC10684180 DOI: 10.14309/ctg.0000000000000620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 07/06/2023] [Indexed: 07/18/2023] Open
Abstract
INTRODUCTION The benefit of adding an immunomodulator to vedolizumab and ustekinumab remains unclear and may compromise the safety of these biologics. We evaluated the prevalence and predictors of immunomodulator use with vedolizumab or ustekinumab in patients with inflammatory bowel disease in a large longitudinal cohort. METHODS Clinical information was ascertained from electronic medical records of patients enrolled in TARGET-IBD, a prospective longitudinal observational cohort of patients with inflammatory bowel disease (IBD) at 34 sites. The prevalence of immunomodulator use with vedolizumab, ustekinumab, and antitumor necrosis factor therapies and predictors of immunomodulator use with vedolizumab and ustekinumab were estimated. Rates of combination therapy were additionally stratified by time from drug approval. RESULTS Four thousand thirty-nine adults with IBD were identified, of whom 18.8% were treated with vedolizumab and 13.0% were treated with ustekinumab. Combination therapy with vedolizumab and ustekinumab exceeded 30% (30.7% and 36.2%, respectively) and was more likely in those with perianal disease or previous biologic exposure. Age and presence of extraintestinal manifestations did not consistently predict the use of an immunomodulator. Combination therapy decreased in the years after drug approval. DISCUSSION Combination therapy with vedolizumab or ustekinumab was common and was associated with perianal disease and greater exposure to other biologics, although the practice is decreasing with time. Further data are needed to determine the efficacy and safety of combination therapy in patients initiating vedolizumab or ustekinumab for IBD.
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Affiliation(s)
- Megan Lutz
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin—Madison, School of Medicine & Public Health, Madison, Wisconsin, USA
| | - Freddy Caldera
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Wisconsin—Madison, School of Medicine & Public Health, Madison, Wisconsin, USA
| | - Katie Schroeder
- Saint Louis University School of Medicine, St. Louis, Missouri, USA
| | - Derek Gazis
- TARGET RWE, Inc., Durham, North Carolina, USA
| | | | - Millie D. Long
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Edward L. Barnes
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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He R, Zhao S, Cui M, Chen Y, Ma J, Li J, Wang X. Cutaneous manifestations of inflammatory bowel disease: basic characteristics, therapy, and potential pathophysiological associations. Front Immunol 2023; 14:1234535. [PMID: 37954590 PMCID: PMC10637386 DOI: 10.3389/fimmu.2023.1234535] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/16/2023] [Indexed: 11/14/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease typically involving the gastrointestinal tract but not limited to it. IBD can be subdivided into Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) are observed in up to 47% of patients with IBD, with the most frequent reports of cutaneous manifestations. Among these, pyoderma gangrenosum (PG) and erythema nodosum (EN) are the two most common skin manifestations in IBD, and both are immune-related inflammatory skin diseases. The presence of cutaneous EIMs may either be concordant with intestinal disease activity or have an independent course. Despite some progress in research on EIMs, for instance, ectopic expression of gut-specific mucosal address cell adhesion molecule-1 (MAdCAM-1) and chemokine CCL25 on the vascular endothelium of the portal tract have been demonstrated in IBD-related primary sclerosing cholangitis (PSC), little is understood about the potential pathophysiological associations between IBD and cutaneous EIMs. Whether cutaneous EIMs are inflammatory events with a commonly shared genetic background or environmental risk factors with IBD but independent of IBD or are the result of an extraintestinal extension of intestinal inflammation, remains unclear. The review aims to provide an overview of the two most representative cutaneous manifestations of IBD, describe IBD's epidemiology, clinical characteristics, and histology, and discuss the immunopathophysiology and existing treatment strategies with biologic agents, with a focus on the potential pathophysiological associations between IBD and cutaneous EIMs.
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Affiliation(s)
- Ronghua He
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Subei Zhao
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingyu Cui
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Yanhao Chen
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Jinrong Ma
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Jintao Li
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Xiaodong Wang
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, Jilin, China
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Lauri G, D'Amico F, Allocca M, Palumbo D, Della-Torre E, De Cobelli F, Doglioni C, Giorgio Arcidiacon P, Capurso G, Danese S. Ustekinumab as Induction and Maintenance Therapy in Patients with Inflammatory Bowel Disease and Type II Autoimmune Pancreatitis: Report of Two Cases. J Crohns Colitis 2023; 17:1552-1554. [PMID: 37086207 DOI: 10.1093/ecco-jcc/jjad072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Indexed: 04/23/2023]
Affiliation(s)
- Gaetano Lauri
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
- Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
| | - Diego Palumbo
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, ItalyUnit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Claudio Doglioni
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Paolo Giorgio Arcidiacon
- Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Gabriele Capurso
- Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy
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Gara SK, Guntipalli P, Marzban S, Taqi M, Aryal V, Khan QUA, Shah SA, Akbariromani H, Salinger D, Diaz-Miret M. Clinical Outcomes of Ustekinumab in Inflammatory Bowel Disease. Cureus 2023; 15:e46833. [PMID: 37954750 PMCID: PMC10636694 DOI: 10.7759/cureus.46833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2023] [Indexed: 11/14/2023] Open
Abstract
Inflammatory bowel diseases including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by abdominal pain, diarrhea, blood in stools, weight loss, and fatigue. It presents in patients with varying severity from mild to severe depending on the inflammation. Detailed analysis and guidelines are required for the safe usage of biological therapies in the treatment of inflammatory bowel diseases as surgery is reserved for more complex cases. There is also geographical variation in inflammatory bowel disease (IBD) incidence and prevalence based on environmental and climate changes, and socio-demographics. Studies also show that there is more hospitalization and reduced health-related quality of life in IBD patients when compared to normal people. We conducted an extensive literature database search for articles with keywords within the last 10 years on adults >18 years of age with IBD and its treatment, especially with ustekinumab. Ustekinumab is a human immunoglobulin G1 (IgG1) kappa monoclonal antibody, that blocks IL-12 and IL-23 and was approved by the FDA for the treatment of moderate to severe IBD, especially in patients who are intolerant to immunomodulators or corticosteroids treatment. There are several retrospective studies that show the effectiveness of ustekinumab dosage escalation every four weeks in IBD patients. This escalation of dose not only improved the clinical outcome but also reduced the worsening of the disease. Previous studies also show the importance of considering dosage escalation before switching biological agents in the IBD treatment. Ustekinumab has also demonstrated both efficacy and safety in the induction and maintenance of the treatment of this disease. There are certain challenges and opportunities associated with ustekinumab usage in IBD patients that require further research. Ustekinumab seems to be more cost-effective in the tumor necrosis factor (TNF)-alpha-inhibitor failure population when compared to previously used biological treatment regimes.
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Affiliation(s)
- Sirisha K Gara
- Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, USA
- Geriatric Research Education and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, USA
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
| | | | - Sima Marzban
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
| | - Muhammad Taqi
- Orthopedic Surgery, Mayo Hospital, King Edward Medical University (KEMU), Lahore, PAK
| | - Vinayak Aryal
- Pathology and Laboratory Medicine, Nepal Cancer Hospital and Research Center, Lalitpur, NPL
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
- Pathology and Laboratory Medicine, MetroHealth System/Case Western Reserve University, Cleveland, USA
| | - Qurat Ul Ain Khan
- Internal Medicine, Services Institute of Medical Sciences, Lahore, PAK
| | - Shahtaj A Shah
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
| | - Hanieh Akbariromani
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
- Clinical Research, Surgical ICU Research Center, Brigham and Women's Hospital, Boston, USA
- Medicine, Islamic Azad University, Tehran, IRN
| | - Darren Salinger
- Research and Academic Affairs, Larkin Community Hospital, South Miami, USA
| | - Miguel Diaz-Miret
- Family Medicine, Larkin Community Hospital Palm Springs Campus, Hialeah, USA
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Miklusiak K, Miklusiak K, Kaczmarczyk O, Cibor D, Zwolińska-Wcisło M. Ustekinumab in the treatment of acute disseminated pyoderma gangrenosum in a patient with Crohn's disease. Dermatol Reports 2023; 15:9630. [PMID: 37908604 PMCID: PMC10614552 DOI: 10.4081/dr.2023.9630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/03/2023] [Indexed: 11/02/2023] Open
Abstract
Pyoderma gangrenosum (PG) is an auto-inflammatory dermatosis characterized by lesions that often cause ulcers. We present a case of successful ustekinumab treatment for acute general PG in a 31-year-old woman with coexisting Crohn's disease (CD). For a month, the patient suffered from skin ulcers, two of them deep and necrotic; a histopathological examination revealed PG. Treatment included: methylprednisolone, azathioprine, betamethasone, gentamicin and zincic ointments, antiseptic compresses, and adalimumab therapy. Due to resistance to the implemented treatment, the patient was enrolled in a clinical trial that included the administration of an anti-cytokines drug, ustekinumab. Subsequently, a significant reduction was observed in the severity of symptoms of PG with no relapse. The use of ustekinumab in patients with PG who have an inadequate response to current treatment or cannot receive first-line treatment can be considered. This applies especially to patients with accompanying autoimmune diseases such as CD.
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Affiliation(s)
| | - Karol Miklusiak
- Polish Red Cross Maritime Hospital with Oncology Centre, Gdynia
| | - Olga Kaczmarczyk
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Cracow, Poland
| | - Dorota Cibor
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Cracow, Poland
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31
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Verstockt B, Salas A, Sands BE, Abraham C, Leibovitzh H, Neurath MF, Vande Casteele N. IL-12 and IL-23 pathway inhibition in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2023; 20:433-446. [PMID: 37069321 PMCID: PMC10958371 DOI: 10.1038/s41575-023-00768-1] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 04/19/2023]
Abstract
Interleukin-12 (IL-12) and interleukin-23 (IL-23), which belong to the IL-12 family of cytokines, have a key role in intestinal homeostasis and inflammation and are implicated in the pathogenesis of inflammatory bowel disease. Upon their secretion by antigen-presenting cells, they exert both pro-inflammatory and anti-inflammatory receptor-mediated effects. An increased understanding of these biological effects, particularly the pro-inflammatory effects mediated by IL-12 and IL-23, has led to the development of monoclonal antibodies that target a subunit common to IL-12 and IL-23 (p40; targeted by ustekinumab and briakinumab), or the IL-23-specific subunit (p19; targeted by risankizumab, guselkumab, brazikumab and mirikizumab). This Review provides a summary of the biology of the IL-12 family cytokines IL-12 and IL-23, discusses the role of these cytokines in intestinal homeostasis and inflammation, and highlights IL-12- and IL-23-directed drug development for the treatment of Crohn's disease and ulcerative colitis.
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Affiliation(s)
- Bram Verstockt
- University Hospitals Leuven, Department of Gastroenterology and Hepatology, KU Leuven, Leuven, Belgium
- KU Leuven Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium
| | - Azucena Salas
- Inflammatory Bowel Disease Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Clara Abraham
- Department of Medicine, Yale University, New Haven, CT, USA
| | - Haim Leibovitzh
- Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Markus F Neurath
- Department of Medicine 1, University Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie DZI, University Erlangen-Nürnberg, Erlangen, Germany
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32
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Herrlinger KR, Stange EF. Prioritization in inflammatory bowel disease therapy. Expert Rev Gastroenterol Hepatol 2023; 17:753-767. [PMID: 37480322 DOI: 10.1080/17474124.2023.2240699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 06/24/2023] [Accepted: 07/21/2023] [Indexed: 07/24/2023]
Abstract
INTRODUCTION Most guidelines for IBD still recommend step-by-step therapy with initially classic drugs such aminosalicylates (in ulcerative colitis) or steroids but avoid prioritizing certain biological drugs and JAK inhibitors in the complicated course. This review provides an aid to pending therapy decisions. AREAS COVERED In this review, we analyze the evidence for Crohn's disease as well as ulcerative colitis in order to optimize and 'personalize' the choice of therapy, especially in difficult cases. The relevant publications in Pubmed were identified in a continuous literature review with the key words 'Crohn´s disease' and 'ulcerative colitis.' EXPERT OPINION Based on this complex data set following standard therapies steroid-refractory Crohn´s disease should preferentially be treated with combined infliximab plus azathioprine or risankizumab, in second line after their failure with ustekinumab or 7adalimumab. In steroid-refractory ulcerative colitis infliximab plus azathioprine or upadacitinib should be preferred in first line, filgotinib, tofacitinib or ustekinumab in second line. A steroid-dependent course in both diseases requires azathioprine or vedolizumab, in second line infliximab or Janus kinase inhibitors. The conclusions drawn from these complex data may be helpful for individual decision making in daily clinical practice.
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Affiliation(s)
| | - Eduard F Stange
- Klinik Für Innere Medizin I, Universitätsklinik Tübingen, Tübingen, Germany
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Souza RF, Caetano MAF, Magalhães HIR, Castelucci P. Study of tumor necrosis factor receptor in the inflammatory bowel disease. World J Gastroenterol 2023; 29:2733-2746. [PMID: 37274062 PMCID: PMC10237104 DOI: 10.3748/wjg.v29.i18.2733] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/14/2023] [Accepted: 04/04/2023] [Indexed: 05/11/2023] Open
Abstract
Ulcerative colitis (UC) and Crohn’s disease (CD) are part of Inflammatory Bowel Diseases (IBD) and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells. In addition, the main inflammatory mediator is related to the tumor necrosis factor-alpha (TNF-α). TNF-α is a me-diator of the intestinal inflammatory processes, thus being one of the main cytokines involved in the pathogenesis of IBD, however, its levels, when measured, are present in the serum of patients with IBD. In addition, TNF-α plays an important role in promoting inflammation, such as the production of interleukins (IL), for instance IL-1β and IL-6. There are two receptors for TNF as following: The tumor necrosis factor 1 receptor (TNFR1); and the tumor necrosis factor 2 receptor (TNFR2). They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity. The soluble TNF form binds to the TNFR1 receptor with, and its activation results in a signaling cascade effects such as apoptosis, cell proliferation and cytokine secretion. In contrast, the transmembrane TNF form can bind both to TNFR1 and TNFR2. Recent studies have suggested that TNF-α is one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD, since TNF levels are present in the serum of both patients with UC and CD. Intravenous and subcutaneous biologics targeting TNF-α have revolutionized the treatment of IBD, thus becoming the best available agents to induce and maintain IBD remission. The application of antibodies aimed at neutralizing TNF-α in patients with IBD that induce a satisfactory clinical response in up to 60% of patients, and also induced long-term maintenance of disease remission in most patients. It has been suggested that anti-TNF-α agents inactivate the pro-inflammatory cytokine TNF-α by direct neutralization, i.e., resulting in suppression of inflammation. However, anti-TNF-α antibodies perform more complex functions than a simple blockade.
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Affiliation(s)
- Roberta Figueiroa Souza
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
| | | | | | - Patricia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil
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Khoshnam-Rad N, Vahedi H, Sadeghi A, Rastegarpanah M, Namazi S, Anushiravani A, Sima AR, Shahrokh S, Alatab S, Malekzadeh R. Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases. Middle East J Dig Dis 2023; 15:83-106. [PMID: 37546508 PMCID: PMC10404092 DOI: 10.34172/mejdd.2023.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 02/11/2023] [Indexed: 08/08/2023] Open
Abstract
Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.
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Affiliation(s)
- Niloofar Khoshnam-Rad
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Homayoon Vahedi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Anahita Sadeghi
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansoor Rastegarpanah
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Soha Namazi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Anushiravani
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Reza Sima
- Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Center, Tehran, Iran
| | - Shabnam Shahrokh
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sudabeh Alatab
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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35
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Lu S, Yao J, Zhi M. Therapeutic effect of ustekinumab on patients with extra-intestinal manifestations of Crohn's disease. Expert Rev Gastroenterol Hepatol 2023; 17:379-384. [PMID: 36896662 DOI: 10.1080/17474124.2023.2189096] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
INTRODUCTION Ustekinumab serves as an important alternative option for patients with various extraintestinal manifestations (EIMs), which leads to poor quality of life and heavy burden of care. Therefore, a comprehensive review summarizing the efficacy and safety of ustekinumab in patients with CDassociated EIMs is needed to provide reference for clinical medication and help with the appliance of precision medicine. AREAS COVERED In this review, we collected and summarized the efficacy and paradoxical side effects of ustekinumab in patients with CDassociated EIMs including musculoskeletal, cutaneous, ocular, and hepatobiliary manifestations. This literature review was performed using PubMed to identify and collect relevant studies published in English. EXPERT OPINION The effectiveness of ustekinumab on patients with CDassociated EIMs is mainly reflected in musculoskeletal and cutaneous manifestations compared to ocular or hepatobiliary manifestations. Relevant data from large scale cohort studies and prospective randomized trials are needed to further demonstrate the efficacy and safety of ustekinumab in patients with multiple EIMs.
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Affiliation(s)
- Shilin Lu
- Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong Province, China
| | - Jiayin Yao
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
- Department of gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
| | - Min Zhi
- Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
- Department of gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China
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Katsanos KH, Fousekis FS, Armuzzi A. The role of ustekinumab and vedolizumab in management of extra intestinal manifestations in inflammatory bowel disease. Dig Liver Dis 2023; 55:149-150. [PMID: 36319583 DOI: 10.1016/j.dld.2022.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/05/2022]
Affiliation(s)
| | - Fotios S Fousekis
- Division of Gastroenterology, University of Ioannina, Ioannina, Greece
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
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Livne-Margolin M, Ling D, Attia-Konyo S, Abitbol CM, Haj-Natour O, Ungar B, Ben-Horin S, Kopylov U. Ustekinumab and vedolizumab for extraintestinal manifestations in inflammatory bowel disease - a retrospective study. Dig Liver Dis 2023; 55:223-229. [PMID: 36241535 DOI: 10.1016/j.dld.2022.09.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 09/12/2022] [Accepted: 09/12/2022] [Indexed: 11/08/2022]
Abstract
INTRODUCTION Extraintestinal manifestations (EIM) are associated with diminished quality of life. The efficacy of Ustekinumab and vedolizumab for EIM treatment is not well established. The aim was to compare the effectiveness of ustekinumab and vedolizumab for treatment of EIM in IBD. METHODS We included IBD patients treated with vedolizumab or ustekinumab in the Gastroenterology department, Sheba Medical Center, for up to 52 weeks between 2015 and 2021. Patients with active EIM before treatment initiation were included. RESULTS 111 patients were included. 53 patients (48%) were treated with ustekinumab; 88% (n-99) had CD. The most common EIM was arthralgia (95/111, 84%). Patients treated with ustekinumab were more likely to be anti-TNF experienced (n-51/53 [96%] compared with vedolizumab n = 36/58 [62%], p < 0.001). Clinical response of EIM at week 52 was achieved in 36% of patients treated with ustekinumab (n-18/50) and 34% of patients (n-19/54) treated with vedolizumab, with no statistically significant difference (p = 0.9). No statistical significance was achieved for patients presented with arthralgia. Clinical response of arthralgia at week 52 was seen in 34% (n-19/55) and 36% (n-18/46) of the patients treated with vedolizumab and ustekinumab, respectively, (p = 0.3). CONCLUSION In this study, no difference was found between vedolizumab and ustekinumab regarding their effect on EIM in IBD patients for up to 52 weeks.
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Affiliation(s)
- Moran Livne-Margolin
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Daniel Ling
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shani Attia-Konyo
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal Medicine E, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Chaya Mushka Abitbol
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Ola Haj-Natour
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Bella Ungar
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shomron Ben-Horin
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Uri Kopylov
- Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Wang CR, Tsai HW. Seronegative spondyloarthropathy-associated inflammatory bowel disease. World J Gastroenterol 2023; 29:450-468. [PMID: 36688014 PMCID: PMC9850936 DOI: 10.3748/wjg.v29.i3.450] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/18/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Na SY, Choi CH, Song EM, Bang KB, Park SH, Kim ES, Park JJ, Keum B, Lee CK, Lee BI, Ryoo SB, Koh SJ, Choi M, Kim JS. Korean clinical practice guidelines on biologics and small molecules for moderate-to-severe ulcerative colitis. Intest Res 2023; 21:61-87. [PMID: 35645321 PMCID: PMC9911265 DOI: 10.5217/ir.2022.00007] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/07/2022] [Indexed: 02/09/2023] Open
Abstract
Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.
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Affiliation(s)
- Soo-Young Na
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea,Correspondence to Chang Hwan Choi, Department of Internal Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea. Tel: +82-2-6299-1418, Fax: +82-2-6299-2064, E-mail:
| | - Eun Mi Song
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Ki Bae Bang
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Jun Park
- Department of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Bora Keum
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Chang Kyun Lee
- Department of Gastroenterology, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Bo-In Lee
- Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung-Bum Ryoo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Joon Koh
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Le Berre C, Danese S, Peyrin-Biroulet L. Can we change the natural course of inflammatory bowel disease? Therap Adv Gastroenterol 2023; 16:17562848231163118. [PMID: 37153497 PMCID: PMC10159495 DOI: 10.1177/17562848231163118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/01/2023] [Indexed: 05/09/2023] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are lifelong diseases characterized by chronic inflammation of the gastrointestinal tract leading to its progressive and irreversible destruction. Whether early initiation of IBD-specific therapy impacts the long-term course of the disease remains unclear and has to be further explored in prospective disease-modification trials. Historically, surgery and hospitalization rates have been the surrogate markers to measure disease progression in IBD, providing an overview of the effectiveness of medical therapies. However, neither surgery nor hospitalization necessarily reflects a fail in therapeutic medical management, and many confounding factors make them biased outcomes. The Selecting Endpoints for Disease-Modification Trials consensus has defined the disease-modification endpoints required for these trials, including the impact of the disease on patient's life (health-related quality of life, disability, and fecal incontinence), the mid-term disease complications (bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extra-intestinal manifestations, permanent stoma, short bowel syndrome), and the development of dysplasia/cancer and mortality in the long term. Most available data in the literature regarding the impact of current therapies on disease progression focused on anti-tumor necrosis factor agents and are based on retrospective or post-hoc studies. Thus, prospective disease-modification trials are pressingly required to explore the effectiveness of early intensified treatment in patients with severe disease or at risk for disease progression.
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Affiliation(s)
| | - Silvio Danese
- Department of Gastroenterology and Digestive
Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele
University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE
U1256, University Hospital of Nancy, University of Lorraine,
Vandoeuvre-lès-Nancy, France
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Bacsur P, Matuz M, Resál T, Miheller P, Szamosi T, Schäfer E, Sarlós P, Iliás Á, Szántó K, Rutka M, Bálint A, Milassin Á, Fábián A, Bor R, Szepes Z, Molnár T, Farkas K. Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn's disease: results from a multicentre cohort study. Therap Adv Gastroenterol 2022; 15:17562848221144349. [PMID: 36600684 PMCID: PMC9806440 DOI: 10.1177/17562848221144349] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 11/23/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%-50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. OBJECTIVES This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn's disease (CD). DESIGN In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. METHODS Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. RESULTS A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. CONCLUSIONS VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.
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Affiliation(s)
- Péter Bacsur
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Mária Matuz
- Institute of Clinical Pharmacy, Faculty of
Pharmacy, University of Szeged, Szeged, Hungary
| | - Tamás Resál
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Pál Miheller
- Department of Surgery and Interventional
Gastroenterology, Faculty of Medicine, Semmelweis University, Budapest,
Hungary
| | - Tamás Szamosi
- Department of Gastroenterology, Military
Hospital – State Health Centre, Budapest, Hungary
| | - Eszter Schäfer
- Department of Gastroenterology, Military
Hospital – State Health Centre, Budapest, Hungary
| | - Patrícia Sarlós
- Division of Gastroenterology, First Department
of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Ákos Iliás
- First Department of Medicine, Faculty of
Medicine, Semmelweis University, Budapest, Hungary
| | - Kata Szántó
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Mariann Rutka
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Anita Bálint
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Ágnes Milassin
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Anna Fábián
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Renáta Bor
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Zoltán Szepes
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
| | - Tamás Molnár
- Department of Medicine, Albert Szent-Györgyi
Medical School, University of Szeged, Szeged, Hungary
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De Galan C, Truyens M, Peeters H, Mesonero Gismero F, Elorza A, Torres P, Vandermeulen L, Amezaga AJ, Ferreiro-Iglesias R, Holvoet T, Zabana Y, Reverter LP, Gonzales GB, Geldof J, Varkas G, De Vos M, Lobatón T. The Impact of Vedolizumab and Ustekinumab on Articular Extra-Intestinal Manifestations in Inflammatory Bowel Disease Patients: A Real-Life Multicentre Cohort Study. J Crohns Colitis 2022; 16:1676-1686. [PMID: 35442433 DOI: 10.1093/ecco-jcc/jjac058] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIMS Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.
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Affiliation(s)
- Cara De Galan
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.,Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium
| | - Marie Truyens
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.,Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium.,Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Harald Peeters
- Department of Gastroenterology, AZ Sint Lucas, Ghent, Belgium
| | | | - Ainara Elorza
- Department of Gastroenterology, Hospital de Galdakao, Bilbao, Spain
| | - Paola Torres
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain
| | - Liv Vandermeulen
- Department of Gastroenterology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel, Brussels, Belgium
| | | | - Rocio Ferreiro-Iglesias
- Department of Gastroenterology, Hospital Clínico Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Tom Holvoet
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.,Department of Gastroenterology, AZ Nikolaas, Sint-Niklaas, Belgium
| | - Yamile Zabana
- Department of Gastroenterology, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Barcelona, Spain
| | - Laia Peries Reverter
- Department of Gastroenterology, Hospital Universitari de Girona Doctor Joseph Trueta, Girona, Spain
| | - Gerard Bryan Gonzales
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.,Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands
| | - Jeroen Geldof
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Gaëlle Varkas
- VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.,Department of Rheumatology, University Hospital Ghent, Ghent, Belgium
| | - Martine De Vos
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium
| | - Triana Lobatón
- Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.,Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
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Biologics for Inflammatory Bowel Disease in Clinical Practice: A Calabria (Southern Italy) Prospective Pharmacovigilance Study. Pharmaceutics 2022; 14:pharmaceutics14112449. [PMID: 36432640 PMCID: PMC9696291 DOI: 10.3390/pharmaceutics14112449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/05/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting. METHODS This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled. RESULTS Overall, 358 patients with a diagnosis of active Crohn's disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; p = 0.47), GOL (7/37; p = 0.78), ADA (13/89; p = 0.18), and VDZ (3/17; p = 0.52), no AEs have been noticed with UST (0/1). CONCLUSIONS Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs.
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Attauabi M, Wewer MD, Bendtsen F, Seidelin JB, Burisch J. Inflammatory Bowel Diseases Affect the Phenotype and Disease Course of Coexisting Immune-Mediated Inflammatory Diseases: A Systematic Review With Meta-Analysis. Inflamm Bowel Dis 2022; 28:1756-1765. [PMID: 35134921 DOI: 10.1093/ibd/izac003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND It is unclear whether inflammatory bowel diseases (IBDs) affect the phenotype and severity of co-occurring immune-mediated inflammatory diseases (IMIDs). We aimed to investigate the characteristics of IMIDs in relation to co-occurring IBD. METHODS We conducted a systematic review of Medline and EMBASE databases from inception to September 2020. We identified studies reporting the phenotype, severity, or disease course of IMIDs among patients with or without co-occurring IBD. A meta-analysis was conducted using random effects models. RESULTS The electronic search yielded 13 220 studies that we narrowed down to 73 eligible studies for full-text review, including 42 on primary sclerosing cholangitis, 12 on axial spondyloarthropathies, and 8 studies on psoriasis. In primary sclerosing cholangitis, IBD was associated with less frequent involvement of extrahepatic bile ducts (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.33-0.75), longer liver transplantation-free survival (hazard ratio, 0.70; 95% CI, 0.60-0.82), and no increased risk of cholangiocarcinoma (RR, 0.88; 95% CI, 0.59-1.31). Patients with axial spondyloarthropathies and co-occurring IBD were characterized by an increased risk of dactylitis (RR, 2.06; 95% CI, 1.24-3.42), a lower Bath Ankylosing Spondylitis Radiology Index (mean difference [MD] = -2.28; 95% CI, -3.26 to -1.30), and better Schober's test results (MD = 1.07; 95% CI, 0.64-1.49). Psoriasis and co-occurring IBD was associated with reduced disease severity (RR, 1.41; 95% CI, 1.02-1.96) and less frequent presentation in nails (RR, 0.14; 95% CI, 0.05-0.42), with no apparent impact on psoriatic arthritis (RR, 0.94; 95% CI, 0.27-3.31). CONCLUSIONS This systematic review with meta-analysis found IBD is associated with a distinct disease phenotype among the IMIDs investigated. Our findings emphasize the importance of multidisciplinary approaches to patients with co-occurring IMIDs and IBD.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Mads Damsgaard Wewer
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
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Martinelli VF, Martinelli Barbosa P, Dantas de Oliveira LS, de Melo LDALV, Casa Nova JM, de Brito CAA. Atypical Forms of Pyoderma Gangrenosum in Inflammatory Bowel Disease: Report of Four Cases and Literature Review. Int Med Case Rep J 2022; 15:449-456. [PMID: 36051090 PMCID: PMC9427006 DOI: 10.2147/imcrj.s376915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/12/2022] [Indexed: 11/30/2022] Open
Abstract
Background Cutaneous involvement is the second-most frequent extraintestinal manifestation of inflammatory bowel disease, with pyoderma gangrenosum (PG) a particularly relevant form because of its frequency, morbidity, and recurrence. The limited number of clinical trials involving PG increases the challenge to gastroenterologists in the management of this condition. Case Presentation Four cases of atypical presentations of PG are reported. A 25-year-old patient with ulcerative colitis presented an extensive chronic ulcerative lesion on her left leg that was associated with significant bleeding; the intestinal disease was in remission under the use of azathioprine. The patient was on long-term use of 60 mg corticosteroid with no improvement in the skin disease; however, initiation of cyclosporine induced remission. In the second case, a 52-year-old woman was a carrier of Crohn’s disease, with a history of partial colectomy. The patient’s skin condition had evolved with a cutaneous lesion localized in the perineal region, buttocks, and colostomy pouch, simulating a case of impetigo, and this had been treated with antibiotic cycles without improvement. Lesion biopsy suggested a diagnosis of PG. Consequently, the patient was started on biological therapy with infliximab, and the PG regressed. In the third case, a 38-year-old woman with a history of pancolitis presented a picture of PG with an extensive and deep ulcerative lesion in the right breast. The lesion regressed after treatment with oral corticosteroid. The final case was a 44-year-old woman with Crohn’s disease suffering from Crohn’s disease pancolitis. The patient’s condition evolved with a mixed pattern with pustules, bullae, and ulcerative lesions in the vulva, oral cavity, gluteus, right auricular region, scalp, and left flank, and was resolved by administration of adalimumab. Conclusion PG is an important and frequent manifestation of inflammatory bowel disease, with a spectrum of clinical variants, significant morbidity, and requiring a variety of therapeutic approaches.
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Affiliation(s)
- Valéria Ferreira Martinelli
- Department of Gastroenterology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Pernambuco, Brazil
- Department of Gastroenterology, Member of Organização Brasileira de Doença de Crohn e Retocolite – GEDIIB, São Paulo, Brazil
| | - Pedro Martinelli Barbosa
- Department of Internal Medicine, Medical Sciences Center, Pernambucana of Health College, Recife, Pernambuco, Brazil
| | | | | | - João Manoel Casa Nova
- Department of Gastroenterology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | - Carlos Alexandre Antunes de Brito
- Department of Gastroenterology, Member of Organização Brasileira de Doença de Crohn e Retocolite – GEDIIB, São Paulo, Brazil
- Department of Internal Medicine, Center of Medical Sciences of Federal University of Pernambuco, Pernambuco, Brazil
- Department of Immunology, Autoimune Research Institute, Recife, Pernambuco, Brazil
- Correspondence: Carlos Alexandre Antunes de Brito, Department of Immunology, Autoimune Research Institute, Avenue Rui Barbosa 715, Recife, Pernambuco, 52011-040, Brazil, Tel +55 81 31480101, Email
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Spondyloarthropathy in Inflammatory Bowel Disease: From Pathophysiology to Pharmacological Targets. Drugs 2022; 82:1151-1163. [PMID: 35900700 DOI: 10.1007/s40265-022-01750-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2022] [Indexed: 11/03/2022]
Abstract
Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded. Evidence for vedolizumab is controversial, as it was associated both with improvement and development of arthralgias, while ustekinumab, the first anti-interleukin 12/23 (IL-12/23) approved for IBD, has demonstrated good efficacy, especially in peripheral arthritis, and more IL-23 inhibitors are being developed in IBD. Tofacitinib was the first Janus kinase (JAK) inhibitor to be approved in IBD, and as it demonstrated efficacy in treating ankylosing spondylitis, it may represent a good choice in axial arthritis, while more selective JAK inhibitors are yet to be approved. Unexpectedly, the first anti-IL17 that was studied in IBD (secukinumab) has shown not to be effective in treating IBD, and the role of anti-IL17 drugs in these diseases needs further investigation. Therefore, as availability of biologics and small molecules is increasing, their positioning in clinical practice is becoming more and more challenging, and multidisciplinary management needs to be implemented in both research and clinical settings in order to enhance early recognition of SpA in IBD patients, optimize treatment and ultimately improve the patients' quality of life.
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Sedano R, Guizzetti L, McDonald C, Beaton M, Chande N, Gregor J, Sey M, Wilson A, Jairath V. Clinical, Endoscopic, and Radiological Effectiveness of Ustekinumab in Bio-naïve Versus Bio-experienced Patients With Crohn's Disease: Real-world Experience From a Large Canadian Center. Inflamm Bowel Dis 2022:6646153. [PMID: 35851799 DOI: 10.1093/ibd/izac149] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Indexed: 12/09/2022]
Abstract
INTRODUCTION With the expanding therapeutic armamentarium for inflammatory bowel disease (IBD), real-world data may help inform drug positioning. We assessed clinical, endoscopic, imaging, and biochemical response/remission outcomes in patients with Crohn's disease (CD) treated with ustekinumab in a large Canadian IBD center. METHODS A retrospective cohort study of CD patients was treated with ustekinumab. Clinical, endoscopic, radiological, and biochemical response and remission outcomes were stratified by prior biologic exposure status. Hazard ratios for biologic exposure status were estimated using Cox proportional hazard models and subgroup-specific incidence rates for healing. RESULTS A total of 231 patients (55.9% female, median 45.8 years) were identified as receiving ustekinumab during the study period, with 2 patients subsequently excluded (N = 229). Of these patients, 79.0% (181 of 229) were bio-experienced, with 38.7% (70 of 181) having failed 1 biologic and 61.3% (111 of 181) having failed ≥2 biologics. At 3 months of follow-up after induction, clinical remission (Harvey-Bradshaw Index ≤4) was achieved by 59.1% (62 of 105) of bio-experienced patients and 79.4% (27 of 34) of bio-naïve patients (relative risk [RR], 1.34; 95% CI, 1.06-1.70; P = .013). Endoscopic remission (absence of mucosal ulcers) was achieved in 37.9% (33 of 87) cases. Rate of endoscopic healing (either endoscopic response or remission) per 1000 person-months was 72.7 (95% CI, 42.4-125.1) and 50.2 (37.9-66.4); and the median time to endoscopic response was 8.4 months (95% CI, 6.4-9.8) and 15.4 months (95% CI, 10.3-17.9) in bio-naïve vs bio-experienced patients, respectively. Imaging response/remission and steroid-free remission rates were higher in bio-naïve patients. CONCLUSION In this large real-world cohort of CD patients with complex phenotypes and high rates of prior biologic exposure, we observed that ustekinumab was effective and safe with higher rates of improvement in bio-naïve subjects across a range of end points.
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Affiliation(s)
- Rocio Sedano
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | | | - Cassandra McDonald
- Lawson Health Research Institute, Western University, London, Ontario, Canada
| | - Melanie Beaton
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Nilesh Chande
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Jamie Gregor
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Michael Sey
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.,Lawson Health Research Institute, Western University, London, Ontario, Canada
| | - Aze Wilson
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.,Department of Medicine, Division of Clinical Pharmacology, Western University, London, Ontario, Canada.,Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada.,Lawson Health Research Institute, Western University, London, Ontario, Canada.,Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
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Tai J, Han M, Kim TH. Therapeutic Strategies of Biologics in Chronic Rhinosinusitis: Current Options and Future Targets. Int J Mol Sci 2022; 23:ijms23105523. [PMID: 35628333 PMCID: PMC9141505 DOI: 10.3390/ijms23105523] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/11/2022] [Accepted: 05/14/2022] [Indexed: 12/25/2022] Open
Abstract
Chronic rhinosinusitis is a chronic inflammatory disease of the upper airways, for which treatment options include medical or surgical therapy. However, there are limitations to conservative treatment strategies, such as the relapse of nasal polyps. In this review, we discuss the rising role of biomolecular mechanisms associated with various biologics that have been approved or are undergoing clinical trials to treat chronic rhinosinusitis. We also highlight the potential molecular therapeutic targets for managing and treating chronic rhinosinusitis.
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Reflecting on the immunopathology of arthritis associated with inflammatory bowel disease: what do we know and what should we know? Clin Rheumatol 2022; 41:2581-2588. [PMID: 35543893 DOI: 10.1007/s10067-022-06201-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 04/27/2022] [Accepted: 05/03/2022] [Indexed: 11/03/2022]
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is clinically closely associated with arthritis. Three major arthritis clinical subtypes have been described, peripheral arthritis type 1 (PeA1), peripheral arthritis type 2 (PeA2), and axial spondyloarthritis (axSpA). While genetic overlaps between IBD and arthritis have been defined, detailed pathophysiology for these three major subtypes of arthritis in patients with IBD has only recently begun to be established. The genetic and molecular mechanisms distinguishing axial and peripheral arthropathies in patients with UC and CD need to be better described. Understanding the pathophysiology for PeA1, PeA2, and axSpA in the settings of both UC and CD is necessary to provide the fundamental biology underlying the clinical phenotypes in IBD arthritis. This has been attempted for CD-associated spondyloarthritis, differentiating this from both CD and axSpA, while observing unique peripheral blood mononuclear cells linking gut inflammation to joint disease. We should know more about the processes by which immune cells are perturbed in these disorders, how they translocate to joints, how they are activated, what other molecules and mediators are involved, and how gut microbes and microbial products damage joints. Information from such studies are needed to elucidate whether distinctions between IBD-related peripheral and axSpA are clinically meaningful. IBD-related peripheral and axSpA studies are needed to elucidate whether distinctions between peripheral and axSpA are clinically meaningful, to better understand immunopathogenesis, and to develop novel targeted therapies.
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D’Amico F, Peyrin-Biroulet L, Danese S. Ustekinumab in Crohn's Disease: New Data for Positioning in Treatment Algorithm. J Crohns Colitis 2022; 16:ii30-ii41. [PMID: 35553665 PMCID: PMC9097676 DOI: 10.1093/ecco-jcc/jjac011] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The treatment of patients with moderate to severe Crohn's disease [CD] is still challenging. Therapeutic options include steroids, immunosuppressants, anti-TNFα agents, vedolizumab, and ustekinumab. Ustekinumab is a monoclonal antibody blocking the p40 subunit of IL-12 and IL-23. It showed to be effective and safe in randomised clinical trials and real-life studies and is currently approved for the management of CD patients who are naive to biologics and those who have already been treated with such medications. However, to date, a detailed and approved therapeutic algorithm is not available. The aim of this review is to report the most recent and updated data on the efficacy and safety of ustekinumab for the treatment of patients with moderate to severe CD and to define the optimal management of these patients.
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Affiliation(s)
- Ferdinando D’Amico
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy,Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Silvio Danese
- Corresponding author: Prof. Silvio Danese, MD, PhD, Gastroenterology and Endoscopy IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Via Olgettina 60, Milan, Italy, Tel.: [+39] 0282244771; fax: [+39] 0282242591;
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