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Balde A, Ramya CS, Nazeer RA. A review on current advancement in zebrafish models to study chronic inflammatory diseases and their therapeutic targets. Heliyon 2024; 10:e31862. [PMID: 38867970 PMCID: PMC11167310 DOI: 10.1016/j.heliyon.2024.e31862] [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: 11/15/2023] [Revised: 04/02/2024] [Accepted: 05/22/2024] [Indexed: 06/14/2024] Open
Abstract
Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic obstructive pulmonary disease (COPD), atherosclerosis and inflammatory bowel diseases (IBD) are primarily focused on because of their adverse effects and fatality rates around the globe in recent times. In order to come up with novel strategies to eradicate these diseases, a clear understanding of the mechanisms of the diseases is needed. Similarly, detailed insight into the mechanisms of commercially available drugs and potent lead compounds from natural sources are also important to establish efficient therapeutic effects. Zebrafish is widely accepted as a model to study drug toxicity and the pharmacokinetic effects of the drug. Moreover, researchers use various inducers to trigger inflammatory cascades and stimulate physiological changes in zebrafish. The effect of these inducers contrasts with the type of zebrafish used in the investigation. Hence, a thorough analysis is required to study the current advancements in the zebrafish model for chronic inflammatory disease suppression. This review presents the most common inflammatory diseases, commercially available drugs, novel therapeutics, and their mechanisms of action for disease suppression. The review also provides a detailed description of various zebrafish models for these diseases. Finally, the future prospects and challenges for the same are described, which can help the researchers understand the potency of the zebrafish model and its further exploration for disease attenuation.
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Affiliation(s)
- Akshad Balde
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Tamil Nadu, India
| | - Cunnathur Saravanan Ramya
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Tamil Nadu, India
| | - Rasool Abdul Nazeer
- Biopharmaceuticals Lab, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603203, Tamil Nadu, India
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Li L, He Y, Wang N, Li Y, Du Y, He N, Wang B, Zhang T. Atractylone in the Atractylodes macrocephala Rhizoma Essential Oil and Its Anti-Inflammatory Activity. Molecules 2023; 28:7340. [PMID: 37959758 PMCID: PMC10648463 DOI: 10.3390/molecules28217340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/21/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
The aim of this study was to conduct a screening of potential therapeutic compounds found in the Atractylodes macrocephala rhizoma essential oil (AO) and explore its mechanism of action in the treatment of ulcerative colitis (UC). An inflammation cell model was employed in conjunction with phospho-antibody array technology to explore potential therapeutic compounds of AO and their anti-inflammatory and antioxidant effects. Furthermore, we assessed their efficacy and mechanisms of action in treating dextran sulfate sodium (DSS)-induced colitis in mice. Via the screening process, we identified atractylone (ATR) as the primary active compound in AO. It has been demonstrated that ATR can both decrease the levels of tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) and increase the expression of adhesion proteins such as claudin, ZO-1, and occludin in vitro. Moreover, ATR has been shown to improve UC symptoms in vivo. Via a non-targeted metabolomics analysis of colon tissue, we identified 57 distinct metabolites that responded to ATR treatment. Subsequent analysis of the metabolic pathways revealed that the action of ATR was primarily focused on the amino acid metabolism pathway. In summary, ATR may alleviate the symptoms of UC by regulating multiple signaling pathways. Additionally, ATR has a comprehensive function in anti-inflammation, antioxidative stress, and intestinal injury reduction.
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Affiliation(s)
- Ling Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (L.L.); (Y.H.); (N.W.); (Y.D.)
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
| | - Yihao He
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (L.L.); (Y.H.); (N.W.); (Y.D.)
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Nan Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (L.L.); (Y.H.); (N.W.); (Y.D.)
| | - Yuting Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China;
| | - Yaoyao Du
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (L.L.); (Y.H.); (N.W.); (Y.D.)
| | - Ning He
- College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
| | - Bing Wang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; (L.L.); (Y.H.); (N.W.); (Y.D.)
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Sassaki LY, Magro DO, Saad-Hossne R, Baima JP, Flores C, Correia LM, Celani LMS, De Abreu Ferrari MDL, Zacharias P, Feitosa MR, Dos Santos CHM, De Freitas Lins Neto MA, Quaresma AB, De Lima Junior SF, De Vasconcelos GBS, Cassol OS, Dos Santos Pinto A, Kurachi G, Goncalves Filho FDA, Gasparini RG, Furlan TK, Catapani WR, Coy CSR, De Souza Menegassi V, Colombo MM, Fróes RDSB, Teixeira FV, Moraes AC, Santana GO, Parente JML, Vilela EG, Queiroz NSF, Kotze PG. Anti-TNF therapy for ulcerative colitis in Brazil: a comparative real-world national retrospective multicentric study from the Brazilian study group of IBD (GEDIIB). BMC Gastroenterol 2022; 22:268. [PMID: 35644668 PMCID: PMC9150299 DOI: 10.1186/s12876-022-02341-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 05/13/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Anti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment. METHODS A national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ2 or Fisher's exact test when appropriated, and Kaplan Meier analysis. RESULTS Overall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan-Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26. CONCLUSIONS IFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission.
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Affiliation(s)
- Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University (UNESP), Botucatu, Brazil
| | | | - Rogerio Saad-Hossne
- Department of Surgery, Medical School, São Paulo State University Unesp, Botucatu, Brazil
| | - Julio Pinheiro Baima
- Department of Internal Medicine, Medical School, São Paulo State University (UNESP), Botucatu, Brazil
| | | | - Lucianna Motta Correia
- Onofre Lopes Universitary Hospital, Federal University of Rio Grande Do Norte, Natal, Brazil
| | | | | | - Patricia Zacharias
- IBD Outpatient Clinics- Colorectal Surgery Unit, Catholic University or Paraná PUCPR, Curitiba, Brazil
| | - Marley Ribeiro Feitosa
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
| | | | | | | | | | | | | | | | | | | | | | - Thaísa Kowalski Furlan
- Gastroenterology, Hospital de Clínicas da Universidade Federal do Paraná - HCUFPR, Curitiba, Brazil
| | | | | | - Vivian De Souza Menegassi
- Hospital Universitário Professor Polydoro Ernani de São Thiago da Universidade Federal de Santa Catarina HU-UFSC, Florianópolis, Santa Catarina Brazil
| | | | | | | | | | | | - José Miguel Luz Parente
- Gastroenterology Division, Medical Health Center, Federal University of Piaui, Teresina, Brazil
| | - Eduardo Garcia Vilela
- Gastroenterology, Hospital of the Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Paulo Gustavo Kotze
- IBD Outpatient Clinics- Colorectal Surgery Unit, Catholic University or Paraná PUCPR, Curitiba, Brazil
| | - GEDIIB (Brazilian Study Group of IBD)
- Department of Internal Medicine, Medical School, São Paulo State University (UNESP), Botucatu, Brazil
- Colorectal Surgery Unit, University of Campinas UNICAMP, Campinas, Brazil
- Department of Surgery, Medical School, São Paulo State University Unesp, Botucatu, Brazil
- Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
- Onofre Lopes Universitary Hospital, Federal University of Rio Grande Do Norte, Natal, Brazil
- Medical School of the Federal University of the Minas Gerais, Belo Horizonte, Brazil
- IBD Outpatient Clinics- Colorectal Surgery Unit, Catholic University or Paraná PUCPR, Curitiba, Brazil
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
- Surgery Department, Universidade Federal de Mato Grosso Do Sul, Campo Grande, Brazil
- Federal University of Alagoas, Maceio, Brazil
- Surgery, Universidade Do Oeste de Santa Catarina UNOESC, Joaçaba, Brazil
- Colorectal Surgery Unit, João de Barros Barreto University Hospital, Federal University of Pará, Belém, Brazil
- Gastroenterologia, Fundação Universidade de Pernambuco, Recife, Brazil
- Hospital de Clínicas de Passo Fundo, Passo Fundo, Brazil
- Hospital Universitario Getulio Vargas, Manaus, Brazil
- Gastroenterology, Gastroclinica Cascavel, Cascavel, Brazil
- Department of surgery, Faculty of Medicine of São José do Rio Preto, São José do Rio Preto, SP Brazil
- SETE - Specialized Medical Center, Marília, São Paulo, Brazil
- Gastroenterology, Hospital de Clínicas da Universidade Federal do Paraná - HCUFPR, Curitiba, Brazil
- Gastroenterology, Faculdade de Medicina do ABC, Santo André, Brazil
- Hospital Universitário Professor Polydoro Ernani de São Thiago da Universidade Federal de Santa Catarina HU-UFSC, Florianópolis, Santa Catarina Brazil
- Gastroenterology, Hospital Doutor Dório Silva, Serra, Brazil
- Gastroenterology, Gastromed, Rio de Janeiro, Brazil
- GastroSaude Clinic, Marilia, Sao Paulo, Brazil
- Hospital Copa D’Or, Rio de Janeiro, Brazil
- Bahia State University UNEB, Salvador, Bahia Brazil
- Gastroenterology Division, Medical Health Center, Federal University of Piaui, Teresina, Brazil
- Gastroenterology, Hospital of the Federal University of Minas Gerais, Belo Horizonte, Brazil
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Khoudari G, Mansoor E, Click B, Alkhayyat M, Saleh MA, Sinh P, Katz J, Cooper GS, Regueiro M. Rates of Intestinal Resection and Colectomy in Inflammatory Bowel Disease Patients After Initiation of Biologics: A Cohort Study. Clin Gastroenterol Hepatol 2022; 20:e974-e983. [PMID: 33065311 DOI: 10.1016/j.cgh.2020.10.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 09/23/2020] [Accepted: 10/08/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS 50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC. METHODS We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics. RESULTS Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The prevalence of intestinal resection was significantly lower in biologics-treated CD patients (9.3%) compared to those who did not receive biologics (12.1%) (p < .001). Similarly, biologic-treated UC patients were significantly less likely to undergo colectomy (7.3%) compared to UC patients who did not receive biologic therapy (11.0%) (p < .001). Tobacco use, Clostridium difficile infection, and perianal disease were associated with intestinal resection in CD. Colon neoplasm and Clostridium difficile infection were associated with colectomy in UC. CONCLUSIONS In this study of a large healthcare administrative database, inflammatory bowel disease (IBD) patients treated with biologics were significantly less likely to undergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.
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Affiliation(s)
| | - Emad Mansoor
- Department of Gastroenterology, Case Western Reserve University/University Hospital, Cleveland, Ohio
| | - Benjamin Click
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio
| | | | - Mohannad Abou Saleh
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Preetika Sinh
- Department of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Jeffry Katz
- Department of Gastroenterology, Case Western Reserve University/University Hospital, Cleveland, Ohio
| | - Gregory S Cooper
- Department of Gastroenterology, Case Western Reserve University/University Hospital, Cleveland, Ohio
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio.
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Ferretti F, Cannatelli R, Monico MC, Maconi G, Ardizzone S. An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis. J Clin Med 2022; 11:jcm11092302. [PMID: 35566428 PMCID: PMC9104748 DOI: 10.3390/jcm11092302] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/17/2022] Open
Abstract
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
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Damião AOMC, Queiroz NSF. Medical Therapy in Chronic Refractory Ulcerative Colitis: When Enough Is Enough. Clin Colon Rectal Surg 2022; 35:32-43. [PMID: 35069028 PMCID: PMC8763462 DOI: 10.1055/s-0041-1740036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small molecules, a subset of medically refractory patients still requires colectomy. Recent population-based studies demonstrate a trend toward a decrease in the rates of surgery for UC patients in the biological era, although the potential of disease modification with these agents is still debated. As the concept of irreversible bowel damage is underexplored in UC, refractory patients can be exposed to multiple treatments losing optimal timing for surgery and further developing complications such as dysplasia/cancer, dysmotility, microcolon, and other functional abnormalities. This review aims to discuss the concept of disease progression in UC, explore the limitations of medical treatment in refractory UC patients, and propose the application of a three-step algorithm that allows timely indication for surgery in clinical practice.
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Affiliation(s)
| | - Natália Sousa Freitas Queiroz
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil,Address for correspondence Natália Sousa Freitas Queiroz, MD, PhD Department of Gastroenterology, University of São Paulo School of MedicineSão Paulo 05403-000Brazil
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Abstract
AbstractThe objective of this study was to evaluate the consensus of expert societies and published guidelines on the management of ulcerative colitis, and to compare with the experience of the authors, in order to standardize procedures that would help the reasoning and decision-making process of the physician. A search was performed in scientific literature, specifically in electronic databases: Medline/Pubmed, SciELO, EMBASE and Cochrane, and the following descriptors were used: ulcerative colitis, acute colitis, clinical treatment, surgery and randomized trial. It can be concluded that the goals of therapy in ulcerative colitis are clinical and endoscopic remission, deep, sustained remission without corticosteroids, prevention of hospitalizations and surgeries, and improved quality of life. The surgical indications are reserved for selected cases, ranging from medical intractability, complications (severe refractory acute colitis, toxic megacolon, perforation and hemorrhage) and malignancy. Information in this review article must be submitted to evaluation and criticism of the specialist responsible for the conduct to be followed, in the face of his/her reality and the clinical status of each patient.The degree of recommendation and strength of evidence were based using the GRADE system (The Grades of Recommendation, Assessment, Development, and Evaluation) described below:1. A: Experimental or observational studies of higher consistency.2. B: Experimental or observational studies of lower consistency.3. C: Case reports (non-controlled studies).4. D: Opinion without critical evaluation, based on consensus, physiological studies or animal models.
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Guasch M, Cañete F, Ordás I, Iglesias-Flores E, Clos A, Gisbert JP, Taxonera C, Vera I, Mínguez M, Guardiola J, Rivero M, Nos P, Gomollón F, Barrio J, de Francisco R, López-Sanromán A, Martín-Arranz MD, Garcia-Planella E, Camargo R, García-López S, de Castro L, Calvet X, Esteve M, Mañosa M, Domènech E. Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. J Gastroenterol Hepatol 2020; 35:2080-2087. [PMID: 32350906 DOI: 10.1111/jgh.15084] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 04/22/2020] [Accepted: 04/27/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIM Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti-TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS Retrospective, cohort study of patients diagnosed within a 6-year period before and after the licensing of anti-TNFs (1990-1995 and 2007-2012 for CD; 1995-2000 and 2007-2012 for UC) were identified in the ENEIDA Registry. Surgery-free survival curves were compared between cohorts. RESULTS A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post-biological cohorts. The cumulative probability of surgery was lower in CD following anti-TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high-volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors. CONCLUSIONS Anti-TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.
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Affiliation(s)
- Montserrat Guasch
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Fiorella Cañete
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
| | - Ingrid Ordás
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Clínic and IDIBAPS (Barcelona, Catalonia), Madrid, Spain
| | | | - Ariadna Clos
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (Madrid), Madrid, Spain
| | - Carlos Taxonera
- Hospital Clínico San Carlos, Instituto de Investigación del Hospital Clínico San Carlos (IdISSC) (Madrid), Madrid, Spain
| | - Isabel Vera
- Hospital Universitario Puerta de Hierro (Madrid), Majadahonda, Spain
| | - Miguel Mínguez
- H. Clínico de Valencia i Universitat de València (València), Valencia, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge IDIBELL and Universitat de Barcelona (L'Hospitalet del Llobregat, Catalonia), Llobregat, Spain
| | - Montserrat Rivero
- Hospital Marqués de Valdecilla and IDIVAL (Santander), Santander, Spain
| | - Pilar Nos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Universitari i Politècnic La Fe (Valencia), Valencia, Spain
| | - Fernando Gomollón
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,IIS Aragón, Hospital Clínico Lozano Blesa (Zaragoza), Zaragoza, Spain
| | | | - Ruth de Francisco
- Hospital Universitario Central de Asturias e Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) (Oviedo), Spain
| | | | | | | | | | | | | | - Xavier Calvet
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Parc Taulí (Sabadell, Catalonia), Spain
| | - Maria Esteve
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain.,Hospital Mútua Terrassa (Terrassa, Catalonia), Spain
| | - Míriam Mañosa
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
| | - Eugeni Domènech
- Hospital Universitari Germans Trias i Pujol (Badalona, Catalonia), Barcelona, Spain.,Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Madrid), Madrid, Spain
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Loftus EV, Sands BE, Colombel JF, Dotan I, Khalid JM, Tudor D, Geransar P. Sustained Corticosteroid-Free Clinical Remission During Vedolizumab Maintenance Therapy in Patients with Ulcerative Colitis on Stable Concomitant Corticosteroids During Induction Therapy: A Post Hoc Analysis of GEMINI 1. Clin Exp Gastroenterol 2020; 13:211-220. [PMID: 32606883 PMCID: PMC7295209 DOI: 10.2147/ceg.s248597] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 05/07/2020] [Indexed: 12/12/2022] Open
Abstract
Background Corticosteroid-free clinical remission is important in ulcerative colitis. Objective This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy in achieving sustained corticosteroid-free clinical remission in moderately to severely active ulcerative colitis. Materials and Methods GEMINI 1 included a 6-week induction period followed by a 46-week maintenance period. Patients received stable corticosteroid dosing at baseline/during induction and tapered dosing during maintenance. Analysis groups included vedolizumab (induction and maintenance); vedolizumab/placebo (vedolizumab induction, placebo maintenance); and placebo (induction and maintenance). The primary endpoint was sustained corticosteroid-free clinical remission (partial Mayo score ≤2, no individual subscore >1, for ≥32 weeks). Multivariate analyses identified covariates associated with the primary endpoint. Safety endpoints included adverse events. Results Baseline demographics and concomitant corticosteroid use were similar across groups (n=454). A greater proportion (95% confidence interval) of the vedolizumab group achieved sustained corticosteroid-free clinical remission (10.2% [6.9 to 13.6]) vs the placebo group (1.4% [0.0 to 7.3]; difference 8.9% [–3.8 to 21.4]). Proportions were similar between the vedolizumab/placebo and placebo groups. Covariates associated with sustained corticosteroid-free clinical remission (odds ratio [95% confidence interval]) were treatment (vedolizumab vs placebo: 9.35 [1.25 to 71.43]; p=0.0605), anti-tumor necrosis factor alpha exposure (yes vs no: 0.26 [0.12 to 0.57]; p=0.0008), and disease duration (≤2 vs >2 years: 2.66 [0.99–7.19]; p=0.0531). Adverse events were similar across groups. Conclusion A numerically greater proportion of vedolizumab-treated patients with ulcerative colitis achieved sustained corticosteroid-free clinical remission. Vedolizumab treatment, no previous anti-tumor necrosis factor alpha exposure, and shorter disease duration were associated with sustained corticosteroid-free clinical remission. Clinicaltrials.gov NCT00783718.
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Affiliation(s)
- Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Bruce E Sands
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
| | - Jean-Frédéric Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - David Tudor
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Parnia Geransar
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
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10
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Barberio B, Zingone F, Frazzoni L, D'Incà R, Maccarone MC, Ghisa M, Massimi D, Lorenzon G, Savarino EV. Real-Life Comparison of Different Anti-TNF Biologic Therapies for Ulcerative Colitis Treatment: A Retrospective Cohort Study. Dig Dis 2020; 39:16-24. [PMID: 32450562 DOI: 10.1159/000508865] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 05/21/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND Head-to-head comparison studies evaluating the effectiveness and tolerability of anti-tumor necrosis factor (anti-TNF) drugs in inflammatory bowel disease patients are lacking. AIM To compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate-to-severe ulcerative colitis (UC). METHODS Retrospectively, 122 UC patients treated with infliximab (IFX) originator and biosimilar, adalimumab (ADA), and golimumab (GOL) were included. We performed an ITT analysis to evaluate clinical response and remission, steroid-free clinical remission, and endoscopy response according to the different time points of the follow-up. Baseline and post induction predictor factors of these outcomes were evaluated using multivariate logistic regression models. Moreover, a propensity score-based weighting analysis was performed. Data were analyzed using R and STATA11 software. RESULTS The overall clinical response was 77% after induction, 81.4% at 30 weeks, and 76.9% at 52 weeks, while the steroid-free clinical remission was 39.7, 46, and 54.6%, respectively. After induction, a higher rate of treatment failure was observed in the GOL group. At the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL. At week 52, endoscopic response was achieved by 46.5% of the population. CONCLUSIONS Among the different anti-TNF treatments, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile.
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Affiliation(s)
- Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy,
| | - Leonardo Frazzoni
- Department of Medical and Surgical Sciences DIMEC, University of Bologna, Bologna, Italy
| | - Renata D'Incà
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Maria Chiara Maccarone
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Davide Massimi
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Greta Lorenzon
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncological and Gastroenterological Sciences (DISCOG), University of Padua, Padua, Italy
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11
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Pantavou K, Yiallourou AI, Piovani D, Evripidou D, Danese S, Peyrin-Biroulet L, Bonovas S, Nikolopoulos GK. Efficacy and safety of biologic agents and tofacitinib in moderate-to-severe ulcerative colitis: A systematic overview of meta-analyses. United European Gastroenterol J 2019; 7:1285-1303. [PMID: 31839954 PMCID: PMC6894001 DOI: 10.1177/2050640619883566] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
Background Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib. Objectives We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC. Methods PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events. Results The overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab. Conclusions Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decision-making.
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Affiliation(s)
| | | | - Daniele Piovani
- Department of Biomedical Sciences,
Humanitas
University, Milan, Italy
- IBD Center, Humanitas Clinical and
Research Center, Milan, Italy
| | | | - Silvio Danese
- Department of Biomedical Sciences,
Humanitas
University, Milan, Italy
- IBD Center, Humanitas Clinical and
Research Center, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology
and Inserm U954, Nancy University Hospital, Lorraine University,
Vandoeuvre-lès-Nancy, France
| | - Stefanos Bonovas
- Department of Biomedical Sciences,
Humanitas
University, Milan, Italy
- IBD Center, Humanitas Clinical and
Research Center, Milan, Italy
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12
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Efficiency and safety of one-year anti-TNF-α treatment in Crohn's disease: a Polish single-centre experience. GASTROENTEROLOGY REVIEW 2019; 15:156-160. [PMID: 32550949 PMCID: PMC7294981 DOI: 10.5114/pg.2019.90079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 08/08/2019] [Indexed: 12/11/2022]
Abstract
Introduction Anti-TNF-α therapy of Crohn’s disease (CD) represents considerable progress in inflammatory bowel disease (IBD) treatment; however, many patients still require surgical intervention. The Polish National Insurance Fund currently only covers up to 2 years of infliximab (IFX) therapy in CD patients and 1 year of adalimumab (ADA). Aim To estimate the effectiveness and side effects of the anti-TNF-α Polish therapeutic program in CD patients. Material and methods In this retrospective study, medical documentation of 80 CD patients treated with anti-TNF-α (IFX or ADA) was analysed. Fifty-two patients finished 1 year of therapy, and 28 individuals did not complete it due to lack of response to treatment or severe side effects. Results After treatment, 27 (67.50%) patients achieved a semi-annual remission and 14 (35%) achieved yearly remission. Twenty percent of patients experienced severe side effects such as anaphylactic shock, pneumonia, shingles, or upper respiratory tract infections. A strong negative correlation between the number of patients in remission and the period since therapy termination (r = –0.996, p < 0.001) was found. During the 1-year follow-up, 20 patients were re-enrolled in the biological therapy program (the median time to next therapy was 231 days IQR: 126.5–300.5) Conclusions Anti-TNF-α treatment in CD is relatively safe. The restricted time period of the therapy affects the clinical course of the disease and entails the need to resume biological therapy.
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13
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Abstract
Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.
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Affiliation(s)
- Derrick D Eichele
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, USA.
| | - Renee Young
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-2000, USA
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14
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Dias CC, Santiago M, Correia L, Portela F, Ministro P, Lago P, Trindade E, Freitas A, Magro F. Hospitalization trends of the Inflammatory Bowel Disease landscape: A nationwide overview of 16 years. Dig Liver Dis 2019; 51:952-960. [PMID: 30826276 DOI: 10.1016/j.dld.2019.01.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/10/2019] [Accepted: 01/22/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION In this study, we aimed to determine the hospitalization rates of Inflammatory Bowel Disease (IBD) in a southern-european country and its associated charges over a period of 16 years. METHODS We identified all discharges with a primary diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2015 in data provided by the Central Administration of Health Services (ACSS). National estimates of hospitalization rates were assessed and adjusted to gender, age, population, and hospitalizations. Hospitalization charges were also assessed. RESULTS There were an estimated 31 358 and 16 669 discharges for CD and UC, respectively. From 2000 to 2015, hospitalization rates per 100000 habitants increased for CD (8.4-11.2) and remained stable for UC (4.4-4.9). The hospitalization rate for IBD increased slightly over time (12.8 per 100 000 habitants in 2000 and 16.1 in 2015). Annual total hospitalization charges amounted to 4.0M€ in 2000 and 5.7M€ in 2015. This increase was mainly due to a rise in the total expenses of CD-related hospitalizations. CONCLUSION CD hospitalization rates per 100000 inhabitants increased over time while remaining constant for UC. Hospitalization charges for IBD increased approximately 2.0M€ during the study period, representing an important burden in the national healthcare system.
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Affiliation(s)
- Cláudia Camila Dias
- Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine of the University of Porto, Portugal; CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Mafalda Santiago
- CINTESIS - Center for Health Technology and Services Research, Porto, Portugal; IBD Portuguese Group (GEDII), Porto, Portugal
| | - Luís Correia
- IBD Portuguese Group (GEDII), Porto, Portugal; Santa Maria Hospital, Gastroenterology Department, Lisbon, Portugal
| | - Francisco Portela
- IBD Portuguese Group (GEDII), Porto, Portugal; Coimbra Hospital, Gastroenterology Department, Coimbra, Portugal
| | - Paula Ministro
- IBD Portuguese Group (GEDII), Porto, Portugal; Viseu Tondela Hospital, Gastroenterology Department, Viseu, Portugal
| | - Paula Lago
- IBD Portuguese Group (GEDII), Porto, Portugal; Santo António Hospital, Gastroenterology Department, Porto, Portugal
| | - Eunice Trindade
- IBD Portuguese Group (GEDII), Porto, Portugal; São João Hospital, Gastroenterology Department, Porto, Portugal
| | - Alberto Freitas
- Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine of the University of Porto, Portugal; CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Fernando Magro
- IBD Portuguese Group (GEDII), Porto, Portugal; São João Hospital, Gastroenterology Department, Porto, Portugal; Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Portugal; MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
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15
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A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis. Dig Liver Dis 2018; 50:1292-1298. [PMID: 30007516 DOI: 10.1016/j.dld.2018.06.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 05/27/2018] [Accepted: 06/13/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. AIMS We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. METHODS 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. RESULTS Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in golimumab patients (p = 0.008) at the end of follow up. These data were confirmed by propensity score analysis. A further analysis considering adalimumab optimization as treatment failure showed that the difference between adalimumab and golimumab was not significant. CONCLUSION Adalimumab and golimumab are effective in the treatment of ulcerative colitis. Adalimumab seems to be more effective than golimumab. This difference is probably affected by the impossibility of golimumab to be optimized in Italy while adalimumab is.
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16
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Can we move directly from 5-ASA to a biologic agent in ulcerative colitis? Best Pract Res Clin Gastroenterol 2018; 32-33:9-15. [PMID: 30060944 DOI: 10.1016/j.bpg.2018.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Accepted: 05/03/2018] [Indexed: 01/31/2023]
Abstract
European consensus guidelines and reimbursement policies position biologic drugs for ulcerative colitis (UC) as a third-line treatment, after failure of 5-aminosalicylic acid (5-ASA) and corticosteroids/thiopurines. While 5-ASA have a very favorable safety profile, (prolonged) use of corticosteroids and thiopurines is associated with potentially serious adverse events. The therapeutic landscape of UC is rapidly evolving and selective biologic drugs with improved safety are being introduced. The first biosimilars have entered the market, leading to improved cost-effectiveness of older biologic drugs. In addition, new insights have been gained in the importance of stringent therapeutic targets such as mucosal and histological healing to improve the long-term outcome of UC patients, and in the role of therapeutic drug monitoring and treatment optimization in this regard. In this manuscript we tackle the question of whether we should move directly from 5-ASA treatment to biologic drugs to offer better and/or safer care to UC patients.
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17
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Argollo MC, Kotze PG, Spinelli A, Gomes TNF, Danese S. The impact of biologics in surgical outcomes in ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33:79-87. [PMID: 30060942 DOI: 10.1016/j.bpg.2018.05.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 05/22/2018] [Indexed: 01/31/2023]
Abstract
Ulcerative Colitis (UC) is an immune mediated condition characterized by inflammation of colonic mucosa, associated with progressive damage of the colon and possible complications, such as hemorrhage, perforation and cancer. It is strongly advocated a treat to target approach in patients with UC consisting in an early and aggressive inflammatory control. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. Even though the first line biologic therapy targeting the tumor necrosis factor-alfa (TNF-α) is associated with improvement of the inflammation in some patients, others do not respond at first or lose response over time. Novel drugs targeting different inflammatory pathways have been studied in UC, however, it remains unclear whether surgical rates have been reduced in the biological era. Controversy also exists if biological agents impair surgical postoperative complication rates in UC. The aim of this review is to describe all relevant data available and briefly summarize the real impact of biologics in surgical outcomes in ulcerative colitis.
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Affiliation(s)
- Marjorie C Argollo
- Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil; IBD Advanced Visiting Fellowship, Humanitas Research Hospital, Rozzano, Milan, Italy.
| | - Paulo Gustavo Kotze
- IBD Outpatient, Catholic University of Paraná, Curitiba, Brazil; IBD Advanced Visiting Fellowship, University of Calgary, Calgary, Canada
| | - Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Tarcia N F Gomes
- Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
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18
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Bonovas S, Pantavou K, Evripidou D, Bastiampillai AJ, Nikolopoulos GK, Peyrin-Biroulet L, Danese S. Safety of biological therapies in ulcerative colitis: An umbrella review of meta-analyses. Best Pract Res Clin Gastroenterol 2018; 32-33:43-47. [PMID: 30060938 DOI: 10.1016/j.bpg.2018.05.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 05/03/2018] [Indexed: 01/31/2023]
Abstract
Biological agents have proven clinical efficacy in the treatment of ulcerative colitis (UC). Their adverse effects have also been studied in a substantial number of primary studies and meta-analyses. Given the large volume of information that has been published, the aim of this umbrella review was to effectively summarize the accumulated evidence from randomized controlled trials (RCTs) on the safety of biological therapies for UC into one accessible and usable document. Pubmed and Scopus databases were systematically searched through November 2017 to identify meta-analyses of RCTs that have investigated potential harms of biological agents (adalimumab, golimumab, infliximab, and vedolizumab) in patients with UC. Ten eligible meta-analyses were included. The body of available evidence supports the safety of biologic therapies in UC. Further research is needed to clarify the risk of any infection with biologics, for elderly and high-risk groups, for longer-term effects, and for head-to-head comparisons between the different biologics.
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Affiliation(s)
- Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, 20089, Rozzano, Milan, Italy.
| | | | | | - Anan Judina Bastiampillai
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, 20089, Rozzano, Milan, Italy.
| | | | - Laurent Peyrin-Biroulet
- Department of Hepato-Gastroenterology and Inserm U954, Nancy University Hospital, Lorraine University, 54511, Vandoeuvre-lès-Nancy, France.
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, 20090, Pieve Emanuele, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, 20089, Rozzano, Milan, Italy.
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19
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Abstract
Children and young adults with ulcerative colitis tend to present with more extensive colonic disease than an adult population. The need for surgical intervention in the pediatric population with ulcerative colitis occurs earlier after diagnosis and has a greater incidence than a comparably matched adult population with an estimated need for colectomy at 5 years following diagnosis of 14-20%. Perhaps, even more than the adult population, there is a desire to restore intestinal continuity for the pediatric patient to achieve as healthy and normal quality of life as possible. With surgery playing such a prominent role in the treatment of ulcerative colitis in this age group, an understanding of the surgical treatment options that are available is important. The surgeon's awareness of the complexities of the different operations associated with proctocolectomy and reestablishing intestinal continuity may help to avoid early complications and minimize the risk of less than ideal long-term outcomes.
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Affiliation(s)
- Daniel P Ryan
- Department of Pediatric Surgery, MassGeneral Hospital for Children, Harvard Medical School, 55 Fruit St, Boston, Massachusetts 02114.
| | - Daniel P Doody
- Department of Pediatric Surgery, MassGeneral Hospital for Children, Harvard Medical School, 55 Fruit St, Boston, Massachusetts 02114
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20
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Takeuchi K, Shimoyama T, Yamamoto T. Comparison of Safety and Efficacy of Tacrolimus versus Infliximab for Active Ulcerative Colitis. Dig Dis 2017; 36:106-112. [PMID: 29050007 DOI: 10.1159/000481815] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 09/25/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND This narrative review was to determine which medication, tacrolimus (TAC) or infliximab (IFX), is safer and more effective in the management of active UC. Our literature search identified 5 studies directly comparing the outcomes of TAC versus IFX for active UC. A review of the 5 studies was undertaken. SUMMARY The incidence of serious adverse events was not significantly different between the TAC and IFX groups. The short-term clinical remission and response rates and the colectomy-free rates were similar between the groups. TAC was usually withdrawn at week 12 and, therefore, the long-term efficacy of TAC could not be properly evaluated. The majority of patients in the IFX group maintained clinical remission in the long-term. The efficacy of IFX as second-line salvage therapy after failure of TAC appeared to be favourable, but the efficacy of TAC after failure of IFX was questionable. Key Messages: Both TAC and IFX appeared to be equally safe and effective in the short-term for patients with active UC. For the moment, treatment choice, TAC or IFX, should be guided by physician and centre experience. Randomised controlled trials are urgently warranted to rigorously compare the efficacy of TAC versus IFX for active UC.
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Affiliation(s)
- Ken Takeuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Centre, Sakura, Japan
| | - Takahiro Shimoyama
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
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21
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Chang J, Leong RW, Wasinger VC, Ip M, Yang M, Phan TG. Impaired Intestinal Permeability Contributes to Ongoing Bowel Symptoms in Patients With Inflammatory Bowel Disease and Mucosal Healing. Gastroenterology 2017; 153:723-731.e1. [PMID: 28601482 DOI: 10.1053/j.gastro.2017.05.056] [Citation(s) in RCA: 198] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 04/02/2017] [Accepted: 05/31/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Many patients with inflammatory bowel diseases (IBD) have ongoing bowel symptoms of diarrhea or abdominal pain despite mucosal healing. We investigated whether impaired intestinal permeability contributes to these symptoms. METHODS We performed a prospective study of intestinal permeability, measured by endoscopic confocal laser endomicroscopy in 110 consecutive subjects (31 with ulcerative colitis [UC], 57 with Crohn's disease [CD], and 22 healthy individuals [controls]) in Sydney, Australia from May 2009 and September 2015. Symptomatic CD was defined by a CD Activity Index score of 150 or more and symptomatic UC by a partial Mayo score of 2 or more. Mucosal healing was defined as CD Endoscopic Index of Severity of 0 in CD or Mayo endoscopic sub-score of 0-1 for patients with UC. Intestinal permeability was quantified by the Confocal Leak Score (CLS; range: 0=no impaired permeability to 100=complete loss of barrier function). The primary endpoint was intestinal permeability in patients with symptomatic IBD in mucosal healing vs patients with asymptomatic IBD in mucosal healing. We determined the sensitivity and specificity of CLS in determining symptoms based on receiver operating characteristic analysis. RESULTS Ongoing bowel symptoms were present in 16.3% of patients with IBD and mucosal healing (15.4% of patients with CD, 17.4% with UC). Patients with symptomatic IBD had a significantly higher median CLS (19.0) than patients with asymptomatic IBD (7.3; P < .001) or controls (5.9, P < .001). There were no significant differences between patients with IBD in remission vs controls (P = .261). Median CLS was significantly higher in patients with symptomatic than asymptomatic CD (17.7 vs 8.1; P = .009) and patients with symptomatic than asymptomatic UC (22.2 vs 6.9; P = .021). A CLS of 13.1 or more identified ongoing bowel symptoms in patients with IBD and mucosal healing with 95.2% sensitivity and 97.6% specificity; the receiver operating characteristic area under curve value was 0.88. Based on this cutoff, 36.2% of patients with IBD in mucosal healing have increased intestinal permeability. On regression analysis, every increase in CLS of 1.9 correlated with an additional diarrheal motion per day (P = .008). CONCLUSIONS In a prospective study of intestinal permeability in patients with IBD and mucosal healing, we associated impaired intestinal permeability with ongoing bowel symptoms; increases in permeability correlated with increased severity of diarrhea. Resolution of mucosal permeability beyond mucosal healing might improve outcomes of patients with IDB (ANZCTR.org.au: ACTRN12613001248752).
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Affiliation(s)
- Jeff Chang
- Gastroenterology and Liver Services, Bankstown Hospital, South Western Sydney Local Health District, Sydney, Australia; Faculty of Medicine, UNSW Australia, Sydney, Australia; Gastroenterology and Liver Services, Concord Hospital, Sydney Local Health District, Sydney Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Bankstown Hospital, South Western Sydney Local Health District, Sydney, Australia; Faculty of Medicine, UNSW Australia, Sydney, Australia; Gastroenterology and Liver Services, Concord Hospital, Sydney Local Health District, Sydney Australia.
| | - Valerie C Wasinger
- Bioanalytical Mass Spectrometry Facility, UNSW Australia, Sydney, Australia
| | - Matthew Ip
- Gastroenterology and Liver Services, Bankstown Hospital, South Western Sydney Local Health District, Sydney, Australia; Faculty of Medicine, UNSW Australia, Sydney, Australia
| | - Michael Yang
- Gastroenterology and Liver Services, Bankstown Hospital, South Western Sydney Local Health District, Sydney, Australia; Faculty of Medicine, UNSW Australia, Sydney, Australia
| | - Tri Giang Phan
- Faculty of Medicine, UNSW Australia, Sydney, Australia; Immunology Division, The Garvan Institute of Medical Research, Sydney, Australia
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Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-α drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNFα drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.
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23
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Fiorino G, Bonovas S, Cicerone C, Allocca M, Furfaro F, Correale C, Danese S. The safety of biological pharmacotherapy for the treatment of ulcerative colitis. Expert Opin Drug Saf 2017; 16:437-443. [PMID: 28279079 DOI: 10.1080/14740338.2017.1298743] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Biological agents are effective in ulcerative colitis (UC). Currently, 3 anti-TNF agents (infliximab, adalimumab, and golimumab) and 1 anti-integrin agent (vedolizumab) are approved for the treatment of UC. The mechanism of action of biologic agents can also give rise to several side effects, some even serious. It remains uncertain to what extent biologic treatments may be associated with an increased rate of infections, malignancies and other adverse events Areas covered: Our aim is to review the relevant data available in the literature and briefly summarize the safety profile of biological therapy in UC. We performed a literature search using the OVID, MEDLINE, PUBMED and EMBASE databases. Also other relevant sources of safety data were also used. Expert opinion: All biological agents currently used in UC are relatively safe. Accurate prevention measures and screening prior to start such therapies, and regular surveillance programs are strongly recommend to minimize any risk of infections, malignancy and other adverse events related to the use of monoclonal antibodies in UC patients.
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Affiliation(s)
- Gionata Fiorino
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Stefanos Bonovas
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Clelia Cicerone
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Mariangela Allocca
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Federica Furfaro
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Carmen Correale
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy
| | - Silvio Danese
- a IBD Center, Department of Gastroenterology , Humanitas Research Hospital , Milan , Italy.,b Department of Biomedical Sciences , Humanitas University , Milan , Italy
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24
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Mao EJ, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 2017; 45:3-13. [PMID: 27862107 DOI: 10.1111/apt.13847] [Citation(s) in RCA: 178] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 08/26/2016] [Accepted: 10/09/2016] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease course is not clearly defined. AIM To investigate the comparative efficacy of currently available inflammatory bowel disease (IBD) therapies to reduce hospitalisation and surgery. METHODS We conducted a systematic review in MEDLINE/PubMed for randomised controlled trials (RCT) published between January 1980 and May 2016 examining efficacy of biological or immunomodulator therapy in IBD. We performed direct comparisons of pooled proportions of hospitalisation and surgery. Pair-wise comparisons using a random-effects Bayesian network meta-analysis were performed to assess comparative efficacy of different treatments. RESULTS We identified seven randomised controlled trials (5 CD; 2 UC) comparing three biologics and one immunomodulator with placebo. In CD, anti-TNF biologics significantly reduced hospitalisation [Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.36-0.60] and surgery (OR 0.23, 95% CI 0.13-0.42) compared to placebo. No statistically significant reduction was noted with azathioprine or vedolizumab. Azathioprine was inferior to both infliximab and adalimumab in preventing CD-related hospitalisation (>97.5% probability). Anti-TNF biologics significantly reduced hospitalisation (OR 0.48, 95% CI 0.29-0.80) and surgery (OR 0.67, 95% CI 0.46-0.97) in UC. There were no statistically significant differences in the pair-wise comparisons between active treatments. CONCLUSIONS In CD and UC, anti-TNF biologics are efficacious in reducing the odds of hospitalisation by half and surgery by 33-77%. Azathioprine and vedolizumab were not associated with a similar improvement, but robust conclusions may be limited due to paucity of RCTs.
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Affiliation(s)
- E J Mao
- Division of Gastroenterology, Alpert Medical School of Brown University, Providence, RI, USA
| | - G S Hazlewood
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.,McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
| | - G G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - L Peyrin-Biroulet
- Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre, France
| | - A N Ananthakrishnan
- Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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25
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Baji P, Gulácsi L, Golovics PA, Lovász BD, Péntek M, Brodszky V, Rencz F, Lakatos PL. Perceived Risks Contra Benefits of Using Biosimilar Drugs in Ulcerative Colitis: Discrete Choice Experiment among Gastroenterologists. Value Health Reg Issues 2016; 10:85-90. [PMID: 27881284 DOI: 10.1016/j.vhri.2016.07.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 07/12/2016] [Accepted: 07/17/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND In middle-income countries, access to biological therapy is limited in ulcerative colitis in terms of the number of patients and the length of therapy. Because of their cost advantages, biosimilars have the potential to improve access to therapy, but physicians have concerns toward their use because of the lack of evidence from randomized clinical trials. OBJECTIVES To explore the preferences of gastroenterologists for biosimilar drugs in ulcerative colitis as well as to compare our results with results of previous studies on gastroenterologists' preferences toward biosimilars. METHODS A discrete choice experiment was carried out involving 51 Hungarian gastroenterologists treating patients with inflammatory bowel disease in May 2014 with the following attributes: type of treatment (biosimilar/originator), severity of disease, availability of continuous medicine supply, and the stopping rule (whether the treatment is covered after 12 months). A conditional logit model was used to estimate the probabilities of choosing a given profile. RESULTS According to the results, the stopping rule was the most important attribute. The type of treatment mattered only for patients already on biologicals. The probabilities of choosing the biosimilar option with all the benefits offered in the discrete choice experiment over the originator option under the present reimbursement conditions are 85% for new patients and 63% for patients already treated. CONCLUSIONS Most gastroenterologists have concerns about using biosimilars. They, however, are willing to consider the use of biosimilars if they could reallocate the potential savings to provide their patients better access to biological treatment.
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Affiliation(s)
- Petra Baji
- Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary; CERGE-EI, Nové Město, The Czech Republic
| | - László Gulácsi
- Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary.
| | - Petra A Golovics
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Barbara D Lovász
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Márta Péntek
- Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary; Department of Rheumatology, Flór Ferenc County Hospital, Kistarcsa, Hungary
| | - Valentin Brodszky
- Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary
| | - Fanni Rencz
- Department of Health Economics, Corvinus University of Budapest, Budapest, Hungary; Semmelweis University Doctoral School of Clinical Medicine, Budapest, Hungary
| | - Péter L Lakatos
- First Department of Medicine, Semmelweis University, Budapest, Hungary
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26
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Kedia S, Ahuja V, Makharia GK. Golimumab for moderately to severely active ulcerative colitis. Expert Rev Clin Pharmacol 2016; 9:1273-82. [PMID: 27498886 DOI: 10.1080/17512433.2016.1221759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Anti-TNF agents are the mainstay of therapy in patients with moderate to severe ulcerative colitis (UC) not responding to 5-aminosalisylic acid, corticosteroids, immunmodulators and for patients dependent on corticosteroids. There is a therapeutic gap of 30%- 60% with infliximab and adalimumab, which is required to be bridged by newer agents. The present review summarizes the literature on the role of golimumab, a new anti TNF agent, in ulcerative colitis. AREAS COVERED Literature search was done on PubMed using the search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016. Golimumab, a fully human monoclonal antibody against TNF-α, was approved by FDA for clinical use in UC in 2013. In vitro studies showed golimumab to be better than infliximab and adalimumab in terms of affinity and neutralization of TNF-α and its conformational stability. Golimumab was found to be effective and safe in inducing and maintaining clinical remission, clinical response and mucosal healing in patients with UC in the two registration trials. Expert commentary: Although there is no difference in terms of efficacy between golimumab, infliximab and adalimumab, golimumab is better than infliximab in terms of route of administration (subcutaneous vs intravenous) and better than adalimumab in terms of frequency of dosing (4 weeks vs 2 weeks).
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Affiliation(s)
- Saurabh Kedia
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Vineet Ahuja
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Govind K Makharia
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
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27
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Ferrari L, Krane MK, Fichera A. Inflammatory bowel disease surgery in the biologic era. World J Gastrointest Surg 2016; 8:363-370. [PMID: 27231514 PMCID: PMC4872064 DOI: 10.4240/wjgs.v8.i5.363] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Revised: 01/13/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Anti-tumour necrosis factor (TNF)-α therapy has revolutionized inflammatory bowel disease (IBD) treatment. Infliximab and adalimumab either as monotherapy or in combination with an immunomodulator are able to induce clinical and biological remission in patients with moderate and severe Crohn’s disease (CD) and ulcerative colitis (UC). These new therapies have led to a shift in the goals of IBD management from just controlling clinical symptoms to preventing disease progression. However, despite these advances in medical therapy, surgery is still required in 30%-40% of patients with CD and 20%-30% of patients with UC at some point during their lifetime. While biologics certainly play a major role in the medical treatment of IBD, there is concern about the effects of these anti-TNF-α agents on postoperative complications and morbidity. The purpose of this article is to review the role of surgery in the treatment of IBD in the age of biologics and the impact of these medications on per-operative outcomes. In this manuscript we review the relationship between biologic agents and surgery in the treatment of IBD. We also discuss in detail the periopetative risks and complications.
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28
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Dulai PS, Singh S, Vande Casteele N, Boland BS, Sandborn WJ. How Will Evolving Future Therapies and Strategies Change How We Position the Use of Biologics in Moderate to Severely Active Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:998-1009. [PMID: 26835982 PMCID: PMC5953904 DOI: 10.1097/mib.0000000000000661] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Several biological agents have been added to our armamentarium of treatment options for moderate to severely active inflammatory bowel diseases, and this number is expected to only increase in the near future. With our growing understanding of disease mechanisms and pharmacokinetics, we are now able to target several mechanisms of action to achieve key endpoints (steroid-free remission and mucosal healing) associated with improved long-term disease-related outcomes. In this context, concerns arise regarding the optimal positioning of currently available biologics and key biologics in development. In this review, we will discuss the currently available evidence for comparative effectiveness of biological agents approved for the use in moderate to severely active inflammatory bowel diseases, with a focus on practical considerations to be made when using these agents in practice. We will further review novel biological agents and small molecule inhibitors in development and discuss future opportunities through which providers may personalize treatment decisions to achieve optimal treatment outcomes.
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Affiliation(s)
- Parambir S. Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, CA
- Robarts Clinical Trials, Robarts Research Institute, La Jolla, CA
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, CA
| | - Niels Vande Casteele
- Division of Gastroenterology, University of California San Diego, La Jolla, CA
- Robarts Clinical Trials, Robarts Research Institute, La Jolla, CA
- Department of Pharmaceutical and Pharmacological Sciences, KU Leven – University of Leuven, Leuven, Belgium
| | - Brigid S. Boland
- Division of Gastroenterology, University of California San Diego, La Jolla, CA
| | - William J. Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, CA
- Robarts Clinical Trials, Robarts Research Institute, La Jolla, CA
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29
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Alexakis C, Pollok RCG. Impact of thiopurines and anti-tumour necrosis factor therapy on hospitalisation and long-term surgical outcomes in ulcerative colitis. World J Gastrointest Surg 2015; 7:360-9. [PMID: 26730281 PMCID: PMC4691716 DOI: 10.4240/wjgs.v7.i12.360] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 09/22/2015] [Accepted: 11/10/2015] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory condition affecting the large bowel and is associated with a significant risk of both requirement for surgery and the need for hospitalisation. Thiopurines, and more recently, anti-tumour necrosis factor (aTNF) therapy have been used successfully to induce clinical remission. However, there is less data available on whether these agents prevent long-term colectomy rates or the need for hospitalisation. The focus of this article is to review the recent and pertinent literature on the long-term impact of thiopurines and aTNF on long-term surgical and hospitalisation rates in UC. Data from population based longitudinal research indicates that thiopurine therapy probably has a protective role against colectomy, if used in appropriate patients for a sufficient duration. aTNF agents appear to have a short term protective effect against colectomy, but data is limited for longer periods. Whereas there is insufficient evidence that thiopurines affect hospitalisation, evidence favours that aTNF therapy probably reduces the risk of hospitalisation within the first year of use, but it is less clear on whether this effect continues beyond this period. More structured research needs to be conducted to answer these clinically important questions.
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30
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Brown C, Gibson PR, Hart A, Kaplan GG, Kachroo S, Ding Q, Hautamaki E, Fan T, Black CM, Hu X, Beusterien K. Long-term outcomes of colectomy surgery among patients with ulcerative colitis. SPRINGERPLUS 2015; 4:573. [PMID: 26543708 PMCID: PMC4628015 DOI: 10.1186/s40064-015-1350-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 09/16/2015] [Indexed: 12/12/2022]
Abstract
The objective of this study was to evaluate long-term health-related quality of life outcomes among patients who had a colectomy within the previous 10 years. A cross-sectional survey was administered to consecutive patients ≥18 years of age with ulcerative colitis who had a colectomy within the last 10 years from centers in Canada, Australia, and the United Kingdom. Data were extracted from medical chart reviews to confirm selected self-reported patient characteristics. Of 351 survey respondents, 49 % were male and the median age was 40 years (interquartile range 30-52). Respondents were diagnosed with UC a median of 9.2 (5.7-15.1) years prior to the survey and first surgery occurred a median of 3.7 (2.1-5.8) years ago. Although most respondents (84 %) reported improved quality of life compared to the status before surgery, 81 % experienced problems in at least one of the following areas: depression, work productivity, restrictions in diet, body image, and sexual function. According to HADS scores, 30 and 17 % of survey respondents experienced anxiety and depression, respectively. Among moderate to severe UC patients pre-colectomy, 27 % of men and 28 % of women reported that their sexual life was worse now than before surgery. The mean EQ-5D utility index score overall was 0.79 (95 % confidence interval 0.77-0.81). Quality of life after colectomy for UC is generally good, but there are persistent quality of life issues that impact multiple domains, including psychological and sexual functioning.
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Affiliation(s)
- Carl Brown
- />Division of General Surgery, Providence Health Care, St. Paul’s Hospital, Room C310, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6 Canada
| | - Peter R. Gibson
- />Department of Gastroenterology, The Alfred Hospital and Monash University, Melbourne, VIC 3004 Australia
| | - Ailsa Hart
- />IBD Unit, St. Mark’s Hospital NWLH NHS Trust, Northwick Park, Harrow, London HA1 3UJ UK
| | - Gilaad G. Kaplan
- />Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB T2N 4N1 Canada
| | | | - Qian Ding
- />Merck & Co. Inc., Rahway, 07065 NJ USA
- />Ferris University, Big Rapids, 49307 MI USA
| | - Emily Hautamaki
- />Oxford Outcomes Inc., an ICON plc company, Bethesda, 20814 MD USA
| | - Tao Fan
- />Merck & Co. Inc., Rahway, 07065 NJ USA
- />Sanofi US and Center for Clinical Epidemiology and Biostatistics, Bridgewater, 08807 NJ USA
- />University of Pennsylvania School of Medicine, Philadelphia, 19104 NJ USA
| | | | - Xiaohan Hu
- />Merck & Co. Inc., Rahway, 07065 NJ USA
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