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Zhao M, Larsen L, Dige A, Poulsen A, Lo B, Attauabi M, Ovesen PD, Wewer MD, Christiansen D, Hvas CL, Petersen AM, Bendtsen F, Seidelin J, Burisch J. Clinical Outcomes After First-Line Anti- Tumor-Necrosis-Factor Treatment of Patients With Inflammatory Bowel Disease-A Prospective Multicenter Cohort Study. J Crohns Colitis 2025; 19:jjae192. [PMID: 39700468 DOI: 10.1093/ecco-jcc/jjae192] [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: 08/20/2024] [Revised: 12/05/2024] [Accepted: 12/18/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND AND AIMS Existing findings on outcomes of anti-tumor-necrosis-factor (TNF) therapy in patients with inflammatory bowel diseases (IBD) are largely based on retrospective studies. We aimed to investigate real-world outcomes of anti-TNF therapy and predictors thereof in a prospective IBD cohort. METHODS In a Danish multicenter cohort of adult bio-naïve patients with IBD treated with anti-TNF, we assessed clinical response and remission to induction therapy using clinical disease activity scoring indices at Week 14. In patients who continued treatment beyond the induction period, we also assessed loss of response (LOR), drug withdrawal, and major IBD surgery during maintenance therapy. RESULTS This study included 774 patients (706 infliximab, 68 adalimumab) followed for a median duration of 125 weeks Clinical response was achieved in 209/331 (67.4%) of ulcerative colitis (UC) and 125/197 (74.0%) of Crohn's disease (CD) patients, while 143/331 (46.1%) UC and 81/197 (47.9%) CD patients achieved clinical remission. In 294 UC and 309 CD patients received maintenance therapy, while 86/294 (29.3%) UC and 78/309 (25.2%) CD patients experienced LOR. Active smoking and less severe disease activity predicted favorable outcomes in UC, while short disease duration, colonic disease, nonstricturing behavior, and concomitant immunomodulator therapy predicted favorable outcomes in CD. CONCLUSIONS Clinical response was achieved in 2 in 3 UC and 3 in 4 CD patients, meanwhile, one-third of UC and one-fourth of CD patients experienced LOR despite the short disease duration in this study. Several clinical features were associated with outcomes and may be useful predictors of anti-TNF treatment response.
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Affiliation(s)
- Mirabella Zhao
- Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
| | - Lone Larsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University, Copenhagen, Denmark
| | - Anders Dige
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Anja Poulsen
- Digestive Disease Center, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Bobby Lo
- Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
| | - Mohamed Attauabi
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Pernille Dige Ovesen
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mads Damsgaard Wewer
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Dagmar Christiansen
- Digestive Disease Center, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark
| | - Andreas Munk Petersen
- Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Microbiology, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Seidelin
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Zhang Y, Xu F, Li Y, Chen B. C-reactive protein-to-albumin ratio and neutrophil-to-albumin ratio for predicting response and prognosis to infliximab in ulcerative colitis. Front Med (Lausanne) 2024; 11:1349070. [PMID: 38533316 PMCID: PMC10963476 DOI: 10.3389/fmed.2024.1349070] [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: 12/04/2023] [Accepted: 02/29/2024] [Indexed: 03/28/2024] Open
Abstract
The C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-albumin ratio (NAR) serve as established markers for inflammatory diseases. However, limited studies have investigated their potential in predicting response and prognosis following infliximab (IFX) treatment. The objective of this paper was to evaluate feasibility of CAR and NAR as biomarkers to assess response to IFX induction therapy. Additionally, we attempted to determine the capacity to predict clinical remission in ulcerative colitis (UC) after 54 weeks of IFX treatment. We enrolled a total of 157 UC patients diagnosed via endoscopic mucosal biopsy at our hospital between October 2018 and June 2023. Additionally, 199 patients presenting with gastrointestinal symptoms, who underwent physical examinations, constituted the control group. Comprehensive clinical data, laboratory indicators, and endoscopic findings were systematically collected. CAR and NAR values were computed before treatment, post-induction, and subsequently at 8-week intervals. Comparisons between two groups were analyzed using the Wilcoxon rank-sum test or the independent samples t-test, and comparisons between multiple groups were analyzed using the one-way ANOVA (analysis of variance) or the Kruskal-Wallis rank sum test. We found CAR and NAR emerged as sensitive biomarkers for assessing disease activity. Notably, our findings indicated their dual predictive capability: foreseeing response post-IFX induction therapy and prognosticating the likelihood of UC patients achieving clinical remission following 54 weeks on IFX therapy.
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Affiliation(s)
| | - Feng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China
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Martins CDA, de Azevedo MFC, Carlos AS, Damião AOMC, Sobrado Junior CW, Nahas SC, Queiroz NSF. Predictive factors of response to infliximab therapy in Brazilian inflammatory bowel disease patients. Therap Adv Gastroenterol 2023; 16:17562848231210053. [PMID: 38026104 PMCID: PMC10652804 DOI: 10.1177/17562848231210053] [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: 02/26/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Background Biological therapies have revolutionized the treatment of patients with inflammatory bowel disease (IBD). Infliximab (IFX) has been shown to be effective in inducing and maintaining remission in patients with Crohn's disease and ulcerative colitis. However, about one-third of the patients are primary non-responders, and up to half can lose response over time. Hence, it is important to assess which factors are related to treatment failure. Objectives We aimed to identify factors predicting clinical and endoscopic remission with IFX treatment during maintenance therapy in a Brazilian IBD referral center. Design We conducted a cross-sectional study to describe demographic, clinical, and IBD therapy-related characteristics of IBD patients treated with IFX for at least 6 months in a Brazilian referral center. Subsequently, we evaluated factors associated with clinical and endoscopic remission (primary and secondary outcomes, respectively). Methods We used descriptive statistics to summarize the essential demographic and clinical characteristics of the population. The association of sociodemographic and clinical variables with outcomes was analyzed using multivariable logistic regression. Results A total of 131 IBD patients (the mean age 41.7 years) were enrolled in this study. Clinical and endoscopic remission were observed in 79.4% and 58.2% of the patients, respectively. In the multivariable analysis, IFX therapy duration and higher albumin levels increased the likelihood of clinical remission, while previous surgery decreased its chance. Prior use of adalimumab and higher C-reactive protein levels reduced the likelihood of endoscopic remission. Conclusion In summary, this study has enhanced our understanding of the predictive factors of treatment response to IFX in a well-characterized Brazilian IBD population. Trial registration 4.254.501 and 2.903.748.
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Affiliation(s)
- Camilla de Almeida Martins
- Department of Gastroenterology and Division of Colorectal Surgery, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | | | - Alexandre Sousa Carlos
- Department of Gastroenterology and Division of Colorectal Surgery, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | | | - Carlos Walter Sobrado Junior
- Department of Gastroenterology and Division of Colorectal Surgery, University of Sao Paulo School of Medicine, São Paulo, Brazil
| | - Sergio Carlos Nahas
- Department of Gastroenterology and Division of Colorectal Surgery, University of Sao Paulo School of Medicine, São Paulo, Brazil
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Fuxman C, Sicilia B, Linares ME, García-López S, González Sueyro R, González-Lamac Y, Zabana Y, Hinojosa J, Barreiro-de Acosta M, Balderramo D, Balfour D, Bellicoso M, Daffra P, Morelli D, Orsi M, Rausch A, Ruffinengo O, Toro M, Sambuelli A, Novillo A, Gomollón F, De Paula JA. GADECCU 2022 Guideline for the treatment of Ulcerative Colitis. Adaptation and updating of the GETECCU 2020 Guideline. GASTROENTEROLOGIA Y HEPATOLOGIA 2023; 46 Suppl 1:S1-S56. [PMID: 36731724 DOI: 10.1016/j.gastrohep.2023.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/04/2023] [Indexed: 02/01/2023]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.
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Affiliation(s)
- Claudia Fuxman
- Servicio de Gastroenterología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
| | - Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, Burgos, España
| | - María Eugenia Linares
- Servicio de Gastroenterología, Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España
| | - Ramiro González Sueyro
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Yago González-Lamac
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, España
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manise, Valencia, España
| | - Manuel Barreiro-de Acosta
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, España
| | - Domingo Balderramo
- Servicio de Gastroenterología, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
| | - Deborah Balfour
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Maricel Bellicoso
- Área de Gastroenterología, Inmunología Buenos Aires, Buenos Aires, Argentina
| | - Pamela Daffra
- Servicio de Gastroenterología, Hospital Central de Mendoza, Mendoza, Argentina
| | - Daniela Morelli
- Departamento de Educación, Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, Argentina
| | - Marina Orsi
- Servicio de Gastroenterología Pediátrica, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Astrid Rausch
- Servicio de Gastroenterología, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Orlando Ruffinengo
- Servicio de Gastroenterología, Hospital Provincial del Centenario, Rosario, Argentina
| | - Martín Toro
- Unidad de Enfermedades Inflamatorias, HIGEA Clínica de Gastroenterología, Mendoza, Argentina
| | - Alicia Sambuelli
- Sección de Enfermedades Inflamatorias Intestinales, Hospital Bonorino Udaondo, Buenos Aires, Argentina
| | - Abel Novillo
- Servicio de Gastroenterología, Sanatorio 9 de Julio, Tucumán, Argentina.
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestiva (CIBEREHD), Zaragoza, España
| | - Juan Andrés De Paula
- Servicio de Gastroenterología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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Iizuka M, Etou T, Sagara S. Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy. World J Gastroenterol 2022; 28:4959-4972. [PMID: 36160647 PMCID: PMC9494931 DOI: 10.3748/wjg.v28.i34.4959] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/16/2022] [Accepted: 08/16/2022] [Indexed: 02/06/2023] Open
Abstract
For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.
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Affiliation(s)
- Masahiro Iizuka
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Takeshi Etou
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Shiho Sagara
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
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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, GEDIIB (Brazilian Study Group of IBD). 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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Visuri I, Eriksson C, Olén O, Cao Y, Mårdberg E, Grip O, Gustavsson A, Hjortswang H, Karling P, Montgomery S, Myrelid P, Ludvigsson JF, Halfvarson J. Predictors of drug survival: A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register. Aliment Pharmacol Ther 2021; 54:931-943. [PMID: 34286871 DOI: 10.1111/apt.16525] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/25/2021] [Accepted: 06/26/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. AIMS To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. METHODS Biologic-naïve patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). RESULTS In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration ≥10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. CONCLUSIONS Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.
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Sicilia B, García-López S, González-Lama Y, Zabana Y, Hinojosa J, Gomollón F. GETECCU 2020 guidelines for the treatment of ulcerative colitis. Developed using the GRADE approach. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 43 Suppl 1:1-57. [PMID: 32807301 DOI: 10.1016/j.gastrohep.2020.07.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Since the first edition of the Guidelines was published in 2013, much information has been generated around the treatment of ulcerative colitis, and new drugs and action protocols have been introduced. Clinical practice has changed substantially, warranting new approaches and a comprehensive review and update of the evidence. MATERIAL AND METHODS Once again, we used the GRADE approach, supported by an electronic tool (https://gradepro.org). The clinical scenarios are the same as in the previous version (induction and maintenance in severe and mild-moderate flare-ups), as are the variables and their evaluation. However, in the updated guidelines, three questions have been deleted, 14 added and 30 maintained, making a total of 44 clinical questions. After an exhaustive review of the evidence, the recommendations are now updated. RESULTS Of the 44 questions analysed, no recommendation could be established in two due to the very low quality of the evidence, while in the other 42, based on different degrees of quality of evidence, recommendations were made according to the GRADE system. In 25 of these questions the final recommendation is strongly in favour, in six strongly against, in seven weakly in favour and in four weakly against. According to the scenarios and recommendations, six algorithms are proposed as a simple guide for practical decision-making. CONCLUSIONS The aim of this update of the 2013 guidelines is to provide answers, based on the GRADE approach, to the different questions we ask ourselves daily when deciding the most appropriate treatment for our patients with ulcerative colitis in the different clinical scenarios.
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Affiliation(s)
- Beatriz Sicilia
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario de Burgos, España
| | - Santiago García-López
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigaciones Sanitarias de Aragón, Zaragoza, España.
| | - Yago González-Lama
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, España
| | - Yamile Zabana
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo Hospital Universitario Mútua Terrassa Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
| | - Joaquín Hinojosa
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Hospital de Manises, Valencia, España
| | - Fernando Gomollón
- Unidad de Enfermedad Inflamatoria Intestinal, Servicio de Aparato Digestivo, Instituto de Investigaciones Sanitarias de Aragón, Hospital Clínico Universitario Lozano Blesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Zaragoza, España
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Gagnon AL, Beauchesne W, Tessier L, David C, Berbiche D, Lavoie A, Michaud-Herbst A, Tremblay K. Adalimumab, Infliximab, and Vedolizumab in Treatment of Ulcerative Colitis: A Long-Term Retrospective Study in a Tertiary Referral Center. CROHN'S & COLITIS 360 2021; 3:otab049. [PMID: 36777273 PMCID: PMC9802068 DOI: 10.1093/crocol/otab049] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Indexed: 11/12/2022] Open
Abstract
Background Biological therapies have changed the landscape of pharmacological management of ulcerative colitis (UC). However, a large proportion of patients do not respond to biologics, lose their response over time, or present adverse drug events. This study aims to assess therapeutic response and treatment persistence to adalimumab, infliximab, and vedolizumab, 3 agents widely used in a tertiary referral center of Saguenay-Lac-Saint-Jean (Quebec, Canada). Methods We conducted a retrospective population-based study with a thorough review of patients' medical charts. Adults at UC diagnosis, with current or past use of adalimumab, infliximab, or vedolizumab, were included in the study. Clinical data were collected in order to assess response phenotypes and persistence to treatment. Kaplan-Meier curves were performed to assess treatment persistence, and predictors for discontinuation were assessed using Cox regression analyses. Results A total of 134 patients were included in this study. For the cases exposed to adalimumab, infliximab, and vedolizumab, 56.9%, 62.5%, and 47.5% were responders, respectively. Mean persistence rates (95% CI) were 5.5 (4.3-6.6), 10.1 (8.7-11.5), and 3.6 (2.9-4.2) years for adalimumab, infliximab, and vedolizumab, respectively. Increased persistence rates were observed in biologic-naïve patients treated with infliximab in comparison to those with the previous exposition to 2 biologics, but no such effect was observed for adalimumab or vedolizumab. Overall, 61.9% of cases had adverse drug events and of these, 6 led to treatment discontinuation. Conclusion This study presents long-term treatment persistence data with adalimumab, infliximab, and vedolizumab, showing that more than half of cases treated with these biologics remained on treatment at least 24 months after initiation.
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Affiliation(s)
- Ann-Lorie Gagnon
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - William Beauchesne
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada,Parmacology–Physiology Department, Université de Sherbrooke, Saguenay, Quebec, Canada
| | - Laurence Tessier
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - Charles David
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada
| | - Djamal Berbiche
- Centre de Recherche Charles-Le Moyne-Saguenay–Lac-Saint-Jean Sur Les Innovations en Santé (CR-CSIS), Université de Sherbrooke, Longueuil, Quebec, Canada
| | - Alexandre Lavoie
- Pharmacy Department, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Saguenay, Quebec, Canada
| | - Alban Michaud-Herbst
- Gastroenterology Department, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Saguenay, Quebec, Canada
| | - Karine Tremblay
- Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean (Chicoutimi University Hospital), Research Centre, Saguenay, Quebec, Canada,Parmacology–Physiology Department, Université de Sherbrooke, Saguenay, Quebec, Canada,Address correspondence to: Karine Tremblay, PhD, Centre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean, 225, St-Vallier Street, Pavillon des Augustines, Saguenay, QC G7H 7P2, Canada ()
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Privitera G, Pugliese D, Onali S, Petito V, Scaldaferri F, Gasbarrini A, Danese S, Armuzzi A. Combination therapy in inflammatory bowel disease - from traditional immunosuppressors towards the new paradigm of dual targeted therapy. Autoimmun Rev 2021; 20:102832. [PMID: 33866066 DOI: 10.1016/j.autrev.2021.102832] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 02/15/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD). AIM To summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies. METHODS A literature search on PubMed and Medline databases was performed to identify relevant articles. RESULTS Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn's Disease and Ulcerative colitis. Data on other combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far. CONCLUSIONS Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.
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Affiliation(s)
- Giuseppe Privitera
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Daniela Pugliese
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
| | - Sara Onali
- Gastroenterology Unit, University Hospital of Cagliari, Department of Science and Public Health, University of Cagliari, Italy
| | - Valentina Petito
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Franco Scaldaferri
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
| | - Antonio Gasbarrini
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan 20089, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
| | - Alessandro Armuzzi
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
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11
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Iizuka M, Etou T, Shimodaira Y, Hatakeyama T, Sagara S. Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis. World J Gastroenterol 2021; 27:1194-1212. [PMID: 33828394 PMCID: PMC8006096 DOI: 10.3748/wjg.v27.i12.1194] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/11/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.
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Affiliation(s)
- Masahiro Iizuka
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Takeshi Etou
- Department of Gastroenterology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Yosuke Shimodaira
- Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Akita 010-8543, Japan
| | - Takashi Hatakeyama
- Department of Nephrology, Akita Red Cross Hospital, Akita 010-1495, Japan
| | - Shiho Sagara
- Akita Health Care Center, Akita Red Cross Hospital, Akita 010-0001, Japan
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Wang Y, Makadia R, Knoll C, Hardin J, Voss EA, Fife D, Davis K, Sloan S. Understanding patient journey in ulcerative colitis prior to biologic initiation: a 5-year exploration. BMC Gastroenterol 2021; 21:121. [PMID: 33731009 PMCID: PMC7967955 DOI: 10.1186/s12876-021-01708-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 02/28/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There has been a more pronounced shift toward earlier, more aggressive therapies in Crohn's disease than in ulcerative colitis (UC). The aim of this study was to describe the pre-biologic treatment and health care experience, including co-morbidities and overall health care utilization, for UC patients who initiated biologic therapies, in the 5 years prior to the initiation of the first biologic agent. METHODS UC patients who initiated a biologic agent approved for UC between 9/15/2005 and 1/30/2018 were identified from the IBM® MarketScan® Commercial Database, a large US database. The date of the first recorded UC biologic exposure was defined as the index date, and ≥ 5 years of pre-index records were required to evaluate patients' treatment, disease progression and overall health care utilization prior to initiating biologic agents. RESULTS Among the 1891 eligible patients, treatment with oral corticosteroids, 5-aminosalicylates, and other non-biologic immunomodulators, all increased progressively across the 5 years prior to the index. From within year-five to within year-one prior to the index, the median duration of oral corticosteroid treatment increased from 34 to 88 days per year and the proportion of patients who experienced more extensive/pancolitis disease increased from 16 to 59%. Overall, the frequency of all-cause health care visits also increased. CONCLUSIONS Patients with UC experienced increasing morbidity and treatment burden in the 5 years prior to initiating biologic therapy. To achieve reduced corticosteroids in UC management, better risk stratification is needed to help identify patients for more timely biologic treatment.
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Affiliation(s)
- Yiting Wang
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
| | - Rupa Makadia
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Christopher Knoll
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Jill Hardin
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Erica A Voss
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Daniel Fife
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Kourtney Davis
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Sheldon Sloan
- Janssen Global Services, LLC, Raritan, 08869, NJ, USA
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13
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Dorrington AM, Selinger CP, Parkes GC, Smith M, Pollok RC, Raine T. The Historical Role and Contemporary Use of Corticosteroids in Inflammatory Bowel Disease. J Crohns Colitis 2020; 14:1316-1329. [PMID: 32170314 DOI: 10.1093/ecco-jcc/jjaa053] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The use of corticosteroids to treat patients with inflammatory bowel disease [IBD] has been the bedrock of IBD therapeutics since the pioneering work of Truelove and Witts in the UK in the 1950s and subsequent large cohort studies in the USA and Europe. Nevertheless, although effective for induction of remission, these agents do not maintain remission and are associated with a long list of recognised side effects, including a risk of increased mortality. With the arrival of an increasing number of therapies for patients with IBD, the question arises as to whether we are using these agents appropriately in contemporary practice. This review discusses the historical background to steroid usage in IBD, and also provides a brief review of the literature on side effects of corticosteroid treatment as relevant to IBD patients. Data on licensed medications are presented with specific reference to the achievement of corticosteroid-free remission. We review available international data on the incidence of corticosteroid exposure and excess, and discuss some of the observations we and others have made concerning health care and patient-level factors associated with the risk of corticosteroid exposure, including identification of 'at-risk' populations.
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Affiliation(s)
- Alexander M Dorrington
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - Gareth C Parkes
- Department of Gastroenterology, Royal London Hospital, Barts Health, London, UK
| | - Melissa Smith
- Department of Gastroenterology, Brighton and Sussex University Hospitals, Brighton, UK
| | - Richard C Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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14
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Ramos L, Hernández Camba A, de la Barreda Heusser R, Vela M, Alonso-Abreu I, Rodríguez G E, Carrillo M, Tardillo C, Rodríguez Y, Figueroa Marrero A, Ceballos D, Cruz N, Kolle-Casso L, Jiménez Sosa A. Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 112:636-641. [PMID: 32579006 DOI: 10.17235/reed.2020.6688/2019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
INTRODUCTION inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. OBJECTIVES to analyze the determining factors of clinical response to anti-TNFs in UC. METHODS a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. RESULTS at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. CONCLUSION in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.
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Affiliation(s)
- Laura Ramos
- Aparato Digestivo, Hospital Universitario de Canarias
| | | | | | - Milagros Vela
- Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria
| | | | | | | | - Carlos Tardillo
- Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria
| | - Yolanda Rodríguez
- Aparato Digestivo, Hospital Universitario Nuestra Señora de Candelaria
| | | | | | - Noelia Cruz
- Aparato Digestivo, Hospital José Molina Orosa
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Lie MRKL, Paulides E, van der Woude CJ. Patient sex does not affect endoscopic outcomes of biologicals in inflammatory bowel disease but is associated with adverse events. Int J Colorectal Dis 2020; 35:1489-1500. [PMID: 32592091 PMCID: PMC7340671 DOI: 10.1007/s00384-020-03663-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE Biological therapies are currently the mainstay in the treatment of patients with inflammatory bowel diseases (IBD). Several factors are known to influence the efficacy and tolerability of biologicals, such as CRP levels or previous biological use. Whether patient sex affects the efficacy or tolerability is unclear but would help with better risk and benefit stratification. This systematic review assesses patient sex on the efficacy and tolerability of biological therapies in IBD patients. METHODS A systematic literature review was performed using Embase (including MEDLINE), MEDLINE OvidSP, Cochrane Central Register of Controlled Trials, Web of Science and PubMed. The primary outcome was the influence of patient sex on endoscopic outcomes in IBD patients treated with biologicals. The secondary outcome was the influence of patient sex on adverse events. Studies were included in the assessment regardless of study type or setting. RESULTS The search yielded 19,461 citations; after review, 55 studies were included in the study, involving 28,465 patients treated with adalimumab, certolizumab pegol, infliximab, or vedolizumab. There was no significant association between patient sex and endoscopic efficacy in 41 relevant studies. Increased adverse events were associated with female sex in 7 out of 14 relevant studies. CONCLUSIONS There is no evidence for a sex difference in endoscopically measured response to biological therapies in IBD patients. However, there is an influence of sex on the occurrence of adverse events.
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Affiliation(s)
- Mitchell R. K. L. Lie
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
| | - Emma Paulides
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
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Ye Q, Hu Z, Yang M, Qin K, Zhou Y. Chinese herbal medicine combination therapy for patients with steroid-dependent ulcerative colitis: Study protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e19729. [PMID: 32311964 PMCID: PMC7220481 DOI: 10.1097/md.0000000000019729] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Accepted: 03/03/2020] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease characterized by continuous and diffuse inflammatory response of colonic mucosa. Steroid-dependent UC is an important type of UC. Chinese herbal medicine is widely used in treating steroid-dependent UC in China. However, there is no systematic review and meta-analysis to collate and evaluate the evidence of these studies. The purpose of this research is to provide evidence of the efficacy and safety of Chinese herbal medicine in treating steroid-dependent UC. METHODS AND ANALYSIS Six databases, including 3 English databases and 3 Chinese databases will be searched. In addition, other grey literatures and ongoing studies will also be searched. Two researchers will independently select eligible studies by reading titles, abstracts and full texts according to the inclusion and exclusion criteria. Risk of bias assessment will be conducted by 2 independent reviewers using Cochrane risk-of-bias tool. The outcomes include steroid-free remission rate, Total clinical effective rate, Incidence of adverse events, Disease activity index (modified Mayo score), Results of enteroscopy (Baron score) and mucosa (geboes index score). Heterogeneity between studies will be assessed by Cochrane X and I tests. We will conduct subgroup analysis and meta-regression to explore the source of heterogeneity. We will also evaluate the stability of the results through sensitivity analysis and publication bias through funnel plot and Egger test. RESULTS The results will be published in peer-reviewed journals. CONCLUSION Our meta-analysis and systematic evaluation results will confirm whether Chinese herbal medicine is effective in the treatment of steroid-dependent UC. It will provide more ideas for future research. OSF REGISTRATION NUMBER DOI: 10.17605/OSF.IO/YP79Z.
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Affiliation(s)
- Qiaobo Ye
- Basic Medical College, Chengdu University of Traditional Chinese Medicine
| | - Zhipeng Hu
- Hospital of Chengdu University of Traditional Chinese Medicine
| | - Maoyi Yang
- Hospital of Chengdu University of Traditional Chinese Medicine
| | - Kaihua Qin
- Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yingguang Zhou
- Basic Medical College, Chengdu University of Traditional Chinese Medicine
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Trough Levels of Infliximab at Week 6 Are Predictive of Remission at Week 14 in Pediatric Crohn's Disease. J Pediatr Gastroenterol Nutr 2020; 70:310-317. [PMID: 31651668 DOI: 10.1097/mpg.0000000000002536] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Infliximab (IFX) is a frequent therapeutic option for Crohn disease (CD) patients. Early detection of responders to IFX is critical for the management of CD in order to avoid long-term exposure to the drug without benefit. This retrospective study aimed at analysing which early parameters recorded during the induction period are able to predict response to IFX during the maintenance period in pediatric CD. PATIENTS AND METHODS Medical records of all CD patients ages from 2 to 18 years who received IFX at a tertiary IBD center were retrospectively analyzed. Children were classified in 3 groups according to their response at week 14 (W14) remission, clinical response or , no response. The factors recorded at W0, W2, and W6, which were associated with remission at W14 were analyzed using a logistic regression. RESULTS Among the 111 patients included, 74.8% patients were responders to IFX at W14, including 38.7% in clinical remission and 36% with partial clinical response. Clinical remission at W14 was associated with normal growth (P < 0.01), and normal albuminemia (P = 0.01) at baseline, It was also associated with trough levels to IFX >8.3 μg/ml at week 6 (P < 0.01). CONCLUSION Trough levels to IFX >8.3 μg/ml at week 6 are predictive of remission at W14 for luminal disease.
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Berends SE, Strik AS, Löwenberg M, D'Haens GR, Mathôt RAA. Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Ulcerative Colitis. Clin Pharmacokinet 2020; 58:15-37. [PMID: 29752633 PMCID: PMC6326086 DOI: 10.1007/s40262-018-0676-z] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology, probably caused by a combination of genetic and environmental factors. The treatment of patients with active UC depends on the severity, localization and history of IBD medication. According to the classic step-up approach, treatment with 5-aminosalicylic acid compounds is the first step in the treatment of mild to moderately active UC. Corticosteroids, such as prednisolone are used in UC patients with moderate to severe disease activity, but only for remission induction therapy because of side effects associated with long-term use. Thiopurines are the next step in the treatment of active UC but monotherapy during induction therapy in UC patients is not preferred because of their slow onset. Therapeutic drug monitoring (TDM) of the pharmacologically active metabolites of thiopurines, 6-thioguanine nucleotide (6-TGN), has proven to be beneficial. Thiopurine S-methyltransferase (TMPT) plays a role in the metabolic conversion pathway of thiopurines and exhibits genetic polymorphism; however, the clinical benefit and relevance of TPMT genotyping is not well established. In patients with severely active UC refractory to corticosteroids, calcineurin inhibitors such as ciclosporin A (CsA) and tacrolimus are potential therapeutic options. These agents usually have a rather rapid onset of action. Monoclonal antibodies (anti-tumor necrosis factor [TNF] agents, vedolizumab) are the last pharmacotherapeutic option for UC patients before surgery becomes inevitable. Body weight, albumin status and antidrug antibodies contribute to the variability in the pharmacokinetics of anti-TNF agents. Additionally, the use of concomitant immunomodulators (thiopurines/methotrexate) lowers the rate of immunogenicity, and therefore the concomitant use of anti-TNF therapy with an immunomodulator may confer some advantage compared with monotherapy in certain patients. TDM of anti-TNF agents could be beneficial in patients with primary nonresponse and secondary loss of response. The potential benefit of applying TDM during vedolizumab treatment has yet to be determined.
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Affiliation(s)
- Sophie E Berends
- Department Hospital Pharmacy, Academic Medical Center, Amsterdam, The Netherlands.
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
| | - Anne S Strik
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Mark Löwenberg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Geert R D'Haens
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Ron A A Mathôt
- Department Hospital Pharmacy, Academic Medical Center, Amsterdam, The Netherlands
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19
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Pugliese D, Armuzzi A. Difference in treatment outcomes between clinical trials and "real-life" clinical practice: ustekinumab in ulcerative colitis. United European Gastroenterol J 2020; 8:11-12. [PMID: 32213049 PMCID: PMC7006003 DOI: 10.1177/2050640619900575] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
MESH Headings
- Antibodies, Monoclonal/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized/pharmacology
- Antibodies, Monoclonal, Humanized/therapeutic use
- Biological Products/pharmacology
- Biological Products/therapeutic use
- Colitis, Ulcerative/diagnosis
- Colitis, Ulcerative/drug therapy
- Colitis, Ulcerative/immunology
- Drug Approval
- Drug Resistance
- Drug Therapy, Combination/methods
- Glucocorticoids/pharmacology
- Glucocorticoids/therapeutic use
- Humans
- Induction Chemotherapy/methods
- Patient Selection
- Randomized Controlled Trials as Topic
- Severity of Illness Index
- Signal Transduction/drug effects
- Signal Transduction/immunology
- Treatment Outcome
- Tumor Necrosis Factor-alpha/antagonists & inhibitors
- Tumor Necrosis Factor-alpha/metabolism
- Ustekinumab/pharmacology
- Ustekinumab/therapeutic use
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Affiliation(s)
- Daniela Pugliese
- IBD Unit Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Alessandro Armuzzi
- IBD Unit Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy Corresponding author: Alessandro Armuzzi, Presidio Columbus Fondazione Policlinico Universitario A. Gemelli IRCCS - Universitá Cattolica, Via G. Moscati 31, Roma 00168, Italy alearmuzzi@yahoo. com
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20
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Fradet C, Kern J, Atanasov P, Wirth D, Borsi A. Impact of surgery and its complications in ulcerative colitis patients in clinical practice: A systematic literature review of real-world evidence in Europe. INTERNATIONAL JOURNAL OF SURGERY OPEN 2020. [DOI: 10.1016/j.ijso.2019.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Macaluso FS, Orlando A. Anti-TNF combination therapy in inflammatory bowel disease: de novo or selective? MINERVA GASTROENTERO 2020; 65:291-297. [DOI: 10.23736/s1121-421x.19.02617-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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22
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1522] [Impact Index Per Article: 253.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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24
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Infliximab clinically treating ulcerative colitis: A systematic review and meta-analysis. Pharmacol Res 2019; 148:104455. [PMID: 31562896 DOI: 10.1016/j.phrs.2019.104455] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/10/2019] [Accepted: 09/12/2019] [Indexed: 12/22/2022]
Abstract
OBJECTIVE This review aimed to evaluate the efficacy and safety of infliximab against ulcerative colitis (UC). METHODS Collection of databases: PubMed, Cochrane Library, Medline, Embase, CBM, and CNKI. This meta-analysis included randomized controlled trials comparing infliximab vs. placebo's, steroids, or immunosuppressants. SEARCH STRATEGY Searching terms were ('infliximab', OR 'anti-tumor necrosis factor', OR 'tumor necrosis factor', OR 'tumor necrosis factor alpha antibody', OR 'tumor necrosis factor antibody', OR 'IFX') and ('ulcerative colitis' OR 'UC'). Study quality: Independently assessed by two reviewers. DATA SYNTHESIS Meta-analysis combined the odds ratios (OR). RESULTS Twenty-two studies (2080 patients) evaluated infliximab therapy in UC, and the patients were randomly assigned into infliximab (1149 cases) and control groups (931 cases). The meta-analysis showed the advantage of infliximab in three endpoints (short/long-term response and long-term remission). The main outcomes considered in this meta-analysis were percentage of response (defined by the authors of each study as partial or complete symptomatic response) and remission (defined by the authors as complete symptomatic response), both at the short-term (the first control performed in the study) and the long-term (the last control performed in the study). Compared to the control group, the infliximab group was significantly more effective (short-term response: OR = 4.01, 95%CI = 3.08-5.23, p < 0.00001; long-term response: OR = 3.53, 95%CI = 2.55-4.89, p < 0.00001; long-term remission: OR = 2.80, 95%CI = 1.89-4.14, p < 0.00001; colectomy (3 months): OR = 0.38, 95%CI = 0.19-0.75, P = 0.005; colectomy (12 months): OR = 0.47, 95%CI = 0.33-0.67, p < 0.0001), but there were no significant differences in the short-term remission (OR = 1.88, 95%CI = 0.91-3.86, P = 0.09), and infliximab was notably effective in all the subgroups with different treatment doses (all p < 0.00001). In the comparison of differences in adverse effects there was no obvious difference between the two groups (OR = 0.76, 95%CI = 0.48-1.19, P = 0.23). CONCLUSION Infliximab is more effective than placebo's, steroids, or immunosuppressants, while the drug safety between the two groups was not obvious. Further studies are necessary to confirm the long-term efficacy of infliximab in ulcerative colitis.
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Kim NH, Lee JH, Hong SN, Yoon H, Kang HW, Lee SH, Im JP, Cha JM, Eun CS, Kim JW, Choi CH, Park DI. Long-term efficacy and safety of CT-P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study. J Gastroenterol Hepatol 2019; 34:1523-1532. [PMID: 30828891 DOI: 10.1111/jgh.14645] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 02/05/2019] [Accepted: 02/26/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM A biosimilar of infliximab, CT-P13 (Remsima®) has the potential to reduce treatment costs and enhance access to biological therapy for inflammatory bowel disease (IBD) patients. However, long-term clinical data on its use for IBD treatment are currently sparse. We aimed to investigate the long-term efficacy and safety of CT-P13 therapy in a large, real-life IBD cohort. METHODS A total of 368 IBD patients (227 with Crohn's disease [CD] and 141 with ulcerative colitis [UC]) treated with CT-P13 at 16 referral hospitals in Korea between July 2012 and December 2017 were retrospectively analyzed. RESULTS The cumulative retention rates at years 1, 3, and 5 were 86.1%, 68.5%, and 58.7% and 69.7%, 46.0%, and 26.7% in anti-tumor necrosis factor (TNF)-naïve CD and UC patients, respectively. The clinical response and remission rates at week 14 and at years 1, 3, and 5 were 94.3%, 92.7%, 76.8%, and 17.6% and 78.6%, 82.4%, 72.2%, and 17.6% in anti-TNF-naïve CD and 85.6%, 80.0%, 55.2%, and 6.7% and 42.6%, 59.8%, 44.2%, and 6.7% in anti-TNF-naïve UC patients, respectively. Among patients who switched from the biologic originator to CT-P13, the cumulative retention rates at years 1, 3, and 5 were 88.5%, 66.1%, and 44.8% in CD, and 73.9%, 42.5%, and 42.5% in UC patients, respectively. Significant improvements in disease activity scores were accompanied by marked reductions in inflammatory marker levels, and no unexpected adverse events including death or malignancy occurred during the study period. CONCLUSIONS Long-term treatment with CT-P13 is effective in inducing and maintaining disease improvement and is well-tolerated in patients with IBD. CT-P13 may be a promising treatment option for IBD.
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Affiliation(s)
- Nam Hee Kim
- Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hyun Lee
- Digestive Endoscopic Center, Seoul Song Do Colorectal Hospital, Seoul, Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyoun Woo Kang
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Suck-Ho Lee
- Digestive Endoscopic Center, Esoo Hospital, Cheonan-si, Korea
| | - Jong Pil Im
- Division of Gastroenterology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Ji Won Kim
- Department of Internal Medicine, SMG-SNU Boramae Medical Center, SNUH College of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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Macaluso FS, Cavallaro F, Felice C, Mazza M, Armuzzi A, Gionchetti P, Vecchi M, Orlando A. Risk factors and timing for colectomy in chronically active refractory ulcerative colitis: A systematic review. Dig Liver Dis 2019; 51:613-620. [PMID: 30826279 DOI: 10.1016/j.dld.2019.01.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 01/20/2019] [Accepted: 01/21/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND In patients with chronic refractory ulcerative colitis (UC) the precise timing for indication to colectomy is unclear. AIMS We performed a systematic review of the literature on the risk factors for colectomy in patients with chronic refractory UC in the biologic era. METHODS PubMed Central/Medline and Embase were systemically searched for records published between January 2000 and December 2017. Current evidence was summarized and filtered by expert opinion. RESULTS 70 studies were included in the qualitative synthesis. Several factors were found to be associated with a higher or reduced risk for colectomy, including variables at baseline - such as progression from proctitis/left-sided to extensive colitis, extensive colitis at diagnosis, high baseline C Reactive Protein or erythrocyte sedimentation rate, male gender, and younger age at diagnosis - previous medical history, and factors arising during therapy with biologics, including the absence of clinical response after induction with infliximab or adalimumab, and the lack of mucosal healing during therapy with anti-TNFs. CONCLUSIONS Two main points may help physicians to decide when the surgical option may be considered in patients with chronic refractory UC: (1) a first risk stratification can be obtained by analyzing factors at baseline and medical history, including the previous exposure to anti-TNFs; (2) during therapy with biologics, the early assessment (after 12-16 weeks of treatment) of clinical and endoscopic response is a strong predictor of the subsequent risk of colectomy.
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Affiliation(s)
| | - Flaminia Cavallaro
- Gastroenterology & Digestive Endoscopy Unit, IRCCS Policlinico San Donato, Milano, Italy
| | - Carla Felice
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Marta Mazza
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Alessandro Armuzzi
- IBD Unit, "Presidio Columbus" Foundation Hospital "A. Gemelli IRCCS" - Sacro Cuore Catholic University, Rome
| | - Paolo Gionchetti
- Department of Medical and Surgical Sciences (DIMEC), Policlinico S.Orsola-Malpighi, University of Bologna, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Organ Transplantation, University of Milan, Italy
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Sood A, Mahajan R, Juyal G, Midha V, Grewal CS, Mehta V, Singh A, Joshi MC, Narang V, Kaur K, Sidhu H. Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis. Intest Res 2018; 17:78-86. [PMID: 30449078 PMCID: PMC6361022 DOI: 10.5217/ir.2018.00089] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/30/2018] [Indexed: 12/26/2022] Open
Abstract
Background/Aims Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Garima Juyal
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
| | | | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Mohan C Joshi
- Multidisciplinary Centre for Advanced Research and Studies (MCARS), Jamia Millia Islamia, New Delhi, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College & Hospital, Ludhiana, India
| | - Hasrat Sidhu
- Department of Internal Medicine, Dayanand Medical College & Hospital, Ludhiana, India
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Day AS, Gulati AS, Patel N, Boyle B, Park KT, Saeed SA. The Role of Combination Therapy in Pediatric Inflammatory Bowel Disease: A Clinical Report from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 66:361-368. [PMID: 29210919 DOI: 10.1097/mpg.0000000000001850] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The treatment goal for children suffering from inflammatory bowel disease has been evolving with biologic therapies like anti-tumor necrosis factor agents assuming a more central role in treatment of more aggressive and extensive phenotype. Earlier introduction of anti-tumor necrosis factor agents have shown to be more effective and may even alter the natural history of inflammatory bowel disease. Development of anti-drug antibodies, however, limits long-term usage and leads to dose adjustment in almost half of patients treated with these medications. One of the strategies to minimize the development of anti-drug antibodies has been concomitant use of immunomodulator medications, resulting in fewer infusion reactions and sustained trough levels, potentially lowering the need for dose adjustments. Balanced with these benefits of optimized dosing and likely more sustained response, however, is the concern about increased risk of complications, such as infections and malignancies. The current manuscript reviews the available pediatric literature regarding efficacy, safety, and side effect profile of combination (immunomodulator and biologics) therapy in pediatric Crohn disease and ulcerative colitis, with particular emphasis on cost constraints, and recommendations for selection of patients who would benefit most from combination therapy.
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Affiliation(s)
- Andrew S Day
- Department of Paediatrics, University of Otago (Christchurch), Christchurch, NZ
| | - Ajay S Gulati
- Department of Pediatrics, Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Nishaben Patel
- Division of Pediatric Gastroenterology/Nutrition, Golisano Children's Hospital, Rochester, NY
| | - Brendan Boyle
- Division of Gastroenterology, Hepatology, Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - K T Park
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Stanford University School of Medicine, Palo Alto, CA
| | - Shehzad A Saeed
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
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Scott FI, Shah Y, Lasch K, Luo M, Lewis JD. Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model. Inflamm Bowel Dis 2018; 24:286-295. [PMID: 29361100 DOI: 10.1093/ibd/izx045] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Vedolizumab, an α4β7 integrin monoclonal antibody inhibiting gut lymphocyte trafficking, is an effective treatment for ulcerative colitis (UC). We evaluated the optimal position of vedolizumab in the UC treatment paradigm. METHODS Using Markov modeling, we assessed multiple algorithms for the treatment of UC. The base case was a 35-year-old male with steroid-dependent moderately to severely active UC without previous immunomodulator or biologic use. The model included 4 different algorithms over 1 year, with vedolizumab use prior to: initiating azathioprine (Algorithm 1), combination therapy with infliximab and azathioprine (Algorithm 2), combination therapy with an alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3), and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life-year (QALY) estimates were derived from the published literature. Primary analyses included simulating 100 trials of 100,000 individuals, assessing clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons and ranges for all variables. RESULTS Algorithm 1 (vedolizumab use prior to all other therapies) was the preferred strategy, resulting in 8981 additional individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious infections per 100,000 patients compared with last-line use (A4). Algorithm 1 also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This benefit increased with longer time horizons. Algorithm 1 was preferred in all sensitivity analyses. CONCLUSION The model suggests that treatment algorithms positioning vedolizumab prior to other therapies should be considered for individuals with moderately to severely active steroid-dependent UC. Further prospective research is needed to confirm these simulated results.
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Affiliation(s)
- Frank I Scott
- Division of Gastroenterology, Department of Medicine, University of Colorado Denver, Aurora, Colorado.,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Yash Shah
- University of Pennsylvania, Philadelphia, Pennsylvania
| | - Karen Lasch
- US Medical Office, Takeda Pharmaceuticals U.S.A., Inc., Deerfield, Illinois
| | - Michelle Luo
- Health Economics and Outcomes Research, Takeda Pharmaceuticals U.S.A., Inc., Deerfield, Illinois
| | - James D Lewis
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.,University of Pennsylvania, Philadelphia, Pennsylvania
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Dunkin D, Berin MC, Mondoulet L, Tobar S, Yeretssian G, Tordesillas L, Iuga A, Larcher T, Gillespie V, Benhamou PH, Colombel JF, Sampson HA. Epicutaneous Tolerance Induction to a Bystander Antigen Abrogates Colitis and Ileitis in Mice. Inflamm Bowel Dis 2017; 23:1972-1982. [PMID: 29019858 PMCID: PMC5659741 DOI: 10.1097/mib.0000000000001273] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although inflammatory bowel disease (IBD) is a failure in maintaining tolerance to the intestinal microbiota, few studies have investigated the use of immunologic tolerance as a treatment approach for IBD. We hypothesized that induction of immune tolerance at a distal site could suppress intestinal inflammation through a process of bystander regulation. METHODS Epicutaneous tolerance was induced by topical application of ovalbumin (OVA) using a Viaskin patch for 48 hours. In some experiments, a single feed of ovalbumin was used to drive epicutaneous tolerance-induced regulatory T cells (Tregs) to the intestine. The mechanism of tolerance induction was tested using neutralizing antibodies against TGF-β, IL-10, and Treg depletion using Foxp3-DTR mice. The capacity of skin-draining Tregs, or epicutaneous tolerance, to prevent or treat experimental IBD was tested using T-cell transfer colitis, dextran sodium sulfate (DSS) colitis, and ileitis in SAMP-YITFc mice. Weight loss, colonic inflammatory cytokines and histology were assessed. RESULTS Epicutaneous exposure to ovalbumin induced systemic immune tolerance by a TGF-β-dependent, but IL-10 and iFoxp3 Treg-independent mechanism. Skin draining Tregs suppressed the development of colitis. Epicutaneous tolerance to a model antigen prevented intestinal inflammation in the dextran sodium sulfate and SAMP-YITFc models and importantly could halt disease in mice already experiencing weight loss in the T-cell transfer model of colitis. This was accompanied by a significant accumulation of LAP and Foxp3 Tregs in the colon. CONCLUSIONS This is the first demonstration that epicutaneous tolerance to a model antigen can lead to bystander suppression of inflammation and prevention of disease progression in preclinical models of IBD.
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Affiliation(s)
- David Dunkin
- *Division of Pediatric Gastroenterology, The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York; †Division of Pediatric Allergy and Immunology, Precision Immunology Institute, The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York; ‡DBV Technologies, Bagneux, France; §Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York; ‖Department of Pathology, Columbia University Medical School, New York, New York; ¶National Veterinary School, Nantes, France; **Department of Comparative Pathology, Icahn School of Medicine at Mount Sinai, New York, New York; and ††Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
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Iizuka M, Etou T, Kumagai M, Matsuoka A, Numata Y, Sagara S. Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis. Intern Med 2017; 56:2705-2710. [PMID: 28924114 PMCID: PMC5675930 DOI: 10.2169/internalmedicine.8428-16] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 03/02/2017] [Indexed: 12/17/2022] Open
Abstract
Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.
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Affiliation(s)
- Masahiro Iizuka
- Health Care Center, Akita Red Cross Hospital, Japan
- Department of Gastroenterology, Akita Red Cross Hospital, Japan
| | - Takeshi Etou
- Department of Gastroenterology, Akita Red Cross Hospital, Japan
| | - Makoto Kumagai
- Medical Technical Section Clinical Engineering Group, Akita Red Cross Hospital, Japan
| | - Atsushi Matsuoka
- Medical Technical Section Clinical Engineering Group, Akita Red Cross Hospital, Japan
| | - Yuka Numata
- Medical Technical Section Clinical Engineering Group, Akita Red Cross Hospital, Japan
| | - Shiho Sagara
- Health Care Center, Akita Red Cross Hospital, Japan
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Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease. Dig Liver Dis 2017; 49:1086-1091. [PMID: 28826571 DOI: 10.1016/j.dld.2017.07.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 07/20/2017] [Accepted: 07/20/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is refractory to treatment in one-half of patients. AIMS To evaluate the occurrence of suboptimal therapy among patients with IBD treated with tumor necrosis factor antagonists (anti-TNFs). METHODS A multinational chart review in Europe and Canada was conducted among IBD patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) who initiated anti-TNF therapy between 2009 and 2013. The primary endpoint was the cumulative incidence of suboptimal therapy during a two-year follow-up period, defined by the presence of the following indicators: dose escalation, discontinuation, switching, non-biologic therapy escalation, or surgery. RESULTS The study included 1195 anti-TNF initiators (538 UC and 657 CD). The majority of patients (64% of UC and 58% of CD) had at least one indicator of suboptimal therapy. The median time to suboptimal therapy indicator was 12.5 and 17.5 months for UC and CD patients, respectively. Among the 111 UC and 174 CD anti-TNF switchers, 51% and 56% had an indicator of suboptimal therapy, respectively. The median time to suboptimal therapy indicator with the second anti-TNF was 14.3 and 13.0 months for UC and CD patients, respectively. CONCLUSION The majority of IBD patients showed suboptimal therapy with current anti-TNFs.
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Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, Kucharzik T, Molnár T, Raine T, Sebastian S, de Sousa HT, Dignass A, Carbonnel F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis 2017; 11:769-784. [PMID: 28513805 DOI: 10.1093/ecco-jcc/jjx009] [Citation(s) in RCA: 863] [Impact Index Per Article: 107.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marcus Harbord
- Imperial College London, and Chelsea and Westminster Hospital, London, UK
| | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | | | - Konstantinos Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Crete, Greece
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Tel-Hashomer Sheba Medical Center, and Sackler School of Medicine, Tel Aviv University, Israel
| | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Tamás Molnár
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Helena Tavares de Sousa
- Gastroenterology Department, Algarve Hospital Center; Biomedical Sciences & Medicine Department, University of Algarve, Faro, Portugal
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt/Main, Germany
| | - Franck Carbonnel
- Department of Gastroenterology, CHU Bicêtre, Université Paris Sud, Paris, France
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Nasuno M, Miyakawa M, Tanaka H, Motoya S. Short- and Long-Term Outcomes of Infliximab Treatment for Steroid-Refractory Ulcerative Colitis and Related Prognostic Factors: A Single-Center Retrospective Study. Digestion 2017; 95:67-71. [PMID: 28052276 DOI: 10.1159/000452459] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The aim of this study was to analyze the short- and long-term outcomes of infliximab (IFX) treatment to cure steroid-refractory ulcerative colitis (UC) and related prognostic factors. METHODS Retrospective data were collected from 125 patients with steroid-refractory UC who received IFX treatment at our center from July 2005 to November 2013. The Lichtiger clinical activity index score was calculated at baseline, 2 weeks, 6 weeks, and 1 year, and the cumulative non-colectomy rate following IFX administration was estimated. Remission rate prognostic factors and the cumulative colectomy rate prognostic factors were evaluated using multivariate logistic regression analysis and multivariate Cox regression analysis, respectively. RESULTS Remission rates at 2 weeks, 6 weeks, and 1 year were 46, 58, and 45%, respectively. The 1-, 3-, and 5-year cumulative non-colectomy rates were 80, 78, and 75%, respectively. Previous treatment with calcineurin inhibitors was a significant prognostic factor for lower remission and cumulative non-colectomy rates, whereas concomitant immunomodulators was a significant prognostic factor for the higher remission rate. Gender (female) was a prognostic factor for higher remission rate at 1 year and higher cumulative non-colectomy rate. CONCLUSIONS This study revealed good short- and long-term outcomes of IFX treatment in patients with steroid-refractory UC. Previous treatment with calcineurin inhibitors was a prognostic factor for poor outcomes of IFX treatment, whereas concomitant immunomodulators and gender (female) were prognostic factors for good outcomes.
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Affiliation(s)
- Masanao Nasuno
- IBD Center, Sapporo-Kosei General Hospital, Sapporo, Japan
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Angelison L, Almer S, Eriksson A, Karling P, Fagerberg U, Halfvarson J, Thörn M, Björk J, Hindorf U, Löfberg R, Bajor A, Hjortswang H, Hammarlund P, Grip O, Torp J, Marsal J, Hertervig E. Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients. Aliment Pharmacol Ther 2017; 45:519-532. [PMID: 28025840 DOI: 10.1111/apt.13893] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 09/21/2016] [Accepted: 11/16/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Real-life long-term data on infliximab treatment in ulcerative colitis are limited. AIM To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. METHODS A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. RESULTS Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. CONCLUSIONS Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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Abstract
The incidence of inflammatory bowel disease (IBD) has increased steadily worldwide, both in adult and in children; approximately 25% of IBD patients are diagnosed before the age of 18. The natural history of IBD is usually more severe in children than in adults, and can be associated with linear growth impairment, delayed puberty onset, reduced bone mass index, malnutrition, and the need for surgery. Biological therapies, especially blocking tumor necrosis factor-α (TNFα), have radically modified the treatment strategies and disease course of IBD in children. In particular, drugs such as Infliximab and Adalimumab are routinely used in the treatment of pediatric IBD. The role of Infliximab and Adalimumab in the management of pediatric IBD has been recently updated in the Consensus guidelines of ECCO/ESPGHAN. Data regarding short-term and long-term efficacy and safety of these drugs in children, and the effects of "top-down" and "step-up" strategies, are lacking. In this paper, the authors will review current indications, efficacy, and safety of biological therapy in pediatric IBD patients, evaluating all articles published after ECCO/ESPGHAN guidelines publication. The authors carried out a systematic search through MEDLINE through PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) Embase, CINAHL, Cochrane Library, and gray literature, from January 2013 to January 2016. Anti-TNFα has been shown to be effective and safe to maintain remission and to achieve mucosal healing. Multicenter trials based on large sample size cohorts are needed to better clarify long-term efficacy of anti-TNFα and the real incidence of treatment-related complications in pediatric IBD.
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Affiliation(s)
- Domenico Corica
- Unit of Pediatrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy
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Nishida Y, Hosomi S, Yamagami H, Yukawa T, Otani K, Nagami Y, Tanaka F, Taira K, Kamata N, Tanigawa T, Shiba M, Watanabe K, Watanabe T, Tominaga K, Fujiwara Y. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis. PLoS One 2017; 12:e0169845. [PMID: 28076386 PMCID: PMC5226844 DOI: 10.1371/journal.pone.0169845] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 12/25/2016] [Indexed: 12/18/2022] Open
Abstract
Objectives Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn’s disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Materials and Methods Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Results Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20–12.4, P = 0.023). Conclusions Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab.
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Affiliation(s)
- Yu Nishida
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shuhei Hosomi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
- * E-mail:
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomomi Yukawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masatsugu Shiba
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenji Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
- Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazunari Tominaga
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Traditional Chinese medicine combination therapy for patients with steroid-dependent ulcerative colitis: study protocol for a randomized controlled trial. Trials 2017; 18:8. [PMID: 28069051 PMCID: PMC5223474 DOI: 10.1186/s13063-016-1763-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 12/18/2016] [Indexed: 02/08/2023] Open
Abstract
Background Approximately 20% of patients with ulcerative colitis become steroid dependent. Azathioprine is recommended in steroid-dependent ulcerative colitis, but its side effects limit its use. Chinese herbal medicine has been widely used to treat ulcerative colitis in China. However, its effectiveness in steroid-dependent patients has not been evaluated. This study aims to investigate the efficacy of traditional Chinese medicine combination therapy with 5-aminosalicylic acid in patients with steroid-dependent ulcerative colitis. Methods/Design This is a parallel, multicenter, randomized controlled trial. One hundred and twenty eligible patients will be randomly assigned to a traditional Chinese medicine group or azathioprine group. All patients will be given basic treatment, which includes steroids and 5-aminosalicylic acid. Patients allocated to the traditional Chinese medicine group will receive basic treatment plus Chinese herbal medicine granules, while patients in the azathioprine group will receive basic treatment plus azathioprine. The whole study will last 24 weeks. The primary outcome measure is the steroid-free remission rate. Secondary outcome measures are health-related quality of life, efficacy of endoscopic response, degree of mucosal healing, and inflammation indicators. Discussion Results from this study may provide evidence for the effectiveness of traditional Chinese medicine combined with 5-aminosalicylic acid in patients with steroid-dependent ulcerative colitis. The findings will provide a basis for further confirmatory studies. Trial registration Chinese Clinical Trial Register, ChiCTR-IPR-15005760. Registered on 2 January 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1763-9) contains supplementary material, which is available to authorized users.
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Barnes EL, Goldin A, Winter RW, Collins E, Cao B, Carrellas M, Crowell AM, Korzenik JR. Sequential Combination Therapy Versus Monotherapy: A Lack of Benefit in Time to Inflammatory Bowel Disease-Related Surgery. Dig Dis Sci 2016; 61:3261-3269. [PMID: 27639871 PMCID: PMC5512691 DOI: 10.1007/s10620-016-4302-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Accepted: 09/07/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND The benefits of combination therapy with infliximab and azathioprine have been demonstrated in clinical trials of patients with ulcerative colitis (UC) and Crohn's disease (CD). Concerns remain regarding the ideal duration and benefits of adding therapies in a sequential manner. AIMS We aim to compare long-term outcomes among patients with inflammatory bowel disease (IBD) treated with sequentially added combination therapy or monotherapy strategies . METHODS We performed a retrospective cohort study involving adult patients with UC and CD. One cohort included patients treated with infliximab, adalimumab, or a thiopurine as monotherapy. A second cohort included patients treated with sequentially added combination therapy including infliximab or adalimumab and a thiopurine. The primary outcome was the rate of IBD-related surgery. RESULTS Among 462 patients, 181 (39 %) were treated with combination therapy. 12 % of patients treated with combination therapy underwent an IBD-related surgery compared to 18 % of patients treated with monotherapy (p = 0.091), with no overall difference in time to IBD-related surgery demonstrated (log-rank test, p = 0.063). When evaluating the subtypes of IBD, there was a significant benefit in time to IBD-related surgery among patients with CD treated with sequentially added combination therapy (HR 0.46, 95 % CI 0.25-0.85) but not UC (HR 0.82, 95 % CI 0.30-2.22). CONCLUSIONS The benefits of sequentially added combination therapy seem blunted when evaluating long-term clinical outcomes. This may be due to a decreased effectiveness of sequential combination therapy, a loss of benefit over time, or a differential effect between subtypes of IBD.
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Affiliation(s)
- Edward L. Barnes
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Alison Goldin
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Rachel W. Winter
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Emily Collins
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Bonnie Cao
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Madeline Carrellas
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Anne Marie Crowell
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Joshua R. Korzenik
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
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Pugliese D, Felice C, Papa A, Gasbarrini A, Rapaccini GL, Guidi L, Armuzzi A. Anti TNF-α therapy for ulcerative colitis: current status and prospects for the future. Expert Rev Clin Immunol 2016; 13:223-233. [PMID: 27687496 DOI: 10.1080/1744666x.2017.1243468] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Anti TNF-α agents have become a significant advance in the management of ulcerative colitis, proving to induce, with rapid onset, clinical and endoscopic remission. However, there is still a considerable unmet medical need in ulcerative colitis. Areas covered: The aim of this review was to summarize the patterns of use and the effectiveness of anti TNF-α in ulcerative colitis, highlighting their current position in treatment algorithms. Moreover, we set out a five-year view hypothesizing different treatment strategies. Expert commentary: The rapid onset of action and the effectiveness in inducing mucosal healing are the most important pros of anti TNF-α, supporting present and future use. Conversely, the relevant risk of loss of response and the safety profile have raised several concerns. In the future, the advent of different molecular targeting therapies can improve the management of UC patients, evolving to individually tailored strategies.
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Affiliation(s)
- Daniela Pugliese
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Carla Felice
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Alfredo Papa
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Antonio Gasbarrini
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Gian Lodovico Rapaccini
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Luisa Guidi
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
| | - Alessandro Armuzzi
- a IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato Columbus , Gemelli Hospital Catholic University Foundation , Rome , Italy
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Shah SC, Colombel JF, Sands BE, Narula N. Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2016; 14:1245-1255.e8. [PMID: 26829025 DOI: 10.1016/j.cgh.2016.01.015] [Citation(s) in RCA: 255] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/20/2016] [Accepted: 01/24/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH. METHODS We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks. RESULTS We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy. CONCLUSIONS In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy.
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Affiliation(s)
- Shailja C Shah
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Jean-Frederic Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Bruce E Sands
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Neeraj Narula
- McMaster University Medical Centre, Hamilton, Ontario, Canada
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Fernández-Salazar L, Muñoz F, Barrio J, Muñoz C, Pajares R, Rivero M, Prieto V, Legido J, Bouhmidi A, Herranz M, Fernández N, Sánchez-Ocaña R, Joao D, Santos F. Infliximab in ulcerative colitis: real-life analysis of factors predicting treatment discontinuation due to lack of response or colectomy: ECIA (ACAD Colitis and Infliximab Study). Scand J Gastroenterol 2016. [PMID: 26200929 DOI: 10.3109/00365521.2015.1070900] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To describe clinical practice with infliximab (IFX) in ulcerative colitis (UC); identification of predictive factors for IFX treatment discontinuation due to insufficient response and for colectomy. MATERIAL AND METHODS Retrospective, multicentric and observational study including every UC IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological data; variables for poor prognosis; IFX prior treatments; characteristics of the IFX treatment; time from the UC diagnosis to induction with IFX; time from induction to colectomy or until data collection. Predictive and protective factors for IFX discontinuation due to lack of response and for colectomy were analyzed with binary logistic regression and Cox analysis. RESULTS Follow-up time from induction with IFX to the collection of data or colectomy: 36.7 ± 25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX + immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%. Independent predictive or protective factors for IFX discontinuation: IMM resistance (OR: 2.9, p = 0.022, 95% CI: 1.2-7.2), prior use of leukocytapheresis (OR: 3.3, p = 0.024, 95% CI: 1.1-9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.9, and HR: 0.4, p = 0.006, 95% CI: 0.2-0.8) and corticosteroid use in induction (HR: 1.9, p = 0.049, 95% CI: 1.0-3.8). Independent predictive or protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036, 95% CI: 1.1-8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.8, and HR: 0.3, p = 0.011, 95% CI: 0.1-0.8) and severe cortico-resistant flare-up (HR: 2.5, p = 0.032, 95% CI: 1.1-5.9). CONCLUSIONS Prior use of IMM and leukocytapheresis, the use of corticosteroids in induction and a severe cortico-resistant flare predict a worse response to IFX and the need for colectomy. Combination therapy is a protective factor for both.
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Affiliation(s)
| | - Fernando Muñoz
- b 2 Gastroenterology Unit, Complejo Asistencial Universitario , León, Spain
| | - Jesús Barrio
- c 3 Gastroenterology Unit, Hospital Universitario Río Hortega , Valladolid, Spain
| | - Concepción Muñoz
- d 4 Gastroenterology Unit, Hospital Virgen de la Salud , Toledo, Spain
| | - Ramón Pajares
- e 5 Gastroenterology Unit, Hospital Infanta Sofía, San Sebastián de los Reyes , Madrid, Spain
| | - Montserrat Rivero
- f 6 Gastroenterology Unit, Hospital Universitario Marqués de Valdecilla , Santander, Spain
| | - Vanessa Prieto
- g 7 Gastroenterology Unit, Complejo Asistencial Universitario , Salamanca, Spain
| | - Jesús Legido
- h 8 Gastroenterology Unit, Complejo Asistencial , Segovia, Spain
| | - Abdel Bouhmidi
- i 9 Gastroenterology Unit, Hospital Santa Bárbara de Puertollano , Ciudad Real, Spain
| | - Maite Herranz
- j 10 Gastroenterology Unit, Complejo Asistencial , Ávila, Spain
| | - Nereida Fernández
- b 2 Gastroenterology Unit, Complejo Asistencial Universitario , León, Spain
| | - Ramón Sánchez-Ocaña
- c 3 Gastroenterology Unit, Hospital Universitario Río Hortega , Valladolid, Spain
| | - Diana Joao
- b 2 Gastroenterology Unit, Complejo Asistencial Universitario , León, Spain
| | - Fernando Santos
- c 3 Gastroenterology Unit, Hospital Universitario Río Hortega , Valladolid, Spain
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Thorne K, Alrubaiy L, Akbari A, Samuel DG, Morrison-Rees S, Roberts SE. Colectomy rates in patients with ulcerative colitis following treatment with infliximab or ciclosporin: a systematic literature review. Eur J Gastroenterol Hepatol 2016; 28:369-82. [PMID: 26825217 DOI: 10.1097/meg.0000000000000568] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review aimed to compile all available published data on colectomy rates following treatment using infliximab or ciclosporin in adult ulcerative colitis patients and to analyse colectomy rates, timing to colectomy and postcolectomy mortality for each treatment. We systematically reviewed the literature after 1990 reporting colectomy rates in ulcerative colitis patients treated with infliximab or ciclosporin, excluding articles on paediatric patients, patients with indeterminate colitis or Crohn's disease and bowel surgery not related to ulcerative colitis. We presented weighted mean colectomy rates and mortality rates. Cox's regression was used to assess time to colectomy adjusting for colitis severity, patient age and sex. We tabulated 78 studies reporting on ciclosporin and/or infliximab and colectomy rates or postcolectomy mortality rates. Not all studies reported data in a standardized manner. Infliximab had a significantly lower colectomy rate than ciclosporin at 36 months when analysing all studies, studies directly comparing infliximab and ciclosporin and studies using severe colitis patients, but not at 3, 12 or 24 months. Severity and age were key indicators in the likelihood of undergoing colectomy after treatment. Postcolectomy mortality rates were less than 1.5% for both drugs. This review indicates that long-term colectomy rates following infliximab are significantly lower than ciclosporin in the longer term, and that postcolectomy mortality following infliximab and ciclosporin is very low. However, many key data items were missing from research articles, reducing our ability to establish with more confidence the actual impact of these two drugs on colectomy rates and postcolectomy mortality rates.
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Affiliation(s)
- Kymberley Thorne
- aSwansea University Medical School, Swansea University, Swansea bDepartment of Gastroenterology, West Wales General Hospital, Carmarthen, UK
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Pugliese D, Felice C, Landi R, Papa A, Guidi L, Armuzzi A. Benefit-risk assessment of golimumab in the treatment of refractory ulcerative colitis. DRUG HEALTHCARE AND PATIENT SAFETY 2016; 8:1-7. [PMID: 26893582 PMCID: PMC4745853 DOI: 10.2147/dhps.s62649] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Significant advances in the management of patients with ulcerative colitis (UC) have been made since the introduction of anti-tumor necrosis factor (TNF)-alpha agents, especially for those who fail or do not tolerate conventional therapies. Two drugs, infliximab first, then adalimumab afterward, showed effectiveness in inducing and maintaining long-term remission both in pivotal trials as well as in clinical practice. However, approximately 25% of patients with UC, who fail or do not tolerate all available therapies, require a colectomy for refractory disease. The therapeutic scenario of UC has been recently upgraded by the introduction of golimumab, the latest anti TNF-alpha agent to be approved. Golimumab is a totally humanized monoclonal antibody, administered by a subcutaneous injection every 4 weeks. Treatment with golimumab has shown to be effective to induce sustained clinical benefit in tough-to-treat patients with UC, including steroid and/or immunosuppressive refractory and steroid-dependent patients. In this review, we summarize all available efficacy and safety data of golimumab in UC, analyzing the potential therapeutic position for the treatment of refractory patients with UC.
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Affiliation(s)
- Daniela Pugliese
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
| | - Carla Felice
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
| | - Rosario Landi
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
| | - Alfredo Papa
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
| | - Luisa Guidi
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
| | - Alessandro Armuzzi
- Inflammatory Bowel Disease Unit, Complesso Integrato Columbus, Catholic University, Rome, Italy
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Kobayashi T, Suzuki Y, Motoya S, Hirai F, Ogata H, Ito H, Sato N, Ozaki K, Watanabe M, Hibi T. First trough level of infliximab at week 2 predicts future outcomes of induction therapy in ulcerative colitis-results from a multicenter prospective randomized controlled trial and its post hoc analysis. J Gastroenterol 2016; 51:241-51. [PMID: 26162647 PMCID: PMC4766223 DOI: 10.1007/s00535-015-1102-z] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 06/25/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response. METHODS Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes. RESULTS Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95% confidence interval 2.84-27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing. CONCLUSIONS IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.
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Affiliation(s)
- Taku Kobayashi
| | - Yasuo Suzuki
| | - Satoshi Motoya
| | - Fumihito Hirai
| | - Haruhiko Ogata
| | - Hiroaki Ito
| | - Noriko Sato
| | | | - Mamoru Watanabe
| | - Toshifumi Hibi
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Abstract
Ulcerative colitis (UC) is a chronic inflammatory condition that is variable in both extent and severity of disease as well as response to therapy. Corticosteroids (CSs) were the first drugs used in the management of UC and are still used for induction of remission. However, because of their extensive side-effect profile, they are not utilized for maintenance of remission. In view of this, CS-free remission has become an important end point while evaluating therapeutic agents used in the management of UC. This review highlights the results of various studies conducted to evaluate the efficacy of different medications to attain CS-free remission in the setting of active UC. The drugs reviewed include established agents such as thiopurines, methotrexate, infliximab, adalimumab, vedolizumab, golimumab, and newer experimental agents, and if all else fails, colectomy will be performed. The efficacy of these drugs is evaluated individually. Our aim is to provide a synopsis of the work done in this field to date.
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Affiliation(s)
- Hafiz M Waqas Khan
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Faisal Mehmood
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Nabeel Khan
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia VA Medical Center, Philadelphia, PA, USA
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Sato S, Chiba T, Nakamura S, Matsumoto T. Changes in cytokine profile may predict therapeutic efficacy of infliximab in patients with ulcerative colitis. J Gastroenterol Hepatol 2015; 30:1467-1472. [PMID: 25968585 DOI: 10.1111/jgh.13008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/01/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM Infliximab is an established therapy for ulcerative colitis (UC). The aim of this study was to examine various serum cytokine levels and to identify possible markers predictive of therapeutic efficacy of infliximab for UC patients. METHODS Twenty-one patients with moderately active UC were given intravenous infliximab (5 mg/kg) at 0, 2, and 6 weeks as induction therapy. The serum levels of 17 cytokines were determined using a Bio-Plex suspension array system before and 8 weeks after induction therapy. Partial Mayo score (PMS) and serum C-reactive protein levels were used for the determination of clinical activities at 0 and 8 weeks after the treatment. The overall therapeutic effect was determined at 26 weeks according to the PMS. RESULTS The median value of the PMS decreased significantly 8 weeks after the treatment (from 6 to 1.5, P < 0.05). However, C-reactive protein levels did not change significantly. Levels of serum interleukin (IL)-8 (P < 0.05) and macrophage inflammatory protein-1β (P < 0.005) significantly decreased 8 weeks after the induction. Serum levels of the other 15 cytokines did not change significantly. At 26 weeks, 13 of 20 patients (65%) were responders while 7 patients were non-responders. Levels of serum IL-6 at 8 weeks were significantly lower in responders than in non-responders (P < 0.05). CONCLUSIONS Serum IL-8 and macrophage inflammatory protein-1β seem to be sensitive markers for UC patients treated with infliximab, while IL-6 at 8 weeks after induction therapy may be predictive of subsequent response to infliximab.
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Affiliation(s)
- Shoko Sato
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Toshimi Chiba
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Shotaro Nakamura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan
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Cui B, Li P, Xu L, Zhao Y, Wang H, Peng Z, Xu H, Xiang J, He Z, Zhang T, Nie Y, Wu K, Fan D, Ji G, Zhang F. Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med 2015; 13:298. [PMID: 26363929 PMCID: PMC4567790 DOI: 10.1186/s12967-015-0646-2] [Citation(s) in RCA: 123] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 08/19/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. METHODS Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. RESULTS Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3-18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. CONCLUSIONS Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. TRIAL REGISTRATION ClinicalTrials.gov, Number NCT01790061.
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Affiliation(s)
- Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Pan Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Lijuan Xu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Youquan Zhao
- Collega of Precision Instrument and Opto-electronics Engineering, Tianjin University, 92 Weijin Road, 300072, Tianjin, China.
| | - Huiquan Wang
- Biomedical Engineering Department, School of Electronics and Information Engineering, Tianjin Polytechnic University, 399 Binshui West Street, 300378, Tianjin, China.
| | - Zhaoyuan Peng
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Hai'e Xu
- Clinical Nutrition, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Jie Xiang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Zhi He
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Yongzhan Nie
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 710032, Xi'an, China.
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 710032, Xi'an, China.
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 710032, Xi'an, China.
| | - Guozhong Ji
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, 210011, Nanjing, China.
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Iwasa R, Yamada A, Sono K, Furukawa R, Takeuchi K, Suzuki Y. C-reactive protein level at 2 weeks following initiation of infliximab induction therapy predicts outcomes in patients with ulcerative colitis: a 3 year follow-up study. BMC Gastroenterol 2015; 15:103. [PMID: 26271624 PMCID: PMC4535387 DOI: 10.1186/s12876-015-0333-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Accepted: 08/05/2015] [Indexed: 01/12/2023] Open
Abstract
Background Poor response to anti-tumour necrosis factor biologicals like infliximab (IFX) is observed in patients with ulcerative colitis (UC), which may lead to prolonged morbidity and waste of medical resources. We aimed to look for potential biomarkers of response to IFX in patients with UC who were to undergo IFX induction therapy. Methods Seventy-two IFX naïve UC patients with partial Mayo (pMayo) score of 4–9 received IFX infusion at weeks 0, 2 and 6 as induction therapy. The pMayo score, trough IFX and C-reactive protein (CRP) concentrations were measured. At week 14, patients who achieved a pMayo score of ≤ 2 with no individual subscore exceeding 1 were judged as responders, while patients who responded, but did not achieve a pMayo score of ≤ 2 were judged as partial responders. Likewise, patients who showed unchanged pMayo score or worsened were judged as non-responders. Patients were followed for up to 3.3 years. Results Response, partial response and no response rates were 40.3, 33.3, and 26.4 %, respectively. CRP level at week 2 in responders was significantly lower vs partial-responders (P = 0.0135) or non-responders (P = 0.0084) in spite of similar trough IFX level. Further, the median CRP (week 2/week 0) ratio was significantly lower in patients who responded vs partial-responders or non-responders, 0.06, 0.39 and 1.00, respectively. When the cut-off value was set at 0.19 for the CRP (week 2/week 0) ratio, this ratio could predict partial-responders with 79.1 % sensitivity and 75.9 % specificity. Patients with the CRP (week 2/week 0) ratio greater than 0.19 were likely to be partial-responder, with odds ratio 10.371 (P < 0.0001; 95 % confidence interval 3.596–33.440). Conclusions In this study, CRP level at week 2 following initiation of IFX induction therapy appeared to be a clinically relevant biomarker of response to IFX in UC patients.
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Affiliation(s)
- Ryota Iwasa
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
| | - Akihiro Yamada
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
| | - Koji Sono
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
| | - Ryuichi Furukawa
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
| | - Ken Takeuchi
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University, Sakura Medical Centre, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan.
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Song Y, Shi YH, He C, Liu CQ, Wang JS, Zhao YJ, Guo YM, Wu RJ, Feng XY, Liu ZJ. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis. World J Gastroenterol 2015; 21:6082-6087. [PMID: 26019477 PMCID: PMC4438047 DOI: 10.3748/wjg.v21.i19.6082] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Revised: 01/16/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn’s disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.
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