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1.
Gastroenterology ; 160(1): 287-301.e20, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32980345

RESUMO

BACKGROUND AND AIMS: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes. METHODS: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment. RESULTS: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. CONCLUSIONS: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.


Assuntos
/metabolismo , Doenças Inflamatórias Intestinais/enzimologia , Mucosa Intestinal/enzimologia , Serina Endopeptidases/metabolismo , /genética , Animais , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /genética , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Estudos Transversais , Modelos Animais de Doenças , Feminino , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/virologia , Estudos Longitudinais , Masculino , Camundongos , Serina Endopeptidases/genética , Transdução de Sinais
2.
Inflamm Bowel Dis ; 27(1): 25-33, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32830267

RESUMO

BACKGROUND: There are scarce data about SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD). Our aim was to analyze the incidence, clinical presentation, and severity of SARS-CoV-2 infection in patients with IBD. METHODS: This is a cross-sectional, observational study. We contacted all the patients being treated at our IBD unit to identify those patients with suspected or confirmed SARS-CoV-2 infection, following the World Health Organization case definition. Data were obtained by patient electronical medical records and by phone interview. RESULTS: Eighty-two of 805 patients with IBD (10.2%; 95% confidence interval [CI], 8.3-12.5) were diagnosed as having confirmed (28 patients, 3.5%; 95% CI, 2.4-5.0) or suspected (54 patients, 6.7%) infection. Patient age was 46 ± 14 years, 44 patients were female (53.7%), 17.3% were smokers, 51.2% had Crohn disease (CD), and 39.0% had comorbidities. Digestive symptoms were reported in 41 patients (50.0%), with diarrhea as the most common (42.7%). One patient (1.2%) was diagnosed with IBD flare-up during SARS-CoV-2 infection. Twenty-two patients (26.8%) temporarily withdrew from their IBD treatment because of COVID-19. Most of the patients had mild disease (79.3%), and 1 patient died (1.2%). In the multivariate analysis, the presence of dyspnea was associated with moderate to severe infection (odds ratio, 5.3; 95% CI, 1.6-17.7; P = 0.01) and myalgias (odds ratio, 4.8; 95% CI, 1.3-17.9; P = 0.02) were related to a milder clinical course. Immunosuppression was not related to severity. CONCLUSIONS: SARS-CoV-2 infection in patients with IBD is not rare. Dyspnea is associated with a more severe infection. Therapy for IBD, including immunomodulators and biologic therapy, is not related to a greater severity of COVID-19, and SARS-CoV-2 infections do not appear to be related to IBD flare-ups.


Assuntos
/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Adulto , Terapia Biológica/métodos , Estudos Transversais , Dispneia/etiologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Incidência , Doenças Inflamatórias Intestinais/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha/epidemiologia
3.
J Gastrointestin Liver Dis ; 29(4): 549-553, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33331349

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) patients management has been challenging during the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patients' management were assessed in our Tertiary Gastroenterology Center in Bucharest, Romania. METHODS: Medical records of IBD patients admitted between 15th of March and 15th of August 2020 were retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019. RESULTS: There was a highly significant shift towards one-day hospitalization during the referral period in 2020 for IBD cases (91% in 2020 vs 82.2% in 2019, p=0.0001). There was no statistically significant difference between the distribution of patient's gender, IBD phenotype or newly diagnosed IBD cases. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs 41.2%, p=0.0001), whereas a substantially higher number of patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p<0.0001). The distribution of the biological agent used was significantly different in 2019 in comparison to the 2020 period mainly due to the increase in vedolizumab prescription in 2020 (p<0.0001). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course. CONCLUSIONS: The COVID-19 pandemic led to reorganizing medical care, limiting the hospital admissions in favor of severe IBD cases, favoring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Prestação Integrada de Cuidados de Saúde/tendências , Hospitalização/tendências , Doenças Inflamatórias Intestinais/tratamento farmacológico , Telemedicina/tendências , Anti-Inflamatórios/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Segurança do Paciente , Estudos Retrospectivos , Romênia/epidemiologia , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
6.
Acta Gastroenterol Belg ; 83(4): 657-659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33321025

RESUMO

Discontinuation of treatment in children with inflammatory bowel disease (IBD) in long-term remission remains debatable. The risk of relapse is one of the main concerns in the consideration of reduction or cessation of treatment. In 2017 all paediatric IBD patients treated with originator infliximab at the Department of Paediatric Gastroenterology, Ghent University Hospital, were switched to biosimilar Remsima®. Faecal calprotectin, infliximab through levels and antibodies, white cell count, haemoglobin and C-reactive protein were measured before and after switching to biosimilar. In total 21 IBD patients (3 Ulcerative Colitis - 19 CD) between 7 and 15 years old were switched. Three (14%) patients with CD in clinical, biochemical and histological remission had an unmeasurable through level and antibodies for infliximab, after 22 to 82 months of use. Switching to another treatment or cessation was discussed with patients and parents, all 3 patients decided to stop treatment. All 3 are still in clinical remission 21 to 24 months after treatment stop. Six-monthly follow-up is foreseen.


Assuntos
Medicamentos Biossimilares , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Medicamentos Biossimilares/uso terapêutico , Criança , Doença de Crohn/tratamento farmacológico , Substituição de Medicamentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Suspensão de Tratamento
7.
Postepy Biochem ; 66(3): 263-269, 2020 09 30.
Artigo em Polonês | MEDLINE | ID: mdl-33315316

RESUMO

Enkephalinases, which belong to the family of zinc metalloproteases play a crucial role in modulation of the endogenous opioid system (EOS) activity. Enkephalinase inhibitors (EI) allow obtaining therapeutic concentrations of selected endogenous peptides. One of the first EIs, racecadotril possesses antidiarrheal properties. Moreover, there is evidence that racecadotril presents fewer adverse events compared to other medications used for the treatment of diarrhea, such as loperamide. Lower potency for developing serious adverse events may be the key to choosing EIs as the preferred therapy in patients with chronic diseases. Additionally, EOS is involved in pain modulation, hence EIs might also be used as potential medications in treatment of pain. This review discusses the use of EIs in the treatment of gastrointestinal diseases, including irritable bowel syndrome and inflammatory bowel disease.


Assuntos
Gastroenteropatias/tratamento farmacológico , Neprilisina/uso terapêutico , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Loperamida/uso terapêutico
8.
Postepy Biochem ; 66(3): 256-262, 2020 09 30.
Artigo em Polonês | MEDLINE | ID: mdl-33315320

RESUMO

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic diseases. The exact etiology of IBD is not well elucidated, however it is defined as a multifactorial disease. In addition, IBD carries the risk of serious complications and increases the risk of colorectal cancer. Also, in recent years, an increased rate of IBD cases has been noted. So far, there is no effective and well-defined therapy for IBD, and currently available drugs mainly provide symptomatic treatment. Unfortunately, conventional treatment does not always bring the expected benefits, moreover, it is often associated with unpleasant side effects. Currently, some research have been focused on unconventional forms of IBD treatment, testing therapies based on natural products. Individual polyphenols, as well as polyphenol-rich preparations and extracts are also valuable in IBD treatment through antioxidant, anti-inflammatory and bactericidal activity. Moreover, described here results of clinical trials suggest that polyphenols can alleviate symptoms and prevent recurrence of IBD.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Polifenóis/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Humanos , Doenças Inflamatórias Intestinais/microbiologia
9.
Postepy Biochem ; 66(1): 42-48, 2020 03 31.
Artigo em Polonês | MEDLINE | ID: mdl-33320478

RESUMO

Sphingosine-1-phosphate (S1P) belongs to the group of biologically active sphingolipids. Because of its ability to regulate the migration of lymphocytes, S1P constitutes an important element of pathophysiology of several diseases, such as: lupus erythematosus, multiple sclerosis or inflammatory bowel diseases. Inflammatory bowel diseases (IBD) are the group of chronic and recurrent diseases of the gastrointestinal tract. The most common among IBD are: Crohn's disease and ulcerative colitis. Drugs that are currently used in the therapy of IBD alleviate symptoms, improve patients' quality of life and induce remission but their efficacy is not satisfactory. Modulators of S1P receptors constitu­te an emerging option in the therapy of IBD. In this review we will discuss the role of S1P, its receptor and enzymes that participate in the metabolism of S1P under physiological conditions and in the course of IBD. Moreover, we will sum up the results of preclinical and clinical studies on S1P receptors modulators in IBD.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Humanos , Qualidade de Vida , Esfingosina/metabolismo
11.
Curr Opin Pharmacol ; 55: 73-81, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33160250

RESUMO

Treatment strategies for inflammatory bowel disease (IBD) now increasingly target deep remission, yet the resultant more aggressive use of medical therapy is associated with potentially serious adverse events and significant costs. It is, therefore, of vital importance to consider when, how and in whom medical therapy may be safely de-escalated. This issue is of great potential relevance in the current SARS-Cov-2 pandemic. In this review, we first discuss the rationale for drug withdrawal in IBD, before considering the available data on withdrawal of 5-aminosalicylates (5-ASA), immunomodulators (IM) and biological therapy in both ulcerative colitis (UC) and Crohn's Disease (CD). We consider how to identify patients most appropriate for drug withdrawal and outline a potential monitoring strategy for the early detection of relapse following drug withdrawal. We conclude with important future perspectives in this challenging field, and highlight ongoing trials that are likely to shape practice in the years to come.


Assuntos
Terapia Biológica/métodos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mesalamina/uso terapêutico , Retirada de Medicamento Baseada em Segurança/métodos , Humanos , Fatores Imunológicos/efeitos adversos , Mesalamina/efeitos adversos
12.
PLoS One ; 15(11): e0242342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33180848

RESUMO

Vedolizumab (VDZ) is a therapeutic monoclonal antibody approved for the treatment of inflammatory bowel diseases (IBD). VDZ selectively binds to the α4ß7 integrin and blocks trafficking of a specific subset of gastrointestinal-homing T-lymphocytes to inflamed tissue. Although VDZ has shown promising results in numerous clinical studies a subgroup of patients do not respond adequately. Mechanistic insights and prognostic biomarkers able to predict which patients might benefit from VDZ therapy are currently lacking. Circulating exosomes were isolated from serum of blood donors and VDZ-treated patients by polymer-based precipitation. The surface expression of α4ß7 integrin was evaluated by flow cytometry and the levels of exosome-bound VDZ were investigated by Promonitor-VDZ ELISA kit. The capacity of exosomes to interfere with the adhesion of VDZ-treated CD4+ T cells was assessed by adhesion assay. In this study, we showed that serum exosomes isolated from both blood donor and ulcerative colitis patients express on their surface the VDZ target α4ß7 integrin. We observed an increased exosomal sequestration of VDZ in anti-TNF exposed patients compared to anti- TNFα naïve patients, according to a greater expression of α4ß7 integrin on vesicles surface. Circulating exosomes could compete for VDZ binding with CD4+ T cells since we found that the amount of VDZ bound to T cells was impaired in the presence of exosomes. In addition, we demonstrated that exosomes bind VDZ, which consequently becomes unable to block MadCAM-1-mediated adhesion of lymphocytes. Circulating exosomes might contribute to drug sequestration, possibly affecting the therapeutic efficacy of VDZ in IBD patients. Our data suggest that previous biologic therapy may have altered the sequestration capacity of circulating exosomes, thus reducing the efficacy of VDZ in patients who failed anti-TNF agents.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Exossomos/genética , Integrinas/genética , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Biomarcadores Farmacológicos/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Colite Ulcerativa/tratamento farmacológico , Exossomos/metabolismo , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica/genética , Ligação Proteica/fisiologia , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/uso terapêutico
13.
Orv Hetil ; 161(47): 1989-1994, 2020 11 22.
Artigo em Húngaro | MEDLINE | ID: mdl-33226355

RESUMO

Összefoglaló. Bevezetés: A gyulladásos bélbetegségek kezelésében a tumornekrózisfaktor-alfa-ellenes (anti-TNFα) antitestek elsodleges választási lehetoséget jelentenek a kortikoszteroid- és immunmoduláns kezelésre refrakter páciensek kezelési stratégiájában. Ezek a hatóanyagok hatékonyak, ám hosszú távú hatásosságukkal kapcsolatban sok az ellentmondás. Célkituzés: Vizsgálatunk célja megvizsgálni az anti-TNFα-terápia (infliximab [IFX], adalimumab [ADA]) hosszú távú hatékonyságát gyulladásos bélbetegek körében. Módszerek: Retrospektív, adatgyujtéses vizsgálatunkba a Szegedi Tudományegyetem I. Sz. Belgyógyászati Klinikáján gondozott, 18-65 év közötti gyulladásos bélbetegeket vontunk be. Az adatgyujtést a Klinika informatikai rendszerébol végeztük a betegek ambuláns megjelenéseinek kezelolapjaiból, illetve a zárójelentésekbol. Eredmények: 102 beteg adatait elemeztük (Crohn-beteg: 67 fo, colitis ulcerosás: 35 fo). A Crohn-betegség diagnózisát követoen átlagosan 7,84 év, a colitis ulcerosa diagnózisát követoen átlagosan 9,86 év telt el az elso anti-TNFα-terápia elkezdéséig. Az elso kezelési ciklus átlagosan 2,64 évig tartott, a ciklus végén az IFX-t kapó betegek 50%-ánál, az ADA-t kapó betegek 46%-ánál volt remisszióban a betegség. A második kezelési ciklus átlagosan 4,67 évig tartott, a ciklus végén az IFX-t kapó betegek 36%-a, az ADA-t kapó betegek 40%-a volt remisszióban. Az elso, illetve a második kezelési ciklus alatt az allergiás reakciók gyakorisága IFX esetében 13% és 18%, ADA esetében 4% és 3% volt. A primer hatástalanság és a másodlagos hatásvesztés az elso ciklusban IFX esetében 4% és 10,5%, ADA esetében 11,5% és 19% volt. A második kezelési ciklusban IFX esetében 9%-ban és 18%-ban, ADA esetében 23%-ban és 10%-ban jelentették a ciklus végét. Következtetés: Az anti-TNFα-terápiák eredményeink alapján hosszú távon is hatékonynak és biztonságosnak bizonyultak. Másodlagos hatásvesztés kisebb arányban fordult elo a vizsgált populációban az irodalmi adatokhoz képest. Orv Hetil. 2020; 161(47): 1989-1994. INTRODUCTION: Anti-tumor necrosis factor-alpha (anti-TNFα) treatment is reserved for steroid-dependent or steroid/immunomodulator-refractory inflammatory bowel diseases patients. These agents are effective, however, their long-term safety is still questionable. OBJECTIVE: We aimed to assess the long-term efficacy and safety of two anti-TNFα therapies. METHODS: In our retrospective study, we reviewed medical records via the administration system of the First Department of Medicine, University of Szeged. Female and male patients, aged between 18-65 years who received anti-TNFα therapy between 2010-2019 were enrolled. RESULTS: 102 patients with inflammatory bowel disease were enrolled (Crohn's disease: 67, ulcerative colitis: 35). The first anti-TNFα therapy was introduced after an average 7.84 and 9.86 years from diagnosis of Crohn's disease and ulcerative colitis. The first treatment period lasted for 2.64 years; 50% of patients receiving IFX and 46% of patients receiving ADA were in remission at the end of the period. The second treatment period lasted for 4.67 years, 36% of IFX-treated patients and 40% of ADA-treated patients were in remission at the end of the period. 13% and 18% of patients treated by IFX and 4% and 3% of patients treated by ADA experienced infusion reaction during the first and the second treatment period. Primary non-response and loss of response rates were 4% and 10.5% (IFX) and 11.5% and 19% (ADA) during the first treatment period. These rates were 9% and 18% (IFX) and 23% and 10% (ADA) during the second treatment period. CONCLUSION: Our study confirmed the long-term efficacy and safety of the anti-TNFα therapies. Loss of response rate is lower in our population compared to the literature. Orv Hetil. 2020; 161(47): 1989-1994.


Assuntos
Adalimumab/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Adolescente , Adulto , Idoso , Colite , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Am J Gastroenterol ; 115(11): 1768-1774, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156094

RESUMO

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.


Assuntos
Produtos Biológicos/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Infliximab/administração & dosagem , Recidiva
15.
Am J Gastroenterol ; 115(11): 1802-1811, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156099

RESUMO

INTRODUCTION: To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/uso terapêutico , Hepatite B/prevenção & controle , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Vacinas contra Hepatite B/imunologia , Humanos , Imunogenicidade da Vacina , Doenças Inflamatórias Intestinais/imunologia , Masculino , Pessoa de Meia-Idade
16.
Arq Gastroenterol ; 57(3): 323-332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027484

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.


Assuntos
Doenças Inflamatórias Intestinais , Fatores Biológicos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Qualidade de Vida , Fator de Necrose Tumoral alfa
19.
Sci Rep ; 10(1): 17099, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051546

RESUMO

Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later. Serum infliximab, antidrug antibody levels and other serum biomarkers were measured at weeks 0, 2, 6, 14 and 22. Remission outcomes were evaluated at weeks 14 and 22. Drug levels were measured prospectively and analysed using MANOVA. Of the 86 patients, 44 (51%) and 42 (49%) were administered the originator and CT-P13, respectively. Originator trough levels were higher than the biosimilar trough levels (35 vs. 21, 20.1 vs. 11, 6.6 vs. 2.9 and 4.3 vs. 1.7 µg/mL at weeks 2, 6, 14 and 22, respectively). A post-hoc analysis demonstrated changes in mean serum drug levels over time (p < 0.001) and according to the drug employed (p = 0.001). At week 22, 13 (81%) patients administered the originator achieved clinical remission compared with 5 (19%) patients with the biosimilar (p = 0.02). None of the patients administered the originator withdrew from the treatment compared with 7 for the biosimilar. During the study, there were significant differences in serum infliximab levels between the originator and the CT-P13 in the patients with IBD. The clinical outcomes were influenced by the type of compound administered.


Assuntos
Anticorpos Monoclonais/farmacocinética , Medicamentos Biossimilares/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/farmacocinética , Adolescente , Adulto , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Biomarcadores/sangue , Medicamentos Biossimilares/sangue , Medicamentos Biossimilares/uso terapêutico , Feminino , Humanos , Doenças Inflamatórias Intestinais/sangue , Infliximab/sangue , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Medicine (Baltimore) ; 99(44): e22897, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126343

RESUMO

Inflammatory bowel disease (IBD) in Asia has become increasingly prevalent. As a treatment of IBD, many immunomodulators and biological agents were introduced and shown to be effective in inducing and maintaining remission. However, many cases with treatment failure were reported. To overcome the failure, combination therapy of immunomodulatory and biologics have emerged, showing better outcomes by optimizing biologic pharmacokinetics and minimizing immunogenicity. Adversely, rates of tuberculosis (TB) have been increased as a result. The aim of this study is to compare the risk of TB according to the therapy using large population data.We used data from the South Korean Health Insurance and Review Agency over the period 2008-2016 and calculated the hazard ratio (HR) for TB in IBD. We compared the risk of TB according to the medication: infliximab only, azathioprine only (AZA), combination of azathioprine and infliximab (CAI), azathioprine monotherapy and infliximab monotherapy (AIM), and azathioprine and infliximab whether simultaneously or separately (AISS).In IBD patients, a total of 249 patients were identified as active TB. After one-to-one matching with age, sex and disease duration, the risks of TB were significantly higher in AZA group (HR, 2.06; 95% CI, 1.35-3.12, P < .001), AIM group (HR, 3.26; 95% CI, 1.18-9.05, P = .02), AISS group (HR, 3.50; 95% CI, 1.92-6.37, P < .001), and CAI group (HR, 5.67; 95% CI, 2.42-10.21, P < .001), and the HR increased gradually in this order. In UC patients, the results were in similar pattern, but this pattern was not observed in CD patients in our study.Our study shows that Korean IBD patients are at risk of TB, and the risk increases with usage of IBD medication; moreover, the risk is the highest if combination therapy is used. These results highlight the importance of screening for TB in IBD patients, especially in combination therapy.


Assuntos
Azatioprina/uso terapêutico , Quimioterapia Combinada/métodos , Infliximab/uso terapêutico , Tuberculose , Imunidade Adaptativa/efeitos dos fármacos , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
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