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‣ Protective effect of octreotide and infliximab in an experimental model of indomethacin-induced inflammatory bowel disease

CURY, Didia H. Bismara; COSTA, Jose Edson; IRIKA, Kioshi; MIJJI, Luciana; GARCEZ, Alessandre; BUCHIGUEL, Carlos; SILVA, Ivani; SIPAHI, Aytan
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
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Indomethacin administration in animals increases permeability of the small intestine, leading to inflammation that mimics Crohn`s disease. Nonsteroidal anti-inflammatory drugs increase the permeability of the intestinal epithelial barrier and should therefore be used with caution in patients with Crohn`s disease. We analyzed the protective effects of octreotide and the tumor necrosis factor-alpha inhibitor infliximab in a rat model of indomethacin-induced enterocolitis. Male Wistar rats received 20 mg of infliximab or 10 mu g of octreotide 24 h prior to injection with indomethacin. Intestinal permeability was analyzed using Cr-51-ethylenediaminetetraacetic acid clearance. No microscopic or macroscopic alterations were observed in the rats receiving infliximab or octreotide, both of which increased permeability (P < 0.001 versus controls). Our macroscopic and microscopic findings might be related to the low specificity of infliximab and suggest that cytokines affect the intestinal epithelial barrier, as evidenced by the protective effect that infliximab had on the permeability parameters evaluated.

‣ Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

Gazzoto Filho, Ademir; Kinote, Andrezza; Pereira, Daniel J.; Rennó, André; Santos, Rodrigo C. dos; Ferreira-Melo, Silvia E.; Velloso, Licio A.; Silva, Silvana Auxiliadora Bordin da; Anhê, Gabriel F.; Moreno Junior, Heitor
Fonte: Elsevier Science; Amsterdam Publicador: Elsevier Science; Amsterdam
Tipo: Artigo de Revista Científica
Português
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High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall...

‣ Avaliação da resposta imune anti-Mycobacterium tuberculosis em pacientes com psoríase moderada a grave submetidos à terapia com inibidor de fator de necrose tumoral, infliximabe; Evaluated of immune responses anti-Mycobacterium tuberculosis in patients with psoriasis moderade to severe undergoing treatment with TNF blocking agent, infliximab

Ortigosa, Luciena Cegatto Martins
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 14/03/2014 Português
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O tratamento de pacientes apresentando doenças inflamatórias imunomediadas com drogas anti-TNF-alfa aumenta o risco da reativação da tuberculose. Isso sugere que tais drogas possam afetar a imunidade celular destes. No entanto, há dados conflitantes sobre se esse tratamento suprime as respostas para o teste tuberculínico (TT) e os ensaios de liberação de interferon-gama (IGRAs) e poucos dados em pacientes com psoríase. O presente estudo avaliou pacientes com psoríase moderada a grave enfocando os efeitos do tratamento com infliximabe em suas respostas imunológicas celulares. Foram avaliadas as respostas imunes celulares de doze pacientes antes e durante o tratamento com infliximabe. As células mononucleares do sangue periférico (PBMC) foram estimuladas com a fito-hemaglutinina (PHA), o superantígeno enterotoxina B (SEB), um lisado de citomegalovírus (CMV), e antígenos de Mycobacterium tuberculosis, e a ativação de linfócitos foi avaliada por ELISPOT para enumerar células secretoras de IFN-y, por ELISA para detecção da secreção de IFN-y, e através da incorporação de[3H] timidina para medir a proliferação. O tratamento com infliximabe não levou à redução de INF-y e da resposta linfoproliferativa nos pacientes. Pelo contrário...

‣ Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

Gazzoto Filho, Ademir; Kinote, Andrezza; Pereira, Daniel J.; Rennó, André; Santos, Rodrigo C. dos; Ferreira-Melo, Silvia E.; Velloso, Licio A.; Bordin, Silvana; Anhê, Gabriel F.; Moreno Júnior, Heitor
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 201-209
Português
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High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall...

‣ Infliximab treatment prevents hyperglycemia and the intensification of hepatic gluconeogenesis in an animal model of high fat diet-induced liver glucose overproduction

Haida,Karissa Satomi; Bertachini,Gabriela; Tavoni,Thauany; Guilhermetti,Márcio; Loures,Marco Rocha; Bazotte,Roberto Barbosa
Fonte: Instituto de Tecnologia do Paraná - Tecpar Publicador: Instituto de Tecnologia do Paraná - Tecpar
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2012 Português
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The effect of infliximab on gluconeogenesis in an animal model of diet-induced liver glucose overproduction was investigated. The mice were treated with standard diet (SD group) or high fat diet (HFD group). HFD group were randomly divided and treated either with saline (100 µl/dose, ip, twice a day) or infliximab (10 µg in 100 µl saline per dose, ip, twice a day, i.e., 0.5 mg/kg per day). SD group also received saline. The treatment with infliximab or saline started on the first day of the introduction of the HFD and was maintained during two weeks. After this period, the mice were fasted (15 h) and anesthetized. After laparotomy, blood was collected for glucose determination followed by liver perfusion in which L-alanine (5 mM) was used as gluconeogenic substrate. HFD group treated with saline showed higher (p < 0.05) liver glucose production from L-alanine and fasting hyperglycemia. However, these metabolic changes were prevented by infliximab treatment. Therefore, this study suggested that infliximab could prevent the glucose overproduction and hyperglycemia related with glucose intolerance and type 2 diabetes.

‣ Estudo das alterações retinianas em olhos de coelhos após injeções intravítreas seriadas de infliximabe; Study of retinal alterations in eyes of rabbits after serial intravitreous injections of infliximab

RASSI, Alan Ricardo
Fonte: Universidade Federal de Goiás; BR; UFG; Doutorado em Ciencias da Saude; Ciencias da Saude Publicador: Universidade Federal de Goiás; BR; UFG; Doutorado em Ciencias da Saude; Ciencias da Saude
Tipo: Tese de Doutorado Formato: application/pdf
Português
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The objective of this study was to determine the levels of toxicity of two and three intravitreous injections of infliximab to the retina and choroid of albino rabbits by means of histological, electroretinographic and clinical ophthalmological tests. Twelve New Zealand albino rabbits (24 eyes) were used in the study. Each eye was given two (n=10) or three (n=10) serial intravitreous 2 mg injections of infliximab dissolved in 0.06 ml of saline, at monthly intervals. A separate group of rabbits (n=4 eyes) served as a control group. Ninety days after the first injection, the rabbits underwent electroretinographic and clinical ophthalmological tests. After being enucleated, the eyes underwent histological examination. No clinical ophthalmologic abnormalities were detected in the 24 eyes studied. The histological change noted was the presence of rare lymphocytes and eosinophiles in the posterior vitreous of four eyes subjected to two injections and six eyes subjected to three injections of infliximab, but it was not considered clinically significant. One clinically significant abnormality was found, a severe inflammatory reaction with vitreous exudates and ganglion cell edema in both eyes of a single rabbit, subjected to two to three injections of infliximab. The electroretinographic tests showed amplitudes that were on the average 12% smaller than those obtained before the treatment. However...

‣ The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended?

Denadai,Rafael; Teixeira,Fábio Vieira; Saad-Hossne,Rogério
Fonte: Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia - IBEPEGE ; Colégio Brasileiro de Cirurgia Digestiva - CBCD ; Sociedade Brasileira de Motilidade Digestiva - SBMD ; Federação Brasileira de Gastroenterologia - FBG; Sociedade Brasileira de Hepatologia - SBH; Sociedade Brasileira de Endoscopia Digestiva - SOBED Publicador: Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia - IBEPEGE ; Colégio Brasileiro de Cirurgia Digestiva - CBCD ; Sociedade Brasileira de Motilidade Digestiva - SBMD ; Federação Brasileira de Gastroenterologia - FBG; Sociedade Brasileira de Hepatologia - SBH; Sociedade Brasileira de Endoscopia Digestiva - SOBED
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2012 Português
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CONTEXT: Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. OBJECTIVE: To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS: A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS: Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION: As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab...

‣ Infliximab reduces cardiac output in rheumatoid arthritis patients without heart failure

Santos,Rodrigo Cardoso; Figueiredo,Valéria Nasser; Martins,Luiz Cláudio; Moraes,Carolina de Haro; Quinaglia,Thiago; Boer-Martins,Leandro; Ferreira-Melo,Sílvia Elaine; Yazbek,Michel Alexandre; Bertolo,Manoel; Moreno Junior,Heitor
Fonte: Associação Médica Brasileira Publicador: Associação Médica Brasileira
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2012 Português
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OBJECTIVE: Human anti-tumor necrosis factor (TNF-α) monoclonal antibody (infliximab) is used to treat autoimmune diseases such as rheumatoid arthritis (RA). Although the risk of worsening heart failure has been described in patients under chronic treatment, the acute cardiovascular effects of this drug are unknown in RA patients without heart failure. METHODS: 14 RA patients with normal echocardiography and no history of heart failure were evaluated during the 2-hour infliximab (3-5 mg/kg) infusion period, using a noninvasive hemodynamic beat-to-beat system (Portapres). Stroke volume (SV); systolic, diastolic and mean blood pressures (SBP, DBP and MBP, respectively); cardiac output (CO); heart rate (HR); and total peripheral vascular resistance (PVR) were recorded. All patients also received saline infusion instead of infliximab as a control. Significant differences in hemodynamic parameters were determined using Tuckey's test. All values were expressed as mean ± standard deviation (SD). RESULTS: Fourteen RA patients (6M/8F) with mean age of 47.2 ± 8.8 years were evaluated. A significant decrease was found in cardiac output and stroke volume (7.04 ± 2.3 to 6.12 ± 2.1 l/min and 91 ± 29.0 to 83 ± 28.8 mL/beat, respectively) after infliximab infusion. Although not statistically significant...

‣ Uso de infliximab en pacientes de un centro reumatológico

Strusberg,Ingrid; Bertoli,Ana M.; de Pizzolato,Ruth C; Fierro,Gonzalo; Strusberg,Alberto M.
Fonte: Medicina (Buenos Aires) Publicador: Medicina (Buenos Aires)
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2005 Português
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El objetivo de este estudio fue obtener información postmarketing sobre el uso de infliximab en un centro reumatológico de atención ambulatoria. Se realizó un análisis retrospectivo y prospectivo de las historias clínicas de pacientes con diagnóstico de artritis reumatoidea ( n=37 ), artritis psoriásica ( n=5 ), enfermedad mixta del tejido conectivo ( n=1 ) y espondilitis anquilosante ( n=2 ) que recibieron infliximab (3 mg / kg ) desde agosto de 2000 a junio de 2003. El análisis descriptivo se realizó con porcentajes, media o mediana y desviación estándar o intervalo intercuartilo . La prueba de Wilcoxon se utilizó para el análisis apareado de dosis de antiinflamatorios no esteroideos y metotrexato , anterior y posterior a la administración de infliximab. Se consideraron significativos valores de p £ 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusión y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estándar. Se presentó un caso de artritis séptica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibió infliximab en dosis de 1.9 mg / kg cada 30 días...

‣ Rol de infliximab en enfermedad inflamatoria intestinal: Experiencia local

Simian,Daniela; Quijada,María Isabel; Lubascher,Jaime; Acuña,Raúl; Quera,Rodrigo
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2013 Português
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Background: Biological therapy has an important role in the treatment of Inflammatory Bowel Disease (IBD). However, the use of these drugs is resisted due to fears about their side effects. Aim: To report the experience with the use of Infliximab in patients with IBD. Material and Methods: Descriptive study of a historical cohort of patients with IBD treated between 2007 and 2012 with Infliximab. A favorable clinical response was considered when general, intestinal and extra-intestinal symptoms subsided after the second or third dose of the drug. Endoscopic or imaging response was evaluated between three and six months of treatment. Results: Twenty five patients aged 18 to 61 years (12 women) were included. Sixteen had Cohn’s Disease and 9 had Ulcerative Colitis. Treatment was indicated due to refractory disease in 13 patients, perianal involvement in nine, stenosis in two and pyoderma gangrenosum in one. Ten patients initiated Infliximab within less than two years of diagnosis. Twenty-two patients received combined treatment with immunosuppressive medications and the other three patients were treated exclusively with Infliximab. A favorable clinical response was observed in 88% after the second dose and 64% had endoscopic or imaging remission after 3-6 months. Twelve patients discontinued Infliximab...

‣ Infliximab en el tratamiento de la enfermedad de Crohn: Estudio preliminar

Gellona V,José; Zarraonandia A,Antón; Zúñiga D,Alvaro; Palma C,Renato; Contreras P,Jaime; Silva Ch,Jaime; González D,Róbinson; Quintana V,Carlos
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2006 Português
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Background: Tumor necrosis factor alpha, interleukin 6 and 1 have a pathogenic role in Crohn's disease. Infliximab, a monoclonal antibody against tumor necrosis factor, is useful in the treatment of Crohn's disease, specially when the disease is active and associated to fistula formation. Aim: To assess the effectiveness of Infliximab in patients with Crohn's disease. Material and methods: Twelve patients with Crohn's disease (aged 16 to 63 years, 10 women) refractory to treatment with steroid, 5-aminosalicylic acid, antimicrobials and immunomodulatory drugs, were studied. A single intravenous 5 mg/kg dose Infliximab was administered. The Crohn's disease activity index (CDAI) was measured before and one week after the administration of the drug. Results: CDAI before and after Infliximab administration was 357±62 and 138±122 score points, respectively (p <0.005). According to this score, five patients had a severe and seven a moderate disease flare. The disease remitted in 7 (58%) and a clinical response was observed in 75%. Conclusions: A single dose of Infliximab was effective to induce remission of the disease in 75% of this selected group of patients with Crohn's disease

‣ Eficacia y seguimiento en el largo plazo de pacientes con psoriasis vulgar moderada a severa en tratamiento con infliximab (Remicade®)

Valdés A,María del Pilar; Schroeder H,Francisca; Roizen G,Vicky; Honeyman M,Juan; Sánchez M,Leonardo
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2006 Português
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Background: Psoriasis has a moderate or severe course in 25% of patients, requiring systemic therapy that is not always successful. Infliximab is a human-murine monoclonal anti tumor necrosis alpha (TNF-a) antibody. This mediator has a role in the pathogenesis of psoriasis. Aim: To evaluate the use of infliximab in psoriatic patients resistant to conventional therapies. Material and Methods: An open prospective study including eight patients with extensive plaque or erythrodermic psoriasis. They were treated with infliximab 5 mg/kg/dose on weeks 0,2 and 6. Patients were evaluated every 2 weeks for a median lapse of 50.1 weeks. Physical examination, PASI scores (Psoriasis Area Severity Index) and a photographic control, were done in each visit. Results: All the patients responded in the first 10 weeks of follow-up. The mean reduction in PASI score was 86.6%. Six patients received fourth infusion of infliximab at 37.3 weeks, on average. The most common adverse events were pruritus and headache. Conclusions: This group of patients with extensive plaque or erythrodermic psoriasis resistant to conventional therapies, had a good response to infliximab

‣ Evaluación del tratamiento con infliximab en enfermos con artritis inflamatoria refractaria a drogas habituales

Labarca S,Cristián; Massardo V,Loreto; García M,Paula I; Jacobelli G,Sergio
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2003 Português
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Tumor necrosis factor antagonists are useful in the treatment of several chronic inflammatory immune mediated diseases. Aim: To assess the effects of infliximab in 21 patients with inflammatory arthropaties, refractary to conventional treatment. Patients and methods: Eleven patients with rheumatoid arthritis, seven with psoriatic arthritis and three with spondyloarthritis were treated. The mean duration of the diseases was 10 years. Infliximab was administered intravenously in a dose of 3 mg/kg body weight. A median of 6 doses in 8 months was administered. Effectiveness was assessed in 19 patients that received three or more doses. Results: Infliximab was effective in 16 patients (10 with rheumatoid arthritis, four with psoriasis and two with spondyloarthritis) and ineffective in three. In responsive patients, a reduction in the number of inflammed joints and morning stiffness and an improvement in functional capacity was observed. Fifteen of the 16 patients perceived an improvement in their health status. This answer was concordant with concomitant medical evaluation in 15. Patients that maintained the treatment felt very well, well or regular, whereas five of six patients that discontinued the treatment felt ill. Thirteen patients had adverse effects. Treatment was discontinued in two patients due to drug induced lupus...

‣ Efficacy of adalimumab in patients with crohn's disease and failure to infliximab therapy: a clinical series

Cordero-Ruiz,Patricia; Castro-Márquez,C.; Méndez-Rufián,V.; Castro-Laria,L.; Caunedo-Álvarez,A.; Romero-Vázquez,J.; Herrerías-Gutiérrez,J. M.
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/06/2011 Português
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Background: adalimumab, a human anti-TNF, is an effective induction and maintenance therapy for patients with moderate to severe Crohn's disease. It seems to be effective in patients with resistance to infliximab, too, though the experience is more limited. Aim: to evaluate the efficacy of adalimumab, in patients with Crohn's disease (CD) and failure to previous treatment with infliximab. B twenty-five patients with CD and failure to previous treatment with infliximab were enrolled; they were treated with 160/80 (24 patients) and 80/40 (1 patient) induction doses. We analyze clinical response to treatment with adalimumab by the Crohn's disease Activity Index (CDAI) and plasma concentration of C-reactive protein (CRP), steroid sparing and complete fistula closure at week 48. Results: eighteen out of twenty-five patients (72%) achieved clinical remission (CDAI score < 150) at week 24 and 15/25 (60%) patients at week 48. There was a statistically significant difference (p < 0.01) in CRP serum levels from 21 to 8 mg/dl at week 48. Nine out of fifteen patients (60%) treated with corticosteroids were able to discontinue steroids. Three out of eleven patients (27%) with fistulizing Crohn's disease had complete fistula closure after the treatment. Seventy two percent of the patients (18/25) needed to increase adalimumab to weekly dose...

‣ Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis

Bermejo,F.; López-Sanromán,A.; Hinojosa,J.; Castro,L.; Jurado,C.; Gómez-Belda,A. B.
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/02/2004 Português
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Background: infliximab is a monoclonal antiTNF-α antibody that has repeatedly shown to be effective in the management of Crohn's disease. However, data are scarce about its efficacy in ulcerative colitis. Aim: to describe the joint experience of three Spanish hospitals in the use of infliximab in patients with active refractory ulcerative colitis. Patients and methods: we present seven cases of ulcerative colitis (6 with chronic active disease despite immunosuppressive therapy, and one with acute steroid-refractory ulcerative colitis) treated with infliximab 5 mg/kg of body weight. Clinical response was evaluated by means of the Clinical Activity Index at 2, 4 and 8 weeks after initial infusion. Biochemical (erythrocyte sedimentation rate and C-reactive protein), endoscopic, and histological changes were also assessed. Results: mean age of patients was 45.8 ± 17 years (range 23-77); 4 were female. No adverse effects were recorded. Inflammatory activity diminished significantly in 6 of 7 patients (85.7%; CI 95%: 42-99%) both from a clinical (p = 0.01) and biochemical (p <0.05) point of view. Five out of six patients (83.3%; 36-99%) with corticosteroid-dependent disease could be successfully weaned off these drugs. Five patients were endoscopicly controlled both before and after therapy...

‣ Predictors of response to infliximab in patients with fistulizing Crohn's disease

Luna-Chadid,M.; Pérez Calle,J.L.; Mendoza,J.L.; Vera,M. I.; Bermejo,A. F.; Sánchez,F.; López San Román,A.; Froilán,C.; González-Lara,V.; García-Paredes,J.; Fernández-Blanco,I.; Abreu,L.; Casis,B.; Solís Herruzo,J. A.; Gisbert,J.P.; Maté-Jiménez
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/06/2004 Português
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Objective: to evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. Methods: consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. Results: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). Conclusions: infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients...

‣ A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients

Pérez-Pitarch,Alejandro; Ferriols-Lisart,Rafael; Alós-Almiñana,Manuel; Mínguez-Pérez,Miguel
Fonte: Revista Española de Enfermedades Digestivas Publicador: Revista Española de Enfermedades Digestivas
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/03/2015 Português
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Background: Infliximab, an anti-tumour necrosis factor approved for treatment of Crohn's disease and ulcerative colitis, is administered at predefined interdose-intervals. On insufficient response or loss of response, treatment can be intensified. The lack or loss of response is likely related to complex pharmacokinetics of infliximab. Aims: To explore optimal dosing strategies of infliximab in treatment-naïve patients with ulcerative colitis through predictive Monte Carlo simulations based on a validated population PK model. Methods: A population of 2,000 treatment-naïve patients was generated by Montecarlo simulation. Six dosing strategies for maintenance therapy were simulated on this population. Strategies 1 and 2 consisted on 5 mg/kg and 6 mg/kg doses, respectively, and 8 weeks inter-dose interval. Strategies 3 and 4 used Individualized doses, adjusted to albumin level, sex and body weight, and a fix inter-dose interval of 8 weeks to achieve a target trough concentration of 5 mg/L or 6 mg/L, respectively. Strategies 5 and 6 used a fix dose of 5 mg/kg and individualized inter-dose intervals, adjusted to the same covariates, to achieve a target concentration, of 5 mg/L or 6 mg/L, respectively. Results: Strategies 2-6 reached trough levels statistically higher than strategy 1 (p < 0.05). Strategy 5 proved to be the best dosing strategy. It was associated with a higher proportion of responder patients than strategy 1 (62 % vs. 40 %) without reaching higher peak concentrations. Conclusions: Optimization of maintenance treatment of colitis with infliximab by a pharmacokinetic approach could benefit infliximab-naive patients with ulcerative colitis.

‣ Dos casos de reactivación de tuberculosis pulmonar por infliximab: Problemas y propuestas de solución

Díaz Verdúzco,Manuel de Jesús
Fonte: Instituto Nacional de Enfermedades Respiratorias Publicador: Instituto Nacional de Enfermedades Respiratorias
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2005 Português
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Introducción: Se han descrito múltiples factores de riesgo para el desarrollo de la tuberculosis; uno recientemente conocido es la inmunosupresión secundaria al uso de infliximab, anticuerpo monoclonal quimérico antifactor de necrosis tumoral-α usado en enfermos con artritis reumatoide o espondilitis anquilosante refractarias a tratamiento y en enfermedad de Crohn fistulizante, entre otros, en los que se ha comunicado reactivación tuberculosa en Estados Unidos y Europa. Presentación de casos: En México sólo se conoce un caso. Presentamos dos más en enfermos con espondiloartropatías HLA-B27 refractarios a tratamiento modificador de la enfermedad. Uno en una mujer de 23 años, después de la segunda dosis de infliximab; otro en un hombre de 32 años, después de la quinta dosis, a la semana 22 de tratamiento. Ambos presentaron forma neumónica cavitada con buena respuesta al tratamiento antituberculoso acortado convencional y suspensión del infliximab. Discusión: La revisión bibliográfica incluye el impacto de los problemas: infliximab-reactivación tuberculosa y la epidemiología tuberculosa actual, medidas preventivas, controversias en detección, tratamiento y fisiopatología de la relación infliximab-reactivación tuberculosa para proponer medidas para su diagnóstico...

‣ Uso do infliximab na consulta de gastrenterologia pediátrica

Marques,Rita; Caldeira,Filipa; Costa,Cláudia; Cunha,José da; Ferreira,Maria Gomes
Fonte: Sociedade Portuguesa de Gastrenterologia Publicador: Sociedade Portuguesa de Gastrenterologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2012 Português
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Introdução: O infliximab e um anticorpo monoclonal utilizado na doença inflamatória intestinal (DII) refrataria. Objetivo: Avaliar a resposta clinica e os efeitos adversos da terapêutica com infliximab na DII em doentes pediátricos. Métodos: Estudo descritivo, analítico e transversal dos doentes da consulta de gastrenterologia pediátrica que ingressaram em protocolo terapêutico com infliximab. Resultados: Dos 6 doentes que realizam terapêutica monoclonal com infliximab, 5 apresentam doença de Crohn moderada a grave e um colite ulcerosa. Verificou-se remissão clinica em 5 doentes. Observou-se resolução das alterações analíticas apos 6 meses de terapêutica. Verificaram-se 2 reações alérgicas ligeiras e uma elevação transitória das transaminases. Conclusões: Em concordância com o descrito na literatura, na nossa população a terapeutica com infliximab tem sido bem tolerada e eficaz no controlo da doença.

‣ Modificação do tratamento com infliximab na doença de Crohn: experiência de um centro

Campos,Teresa Almeida; Águeda,Sofia; Rebelo,Joana; Gonçalves,Américo; Lima,Rosa; Tavares,Marta; Trindade,Eunice; Dias,Jorge Amil
Fonte: Sociedade Portuguesa de Gastrenterologia Publicador: Sociedade Portuguesa de Gastrenterologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2014 Português
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Introdução: Em idade pediátrica, o tratamento da doença de Crohn deve não só assegurar o controlo dos sintomas, mas também induzir remissão, permitindo o normal crescimento e desenvolvimento dos doentes. O infliximab tem-se mostrado eficaz no controlo da doença em crianças e adolescentes sem resposta ao tratamento de primeira linha, embora em 30-55% destes ocorra falência, com necessidade de ajuste terapêutico. Estudos pediátricos recentes mostraram eficácia semelhante entre a redução do intervalo de 8 para 6/7 semanas e o aumento da dose para 10 mg/kg ou encurtamento do intervalo até 4 semanas. Objetivo e métodos: Estudo descritivo, retrospetivo dos doentes pediátricos com diagnóstico de doença de Crohn, que efetuaram tratamento com infliximab nos últimos 5 anos, e avaliação das situações de falência terapêutica. Resultados: Foram incluídos 16 doentes (10 M, 6 F) em que, por não ser conseguida remissão duradoura da doença, foi instituído tratamento com infliximab em esquema de indução, seguido de 5 mg/kg cada 8 semanas. Na maioria dos doentes, este tratamento foi iniciado 10 meses após o diagnóstico. Em 8 (50%) verificou-se recaída clínica e/ou analítica, em média após 10 ciclos de tratamento (mediana de 6...