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[PMID]:28453766
[Au] Autor:Lim KJ; Lee SJ; Kim S; Lee SY; Lee MS; Park YA; Choi EJ; Lee EB; Jun HK; Cho JM; Lee S; Kwon KS; Lim BP; Jeon MS; Shin EC; Choi YS; Fudim E; Picard O; Yavzori M; Ben-Horin S; Chang SJ
[Ad] Endereço:R&D Division, Celltrion Inc., Incheon, Korea.
[Ti] Título:Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13: Implications for Treatment of Inflammatory Bowel Disease.
[So] Source:J Crohns Colitis;11(5):593-602, 2017 May 01.
[Is] ISSN:1876-4479
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background and Aims: CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD. Methods: CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC]. Results: CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients. Conclusions: These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/farmacologia
Medicamentos Biossimilares/farmacologia
Fármacos Gastrointestinais/farmacologia
Doenças Inflamatórias Intestinais/tratamento farmacológico
Infliximab/farmacologia
Intestinos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Medicamentos Biossimilares/uso terapêutico
Células CACO-2/efeitos dos fármacos
Citocinas/metabolismo
Fármacos Gastrointestinais/uso terapêutico
Seres Humanos
Técnicas In Vitro
Infliximab/uso terapêutico
Intestinos/citologia
Intestinos/imunologia
Macrófagos/efeitos dos fármacos
Fator de Necrose Tumoral alfa/metabolismo
Cicatrização/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Biosimilar Pharmaceuticals); 0 (CT-P13); 0 (Cytokines); 0 (Gastrointestinal Agents); 0 (Tumor Necrosis Factor-alpha); B72HH48FLU (Infliximab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/ecco-jcc/jjw183


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[PMID]:28453755
[Au] Autor:Davidov Y; Ungar B; Bar-Yoseph H; Carter D; Haj-Natour O; Yavzori M; Chowers Y; Eliakim R; Ben-Horin S; Kopylov U
[Ad] Endereço:Department of Gastroenterology, Sheba Medical Center, Tel-Aviv, Israel.
[Ti] Título:Association of Induction Infliximab Levels With Clinical Response in Perianal Crohn's Disease.
[So] Source:J Crohns Colitis;11(5):549-555, 2017 May 01.
[Is] ISSN:1876-4479
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response. Methods: Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study. Response was defined as cessation or significant improvement of fistula drainage. Patients with unavailable IFX level or ATI measurements and/or missing clinical follow-up at Week 14 were excluded. Results: A total of 36 patients with perianal fistulae were included; 25/36 [69.4%] responded to treatment by Week 14. The median induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were higher compared with those of the non-responders group [20/5.6 µg/mL, P = 0.0001; 13.3/2.55 µg/mL P = 0.0001; 4.1/0.14 µg/mL, P = 0.01]. On multivariate analysis, IFX leve at Weeks 2 and 6 were significantly associated with fistula response at Weeks 14 and 30. IFX drug levels of 9.25 µg/mL at Week 2 and 7.25 µg/mL at Week 6 were the best predictors of fistula response. Conclusion: High IFX trough levels during induction are associated with favorable fistula response to anti-TNF treatment. If validated in a larger prospective study, our findings may help guide anti-TNF treatment in patients with perianal CD, and suggest serum level-guided treatment escalation in non-responders or prompt changing of biologic treatment in non-responders.
[Mh] Termos MeSH primário: Doença de Crohn/tratamento farmacológico
Fármacos Gastrointestinais/uso terapêutico
Infliximab/uso terapêutico
Fístula Retal/etiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Doença de Crohn/complicações
Feminino
Fármacos Gastrointestinais/administração & dosagem
Fármacos Gastrointestinais/sangue
Seres Humanos
Infliximab/administração & dosagem
Infliximab/sangue
Masculino
Fístula Retal/tratamento farmacológico
Estudos Retrospectivos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Gastrointestinal Agents); B72HH48FLU (Infliximab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/ecco-jcc/jjw182


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[PMID]:29295985
[Au] Autor:Conrad C; Di Domizio J; Mylonas A; Belkhodja C; Demaria O; Navarini AA; Lapointe AK; French LE; Vernez M; Gilliet M
[Ad] Endereço:Department of Dermatology, University Hospital CHUV, Lausanne, 1011, Switzerland. curdin.conrad@chuv.ch.
[Ti] Título:TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.
[So] Source:Nat Commun;9(1):25, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Autoimunidade/imunologia
Interferon Tipo I/imunologia
Psoríase/imunologia
Fator de Necrose Tumoral alfa/imunologia
[Mh] Termos MeSH secundário: Adalimumab/efeitos adversos
Adalimumab/imunologia
Adalimumab/uso terapêutico
Adolescente
Adulto
Idoso
Animais
Anticorpos Monoclonais/efeitos adversos
Anticorpos Monoclonais/uso terapêutico
Autoimunidade/efeitos dos fármacos
Células Cultivadas
Doença de Crohn/tratamento farmacológico
Doença de Crohn/imunologia
Doença de Crohn/metabolismo
Citocinas/genética
Citocinas/imunologia
Citocinas/metabolismo
Células Dendríticas/efeitos dos fármacos
Células Dendríticas/imunologia
Células Dendríticas/metabolismo
Feminino
Seres Humanos
Infliximab/efeitos adversos
Infliximab/imunologia
Infliximab/uso terapêutico
Interferon Tipo I/genética
Interferon Tipo I/metabolismo
Masculino
Camundongos Endogâmicos BALB C
Meia-Idade
Psoríase/induzido quimicamente
Linfócitos T/efeitos dos fármacos
Linfócitos T/imunologia
Linfócitos T/metabolismo
Fator de Necrose Tumoral alfa/antagonistas & inibidores
Fator de Necrose Tumoral alfa/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Cytokines); 0 (Interferon Type I); 0 (Tumor Necrosis Factor-alpha); B72HH48FLU (Infliximab); FYS6T7F842 (Adalimumab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02466-4


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[PMID]:28468639
[Au] Autor:Sasajima H; Yagi S; Osada H; Zako M
[Ad] Endereço:Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi, Japan.
[Ti] Título:Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.
[So] Source:J Med Case Rep;11(1):124, 2017 May 04.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. CASE PRESENTATION: A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. CONCLUSIONS: Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.
[Mh] Termos MeSH primário: Síndrome de Behçet/tratamento farmacológico
Toxinas Botulínicas/efeitos adversos
Hiperidrose/tratamento farmacológico
Infliximab/administração & dosagem
Neurotoxinas/administração & dosagem
Uveíte/induzido quimicamente
[Mh] Termos MeSH secundário: Seres Humanos
Injeções Subcutâneas
Masculino
Meia-Idade
Tomografia de Coerência Óptica
Uveíte/diagnóstico por imagem
Uveíte/tratamento farmacológico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotoxins); B72HH48FLU (Infliximab); EC 3.4.24.69 (Botulinum Toxins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s13256-017-1288-1


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[PMID]:28459157
[Au] Autor:Ozer EK; Goktas MT; Kilinc I; Toker A; Bariskaner H; Ugurluoglu C; Iskit AB
[Ad] Endereço:a Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, Turkey.
[Ti] Título:Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats.
[So] Source:Can J Physiol Pharmacol;95(7):866-872, 2017 Jul.
[Is] ISSN:1205-7541
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.
[Mh] Termos MeSH primário: Aorta/efeitos dos fármacos
Circulação Sanguínea/efeitos dos fármacos
Infliximab/farmacologia
Mesentério/irrigação sanguínea
Insuficiência de Múltiplos Órgãos/complicações
Sepse/mortalidade
Sepse/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Aorta/fisiopatologia
Feminino
Interleucina-6/metabolismo
Contração Muscular/efeitos dos fármacos
Músculo Liso Vascular/efeitos dos fármacos
Músculo Liso Vascular/fisiopatologia
Ratos
Ratos Wistar
Sepse/complicações
Sepse/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-6); B72HH48FLU (Infliximab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1139/cjpp-2016-0628


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[PMID]:29390339
[Au] Autor:Chen Y; Shen Y; Ma HF; Cai JF; Hua YQ; Zou J; Guan JL
[Ad] Endereço:Rheumatology and Immunology Department.
[Ti] Título:Infliximab associated with life-threatening lung infection in a patient with Behcet disease with intestinal and hematopoietic system involvement: A case report.
[So] Source:Medicine (Baltimore);96(50):e9202, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Tumor necrosis factor (TNF-α) participates in the pathophysiology of Behcet's disease (BD) and myelodysplastic syndrome (MDS). Infliximab is recommaned for the most severe type of BD, however, there is little evidence for its effectiveness in BD associated MDS. PATIENT CONCERNS: A 46-year-old female, initially diagnosed with intestinal BD and leukopenia was later diagnosed as MDS. Treatement with infliximab and other immunoregulators lead to life-threatening pneumonia. DIAGNOSIS: Intestinal BD associated with MDS involving trisomy 8. INTERVENTIONS: The patient initially treated with methylprednisolone, thalidomide, cyclosporine A, and infliximab, which lead to severe lung infection. Therefore, the patient was transferred to Intensive Care Unit for life supportive, anti-infection and immune improving therapy. OUTCOMES: The patient survived from the lung infection. With combination of methylprednisolone, thalidomide and cyclosporine A, the patient recovered from her intestinal ulceration and MDS manifestations. LESSONS: Infliximab treatment may not benefit a patient with BD associated with MDS but place the patient at risk of infection.
[Mh] Termos MeSH primário: Antirreumáticos/efeitos adversos
Antirreumáticos/uso terapêutico
Síndrome de Behçet/complicações
Síndrome de Behçet/tratamento farmacológico
Infliximab/efeitos adversos
Infliximab/uso terapêutico
Síndromes Mielodisplásicas/tratamento farmacológico
Síndromes Mielodisplásicas/etiologia
Pneumonia/induzido quimicamente
[Mh] Termos MeSH secundário: Ciclosporina/uso terapêutico
Feminino
Glucocorticoides/uso terapêutico
Seres Humanos
Imunossupressores/uso terapêutico
Metilprednisolona/uso terapêutico
Meia-Idade
Talidomida/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antirheumatic Agents); 0 (Glucocorticoids); 0 (Immunosuppressive Agents); 4Z8R6ORS6L (Thalidomide); 83HN0GTJ6D (Cyclosporine); B72HH48FLU (Infliximab); X4W7ZR7023 (Methylprednisolone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009202


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[PMID]:29269695
[Au] Autor:Hamada K; Takei R; Sakiyama Y; Moriyama H; Hashiguchi A; Takashima H
[Ad] Endereço:Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences.
[Ti] Título:[A case of chronic progressive neuro-Behçet disease with extensive cerebral atrophy and elevated CSF IL-6 activity treated with infliximab].
[So] Source:Rinsho Shinkeigaku;58(1):30-34, 2018 Jan 26.
[Is] ISSN:1882-0654
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:A 43-year-old man without a previous episode of uveitis presented with slowly progressive neurological symptoms that appeared within the past year such as dysarthria, ataxic gait, and behavioral changes. Brain MRI findings showed atrophic lesions in the brainstem and cerebellum. Because these clinical symptoms and abnormal MRI findings indicated spinocerebellar degeneration as the initial diagnosis, he was admitted to our hospital. On admission, we noticed that he had non-neurological manifestations of Behçet disease, such as stomatitis, genital ulcers, and folliculitis. HLA-B51 was positive. He also showed pleocytosis (29 cells/mm , predominantly mononuclear cells) and elevated cerebrospinal fluid (CSF) IL-6 levels (213 pg/ml), hence he was diagnosed with chronic progressive neuro-Behçet disease (CPNBD). The therapeutic effect of a high-dose intravenous methylprednisolone pulse (1,000 mg/day for 3 days) and methotrexate (maximum dosage, 16 mg/week) was poor against both neurological symptoms and CSF findings. Intravenous infliximab therapy (5 mg/kg, 2 weeks) dramatically decreased CSF IL-6 levels (13 pg/ml) but clinical symptoms remained unchanged. MRI findings of extensive cerebral atrophy and increased CSF IL-6 levels at the pretreatment time point reflected irreversible neurological involvement in CPNBD. For cases with progressive psychiatric symptoms and cerebellar ataxia in the early stage of the disease, skin manifestations should be examined immediately, CSF IL-6 levels measured, and immunosuppressive therapy initiated before CPNBD progresses to brainstem atrophy.
[Mh] Termos MeSH primário: Síndrome de Behçet/diagnóstico
Síndrome de Behçet/tratamento farmacológico
Encéfalo/patologia
Infliximab/administração & dosagem
Interleucina-6/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: Adulto
Atrofia
Síndrome de Behçet/líquido cefalorraquidiano
Síndrome de Behçet/patologia
Biomarcadores/líquido cefalorraquidiano
Doença Crônica
Progressão da Doença
Seres Humanos
Masculino
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Interleukin-6); B72HH48FLU (Infliximab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.5692/clinicalneurol.cn-001086


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[PMID]:29364909
[Au] Autor:de Bruyn JR; Becker MA; Steenkamer J; Wildenberg ME; Meijer SL; Buskens CJ; Bemelman WA; Löwenberg M; Ponsioen CY; van den Brink GR; D'Haens GR
[Ad] Endereço:Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
[Ti] Título:Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease.
[So] Source:PLoS One;13(1):e0190999, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. METHODS: In a previous trial, patients with ileocecal Crohn's disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). RESULTS: Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn's disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. DISCUSSION: Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn's disease.
[Mh] Termos MeSH primário: Doença de Crohn/tratamento farmacológico
Fármacos Gastrointestinais/uso terapêutico
Infliximab/uso terapêutico
Enteropatias/complicações
[Mh] Termos MeSH secundário: Adulto
Doença de Crohn/complicações
Doença de Crohn/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Feminino
Fibrose
Seres Humanos
Enteropatias/metabolismo
Enteropatias/patologia
Mucosa Intestinal/enzimologia
Masculino
Meia-Idade
Pró-Colágeno N-Endopeptidase/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Extracellular Matrix Proteins); 0 (Gastrointestinal Agents); B72HH48FLU (Infliximab); EC 3.4.24.14 (Procollagen N-Endopeptidase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190999


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[PMID]:28448562
[Au] Autor:Moots RJ; Xavier RM; Mok CC; Rahman MU; Tsai WC; Al-Maini MH; Pavelka K; Mahgoub E; Kotak S; Korth-Bradley J; Pedersen R; Mele L; Shen Q; Vlahos B
[Ad] Endereço:Aintree University Hospital, University of Liverpool, Liverpool, United Kingdom.
[Ti] Título:The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.
[So] Source:PLoS One;12(4):e0175207, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. METHODS: This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. RESULTS: Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. CONCLUSION: ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. TRIAL REGISTRATION: This study was registered on www.ClinicalTrials.gov (NCT01981473).
[Mh] Termos MeSH primário: Anticorpos/imunologia
Antirreumáticos/imunologia
Antirreumáticos/farmacologia
Artrite Reumatoide/tratamento farmacológico
Artrite Reumatoide/imunologia
[Mh] Termos MeSH secundário: Adalimumab/efeitos adversos
Adalimumab/imunologia
Adalimumab/farmacologia
Adalimumab/uso terapêutico
Antirreumáticos/uso terapêutico
Relação Dose-Resposta a Droga
Etanercepte/efeitos adversos
Etanercepte/imunologia
Etanercepte/farmacologia
Etanercepte/uso terapêutico
Feminino
Seres Humanos
Infliximab/efeitos adversos
Infliximab/imunologia
Infliximab/farmacologia
Infliximab/uso terapêutico
Internacionalidade
Masculino
Meia-Idade
Segurança
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Antirheumatic Agents); B72HH48FLU (Infliximab); FYS6T7F842 (Adalimumab); OP401G7OJC (Etanercept)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175207


  10 / 8650 MEDLINE  
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[PMID]:28817809
[Au] Autor:Ohem J; Hradsky O; Zarubova K; Copova I; Bukovska P; Prusa R; Malickova K; Bronsky J
[Ad] Endereço:Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles, University and Motol University Hospital, Prague, Czech Republic.
[Ti] Título:Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors.
[So] Source:Dig Dis;36(1):40-48, 2018.
[Is] ISSN:1421-9875
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. SUMMARY: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.
[Mh] Termos MeSH primário: Doença de Crohn/tratamento farmacológico
Infliximab/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Área Sob a Curva
Biomarcadores/metabolismo
Sedimentação Sanguínea
Proteína C-Reativa/metabolismo
Criança
Doença de Crohn/sangue
Fezes/química
Feminino
Seres Humanos
Inflamação/patologia
Infliximab/administração & dosagem
Complexo Antígeno L1 Leucocitário/metabolismo
Masculino
Curva ROC
Indução de Remissão
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Leukocyte L1 Antigen Complex); 9007-41-4 (C-Reactive Protein); B72HH48FLU (Infliximab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1159/000477962



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