Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.040
Filtrar
1.
Medicine (Baltimore) ; 99(2): e18723, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914087

RESUMO

Effectiveness, efficacy and safety of biosimilar infliximab (CT-P13) in inflammatory bowel disease (IBD) patients has been shown in previous studies. Limited data exist on health-related quality of life (HRQoL) of switching originator to biosimilar infliximab (IFX) in IBD patients. The objective of this study was to evaluate impact of switching originator to biosimilar IFX on HRQoL, disease activity, and health care costs in IBD maintenance treatment.In this single-center prospective observational study, all IBD patients receiving maintenance IFX therapy were switched to biosimilar IFX. HRQoL was measured using the generic 15D health-related quality of life instrument (15D) utility measurement and the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ). Crohn Disease Activity Index (CDAI) or Partial Mayo Score (pMayo), and fecal calprotectin (FC) served for evaluation of disease activity. Data were collected at time of switching and 3 and 12 months after switching. Patients' characteristics, clinical background information and costs were collected from patient records and the hospital's electronic database.Fifty-four patients were included in the analysis. No statistically significant changes were observed in 15D, CDAI, pMayo, and FC during 1-year follow-up. IBDQ scores were higher (P = .018) in Crohn disease 3 months after switching than at time of switching. Costs of biosimilar IFX were one-third of costs of originator one. Total costs related to secondary health care (excluding costs of IFX), were similar before and after the onset of biosimilar IFX.HRQoL and disease activity were after switching from originator to biosimilar IFX comparable, but the costs of biosimilar IFX were only one-third of those of the originator one.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Qualidade de Vida , Adulto , Anticorpos Monoclonais/economia , Medicamentos Biossimilares/economia , Substituição de Medicamentos/economia , Feminino , Fármacos Gastrointestinais/economia , Recursos em Saúde/economia , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Infliximab/economia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão
2.
Gut ; 69(2): 274-282, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31196874

RESUMO

OBJECTIVES: To better understand the real-world impact of biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs. DESIGN: We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition. RESULTS: Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18). CONCLUSIONS: Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Hospitalização/estatística & dados numéricos , Doenças Inflamatórias Intestinais/tratamento farmacológico , /uso terapêutico , Adulto , Colectomia/estatística & dados numéricos , Colectomia/tendências , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Custos de Medicamentos/estatística & dados numéricos , Custos de Medicamentos/tendências , Feminino , Hospitalização/tendências , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fatores Socioeconômicos
3.
Gut ; 69(1): 32-41, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30979718

RESUMO

INTRODUCTION: The optimal trial design for assessing novel therapies in paediatric IBD (PIBD) is a subject of intense ongoing global discussions and debate among the different stakeholders. However, there is a consensus that the current situation in which most medications used in children with IBD are prescribed as off-label without sufficient paediatric data is unacceptable. Shortening the time lag between adult and paediatric approval of drugs is of the upmost importance. In this position paper we aimed to provide guidance from the global clinical research network (Pediatric Inflammatory Bowel Disease Network, PIBDnet) for designing clinical trials in PIBD in order to facilitate drug approval for children. METHODS: A writing group has been established by PIBDnet and topics were assigned to different members. After an iterative process of revisions among the writing group and one face-to-face meeting, all statements have reached consensus of >80% as defined a priori. Next, all core members of PIBDnet voted on the statements, reaching consensus of >80% on all statements. Comments from the members were incorporated in the text. RESULTS: The commentary includes 18 statements for guiding data extrapolation from adults, eligibility criteria to PIBD trials, use of placebo, dosing, endpoints and recommendations for feasible trials. Controversial issues have been highlighted in the text. CONCLUSION: The viewpoints expressed in this paper could assist planning clinical trials in PIBD which are both of high quality and ethical, while remaining pragmatic.


Assuntos
Ensaios Clínicos como Assunto/métodos , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fatores Etários , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Criança , Ensaios Clínicos como Assunto/normas , Relação Dose-Resposta a Droga , Aprovação de Drogas/métodos , Fármacos Gastrointestinais/administração & dosagem , Humanos , Seleção de Pacientes , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento
4.
J Enzyme Inhib Med Chem ; 35(1): 1-20, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31619080

RESUMO

Inflammatory bowel disease (IBD) is a chronic immuno-inflammation in gastrointestinal tract. We have evaluated the activity of the compounds to inhibit the adhesion of monocytes to colon epithelial cells is triggered by a pro-inflammatory cytokine, tumour necrosis factor (TNF)-α. The in vitro activity of the compounds, 13b (an ureido-derivative), 14c, 14j, 14k, 14n (thioureido-), 18c and 18d (sulfonamido-), was in correlation with in vivo anti-colitis activity revealed as significant recovery in body- and colon-weights and colon myeloperoxidase level, a biochemical marker of inflammation reflecting neutrophil infiltration. In vivo, TNBS-induced changes in the expression of inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-10, and TGF-ß), NLRP3 inflammasome components (NLRP-3, Caspase-1, and IL-18), and epithelial junction molecules (E-cadherin, claudin2/3, and ZO-1) were blocked and recovered by oral administration of the compounds (1 mg/kg). Compound 14n which showed the best efficacy can be a promising lead for orally available therapeutics for pathology of IBD.


Assuntos
Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Piridinas/farmacologia , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Células Cultivadas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/patologia , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Ácido Trinitrobenzenossulfônico , Células U937
6.
Harefuah ; 158(11): 752-754, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721521

RESUMO

INTRODUCTION: TNFα antagonists, such as infliximab and adalimumab, are widely used for induction and maintenance of remission in pediatric patients with inflammatory bowel disease (IBD). Numerous studies in adult and pediatric patients have demonstrated that monitoring of anti-TNFα drug level improves various outcomes, especially in cases of primary non-response or loss-of-response. In this article we present the recommendations of the Israeli Pediatric Gastroenterology Association regarding measuring anti-TNFα drug and anti-drug levels in pediatric IBD patients. The recommendation to perform these studies will be provided only by a pediatric gastroenterologist based on clinical, laboratory, endoscopic or radiologic signs of active inflammation. We also recommend performing these studies once a year in patients with clinical and biochemical remission. We believe that implementing these recommendations will improve the care provided for pediatric patients with IBD.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Criança , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pacientes , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
Clin Biochem ; 74: 73-75, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669514

RESUMO

BACKGROUND: Infliximab (IFX) is a monoclonal antibody used to treat patients with inflammatory bowel disease (IBD). For IFX therapeutic drug monitoring (TDM), the most commonly used analysis is enzyme-linked immunosorbent assays (ELISA) which do not allow results to be provided in real-time. The aim of this study was to compare the in-house ELISA (Promonitor IFX) with the much faster assay Quantum Blue® IFX (QB) for quantification of serum IFX concentration among IBD patients in maintenance IFX therapy. METHODS: We studied 30 serum samples from outpatients in IFX maintenance therapy at Copenhagen University Hospital Hvidovre, Denmark. Samples were used to compare IFX measurements from Promonitor IFX with QB. Therapeutic intervals of <3 µg/mL, 3-7 µg/mL and >7 µg/mL were equally covered. Differences were evaluated using Bland-Altman plots and Student t-test. Correlation was evaluated using x,y-plot and Pearson's correlation coefficient. The intermediate imprecision (CV%) of QB was measured at two levels (3 µg/mL and 7 µg/mL). For qualitative comparison, weighted kappa statistics (κ) were determined after stratification of results by therapeutic interval. RESULTS: Promonitor IFX and QB were strongly correlated (r = 0.92, p < 0.001). The mean difference between Promonitor IFX and QB was -0.57 µg/mL (p = 0.2). The CV% of QB was 16.3% at 3 µg/mL and 16.7% at 7 µg/mL. Classification of results according to therapeutic interval showed almost perfect agreement (κ = 0.81). CONCLUSIONS: QB is a suitable alternative to Promonitor IFX for TDM in patients treated with IFX for IBD. The results revealed a strong correlation between methods, in particular at lower IFX concentrations, representing the most interesting clinical range. When the samples were stratified according to the therapeutic interval, an almost perfect agreement between the methods was observed.


Assuntos
Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Fármacos Gastrointestinais/sangue , Doenças Inflamatórias Intestinais/sangue , Infliximab/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Dinamarca , Fármacos Gastrointestinais/uso terapêutico , Hospitais Universitários , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pesquisa Qualitativa
9.
Surg Clin North Am ; 99(6): 1083-1094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676049

RESUMO

Patients with ulcerative colitis and Crohn's disease often present to surgery malnourished and on combination immunosuppression. These factors affect operation selection and postoperative outcomes. Corticosteroids have a well-established detrimental effect on postoperative outcomes, whereas the impact of biologic agents is more controversial. In a patient exposed to these medications, and in the presence of other risk factors, temporary intestinal diversion is likely the best choice. Enteral nutrition may help optimize malnourished patients at high risk of adverse postoperative outcomes.


Assuntos
Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Colectomia/métodos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Tomada de Decisão Clínica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Nutrição Enteral/métodos , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Desnutrição/terapia , Período Pré-Operatório , Prognóstico , Resultado do Tratamento
10.
Arq Gastroenterol ; 56(3): 318-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633732

RESUMO

BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Terapia Biológica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , América Latina , Revisão Sistemática como Assunto
11.
Postepy Biochem ; 65(3): 227-230, 2019 10 01.
Artigo em Polonês | MEDLINE | ID: mdl-31643171

RESUMO

Inflammatory bowel diseases (IBD) are a group of diseases which concern an increasing number of patients and are more and more often recognized at a young age. Because of unknown etiology, IBD treatment involves mainly non-specific suppression of inflammatory condition and is based among others on steroids. Glucocorticosteroids display anti-inflammatory action by affecting the course of immune responses, but they also possess several side effects which manifest predominantly during a long-term therapy. These concern, among others the eye and manifest by impaired vision; if left untreated, can lead to blindness. The glucocorticosteroid induced cataract is one of the most common complications of treatment with glucocorticosteroids. In the absence of pharmacological options which have a protective effect, the glucocor­ticosteroid induced cataract is a major problem not only for patients but also clinicians and needs immediate solutions.


Assuntos
Catarata/induzido quimicamente , Catarata/complicações , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Catarata/prevenção & controle , Glucocorticoides/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia
12.
Fitoterapia ; 139: 104367, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629045

RESUMO

Ca2+-activated Cl- channels (CaCCs) wildly exist in many tissues which play an important role in ion transport and excitation conduction, especially fluid secretion and smooth muscle contraction in epithelial tissues. TMEM16A as a classic CaCC expresses in the intestine, and has become a potential target of intestinal physiological and pathological researches and therapeutic drug screening. In this study, we identified trans-δ-viniferin (TVN), a resveratrol dimmer, could inhibit TMEM16A activity in TMEM16A expressed FRT cells with IC50 of 19.7 µM, it also prevented Ca2+-activated Cl- current in HT-29 cells with IC50 of 4.65 µM and in colonic mucosa. In the mechanism studies, TVN showed no significant inhibition on CFTR and basal Na+/K+-ATPase in both intestinal epithelial cells and colonic tissues, except for inhibition of calcium concentration and Ca2+-activated K+ channel to some degree. In anti-diarrheal studies, TVN could effectively prevent diarrhea caused by rotavirus infection and reduce the pellet number in IBS-D mice. These physiological effects are at least partially attributed to the inhibitory effect of TVN on CaCC-mediated intestinal fluid secretion and the reduction of smooth muscle contraction force by inhibiting TMEM16A. Collectively, the present study identified a new pharmacological target of TVN which provided the theoretical basis for the application of TVN in the treatment of rotavirus-infected diarrhea and IBS-D.


Assuntos
Benzofuranos/farmacologia , Canais de Cloreto/antagonistas & inibidores , Diarreia/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Resorcinóis/farmacologia , Estilbenos/farmacologia , Animais , Cálcio/análise , Diarreia/virologia , Motilidade Gastrointestinal/efeitos dos fármacos , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Ratos , Rotavirus
13.
Medicine (Baltimore) ; 98(38): e17208, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567972

RESUMO

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case-control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Doenças Inflamatórias Intestinais/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Becaplermina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-6/sangue , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Receptores de Interleucina-1/sangue
14.
Harefuah ; 158(9): 571-575, 2019 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-31507106

RESUMO

INTRODUCTION: Infliximab is a protein with an anti TNF-α activity which is given in an intra-venous manner to treat inflammatory bowel disease and inflammatory joint disease. This treatment may cause infusion reaction events, but this may be prevented using treatment with pre-medication. OBJECTIVES: To assess the incidence of infusion reaction in patients with inflammatory bowel disease and patients with rheumatic disease who are treated with Infliximab, with or without corticosteroid premedication respectively. To determine whether premedication with corticosteroids decreases the incidence of infusion reactions. METHODS: We conducted a retrospective cohort study at the Soroka Medical Center that includes records from 92 patients treated with Infliximab: Group A includes 70 inflammatory joint disease patients who were not treated with hydrocortisone premedication and, group B includes 22 inflammatory bowel disease patients who were treated with hydrocortisone premedication. Incidence and severity of infusion reaction were assessed. RESULTS: The incidence of infusion reactions in the group which did not receive premedication was 26.1% (18/69), while in the group receiving premedication the incidence was 13.6% (3/22). Results are not statistically significant but reflect a trend. Most reactions occurred in the second treatment and most were of medium severity. CONCLUSIONS: The results seem to reflect a positive trend favoring the use of premedication with hydrocortisone before Infliximab infusion, especially given the minor side-effects of this treatment.


Assuntos
Corticosteroides/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Fator de Necrose Tumoral alfa , Humanos , Estudos Retrospectivos
15.
Praxis (Bern 1994) ; 108(12): 799-806, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31530124

RESUMO

From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases Abstract. Inflammatory bowel diseases (IBD) are frequently accompanied by non-inflammatory joint pain and inflammatory spondyloarthritides. Spondyloarthritides can restrict joint function and typically manifest with inflammatory back pain with nightly pain and morning stiffness that improves upon exercising. In other patients, small or large peripheral joints are predominantly involved. Treatment comprises pain medication including COX-II selective non-steroidal anti-inflammatory drugs (NSAID), since non-selective NSAID can aggravate IBD. For axial manifestations, physiotherapy and tumor necrosis factor (TNF) inhibitors are effective, while for peripheral manifestations steroid injections, sulfasalazine and TNF inhibitors are useful. Osteopenia and osteoporosis may result from inflammation, malabsorption and/or steroids. Long-lasting disease activity or steroid treatment should prompt osteoporosis screening. Adequate calcium and vitamin D intake must be ensured and treatment with bisphosphonates evaluated.


Assuntos
Doenças Inflamatórias Intestinais , Osteoporose , Espondilartrite , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
16.
Internist (Berl) ; 60(10): 1043-1058, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31501913

RESUMO

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor­α, interleukin-12 and -23; α4ß7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores ErbB/efeitos dos fármacos , Gastroenterologia , Humanos , Fatores Imunológicos/farmacologia , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
17.
Gastroenterology ; 157(5): 1338-1351.e8, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31401142

RESUMO

BACKGROUND & AIMS: Some patients develop anti-drug antibodies (ADAs), which reduce the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF), in the treatment of immune-mediated diseases, including inflammatory bowel diseases. ADAs arise inconsistently, and it is not clear what factors determine their formation. We investigated features of the immune system, the infliximab antibody, and its complex with TNF that might contribute to ADA generation. METHODS: C57BL/6 mice were given injections of infliximab and recombinant human TNF or infliximab F(ab')2 fragments. Blood samples were collected every 2-3 days for 2 weeks and weekly thereafter for up to 6 weeks; infliximab-TNF complexes and ADAs were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal biopsy and blood samples were obtained from patients having endoscopy who had received infliximab therapy for inflammatory bowel diseases; infliximab-TNF complexes were measured with ELISA. Infliximab-specific plasma cells were detected in patient tissue samples by using mass cytometry. We studied activation of innate immune cells in peripheral blood mononuclear cells (PBMCs) from healthy donors incubated with infliximab or infliximab-TNF complexes; toll-like receptors (TLRs) were blocked with antibodies, endocytosis was blocked with the inhibitor PitStop2, and cytokine expression was measured by real-time polymerase chain reaction and ELISAs. Uptake of infliximab and infliximab-TNF complexes by THP-1 cells was measured with confocal microscopy. RESULTS: Mice given increasing doses of infliximab produced increasing levels of ADAs. Blood samples from mice given injections of human TNF and infliximab contained infliximab-TNF complexes; complex formation was associated with ADA formation with an area under the curve of 0.944 (95% confidence interval, 0.851-1.000; P = .003). Intestinal tissues from patients, but not blood samples, contained infliximab-TNF complexes and infliximab-specific plasma cells. Incubation of PBMCs with infliximab-TNF complexes resulted in a 4.74-fold increase in level of interleukin (IL) 1ß (IL1B) messenger RNA (P for comparison = .005), increased IL1B protein secretion, and a 2.69-fold increase in the expression of TNF messenger RNA (P for comparison = 0.013) compared with control PBMCs. Infliximab reduced only IL1B and TNF expression. Antibodies against TLR2 or TLR4 did not block the increases in IL1B or TNF expression, but endocytosis was required. THP-1 cells endocytosed higher levels of infliximab-TNF complexes than infliximab alone. CONCLUSIONS: In mice, we found ADA formation to increase with dose of infliximab given and concentration of infliximab-TNF complexes detected in blood. Based on studies of human intestinal tissues and blood samples, we propose that infliximab-TNF complexes formed in the intestine are endocytosed by and activate innate immune cells, which increase expression of IL1B and TNF and production of antibodies against the drug complex. It is therefore important to optimize the infliximab dose to a level that is effective but does not activate an innate immune response against the drug-TNF complex.


Assuntos
Anticorpos/sangue , Fragmentos Fab das Imunoglobulinas/imunologia , Doenças Inflamatórias Intestinais/imunologia , Infliximab/imunologia , Intestinos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Estudos de Casos e Controles , Endocitose , Feminino , Humanos , Imunidade Inata , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Injeções Intravenosas , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Células THP-1 , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
18.
Pediatr Neonatol ; 60(4): 396-404, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409456

RESUMO

BACKGROUND: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis - inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children. METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia. RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived. CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Cirrose Hepática Biliar/etiologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Colangite Esclerosante/complicações , Colangite Esclerosante/fisiopatologia , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Progressão da Doença , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/fisiopatologia , Humanos , Hipertensão Portal/etiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Hepatopatias/etiologia , Transplante de Fígado , Malásia , Masculino , Estudos Retrospectivos , Singapura , Adulto Jovem
19.
Am J Health Syst Pharm ; 76(17): 1296-1304, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418790

RESUMO

PURPOSE: The development of a tool to measure medication safety, therapeutic efficacy, and other quality outcomes in patients receiving self-injectable biologic therapy for the management of inflammatory bowel disease (IBD) at a health-system specialty pharmacy is described. SUMMARY: Through a collaborative initiative by pharmacists, gastro-enterologists, and representatives of a pharmacy benefit manager and a pharmaceutical company, a set of clinical and specialty pharmacy quality measures was developed. The clinical measures are intended for use in assessing patient safety, disease status, treatment efficacy, and healthcare resource utilization during 3 assessments (pre-treatment, on-treatment, and longitudinal). The specialty pharmacy measures can be used to assess medication adherence, medication persistence, specialty pharmacy accreditation, and patient satisfaction. The proposed quality measures provide a foundation for evaluating the quality of IBD care and improving patient outcomes within a health-system specialty pharmacy. Future efforts to validate and implement the tool in clinical practice are planned. CONCLUSION: The proposed quality measures provide a foundation for future inquiry regarding the appropriateness and feasibility of integrating the measures into clinical care. Further work is needed to implement and validate these quality measures and determine their impact in optimizing health outcomes.


Assuntos
Produtos Biológicos/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Serviço de Farmácia Hospitalar/organização & administração , Autoadministração/normas , Terapia Biológica/métodos , Terapia Biológica/normas , Comportamento Cooperativo , Indústria Farmacêutica/organização & administração , Gastroenterologistas/organização & administração , Humanos , Farmacêuticos/organização & administração
20.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31443089

RESUMO

Crohn's Disease (CD), one of the types of inflammatory bowel disease, poses a significant challenge to modern healthcare. This condition severely impacts patients' quality of life, and its incidence is continuously rising. Despite constant research, current treatment options are limited and largely unsuccessful and result in serious side effects, therefore new therapy alternatives are needed. Liposomal formulation provides a new hope for disease management. In our study, we characterized the anti-inflammatory activity of mesalazine (5-ASA) and chlorogenic acid (CGA) encapsulated in liposomal formulation in the animal model of CD. Liposomes were obtained by thin film hydration method and characterized in terms of suspension stability and particle size and distribution. Colitis was induced in mice by intracolonic (i.c.) administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The effect of treatment with liposomal suspensions of 5-ASA and CGA was evaluated macroscopically and by measuring myeloperoxidase (MPO) activity. We observed that liposome-encapsulated 5-ASA (5 mg/kg), but not CGA (20 mg/kg) attenuated colitis as evidenced by a decreased macroscopic and microscopic scores. It may be hypothesized that the composition of liposomal lipid bilayer as well as the switch in macrophage populations leading to unfavorable accumulation of anti-inflammatory agents in the cells may underly the efficiency of obtained liposomes and need to be taken into consideration in further studies on drug delivery.


Assuntos
Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Lipossomos/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Mesalamina/química , Mesalamina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Qualidade de Vida , Ácido Trinitrobenzenossulfônico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA