Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 52
Filtrar
1.
Gastroenterology ; 165(4): 963-975.e5, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499955

RESUMO

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Doenças Inflamatórias Intestinais/patologia , Fator de Necrose Tumoral alfa , Terapia Biológica , Indução de Remissão
2.
Am J Gastroenterol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39298569

RESUMO

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.

3.
J Clin Gastroenterol ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39102457

RESUMO

GOALS: This study evaluated the real-world effectiveness and safety of vedolizumab versus adalimumab over 12 months of treatment in biologic-naive patients with Crohn's disease (CD), using data from the EVOLVE study. BACKGROUND: A comparison of vedolizumab and adalimumab may help to better position them in the therapeutic algorithm for moderate-to-severe CD. STUDY: Data were collected from medical records of patients with CD aged ≥18 years initiating treatment with adalimumab or vedolizumab between May 2014 and July 2017. Adjusted analyses were performed using inverse probability weighting to account for differences in baseline characteristics. Cumulative rates for clinical effectiveness outcomes and treatment persistence were estimated using Kaplan-Meier analyses. Disease-related exacerbations, serious adverse events (SAEs), and serious infections (SIs) were also assessed. RESULTS: Data from 218 vedolizumab- and 144 adalimumab-treated patients were analyzed. Adjusted cumulative rates of clinical remission were greater with vedolizumab than with adalimumab (66.3% vs. 46.4%; P=0.006). Probability of treatment persistence was higher with vedolizumab (89.3% vs. 77.5%; P=0.024); probabilities of clinical response (68.5% vs. 61.1%; P=0.586) and mucosal healing (67.7% vs. 56.0%; P=0.562) were similar. SAEs were less likely to occur with vedolizumab [hazard ratio, 0.45 (95% confidence interval, 0.22-0.93)]; however, the likelihood of SIs [0.27 (0.06-1.20)], CD exacerbations [0.91 (0.56-1.47)], and CD-related surgeries [1.55 (0.21-11.15)] was comparable between the 2 groups. CONCLUSIONS: In a real-world setting, biologic-naive patients with CD treated with vedolizumab demonstrated a greater likelihood of drug persistence and achieving clinical remission, with equivalent rates of response and mucosal healing versus adalimumab-treated patients.

4.
Curr Gastroenterol Rep ; 26(5): 145-156, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353899

RESUMO

PURPOSE OF REVIEW: Treatment of Inflammatory Bowel Diseases (IBD) is challenging; thus, the need for newer therapeutic options with an oral route of administration has led to the development of novel small molecules drugs (SMDs). We aim to highlight the most common Adverse events (AEs) associated with SMDs and recommendations on monitoring for AEs before and during treatment. RECENT FINDINGS: SMDs, such as Tofacitinib, a JAK inhibitor, have been associated with laboratory abnormalities, infections, and risk of thromboembolic events. Therefore, oral agents with greater selectivity in JAK inhibition, such as tofacitinib and upadacitinib, were later developed. Ozanimod and etrasimod, S1PR agonists, require closer safety profile monitoring by clinicians. Multiple therapies have been recently developed with variable efficacy. However, they have been associated with AEs, and some require close monitoring prior to and during therapy. Clinicians should highlight these adverse events to patients while reassuring the safety profile of these novel SMDs for IBD is favorable.


Assuntos
Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Administração Oral , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Monitoramento de Medicamentos/métodos , Pirimidinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis , Piperidinas
5.
Clin Gastroenterol Hepatol ; 21(11): 2908-2917.e10, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36280102

RESUMO

BACKGROUND AND AIMS: The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics. METHODS: This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs). RESULTS: A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 108 red blood cells (RBCs), and those receiving combination therapy with thiopurine or oral methotrexate had significantly higher infliximab concentrations when compared with monotherapy (median levels of 17.4 µg/mL on thiopurine with 6-TGN ≥146 pmol per 8 × 108 RBCs, 17.1 on methotrexate, and 3.9 on infliximab monotherapy; P = .001 for both comparisons). However, there was no association between the use of immunomodulators and 6-TGN concentrations with vedolizumab (median levels of 8.8 on thiopurine with 6-TGN ≥152 pmol per 8 × 108 RBCs, 6.8 on methotrexate, and 10.5 on vedolizumab monotherapy; P > .05 for both comparisons) or ustekinumab median concentrations (median levels of 5.0 on thiopurine with 6-TGN ≥154 pmol per 8 × 108 RBCs, 5.2 on methotrexate and 7.0 on ustekinumab monotherapy; P > .05 for both comparisons). Fourteen (12%) patients had anti-infliximab antibodies, while 1 patient had ADAs in each of the other drug cohorts. CONCLUSIONS: Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.


Assuntos
Azatioprina , Doenças Inflamatórias Intestinais , Humanos , Infliximab/uso terapêutico , Azatioprina/uso terapêutico , Ustekinumab/uso terapêutico , Mercaptopurina , Metotrexato/uso terapêutico , Estudos Prospectivos , Fatores Imunológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Imunossupressores/uso terapêutico
6.
Am J Gastroenterol ; 118(11): 2005-2013, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37207314

RESUMO

INTRODUCTION: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD. METHODS: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement. RESULTS: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per µg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001). DISCUSSION: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission.


Assuntos
Doenças Inflamatórias Intestinais , Gordura Intra-Abdominal , Humanos , Infliximab/uso terapêutico , Estudos Transversais , Estudos Prospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Indução de Remissão
7.
Gastroenterol Hepatol ; 46(2): 139-147, 2023 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36243253

RESUMO

The prevalence of inflammatory bowel disease (IBD) continues to rise around the globe. Although the percentage of pediatric IBD patients seems to be increasing, rates are surprisingly heterogeneous among different populations. Although the pathogenesis of IBD is believed to be multifactorial, a genetic predisposition may be especially relevant in pediatric-onset IBD. Phenotypic characteristics can also be significantly different when comparing pediatric and adult-onset IBD. Patients that develop the disease at a younger age usually present with more extensive and more aggressive disease and develop complications faster when compared to those that develop it during adulthood. Children with IBD are found to have frequent mood disorders and have a higher risk of developing socio-economic hardship, failing to meet development milestones. Therefore, IBD management should always involve a multidisciplinary team that is not limited to medical providers. Most institutions do not have an established transition protocol and lack the resources and training for transition care. Although there is no consensus on an optimal timing to transition the patient's care to an adult team, it is usually accepted they should be eligible for adult care when most of the key transition points have been met. Management strategies should be tailored to each patient's developmental level and environment. A successful transition can improve the long-term outcomes such as sustained remission, medication adherence, mental health and social and academic performance, while decreasing healthcare utilization. Every institution that manages pediatric IBD patients should have a well-established transition protocol in order to make sure to maintain continuity of care.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Cuidado Transicional , Adulto , Humanos , Criança , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/complicações
8.
Am J Gastroenterol ; 117(8): 1288-1295, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35416799

RESUMO

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Assistência ao Convalescente , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/patologia , Hospitais , Humanos , Metilprednisolona/uso terapêutico , Alta do Paciente , Inibidores do Fator de Necrose Tumoral
9.
Curr Opin Gastroenterol ; 38(4): 328-336, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35762692

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to highlight new and emerging therapies in inflammatory bowel disease (IBD) and provide insight on how these therapies can be integrated into clinical practice. RECENT FINDINGS: The article covers clinical and real-world data for Janus kinase inhibitors, anti-interleukin antibodies, sphingosine-1-phosphate receptor modulators, and anti-integrin therapies. It also explores the potential role of antifibrotic agents, microbiota-based innovations, and for personalized medicine in IBD. SUMMARY: The treatment of IBD has evolved significantly in the last two decades, with a host of new treatment options available and arising for patients. With these advancements, positioning these drugs in a treatment algorithm to create a more personalized approach to improve efficacy and prognosis is critical.


Assuntos
Doenças Inflamatórias Intestinais , Microbiota , Algoritmos , Doença Crônica , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Medicina de Precisão
10.
Am J Gastroenterol ; 116(10): 2014-2025, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34388143

RESUMO

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1-10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10-15 µg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti-tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti-tumor necrosis factors.


Assuntos
Produtos Biológicos/uso terapêutico , Monitoramento de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Atitude do Pessoal de Saúde , Consenso , Técnica Delphi , Humanos , Padrões de Prática Médica
11.
Dig Dis Sci ; 66(10): 3563-3569, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33089483

RESUMO

BACKGROUND: The aim of this study was to assess the relationship between serum vedolizumab (VDZ) concentrations and antibodies to VDZ (ATV) in a large cohort of patients with inflammatory bowel diseases. Furthermore, we evaluated the association between serum VDZ concentrations and a novel serum-based biomarker panel designated as the endoscopic healing index (EHI), developed and validated for identifying mucosal inflammation in patients with Crohn's disease (CD). METHODS: Retrospective study where results from patient samples submitted to a commercial clinical laboratory were included. Serum VDZ and ATV levels were analyzed using a drug-tolerant assay. In CD patients for whom both VDZ and EHI were available, VDZ concentrations were correlated with EHI. serum VDZ threshold analysis was performed using ROC curves, and the serum VDZ concentrations that best differentiated EHI < 20 (previously associated with endoscopic remission) were chosen. RESULTS: A total of 9356 patients were included in the VDZ/ATV analysis. Detectable ATV was observed in 2.9% patients with significantly lower serum VDZ concentrations when compared to those with undetectable ATV [3.9 µg/mL (0-9.0) vs. 11.3 µg/mL (5.9-20.6), p < 0.0001]. Of the patients with serum VDZ result, 287 patients had a concomitant EHI test. An inverse correlation was observed between VDZ concentration and EHI (rho = - 0.20, p < 0.001). A serum VDZ concentration ≥ 15.7 µg/ml was best correlated wi th an EHI < 20 [AUROC: 0.67 (95% CI 0.57-0.77)]. CONCLUSIONS: Incidence of ATVs was low, but significantly associated with lower VDZ levels. A serum VDZ concentration threshold of ≥ 15.7 µg/ml was associated with endoscopic remission as defined by an EHI < 20.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos/sangue , Fármacos Gastrointestinais/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/sangue , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/sangue , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
12.
Gastroenterology ; 166(2): 357-358, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37952900
14.
J Clin Gastroenterol ; 53(3): 210-215, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29517712

RESUMO

BACKGROUND: A significant number of patients receiving therapy with antitumor necrosis factor (TNF) agents for Crohn's disease experience primary or secondary nonresponse. The aim of this study was to assess whether patients with nonresponse to anti-TNF agents have increased expression of alternative cytokine pathways. METHODS: We designed a prospective, cross-sectional study that included patients with Crohn's disease receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 µg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin (IL)-8, IL-1ß, and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least 1 ulceration ≥5 mm. RESULTS: In total, 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1ß when compared with those without intestinal inflammation (45.9 vs. 35.8 ng/mL, P<0.0001 and 3.2 vs. 1.5 pg/mL, P=0.002, respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1ß had a good correlation (receiver operating characteristic ≥0.8) with inflammation in this cohort of patients with "anti-TNF resistance." The results were similar in the group of patients with previous anti-TNF exposure. CONCLUSION: Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of nonresponse as well as potential targets of therapy in anti-TNF nonresponders.


Assuntos
Doença de Crohn/tratamento farmacológico , Citocinas/metabolismo , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Doença de Crohn/fisiopatologia , Estudos Transversais , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/farmacocinética , Adulto Jovem
15.
Dig Dis Sci ; 64(6): 1651-1659, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30835029

RESUMO

BACKGROUND: The aim of this study was to assess the relationship of serum vedolizumab concentrations (SVC) during induction and endoscopic remission in patients with inflammatory bowel diseases (IBD) after 52 weeks of therapy with vedolizumab. We also sought to assess the incidence of antibody to vedolizumab (ATV) formation, the effect of ATV on drug pharmacokinetics and efficacy, and identify variables associated with SVC through the first 30 weeks of treatment. METHODS: This is a prospective cohort study of patients with active IBD initiating standard therapy with vedolizumab. Collected variables included demographics, clinical disease activity, biomarkers, pre-infusion SVC, and ATV measured at weeks 2, 6, 14, 22, and 30. Primary outcome was steroid-free endoscopic remission at week 52. RESULTS: Fifty-five patients were included. Patients that achieved steroid-free endoscopic remission by week 52 had higher SVC at weeks 2, 6, 14, 22, and 30, but only achieved statistical significance at weeks 2 and 6. Only 3 out of the 55 study subjects (5.5%) had detectable ATV through the follow-up. Overall, there were a positive correlation between SVC and serum albumin and a negative correlation with C-reactive protein, fecal calprotectin, and body mass. Vedolizumab concentrations ≥ 23.2 mcg/ml at week 2 were associated with endoscopic remission at week 52 (OR 8.8 [95% CI 2.6-29.7], p < 0.001). CONCLUSIONS: Vedolizumab concentrations during induction were associated with endoscopic remission at week 52. Interventional studies looking into improved efficacy with higher drug exposure are warranted.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos , Fármacos Gastrointestinais/farmacocinética , Adulto , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Neutralizantes/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Quimioterapia Combinada , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/antagonistas & inibidores , Fármacos Gastrointestinais/sangue , Fármacos Gastrointestinais/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Esteroides/uso terapêutico , Resultado do Tratamento
16.
Dig Dis Sci ; 64(12): 3674-3675, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31642007

RESUMO

The original version of the article unfortunately contained a couple of errors. In 'methods' section, in 'Outcomes' subsection, the sentence 'Endoscopic remission was defined as an SESCD ≤ 2 in patients with CD and an EMS ≤ 2 in UC patients while off corticosteroids.'

17.
Am J Gastroenterol ; 118(12): 2309-2310, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38033232
18.
J Clin Gastroenterol ; 52(6): 537-544, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28723860

RESUMO

GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured. Predictive variables included demographics, disease phenotype, 6-TGN levels (nadir, median, and peak levels). The primary outcome was the development of a disease relapse. The secondary outcome was the need for IBD surgery. RESULTS: Two hundred eighteen 6-TGN samples from 87 patients were analyzed. Nadir and median 6-TGN levels were significantly higher in patients who did not relapse [185 and 233 pmol per 8×10 red blood cells (RBCs)] as compared with levels in patients who did relapse (150 and 167 pmol per 8×10 RBCs, P=0.025) but there was no significant difference in peak 6-TGN level. When adjusted for confounding factors, a nadir 6-TGN level ≥161 and a median 6-TGN level ≥264 were associated with a significant decrease in the rate of disease exacerbation (hazard ratio: 0.5; 95% confidence interval, 0.26-0.87; P=0.016 and hazard ratio: 0.4; 95% confidence interval, 0.2-0.82; P=0.14). CONCLUSIONS: Serial thiopurine metabolite level assessments and dose adjustment aiming to maintain higher 6-TGN levels may be helpful to improve long-term outcomes in patients with IBD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/uso terapêutico , Nucleotídeos de Guanina/sangue , Mercaptopurina/uso terapêutico , Tionucleotídeos/sangue , Adulto , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto Jovem
19.
Gut ; 65(2): 249-55, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25670812

RESUMO

OBJECTIVE: The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. DESIGN: Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. RESULTS: There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03). CONCLUSIONS: Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.


Assuntos
Adalimumab/análise , Doenças Inflamatórias Intestinais/sangue , Infliximab/análise , Fator de Necrose Tumoral alfa/análise , Adalimumab/sangue , Estudos Transversais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/sangue , Mucosa Intestinal/química , Fator de Necrose Tumoral alfa/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA