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1.
Dig Liver Dis ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281870

RESUMO

BACKGROUND: Data on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited. AIMS: To evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent. METHODS: In this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14. RESULTS: Overall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5-8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06-7.54], p = 0.037) and W52(OR=2.68[1.16-6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14-0.98], p = 0.046). After a median follow-up of 20.9 months[11.7-33.7]), 50.0%(52/104) patients had discontinued infliximab. CONCLUSION: Infliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant.

2.
Aliment Pharmacol Ther ; 59(4): 526-534, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38037279

RESUMO

BACKGROUND: The long-term risk of relapse after switching from intravenous (IV) to subcutaneous (SC) infliximab remains unknown in inflammatory bowel disease (IBD). AIMS: To assess the long-term effectiveness and acceptability of switching from IV to SC infliximab in patients with IBD treated with or without an intensified IV regimen. METHODS: We extended the follow-up of the REMSWITCH study including patients with IBD in clinical remission who were switched from IV to SC infliximab (120 mg/2 weeks). Relapse was defined as clinical relapse or faecal calprotectin increase ≥150 µg/g compared to baseline. RESULTS: After median follow-up of 18 [15-20] months, among 128 patients, rates of relapse were 13.8% (8/58), 18.4% (7/38), 35.3% (6/17) and 86.7% (13/15) at last follow-up (p < 0.001), in those receiving 5 mg/kg/8 weeks, 10 mg/kg/8 weeks, 10 mg/kg/6 weeks and 10 mg/kg/4 weeks at baseline, respectively. Among relapsing patients, dose escalation led to clinical remission in 82.1% (23/28). In multivariable analyses, factors associated with higher risk of relapse were IV infliximab 10 mg/kg/4 weeks (OR = 61.0 [6.1-607.0], p < 0.001) or 10 mg/kg/6 weeks (OR = 4.7 [1.1-20.2], p = 0.017), and decreased (OR = 5.6 [1.5-20.3], p = 0.004) or stable (OR = 5.0 [1.6-15.0], p = 0.009) serum levels of infliximab between baseline and first post-switch visit. Acceptability was improved at 6 months and did not decrease over time (6.9 ± 1.6 before the switch vs. 8.8 ± 1.3 at 6 months and 8.8 ± 1.3 at last follow-up; p < 0.001). No severe adverse events were reported. CONCLUSIONS: Switching from IV to SC infliximab 120 mg every other week is safe and well accepted leading to low long-term risk of relapse. Tight monitoring and dose escalation should be recommended for patients receiving 10 mg/kg/6 weeks and 4 weeks, respectively.


Assuntos
Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Humanos , Medicamentos Biossimilares/uso terapêutico , Fármacos Gastrointestinais , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Infliximab/efeitos adversos , Recidiva , Fatores de Tempo , Resultado do Tratamento
3.
ESMO Open ; 8(5): 101628, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37713929

RESUMO

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Laboratórios , Estudos Retrospectivos , Pandemias , Mutação , Receptores ErbB/genética , Europa (Continente)
4.
Gynecol Obstet Fertil Senol ; 50(2): 201-204, 2022 02.
Artigo em Francês | MEDLINE | ID: mdl-34403829

RESUMO

Buschke Lownestein's tumour is a giant acuminate condyloma characterised by its degenerative potential, its invasive nature and its recurrence after treatment. It is a rare condition, transmitted mainly by sexual transmission and induced by to the human papillomavirus (HPV). The discussion will be illustrated by a clinical case The treatment is still under discussion but surgery seems to be the best option. Management during pregnancy is more complex since it must take into account the mother and her fetus. The delivery route is still debated. The post-treatment evolution was satisfactory and without recurrence until the delivery which, due to the antecedent of 3 caesarean sections, was carried out by cesarean section. HPV vaccination, sex education and early treatment of condyloma lesions should prevent and in any case improve the prognosis of this disease.


Assuntos
Tumor de Buschke-Lowenstein , Condiloma Acuminado , Tumor de Buschke-Lowenstein/patologia , Tumor de Buschke-Lowenstein/cirurgia , Cesárea , Condiloma Acuminado/patologia , Condiloma Acuminado/cirurgia , Feminino , Humanos , Papillomaviridae , Gravidez
5.
J Crohns Colitis ; 15(6): 1000-1008, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-33313808

RESUMO

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.


Assuntos
Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Intestinos , Técnica Delphi , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/normas , Endoscopia Gastrointestinal/estatística & dados numéricos , Humanos , Intestinos/diagnóstico por imagem , Intestinos/patologia , Microscopia de Vídeo/métodos , Variações Dependentes do Observador , Melhoria de Qualidade , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Terminologia como Assunto
6.
J Crohns Colitis ; 14(11): 1524-1534, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-32533769

RESUMO

BACKGROUND: Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn's disease [CD]. AIMS: We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. METHODS: All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn's Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52. RESULTS: Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7-34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3-13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > -30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0-0.9]; p = 0.037). CONCLUSION: Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.


Assuntos
Adalimumab , Doença de Crohn , Infliximab , Mucosa Intestinal , Imageamento por Ressonância Magnética/métodos , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Biomarcadores Farmacológicos/análise , Proteína C-Reativa/análise , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/fisiopatologia , Estudos de Viabilidade , Feminino , França/epidemiologia , Humanos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão/métodos , Índice de Gravidade de Doença , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos
7.
J Hosp Infect ; 103(3): 251-258, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31233849

RESUMO

BACKGROUND: Antimicrobial misuse leading to drug resistance is a growing concern for clinicians. Improving antimicrobial stewardship programmes through development of new tools could be part of the solution. AIM: To evaluate antimicrobial use in hospitalized patients after implementation of an antimicrobial checklist for ward-based clinical pharmacists. METHODS: A checklist based on quality indicators of optimal antimicrobial use was implemented to standardize hospital pharmacists' assessments of antimicrobial therapy. Antimicrobial use metrics from adults hospitalized during the control and intervention periods were assessed in an interrupted time series analysis of individual patient data. The primary endpoint was days of therapy (DOT) for all antimicrobials per 1000 days present for included patients. Secondary endpoints were the DOT of extended-spectrum antimicrobials (DOT-ES), length of therapy of all antimicrobials (LOT) and the number of pharmacist interventions. FINDINGS: One-thousand six-hundred and nineteen patients were included: 800 and 819 in the pre- and post-checklist implementation periods, respectively. As indicated by the point estimates and their 95% confidence intervals (CIs), there were no changes in trend for DOT, DOT-ES or LOT. A change in level was not found for the DOT, while a change of -118 DOT-ES [-209,-28] and -51 LOT [-97,-4] was documented. Furthermore, pharmacists' interventions regarding antimicrobials increased by 18.7% (14.0, 23.5) and progress notes by 32.3% (27.8, 36.8). CONCLUSION: An antimicrobial checklist used by ward-based clinical pharmacists did not decrease DOT for all antimicrobials, but decreased DOT-ES and LOT upon its implementation.


Assuntos
Anti-Infecciosos/uso terapêutico , Gestão de Antimicrobianos/métodos , Lista de Checagem , Uso de Medicamentos/estatística & dados numéricos , Farmacêuticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais , Humanos , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Adulto Jovem
9.
Encephale ; 45(4): 327-332, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-30879781

RESUMO

INTRODUCTION: Geriatrics Mobile Units are a new organisation operating in nursing homes. Their mission is to propose globally oriented neuro-psychiatric and geriatric care. The purpose of the study is to assess their activity and impact over a 21-month period. METHOD: A prospective single center study of UMNPG's data including intervention characteristics, patient characteristics, recommendations and reassessment after intervention. The Neuropsychiatric Inventory Nursing Home version (NPI-NH) was measured during intervention and reassessed after 30 days (Student's t-test). RESULTS: From March 2014 to December 2015, UMNPG conducted 288 interventions mainly for medical advices (81%), clinical assessments (54%) and health care team support (46%). The average age was 84.6±7.3years, 73.3% of whom were women. The patients were dependent (62% of GIR 1 or 2) with dementia (60%) and under several medications (83.7%). The symptoms were mainly agitation/aggression (76.4%), anxiety (75%), depression (66.7%), irritability (60.4%), aberrant motor behaviour (55.9%) and delusions (48.6%). The main proposals of UMNPG were a change in treatment (79.5%), a health care team support (85.4%) and hospitalization (8.4%). The rate of follow-up on recommendation was 83% on the 15th day and 80% on the 30th day. The rate of avoided hospitalizations was 16%. The average NPI-NH decreased (on day 0 NPI=50±19.2; on day 30 NPI=33.9±19.6, p<0.001). CONCLUSION: UMNPG-EHPAD intervenes for frail elderly residents with multiple disorders in crisis situations. Medical recommendations help to support people in nursing homes and decrease NPI-NH. UMNPG-EHPAD is part of geriatric network strengthening the city/hospital connection.


Assuntos
Psiquiatria Geriátrica/métodos , Psiquiatria Geriátrica/organização & administração , Serviços Hospitalares de Assistência Domiciliar , Unidades Móveis de Saúde , Casas de Saúde , Equipe de Assistência ao Paciente , Idoso , Idoso de 80 Anos ou mais , Procedimentos Clínicos , Demência/diagnóstico , Demência/psicologia , Demência/terapia , Feminino , França , Avaliação Geriátrica/métodos , Psiquiatria Geriátrica/normas , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Serviços Hospitalares de Assistência Domiciliar/normas , Humanos , Comunicação Interdisciplinar , Masculino , Unidades Móveis de Saúde/organização & administração , Unidades Móveis de Saúde/normas , Neuropsiquiatria/métodos , Neuropsiquiatria/organização & administração , Neuropsiquiatria/normas , Testes Neuropsicológicos , Casas de Saúde/organização & administração , Casas de Saúde/normas , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/normas , Estudos Prospectivos , Inquéritos e Questionários
10.
J Crohns Colitis ; 13(Supplement_1): S616, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30794285

RESUMO

doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section.

12.
Aliment Pharmacol Ther ; 47(5): 588-595, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29315694

RESUMO

BACKGROUND: Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM: To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS: Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION: In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.


Assuntos
Doença de Crohn/tratamento farmacológico , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos , Adulto , Estudos de Coortes , Doença de Crohn/epidemiologia , Resistência a Medicamentos/efeitos dos fármacos , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
13.
Aliment Pharmacol Ther ; 47(4): 485-493, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29250803

RESUMO

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Adolescente , Adulto , Artrite/epidemiologia , Artrite/etiologia , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , França/epidemiologia , Humanos , Inflamação/epidemiologia , Inflamação/etiologia , Doenças Inflamatórias Intestinais/epidemiologia , Pessoa de Meia-Idade , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Adulto Jovem
14.
Aliment Pharmacol Ther ; 46(11-12): 1077-1084, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29027693

RESUMO

BACKGROUND: Anti-tumour necrosis factor (TNF) agents have improved the care of Crohn's disease (CD). After the first anti-TNF discontinuation, it is possible to switch to another anti-TNF. Three anti-TNF agents are available for ulcerative colitis (infliximab, adalimumab and golimumab), but only the first 2 have been approved for CD because golimumab has not been studied for this indication. AIM: To report the efficacy and safety of golimumab in CD. METHODS: Crohn's disease patients who received golimumab were identified in 12 French tertiary centres and were retrospectively analysed. The primary endpoint was the duration of golimumab treatment before escalation or discontinuation. The clinical response was defined as a decrease of more than 3 points in the Harvey-Bradshaw index or by global physician assessment. RESULTS: One hundred and fifteen patients were included. The golimumab treatment duration was 9.8 months (0.55-44), and 48.7% of the patients were still under treatment at the end of follow-up. Clinical response was observed in 55.8% of the patients after a mean duration of 3.8 months. The probability of remaining under treatment without escalation at 6, 12 and 24 months was 54.6%, 34.9% and 19.3% respectively. In multivariate analysis, discontinuation of the first anti-TNF agent due to intolerance (odds ratio, OR = 2.16; 95% CI, confidence interval [1.25-3.86]; P = .005) and co-immunosuppression for more than 6 months (OR = 3.98; 95% CI [2.3-7.1]; P < .0001) were predictive factors of efficacy. Six per cent of the patients discontinued treatment due to intolerance. CONCLUSION: After failure of infliximab or adalimumab for Crohn's disease, golimumab was safe and seemed beneficial in half of the patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Ann Oncol ; 28(11): 2860-2865, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29045560

RESUMO

BACKGROUND: Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. METHODS: this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage). RESULTS: Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis. CONCLUSION: This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Gastroenteropatias/etiologia , Inflamação/etiologia , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Taxa de Sobrevida
16.
Aliment Pharmacol Ther ; 46(3): 310-321, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28593685

RESUMO

BACKGROUND: We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. AIMS: To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. METHODS: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. RESULTS: At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. CONCLUSION: Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Eur J Pain ; 21(9): 1550-1560, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28508514

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory conditions that predominately affect the gastrointestinal tract and can induce abdominal pain. Besides, many IBD patients complain about headaches in daily practice. The objective was to assess the prevalence of headaches, including migraines and pain with neuropathic characteristics (NC), in IBD patients compared to historical controls from the general population. METHODS: Overall, 203 consecutive tertiary-care centre patients completed validated self-administered questionnaires and benefitted from a clinical evaluation performed by an IBD physician at the same time. RESULTS: In our cohort, 75% of the patients experienced pain in the previous 3 months. Migraine prevalence was two-fold higher in IBD patients compared to the general population (41% vs. 21.3%, p < 0.001). Migraine was associated with a younger age, female gender and higher depression scores. Although migraine impact was very important for 30% of the patients (61/203), specific acute therapeutics were prescribed in only 22% of cases (18/83). Chronic pain with NC was more frequent than in the general population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the presence of extra-intestinal manifestations (p < 0.001). Abdominal pain concerned 19% of the patients during the previous week and was, as expected, associated with disease activity. CONCLUSIONS: Migraine prevalence is strongly increased in IBD patients followed in tertiary care. A systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics. Further studies are needed to confirm whether migraine should be classified as IBD extra-intestinal manifestations. SIGNIFICANCE: Migraine prevalence was two-fold higher in IBD patients compared to the general population, was generally poorly treated and a systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Centros de Atenção Terciária
18.
Aliment Pharmacol Ther ; 43(10): 1069-79, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26953251

RESUMO

BACKGROUND: Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). AIM: To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. METHODS: Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. RESULTS: In 54 Crohn's disease patients, faecal CHI3L1 (ρ = 0.70, P < 0.001) and calprotectin (ρ = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (ρ = 0.78 vs. ρ = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 µg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (ρ = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin>250 µg/g showing a sensitivity of 86.4% and a specificity of 80.0%. CONCLUSION: Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.


Assuntos
Adipocinas/análise , Fezes/química , Doenças Inflamatórias Intestinais/fisiopatologia , Lectinas/análise , Complexo Antígeno L1 Leucocitário/análise , Adulto , Biomarcadores , Proteína 1 Semelhante à Quitinase-3 , Colite Ulcerativa/fisiopatologia , Colonoscopia , Doença de Crohn/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Íleo , Mucosa Intestinal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Índice de Gravidade de Doença
19.
J Crohns Colitis ; 9(12): 1113-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26351383

RESUMO

BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 µg/g, 1251.0 µg/g, and 1800.0 µg/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 µg/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal ≥ 200 µg/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 µg/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface.


Assuntos
Colonoscopia , Doença de Crohn/diagnóstico , Fezes/química , Complexo Antígeno L1 Leucocitário/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Doença de Crohn/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Método Simples-Cego
20.
Aliment Pharmacol Ther ; 42(4): 452-60, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26088810

RESUMO

BACKGROUND: Magnetic resonance entero-colonography enables accurate assessment of ileocolonic Crohn's disease, but the need for bowel cleansing and rectal enema limits considerably its use in daily practice. AIM: We evaluated the accuracy of diffusion-weighted magnetic resonance entero-colonography with neither bowel cleansing nor rectal enema to assess endoscopic activity. METHODS: Forty-four Crohn's disease patients underwent prospectively and consecutively diffusion-weighted magnetic resonance entero-colonography [with apparent diffusion coefficient (ADC) and Clermont score calculation] and ileocolonoscopy [with Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simplified Endoscopic score for Crohn's Disease (SES-CD) calculation]. RESULTS: Mean ADC was inversely correlated with total CDEIS (ρ = -0.40; P = 0.0067) and total SES-CD (ρ = -0.33; P = 0.032). Considering the 194 segments, ADC was inversely correlated with segmental CDEIS (-0.48; P < 0.001) and segmental SES-CD (-0.44; P < 0.001). ADC values were lower in segments with deep ulcers (1.30 ± 0.23) or superficial ulcerations (1.75 ± 0.64) than in non-ulcerated segments (2.15 ± 0.5) (P = 0.001). Using a receiver operating curve, we determined that segmental ADC <1.42 detected endoscopic deep ulcerations with sensitivity = 0.91 and specificity = 0.83 (Area under the curve = 0.84; P < 0.001). Segmental ADC <1.88 detected endoscopic superficial ulcerations with sensitivity = 0.64 and specificity = 0.75. The segmental ADC values decreased when the ulcerations size increased (P = 0.0001). Clermont score correlated with ileal CDEIS (0.63; P < 0.05) and ileal SES-CD (0.58; P < 0.05). Clermont score was higher in ulcerated segments (23.3 ± 8.4) than in non-ulcerated segments (12.4 ± 10.0) (P = 0.006) and increased with ulcers size (P = 0.012). Clermont score >18.9 detected ulcerations with sensitivity = 0.79 and specificity = 0.73. CONCLUSION: Diffusion-weighted magnetic resonance entero-colonography using apparent diffusion coefficient and Clermont score was effective to indirectly detect endoscopic ulcerations in ileocolonic Crohn's disease.


Assuntos
Doença de Crohn/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Íleo/patologia , Intestinos/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Adulto Jovem
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