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1.
Clin Gastroenterol Hepatol ; 19(4): 668-679.e8, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32629124

RESUMO

BACKGROUND & AIMS: There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy. METHODS: In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2=13.9%; Q test P = .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2 = 11%; Q test P = .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2 = 0; Q test P=.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2 = 47%; Q test P = .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2 = 0; Q test P = .110). CONCLUSIONS: In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Produtos Biológicos/efeitos adversos , Humanos , Fatores Imunológicos/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Ustekinumab/efeitos adversos
2.
Clin Gastroenterol Hepatol ; 18(10): 2256-2261, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31743755

RESUMO

BACKGROUND & AIMS: Mucosal healing (MH) has been associated with good outcomes of patients with Crohn's disease (CD). It is not clear what levels of endoscopic healing, based on CD endoscopic index score (CDEIS), associate with different courses of disease progression. We assessed long-term outcomes of patients with CD according to different levels of MH. METHODS: We performed a retrospective study of 84 patients with CD and MH who received biologic therapy (80% with infliximab) from 2008 through 2015 at 2 university hospitals in France and compared outcomes of patients with CD endoscopic index scores (CDEISs) of 0 vs CDEISs greater than 0 but less than 4. Patients were followed until treatment failure or through June 2016. The primary outcome measure was treatment failure, defined by the need for biologic optimization, initiation of corticosteroids, or a Harvey-Bradshaw score above 4 associated with change in treatment, CD-related hospitalization, and/or intestinal resection. RESULTS: After a median follow-up time of 4.8 years (interquartile range, 2.1-7.2), 27 patients (32%) had treatment failure and 3 patients (3.6%) underwent an intestinal resection. Rates of treatment failure were 25% in patients with a CDEIS of 0 and 48% in patients with CDEISs greater than 0 but less than 4 (P = .045). Median times to treatment failure were 21 months (interquartile range, 5-43 months) in patients with a CDEIS of 0 and 13 months (interquartile range, 3.6-35 months) in patients with CDEISs greater than 0 but less than 4 (P = .047). None of the patients with a CEDIS of 0 underwent intestinal resection whereas 11% patients with CDEISs greater than 0 but less than 4 required intestinal resection (P = .031). Patients with a CDEIS of 0 also had a significant lower rate of CD-related hospitalizations than patients with CDEISs greater than 0 but less than 4 (3.5% vs 18%; P = .013). In multivariate analysis, CDEISs greater than 0 but less than 4 (vs CDEIS = 0) was the only factor associated with treatment failure (hazard ratio, 2.6; 95% CI, 1.2-5.8; P = .02). CONCLUSIONS: Complete endoscopic healing (CDEIS = 0) is associated with better long-term outcomes than partial endoscopic healing (CDEIS = 1-4) in patients with CD, as well as fewer surgeries and hospitalizations and an overall decreased risk of treatment failure.


Assuntos
Doença de Crohn , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal , Humanos , Mucosa Intestinal , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Cancer Med ; 12(5): 5341-5351, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36394147

RESUMO

BACKGROUND: Around 50% of gastric cancers are diagnosed at an advanced stage. Several chemotherapy regimens are now internationally validated. Few data are available on the routine daily management of advanced gastric or gastroesophageal junction cancers. We aimed to describe chemotherapy practices, tolerance, and efficacy overall survival (OS) and Progression free survival (PFS) in a prospective French cohort. METHODS: Patients starting palliative chemotherapy were prospectively enrolled in 49 French centres. The primary objective was to report and describe patients' characteristics and treatment strategies. Secondary objectives were OS, PFS, objective response rate, adverse events rate, performance status deterioration during the chemotherapy. RESULTS: A total of 182 patients were included; 179 were analysed. Most patients received platinium-based chemotherapy as the first treatment and FOLFIRI as second; 62.0% of patients received a second line, and 32.4% a third line. More than two thirds of Her2-positive patients were first treated with trastuzumab. The FOLFIRI regimen was the most frequently used second-line therapy. Median OS was 13.3 months, similar whatever the chemotherapy or combinations used in the first line. One- and 2-year OS increased with the number of chemotherapy lines received, from respectively 24.7% and 5.7% (1 line), to 46.9% and 12.4% (2 lines) and 88.1% and 29.9% (3 or more lines) (p < 0.0001). CONCLUSION: Our study showed that treatment strategies in France are based on a succession of doublets, making it possible to offer a second and third line of treatment more often. This treatment strategy must be taken into account for future trials with immunotherapy combinations.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudos Prospectivos , Junção Esofagogástrica , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
Dig Liver Dis ; 55(4): 541-548, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36115817

RESUMO

BACKGROUND: Colon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients. METHODS: The purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled. RESULTS: The analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3-5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2. CONCLUSION: No safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Fragilidade , Humanos , Idoso , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Oxaliplatina/uso terapêutico , Fluoruracila/uso terapêutico , Capecitabina/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/etiologia , Intervalo Livre de Doença , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias , Leucovorina/uso terapêutico
5.
Clin Res Hepatol Gastroenterol ; 45(5): 101569, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33199239

RESUMO

INTRODUCTION: Surgical resection is not curative in Crohn's disease (CD) and, recurrence after surgery is a common situation. The identification of patients at high risk of recurrence remains disappointing in clinical practice. OBJECTIVE: To evaluate the impact of residual microscopic disease on margins on the risk of recurrence after ileocaecal resection in CD. PATIENTS AND METHODS: All patients who underwent ileocaecal resection between January 1992 and December 2016 were prospectively identified. Demographic data, clinical, surgical and histological variables were retrospectively collected. Positive histologic margin was assessed prospectively and defined by the presence of acute inflammatory lesions on margins: erosion, ulceration, chorion infiltration by neutrophils, cryptic abscesses or cryptitis. RESULTS: One hundred twenty five patients were included, with a median follow-up of 8 years (Interquartile Range (IQR), 4.3-15.2). Half (49.6%, n = 62) were women, and the median age at surgery was 33 years (IQR, 24-42). Fifty-six (44.8%) had positive inflammatory margins. Five years after surgery, respectively 29 (51%) and 23 (34%) patients with positive and negative margins had clinical recurrence (p = 0.034). At the end of the follow-up, respectively 60% (n = 34) and 47% (n = 33) patients had clinical recurrence (p = 0.07). CD-related hospitalizations were observed in respectively 37.5% (n = 21) and 18.8% (n = 13) with positive and negative margins (p = 0.02). Fourteen patients (25%) with positive intestinal margins had surgical recurrence at the end of the follow-up compared to 5 patients (7%) with negative margins (p = 0.04). Multivariate analysis confirmed that positive intestinal margin was independently associated with surgical recurrence (OR, 4.7 (CI95%, 1.4-15.3), p = 0.01). CONCLUSION: Positive histologic margin was associated with an increased risk of clinical and surgical recurrence after ileocaecal resection for Crohn's disease.


Assuntos
Ceco , Doença de Crohn , Íleo , Adulto , Ceco/patologia , Ceco/cirurgia , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Feminino , Humanos , Íleo/patologia , Íleo/cirurgia , Masculino , Margens de Excisão , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
6.
Clin Res Hepatol Gastroenterol ; 44(6): 968-972, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32336615

RESUMO

INTRODUCTION: Most anal fistulas are crypto-glandular. Nevertheless, anal fistulas can reveal Crohn's disease (CD). The aim of our study was to evaluate the risk of developing CD in patients undergoing surgery for anal fistula. PATIENTS AND METHODS: All patients undergoing surgery for anal fistula in our center between January 1, 2008 and January 31, 2017 were identified through a prospective administrative database. Demographic, clinical, and laboratory data were retrospectively collected. RESULTS: Ninety-three patients underwent anal exploration under general anesthesia. The median age at diagnosis of fistula was 43 years (IQR, 34-56) and 27% (n=29) were women. Twenty-seven percent (n=16) had had at least one previous fistula episode. After a median follow-up of 16.8 months (IQR, 7.2-42.0), seven (7.4%) patients were diagnosed with CD. The median time between the diagnosis of fistula and that of CD was 7.6 months (IQR, 2.7, 26.1). Chronic diarrhea (P=0.0003), weight loss (P=0.001), and chronic abdominal pain (P=0.002) were associated with the diagnosis of CD. Characteristics of the fistulas (number, simple/complex, abscess), smoking, extra-digestive manifestations of CD, or a family history of IBD were not associated with the diagnosis of CD. CONCLUSION: A medical history of anal fistula surgery resulted in the diagnosis of CD in 7% of cases. Weight loss and the presence of digestive symptoms were associated with the diagnosis of CD. These elements could be used to select patients requiring endoscopic exploration after anal fistula.


Assuntos
Doença de Crohn/diagnóstico , Fístula Retal/cirurgia , Dor Abdominal/etiologia , Adulto , Dor Crônica/etiologia , Diarreia/etiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Redução de Peso
7.
Dig Liver Dis ; 51(4): 484-488, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30686715

RESUMO

INTRODUCTION: Up to 25% of patients treated with infliximab experience hypersensitivity reactions. Prophylactic premedication prior to infliximab infusion, comprising corticosteroids and/or antihistamines, is widely used in clinical practice but its efficacy has recently been called into question due to the lack of pathophysiological rationale and validation by controlled trials. MATERIALS AND METHODS: We conducted a comprehensive literature search of multiple electronic databases from inception to June 2017 to identify studies reporting the impact of corticosteroid and/or antihistamine premedication on the risk of acute (<24 h) hypersensitivity reaction to infliximab in immune-mediated inflammatory diseases (IMIDs). Random-effects meta-analysis was performed. RESULTS: Ten studies, eight observational studies and two randomized control trials, were identified including a total of 3892 patients with IMIDs, and 1,385 patients with IBD. Corticosteroid premedication was not associated with a decreased risk of hypersensitivity reaction in either IMIDs (7 studies; OR, 1.07, 95%CI, 0.64-1.78; I2 = 57.5%) or IBD (3 studies; OR, 1.04, 95% CI, 0.52-2.07; I2 = 57%). Antihistamine premedication was not associated with a decreased risk of hypersensitivity reaction in IMIDs (3 studies: OR, 1.39, 95% CI, 0.70-2.73; I2 = 85%). The combination of corticosteroids and antihistamines did not decrease the risk of acute infliximab infusion reaction in IMIDs (6 studies; OR, 2.12, 95% CI, 0.61-7.35; I2 = 94%), but was associated with an increased risk in IBD (4 studies, OR, 4.17, 95% CI, 1.61-10.78; I2 = 77%). CONCLUSION: Corticosteroid and/or antihistamine premedication is not associated with a decreased risk of acute hypersensitivity reactions to infliximab in patients with IMIDs. We believe that these premedications should no longer be part of standard protocols.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Reação no Local da Injeção/prevenção & controle , Pré-Medicação , Corticosteroides/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Infusões Intravenosas/efeitos adversos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
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