Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 61
Filter
1.
Dig Liver Dis ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981787

ABSTRACT

BACKGROUND: Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them. AIMS: To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women. METHODS: We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year. RESULTS: Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %. CONCLUSION: In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

2.
Dig Liver Dis ; 2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38281870

ABSTRACT

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.

3.
Aliment Pharmacol Ther ; 59(4): 526-534, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38037279

ABSTRACT

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.


Subject(s)
Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Humans , Biosimilar Pharmaceuticals/therapeutic use , Gastrointestinal Agents , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/chemically induced , Infliximab/adverse effects , Recurrence , Time Factors , Treatment Outcome
4.
ESMO Open ; 8(5): 101628, 2023 10.
Article in English | MEDLINE | ID: mdl-37713929

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Laboratories , Retrospective Studies , Pandemics , Mutation , ErbB Receptors/genetics , Europe
5.
Gynecol Obstet Fertil Senol ; 50(2): 201-204, 2022 02.
Article in French | MEDLINE | ID: mdl-34403829

ABSTRACT

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.


Subject(s)
Buschke-Lowenstein Tumor , Condylomata Acuminata , Buschke-Lowenstein Tumor/pathology , Buschke-Lowenstein Tumor/surgery , Cesarean Section , Condylomata Acuminata/pathology , Condylomata Acuminata/surgery , Female , Humans , Papillomaviridae , Pregnancy
6.
J Crohns Colitis ; 15(6): 1000-1008, 2021 Jun 22.
Article in English | MEDLINE | ID: mdl-33313808

ABSTRACT

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.


Subject(s)
Crohn Disease/diagnosis , Endoscopy, Gastrointestinal , Intestines , Delphi Technique , Endoscopy, Gastrointestinal/methods , Endoscopy, Gastrointestinal/standards , Endoscopy, Gastrointestinal/statistics & numerical data , Humans , Intestines/diagnostic imaging , Intestines/pathology , Microscopy, Video/methods , Observer Variation , Quality Improvement , Reproducibility of Results , Severity of Illness Index , Terminology as Topic
7.
J Crohns Colitis ; 14(11): 1524-1534, 2020 Nov 07.
Article in English | MEDLINE | ID: mdl-32533769

ABSTRACT

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.


Subject(s)
Adalimumab , Crohn Disease , Infliximab , Intestinal Mucosa , Magnetic Resonance Imaging/methods , Adalimumab/administration & dosage , Adalimumab/adverse effects , Adult , Biomarkers, Pharmacological/analysis , C-Reactive Protein/analysis , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Crohn Disease/physiopathology , Feasibility Studies , Female , France/epidemiology , Humans , Infliximab/administration & dosage , Infliximab/adverse effects , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/pathology , Leukocyte L1 Antigen Complex/analysis , Male , Predictive Value of Tests , Prognosis , Remission Induction/methods , Severity of Illness Index , Tumor Necrosis Factor Inhibitors/administration & dosage , Tumor Necrosis Factor Inhibitors/adverse effects
8.
J Hosp Infect ; 103(3): 251-258, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31233849

ABSTRACT

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.


Subject(s)
Anti-Infective Agents/therapeutic use , Antimicrobial Stewardship/methods , Checklist , Drug Utilization/statistics & numerical data , Pharmacists , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hospitals , Humans , Interrupted Time Series Analysis , Male , Middle Aged , Non-Randomized Controlled Trials as Topic , Young Adult
10.
Encephale ; 45(4): 327-332, 2019 Sep.
Article in French | MEDLINE | ID: mdl-30879781

ABSTRACT

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.


Subject(s)
Geriatric Psychiatry/methods , Geriatric Psychiatry/organization & administration , Home Care Services, Hospital-Based , Mobile Health Units , Nursing Homes , Patient Care Team , Aged , Aged, 80 and over , Critical Pathways , Dementia/diagnosis , Dementia/psychology , Dementia/therapy , Female , France , Geriatric Assessment/methods , Geriatric Psychiatry/standards , Home Care Services, Hospital-Based/organization & administration , Home Care Services, Hospital-Based/standards , Humans , Interdisciplinary Communication , Male , Mobile Health Units/organization & administration , Mobile Health Units/standards , Neuropsychiatry/methods , Neuropsychiatry/organization & administration , Neuropsychiatry/standards , Neuropsychological Tests , Nursing Homes/organization & administration , Nursing Homes/standards , Patient Care Team/organization & administration , Patient Care Team/standards , Prospective Studies , Surveys and Questionnaires
11.
J Crohns Colitis ; 13(Supplement_1): S616, 2019 Jan 25.
Article in English | MEDLINE | ID: mdl-30794285

ABSTRACT

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.

13.
Aliment Pharmacol Ther ; 47(5): 588-595, 2018 03.
Article in English | MEDLINE | ID: mdl-29315694

ABSTRACT

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.


Subject(s)
Crohn Disease/drug therapy , Ustekinumab/administration & dosage , Ustekinumab/adverse effects , Adult , Cohort Studies , Crohn Disease/epidemiology , Drug Resistance/drug effects , Endoscopy , Female , Follow-Up Studies , Humans , Male , Pregnancy , Retrospective Studies , Time Factors , Treatment Outcome , Tumor Necrosis Factor-alpha/therapeutic use
14.
Aliment Pharmacol Ther ; 47(4): 485-493, 2018 02.
Article in English | MEDLINE | ID: mdl-29250803

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis/drug therapy , Inflammation/drug therapy , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Skin Diseases/drug therapy , Adolescent , Adult , Arthritis/epidemiology , Arthritis/etiology , Cohort Studies , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/epidemiology , Crohn Disease/complications , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Female , France/epidemiology , Humans , Inflammation/epidemiology , Inflammation/etiology , Inflammatory Bowel Diseases/epidemiology , Middle Aged , Skin Diseases/epidemiology , Skin Diseases/etiology , Young Adult
15.
Aliment Pharmacol Ther ; 46(11-12): 1077-1084, 2017 12.
Article in English | MEDLINE | ID: mdl-29027693

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Crohn Disease/drug therapy , Gastrointestinal Agents/therapeutic use , Adolescent , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Gastrointestinal Agents/administration & dosage , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
16.
Ann Oncol ; 28(11): 2860-2865, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29045560

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Gastrointestinal Diseases/etiology , Inflammation/etiology , Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/immunology , Neoplasms/pathology , Prognosis , Programmed Cell Death 1 Receptor/immunology , Retrospective Studies , Survival Rate
17.
Aliment Pharmacol Ther ; 46(3): 310-321, 2017 08.
Article in English | MEDLINE | ID: mdl-28593685

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Tumor Necrosis Factor-alpha/antagonists & inhibitors
18.
Eur J Pain ; 21(9): 1550-1560, 2017 10.
Article in English | MEDLINE | ID: mdl-28508514

ABSTRACT

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.


Subject(s)
Inflammatory Bowel Diseases/epidemiology , Migraine Disorders/epidemiology , Adult , Cohort Studies , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Surveys and Questionnaires , Tertiary Care Centers
19.
Aliment Pharmacol Ther ; 43(10): 1069-79, 2016 May.
Article in English | MEDLINE | ID: mdl-26953251

ABSTRACT

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.


Subject(s)
Adipokines/analysis , Feces/chemistry , Inflammatory Bowel Diseases/physiopathology , Lectins/analysis , Leukocyte L1 Antigen Complex/analysis , Adult , Biomarkers , Chitinase-3-Like Protein 1 , Colitis, Ulcerative/physiopathology , Colonoscopy , Crohn Disease/physiopathology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Ileum , Intestinal Mucosa/physiopathology , Male , Middle Aged , Sensitivity and Specificity , Severity of Illness Index
20.
J Crohns Colitis ; 9(12): 1113-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26351383

ABSTRACT

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.


Subject(s)
Colonoscopy , Crohn Disease/diagnosis , Feces/chemistry , Leukocyte L1 Antigen Complex/metabolism , Adult , Aged , Biomarkers/metabolism , Crohn Disease/metabolism , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prospective Studies , ROC Curve , Sensitivity and Specificity , Severity of Illness Index , Single-Blind Method
SELECTION OF CITATIONS
SEARCH DETAIL
...