Publications by authors named "Nicolas Williet"

48 Publications

No Difference of Adalimumab Pharmacokinetics When Dosed at 40 mg Every Week or 80 mg Every Other Week in IBD Patients in Clinical Remission After Adalimumab Dose Intensification.

Dig Dis Sci 2020 Sep 16. Epub 2020 Sep 16.

Groupe Immunité des muqueuses et Agents Pathogènes (GIMAP), INSERM U1111- International center for research in infectiology (CIRI), Saint-Etienne, France.

Introduction: The pharmacokinetic equivalence of dose intensification with adalimumab (ADA) 80 mg every other week (EOW) compared to weekly 40 mg has only been supported by modeling systems.

Aim Of The Study: To compare the trough levels of ADA (TLA) and the occurrence of anti-ADA antibodies (AAA) between these two treatment regimens.

Patients And Methods: This was a prospective study including all consecutive patients with inflammatory bowel disease (IBD) who had reached a longstanding and deep remission under treatment with ADA 40 mg once a week. In these patients, the ADA regimen was changed from 40 mg/week to 80 mg EOW. TLA and AAA levels using a drug-tolerant assay were monitored before and ten weeks after from the change in the ADA regimen and the results compared by a Wilcoxon paired test.

Results: Sixty-two patients (60% CD, mean age 35 years) were included. Before and ten weeks after the changes of ADA regimen, the median TLA were (6.9 µg/mL versus 7.0 µg/mL, respectively; P = 0.34) and the AAA levels (3.4 µg/ml-eq versus 3.0 µg/ml-eq, respectively; P = 0.25.) were quite similar. Likewise, quartiles of TLA (Kendall test r = 0.91; P < 0.001) and AAA (r = 0.78; P < 0.001) did not differ before and after ADA regimen. When stratifying all the patients into 4 groups based on drug/antibody levels (immunogenic, subtherapeutic, therapeutic, or supratherapeutic), no patient needed for returning to the previous weekly regimen. In terms of acceptability, more than 60% of patients preferred an injection EOW compared once a week.

Conclusions: In IBD patients who achieved a deep clinical remission under ADA 40 mg once a week, the pharmacokinetic of ADA was similar when ADA regimen was changed to 80 mg EOW. Given the patient's preference for the latter regimen, a modification of injection regimen should be systematically proposed.
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http://dx.doi.org/10.1007/s10620-020-06567-xDOI Listing
September 2020

Safety of endoscopic retrograde cholangiopancreatography in the pediatric population: a multicenter study.

Endoscopy 2020 Jun 29. Epub 2020 Jun 29.

Department of Endoscopy and Hepatogastroenterology, Regional University Hospital of Nancy, Nancy, France.

Introduction: The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers.

Methods: All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included.

Results: 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95 % confidence interval [CI] 0.01 - 0.75;  = 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 - 31.05;  = 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality.

Conclusion: Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.
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http://dx.doi.org/10.1055/a-1209-0155DOI Listing
June 2020

Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial.

Gut 2020 07 24;69(7):1206-1212. Epub 2020 Jan 24.

Department of Immunology, CIC 1408, GIMAP, CHU Saint-Étienne, Saint-Etienne, Rhône-Alpes, France

Objectives: In patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppressive drug. The aim of our study was to compare in these patients two strategies: either switch to a second anti-TNF alone or with addition of azathioprine (AZA). After randomisation outcomes (time to clinical and pharmacokinetic failure) were compared between the two groups during a 2-year follow-up period.

Design: Consecutive IBD patients in immune-mediated LOR to a first optimised anti-TNF given in monotherapy were randomised to receive either AZA or nothing with induction by a second anti-TNF in both arms. Clinical failure was defined for Crohn's disease (CD) as a Harvey-Bradshaw index ≥5 associated with a faecal calprotectin level >250 µg/g stool and for UC as a Mayo score >5 with endoscopic subscore >1 or as the occurrence of adverse events requiring to stop treatment. Unfavourable pharmacokinetics of the second anti-TNF were defined by the appearance of undetectable trough levels of anti-TNF with high antibodies (drug-sensitive assay) or by that of antibodies (drug-tolerant assay).

Results: Ninety patients (48 CDs) were included, and 45 of them received AZA after randomisation. The second anti-TNF was adalimumab or infliximab in 40 and 50 patients, respectively. Rates of clinical failure and occurrence of unfavourable pharmacokinetics were higher in monotherapy compared with combination therapy (p<0.001; median time of clinical failure since randomisation 18 vs >24 months). At 24 months, survival rates without clinical failure and without appearance of unfavourable pharmacokinetics were respectively 22 versus 77% and 22% versus 78% (p<0.001 for both) in monotherapy versus combination therapy. Only the use of combination therapy was associated with favourable outcomes after anti-TNF switch.

Conclusion: In case of immune-mediated LOR to a first anti-TNF, AZA should be associated with the second anti-TNF.

Trial Registration Number: 03580876.
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http://dx.doi.org/10.1136/gutjnl-2019-319758DOI Listing
July 2020

Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Pancreatic Solid Pseudopapillary Neoplasm Before Surgical Resection: A European Multicenter Registry-Based Study on 149 Patients.

Pancreas 2020 01;49(1):34-38

Digestive Endoscopy Unit, Beaujon University Hospital, Clichy-la-Garenne, France.

Objectives: The results of only a few endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid pseudopapillary neoplasm (SPN) have been published, and the safety of the procedure has never been investigated. Our study compared the recurrence rate in patients with and without preoperative EUS-FNA.

Methods: This European multicenter registry-based study was conducted in 22 digestive units, and retrospectively included all patients who underwent complete resection of a pancreatic SPN from 2000 to 2018. Patients with and without initial EUS-FNA were compared, and postsurgery recurrence and the associated risk factors were evaluated.

Results: A complete resection of a pancreatic SPN was performed in 149 patients (133 women, 89%), with a mean age of 34 (standard deviation, 14) years. There were no significant differences between the with (78 patients) and without (71 patients) EUS-FNA groups, except for age and tumor size and location.Preoperative EUS-FNA allowed pancreatic SPN diagnosis in 63/78 cases (81%). After a mean follow-up of 43 (standard deviation, 36) months, recurrence was noted in 4 patients (2.7%). Preoperative EUS-FNA was not correlated with recurrence, but an older age (P = 0.005) was significant.

Conclusions: Preoperative EUS-FNA does not affect pancreatic SPN recurrence. In this series, old age was significantly correlated with recurrence.
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http://dx.doi.org/10.1097/MPA.0000000000001460DOI Listing
January 2020

The Simplified Magnetic Resonance Index of Activity (MARIA) for Crohn's Disease Is Strongly Correlated With the MARIA and Clermont Score: An External Validation.

Gastroenterology 2020 01 5;158(1):282-283. Epub 2019 Nov 5.

Department of Hepatogastroenterology, University Hospital of Saint-Etienne and, EA-30 64, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, Saint-Etienne, France.

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http://dx.doi.org/10.1053/j.gastro.2019.08.061DOI Listing
January 2020

Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.

Clin Res Hepatol Gastroenterol 2020 06 10;44(3):295-301. Epub 2019 Oct 10.

Department of Gastroenterology and Digestive Oncology, Georges-Pompidou European Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), Sorbonne Paris Cité Paris Descartes University, Paris, France.

Background: A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.

Methods: Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.

Results: Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).

Conclusion: This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
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http://dx.doi.org/10.1016/j.clinre.2019.08.009DOI Listing
June 2020

Folfirinox gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study.

Therap Adv Gastroenterol 2019 25;12:1756284819878660. Epub 2019 Sep 25.

Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France.

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce.

Methods: Data from two independent cohorts enrolling patients treated with FFX ( = 107) or GN ( = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable.

Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10-21) than in GN groups (9 months; 95% CI: 8-12) before ( = 0.008) and after ( = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months;  = 0.053). After matching ( = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67;  = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX-GN sequence) was higher (46.9%) than the reverse sequence (20.4%;  = 0.01), which suggests a higher feasibility for the FFX-GN sequence. Corresponding median OS were 19 months 9.5 months, respectively ( = 0.094).

Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.
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http://dx.doi.org/10.1177/1756284819878660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764033PMC
September 2019

Gastrointestinal anastomosis using a new lumen-apposing metal stent for biliary drainage is a good option in the palliative setting.

Endoscopy 2019 11 4;51(11):E335-E336. Epub 2019 Jun 4.

Department of Hepato-gastro-enterology, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

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http://dx.doi.org/10.1055/a-0924-5380DOI Listing
November 2019

Concentrations of Ustekinumab During Induction Therapy Associate With Remission in Patients With Crohn's Disease.

Clin Gastroenterol Hepatol 2019 11 6;17(12):2610-2612. Epub 2019 Mar 6.

Department of Gastroenterology, Lyon-Sud University Hospital, Hospices Civils de Lyon, Pierre Bénite, and University Claude Bernard Lyon 1, Lyon, France; INSERM U1111, International Center for Research in Infectiology, Lyon, France. Electronic address:

Ustekinumab is approved for treatment of Crohn's disease (CD). Few data are available to assess the usefulness of monitoring inflammatory biomarkers and therapeutic drug monitoring to predict response to ustekinumab. We conducted a prospective study to assess the relationships between these parameters and the clinical outcome at week 16 in active CD patients receiving ustekinumab.
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http://dx.doi.org/10.1016/j.cgh.2019.02.042DOI Listing
November 2019

First Characterization with Ultrasound Contrast Agent of a Fibrovascular Polyp Before Its Endoscopic Resection: A Case Report (with Videos).

Clin Endosc 2019 Mar 5;52(2):186-190. Epub 2018 Oct 5.

Department of Hepatogastroenterology, University Hospital of Saint-Etienne, Saint-Priest en Jarez, France.

We described for the first time the contrast enhancement of a giant fibrovascular esophageal polyp using ultrasound contrast agent, Sonovue® (Bracco, Milan, Italy) during echoendoscopy. Fine Doppler was unsuccessful in showing vascularization due to the mobile characteristic of the tumor. In contrast, via Sonovue® , tissue microcirculation was highlighted inside the entire head of the polyp, leading to better appreciate the risk of bleeding related to its resection. In a second part, we showed the feasibility of classic polypectomy for this giant polyp (5×5 cm) without complication and results of control endoscopy at 3 months. The present case is summarized in a video.
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http://dx.doi.org/10.5946/ce.2018.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453852PMC
March 2019

Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC).

Dig Liver Dis 2018 12 18;50(12):1257-1271. Epub 2018 Aug 18.

Department of Digestive Oncology, Beaujon University Hospital (AP-HP), Paris VII Diderot University, Clichy-la-Garenne, France. Electronic address:

Background: This document is a summary of the French intergroup guidelines regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018.

Design: This collaborative work was produced under the auspices of all French medical and surgical societies involved in the management of PA. It is based on the previous guidelines, recent literature review and expert opinions. Recommendations were graded in three categories, according to the level of evidence.

Results: Over the last seven years, significant changes in PA management have been implemented in clinical practice. Imaging/staging: diffusion magnetic resonance imaging is useful before surgery to rule out small liver metastases.

Surgery: centralization of pancreatic surgery in expert centers is associated with a decreased postoperative mortality. Adjuvant chemotherapy: modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine plus nab-paclitaxel combination are first-line standards in fit patients; second-line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line gemcitabine.

Conclusion: Guidelines for management of PA are continuously evolving and need to be regularly updated. This constant progress is made possible through clinical and translational research. However, as each individual case is particular, they cannot substitute to multidisciplinary tumor board discussion.
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http://dx.doi.org/10.1016/j.dld.2018.08.008DOI Listing
December 2018

Intensification of induction chemotherapy before consolidation chemoradiotherapy improves progression-free survival and time without treatment in patients with locally advanced pancreatic cancers.

Oncotarget 2018 Aug 10;9(62):31999-32009. Epub 2018 Aug 10.

Hepatogastroenterology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.

Aims: To assess the interest of induction chemotherapy (ICT) intensification before chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer.

Methods: Charts of patients treated between February 2010 and November 2016 with consolidation capecitabin based-CRT were retrospectively reviewed in this bicentric study. Patients who underwent Gemcitabine as ICT (Group G) were compared to patients treated with intensive ICT (group I). Primary objectives were progression-free survival (PFS), defined as the time from the first day of ICT to progression or last follow-up, and Time without treatment (TWT), as the time from the last day of CRT to progression.

Results: Patients' characteristics were balanced between group I (Folforinox: = 24; GemOx: = 6) and group G ( = 16) including mean age (63.7 vs 68.1 years), and performance status (PS 0-1 :90% vs 93.7%). Median PFS (17.8 months vs 12 months; = 0.02) and TWT (7.4 months vs 2.5 months = 0.01) were statistically better in group I vs group G. These results remained statistically and clinically significant by comparing Folfirinox subgroup to Gemcitabine. A trend to a better median overall survival was observed in group I (20.4 months) vs group G (18.3 months; = 0.07). After adjusting for ICT duration, PS, and CA19.9 level, ICT intensification remains independently prognostic. Toxicity profile was in accordance with Literature.

Conclusion: This study shows ICT intensification before CRT is an interesting approach in patients with locally advanced pancreatic cancer. Further studies are needed to confirm these results, and to assess the specific role of CRT in this setting.
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http://dx.doi.org/10.18632/oncotarget.25877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112837PMC
August 2018

Efficacy and Safety of Infliximab Tolerance Induction in Patients with Inflammatory Bowel Diseases who Experienced Acute Infusion Reactions.

Dig Dis 2018 21;36(6):417-426. Epub 2018 Aug 21.

Hospices Civils de Lyon, Department of Gastroenterology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.

Background And Aims: One of the reasons for the failure of infliximab (IFX) is immediate hypersensitivity reactions (IHR). We aimed to report the efficacy and safety of a tolerance induction protocol in inflammatory bowel diseases (IBD) patients who had previously experienced IHR during IFX infusions.

Patients And Methods: We reported all cases of IBD patients who had previously experienced IHR due to IFX and who were submitted to a standardized protocol of tolerance induction to IFX from 2010 to 2015.

Results: IHR occurred in a majority of patients (69%) during the first 3 infusions and for half of them after a period of IFX withdrawn. Skin prick tests were negative and only 2 intradermal tests were positive. Basophil activation tests and antidrug antibody measurements were performed in 8 out of 16 patients and were positive in 3 and 4 patients respectively. Induction of tolerance was successful in 69% of patients and IFX was pursued with clinical efficacy > 1 year in 7 patients (44%). Allergologic investigations were not predictive of tolerance induction success.

Conclusion: A majority of IHR to IFX infusions occurred during the beginning or restarting of treatment and was related to a nonallergic hypersensitivity. Induction of tolerance to IFX is feasible and effective and may safely allow retreatment of IFX in almost 70% of IBD patients.
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http://dx.doi.org/10.1159/000491078DOI Listing
November 2018

Soluble Mucosal Addressin Cell Adhesion Molecule 1 and Retinoic Acid are Potential Tools for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Treated with Vedolizumab: A Proof of Concept Study.

J Crohns Colitis 2018 Aug;12(9):1089-1096

INSERM U1111, CIRI, Lyon, France.

Background And Aims: Vedolizumab [VDZ], a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease [IBD] who have not adequately responded to standard therapies, and high vedolizumab trough levels [VTLs] have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is upregulated by retinoic acid [RA]. The aim of this study was to determine the relationships between soluble MAdCAM-1 [sMAdCAM-1] and RA concentrations during clinical remission with VDZ maintenance therapy.

Methods: In a retrospective study performed in IBD patients treated with VDZ, we measured VTL, sMAdCAM-1 and RA concentrations.

Results: Among the 62 included patients [38 Crohn's disease], 24 relapsed and 38 stayed in remission from Weeks 10 to 30 after VDZ initiation. During this maintenance therapy, the median values of VTLs and RA were 15.4 µg/mL and 0.97 ng/mL, respectively, whereas sMAdCAM-1 was undetectable [<0.41 ng/mL] in 67.3% of samples. The positive predictive value [PPV] of undetectable sMAdCAM-1 for clinical remission was 80.0%, with a corresponding sensitivity of 74.6%. On multivariate analysis, undetectable sMAdCAM-1 and high VTLs [>19 µg/mL] were independently associated with clinical remission [OR = 7.5, p = 0.006 and OR = 2.2, p = 0.045, respectively]. The combination of sMAdCAM-1 < 0.41 ng/mL and VTL > 19 µg/mL was the best pharmacokinetic profile, with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher [p = 0.0001] before VDZ therapy than during the follow-up [sMAdCAM-1: 40.5 vs < 0.41 ng/mL; RA: 1.7 vs 0.97 ng/mL]. Only RA > 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (Area Under a Receiver Operating Characteristic curve [AUROC] = 80.7%).

Conclusions: Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies.
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http://dx.doi.org/10.1093/ecco-jcc/jjy077DOI Listing
August 2018

Is the Pharmacokinetic Profile of a First Anti-TNF Predictive of the Clinical Outcome and Pharmacokinetics of a Second Anti-TNF?

Inflamm Bowel Dis 2018 08;24(9):2078-2085

Department of Gastroenterology, Hospices Civils de Lyon, University Claude Bernard Lyon and INSERM, Lyon, France.

Aim: The aim of this study was to evaluate prospectively the clinical outcomes and pharmacokinetics of a second anti-TNF according to the pharmacokinetics of the first anti-TNF in patients with inflammatory bowel disease (IBD).

Methods: In patients in loss of response (LOR) to a first optimized anti-TNF and switched to a second anti-TNF, pharmacokinetics of anti-TNF were measured at the switch time, 30 weeks later, at the time of LOR, or at the end of the study (102 weeks).

Results: At the switch time, patients (n = 59) belonged to 4 groups according to the pharmacokinetics of the first anti-TNF: group 1 (n = 18), therapeutic trough levels; group 2 (n = 13) undetectable trough levels with antibodies against anti-TNF; group 3 (n = 13) without antibodies against anti-TNF; and group 4 (n = 15) subtherapeutic trough levels. After switching, the failure rates at week 30 and during the follow-up were as follows, respectively: in group 1 with therapeutic levels, 50% and 78%, despite therapeutic levels of the second anti-TNF in 83% of cases; in group 2 with undetectable levels and antibodies, 15% and 69% with undetectable levels of the second anti-TNF and antibodies in 85% of cases; in group 3 with undetectable levels without antibodies, 0% and 31% with therapeutic levels in 77% of cases; in group 4 with subtherapeutic levels, 13% and 33% with therapeutic levels in 73% of cases. Clinical remission rates were significantly lower (P ≤ 0.05) in groups 1 and 2 with therapeutic or undetectable levels with antibodies than in the 2 other groups.

Conclusion: In the case of LOR with therapeutic levels of the first anti-TNF or undetectable levels with antibodies, the switch to a second anti-TNF results in pharmacokinetic profile similar to the first one and again in LOR in most of the patients.
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http://dx.doi.org/10.1093/ibd/izy111DOI Listing
August 2018

Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials.

Endoscopy 2018 09 26;50(9):846-860. Epub 2018 Apr 26.

Gastroenterology and Endoscopy Unit, Edouard Herriot Hospital, Lyon, France.

Background: Yield of Endocuff-assisted colonoscopy (EAC) compared with standard colonoscopy is conflicting in terms of adenoma detection rate (ADR). A meta-analysis of randomized controlled trials (RCTs) appears necessary.

Methods: PubMed and Google Scholar were searched in December 2017. Abstracts from Digestive Disease Week and United European Gastroenterology Week meetings were also searched to 2017. All RCTs comparing EAC with standard colonoscopy were included. Analysis was conducted by using the Mantel-Haenszel models. Heterogeneity was quantified using the test.

Results: Of the 265 articles reviewed, 12 RCTs were included, with a total of 8376 patients (EAC group 4225; standard colonoscopy group 4151). In the meta-analysis, ADR was significantly increased in the EAC group vs. the standard colonoscopy group (41.3 % vs. 34.2 %; risk ratio [RR] = 1.20, 95 % confidence interval [CI] 1.06 to 1.36;  = 0.003;  = 79 %), especially for operators with low-to-moderate ADRs (< 35 %): RR = 1.51, 95 %CI 1.35 to 1.69;  < 0.001;  = 43 %). In contrast, this benefit was not reached for operators with high ADRs (> 45 %): RR = 1.01, 95 %CI 0.93 to 1.09;  = 0.87;  = 0.0 %). The mean number of adenomas per patient tended to be higher with EAC (mean difference = 0.11 adenomas/patient, 95 %CI - 0.17 to 0.38). Similar results were shown for polyp detection rates (61.6 % vs. 51.4 %; RR = 1.20, 95 %CI 1.06 to 1.36;  = 0.004). Use of the Endocuff did not impact the cecal intubation rate (95.1 % vs. 95.7 %;  = 0.08), or the procedure time compared with standard colonoscopy. Adverse events related to Endocuff were rare and exclusively mild mucosal erosion (4.0 %; 95 %CI 2.0 % to 8.0 %).

Conclusion: With moderate-quality evidence, this study showed an improvement in ADR with EAC without major adverse events, especially for operators with low-to-moderate ADRs.
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http://dx.doi.org/10.1055/a-0577-3500DOI Listing
September 2018

IBD-INFO Questionnaire: A Multicenter French Up-to-Date Survey of Patient Knowledge in Inflammatory Bowel Disease.

Inflamm Bowel Dis 2018 04;24(5):943-952

Department of Gastroenterology, Lyon-Sud hospital, Hospices Civils de Lyon, Université Claude Bernard Lyon, Lyon, France.

Background: It has been demonstrated in many chronic conditions, including inflammatory bowel disease (IBD), that better patient knowledge about pathology and treatment improves the course and management of disease. The aim of this study was to develop an updated self-questionnaire to assess patients' level of knowledge of IBD.

Methods: The IBD-INFO included 3 parts: an original part (Q1) and 2 parts from the translation of the preexisting questionnaires Crohn's and Colitis Knowledge score (CCKNOW) (Q2) and Crohn's and Colitis Pregnancy Knowledge score (CCPKNOW) (Q3). The reliability and discriminatory ability of the questionnaire were validated in 3 groups of non-IBD volunteers with various theoretical knowledge levels. The final questionnaire (64 validated questions) was then tested on 364 in- and out- IBD patients from 4 French university hospitals. The score for each part of the questionnaire was calculated, and factors associated with low scores were identified by univariate and multivariate logistic regression analyses.

Results: The scores obtained by the 3 non-IBD volunteer groups differed significantly (P < 0.0001), and the IBD-INFO questionnaire showed excellent internal reliability and consistency (α = 0.98). The median total score obtained by the IBD patients was 27/64 (range, 0-59), and scores for Q1, Q2, and Q3 were, respectively, 10/23 (range, 0-21), 11/24 (range, 0-23), and 4/17 (range, 0-16). In multivariate analysis, lack of a university degree, not being a member of a patient association, not receiving anti-tumor necrosis factor alpha (anti-TNFα) treatment, duration of IBD ≤3 years, male sex, and age >38 years were independent risk factors of a poor IBD-INFO knowledge score. The areas of knowledge least mastered were vaccination, IBD-related cancers, treatments, and pregnancy.

Conclusions: Using the IBD-INFO, an updated self-administered questionnaire built to assess IBD patients' knowledge, several risk factors have been highlighted that allow better targeting of patients and areas requiring an improvement in the level of information.
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http://dx.doi.org/10.1093/ibd/izx073DOI Listing
April 2018

Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: a multicenter AGEO study.

Oncotarget 2017 Nov 8;8(60):101383-101393. Epub 2017 Sep 8.

Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

Introduction: Trastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression.

Methods: This retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method and compared using log-rank test. The prognostic variables with values ≤ 0.05 in univariate analysis were eligible for the Cox multivariable regression model.

Results: From May 2010 to December 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; ECOG performance status [PS] 0-1, 71.2%). The continuation (n=39) versus discontinuation (n=65) of trastuzumab beyond progression was significantly associated with an improvement of median PFS (4.4 versus 2.3 months; =0.002) and OS (12.6 versus 6.1 months; =0.001. In the multivariate analysis including the ECOG PS, number of metastatic sites and measurable disease, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.56; 95% CI, 0.35-0.89; =0.01) and OS (HR, 0.47; 95% CI, 0.28-0.79; =0.004).

Conclusion: This study suggests that continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer. These results deserve a prospective randomized validation.
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http://dx.doi.org/10.18632/oncotarget.20711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731882PMC
November 2017

Cytomegalovirus and inflammatory bowel diseases, with a special focus on its role in ulcerative colitis.

Virologie (Montrouge) 2017 Dec;21(6):287-302

EA3064, Groupe immunité des muqueuses et agents pathogènes (Gimap), Campus Santé Innovations, Faculté de médecine, 10 rue de la Marandière, BP 80019, 42270 Saint-Priest-en-Jarez, Laboratoire des agents infectieux et hygiène, CHU de Saint-Étienne, France.

Cytomegalovirus (CMV) infects approximately 50 % of adults in France and persists lifelong as a latent agent in different organs, including the gut. A close relationship is observed between inflammation that favors viral expression, and viral replication that modulates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBD), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation in link with Th2 cytokines, together with immunomodulatory drugs used for controlling flares-up, favors viral reactivation within the gut, which increases mucosal inflammation ; it results in an important risk of impairing corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in case of CMV colitis), precipitating the need for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during IBD and underlines the interest of using ganciclovir for treating flares-up associated to CMV colitis in UC patients.
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http://dx.doi.org/10.1684/vir.2017.0713DOI Listing
December 2017

Distinct Thresholds of Infliximab Trough Level Are Associated with Different Therapeutic Outcomes in Patients with Inflammatory Bowel Disease: A Prospective Observational Study.

Inflamm Bowel Dis 2017 11;23(11):2048-2053

*Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France; †Department of Gastroenterology, Hospices Civils de Lyon, and INSERM U1111, Lyon, France; ‡Department of Statistics, University of Lyon, Lyon, France; §Department of Gastroenterology, University Hospital of Nancy, Nancy, France; and ‖Department of Immunology, CIC1408, GIMAP EA3064, University Hospital of Saint Etienne, Saint Etienne, France.

Background: Several studies have reported a strong correlation between infliximab (IFX) trough levels (trough levels of infliximab [TLI]) and clinical remission (CR). We aimed to determine threshold values of TLI associated with the occurrence of CR, with or without normal inflammatory biomarkers, including serum C-reactive protein (CRP) and fecal calprotectin (fCal).

Methods: We included prospectively all consecutive patients with inflammatory bowel disease under IFX therapy (5 mg/kg every 8 wk) for at least 6 months. Disease activity (using the Crohn's Disease Activity Index or Mayo score) was recorded, and TLI, CRP, and fCal were measured before IFX infusion.

Results: Two hundred thirteen patients (131 Crohn's disease) were included. The median TLIs were higher in patients who achieved CR compared with those in patients who did not (2.6 versus 1.2 μg/mL, P < 0.01). The median TLI were higher in patients achieving CR with CRP normalization or CR with fCal <250 μg/g in comparison with patients with persistent elevated CRP or fCal (3.5 versus 1.6 μg/mL, P < 0.01 and 4.9 versus 1.8 μg/mL, P < 0.001, respectively). Finally, the median TLIs were higher in patients achieving CR with normal CRP and fCal <50 μg/g in comparison with patients without strictly normal biomarkers (5.9 versus 2.1 μg/mL, P < 0.001). The more the expected level of response to IFX was stringent, the more the median TLI and optimal thresholds were high.

Conclusions: Threshold values of TLI differ according to therapeutic outcomes expected in patients with inflammatory bowel disease under maintenance therapy with IFX.
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http://dx.doi.org/10.1097/MIB.0000000000001223DOI Listing
November 2017

Tolerance and outcomes of sorafenib in elderly patients treated for advanced hepatocellular carcinoma.

Dig Liver Dis 2017 Sep 23;49(9):1043-1049. Epub 2017 Jun 23.

Hepato-Gastroenterology Department, University Hospital of Saint-Etienne, Saint Priest en Jarez, France; University Jean Monnet, LINA EA 4624, France.

Introduction: Use of sorafenib remains debated in elderly patients treated for advanced hepatocellular carcinoma (HCC).

Methods: This was a bicentric retrospective study including all patients ≥75years and treated with sorafenib for advanced HCC between January 2010 and March 2014.

Results: Of the 51 patients included (median age: 78 years, range: 75-92; performance status (PS) 0-1: 98%; cirrhosis: 88.2%; Child-Pugh A: 95.6%) all experienced at least one adverse event (AE). About 2/3 of them (66.7%) had grade 3-4 toxicities, including fatigue (43.1%), hand foot skin syndrome (11.8%), anorexia (9.8%) or diarrhea (9.8%). After adjustment for arterial hypertension, heart failure, other(s) cardiovascular history(ies), and sorafenib dose at baseline, only patients ≥80 years were associated with severe AE (OR: 13.3; p=0.009). Discontinuation for toxicity was reported in 31 (60.8%) patients, mainly within the 3rd months, especially in those who had PS ≥1 at baseline (OR: 10.4; p=0.01), or other cardiovascular histories (OR: 30.9; p=0.016). In this setting, overall survival was significantly reduced (HR: 4.5; p<0.0001).

Conclusion: Tolerance of Sorafenib seems to be low in elderly, especially for patients aged ≥80 years or with PS ≥1. Starting with reduced dose of sorafenib does not seem to impact results. Some of these patients may truly benefit from the treatment in terms of survival.
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http://dx.doi.org/10.1016/j.dld.2017.06.008DOI Listing
September 2017

Barrett's Oesophagus and Oesophageal Carcinogenesis Following Obesity Surgery: Helicobacter Pylori Must Be Eradicated?

Obes Surg 2017 09;27(9):2464-2465

Department of General Surgery, CHU Hospital, Jean Monnet University, Avenue Albert Raimond, 42270, Saint Etienne, France.

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http://dx.doi.org/10.1007/s11695-017-2785-4DOI Listing
September 2017

Outcomes of Bariatric Surgery in Patients with Inflammatory Bowel Disease.

Obes Surg 2017 08;27(8):2177-2178

Department of General Surgery, CHU Hospital, Jean Monnet University, Avenue Albert Raimond, 42270, Saint Etienne, France.

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http://dx.doi.org/10.1007/s11695-017-2759-6DOI Listing
August 2017

Golimumab pharmacokinetics in ulcerative colitis: a literature review.

Therap Adv Gastroenterol 2017 Jan 15;10(1):89-100. Epub 2016 Nov 15.

Department of Gastroenterology, Service de Gastrologie-Entérologie-Hépatologie, CHU de Saint-Etienne, 42023 Saint-Etienne, France.

Golimumab (GLM) is the latest anti-tumor necrosis factor (TNF) that gained its marketing license. Thanks to the PURSUIT induction and maintenance trials, it was approved for the treatment of ulcerative colitis (UC) in 2013. The other anti-TNF drugs available are infliximab and adalimumab. These two drugs have validated algorithms concerning prescription and therapeutic drug monitoring (TDM) but little is known about GLM. The available data on GLM's exposure-response relationship in UC are from the PURSUIT trials and are recently published. The data reveal all the factors that may impact the pharmacokinetic (PK) parameters: dosage, body weight (BW), concomitant drugs, the presence of anti-drug antibodies (ADAbs), sex and age. In addition, the GLM trough level at steady-state appears to be correlated with the patient's improvement which may make it a precious indicator to predict the clinical response. There is, however, no consensus on a possible therapeutic level or cutoff associated with clinical response, remission, or any other outcome measure such as endoscopic healing in UC. This lack of a threshold value, and its validation with different assay techniques, makes it difficult to use GLM TDM in clinical practice. As with other anti-TNF agents, GLM is associated with development of ADAbs, of which the prevalence and effects are still insufficiently described. The objective of this review is to describe current data and understanding of the PK of GLM including serum concentrations of GLM and ADAbs in UC patients. Better understanding of these parameters could lead to improved patient care with GLM.
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http://dx.doi.org/10.1177/1756283X16676194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330616PMC
January 2017

Trend towards dose reduction of azathioprine as monotherapy in inflammatory bowel disease patients: what about for combination therapy?

Therap Adv Gastroenterol 2017 Jan 10;10(1):5-10. Epub 2016 Oct 10.

Department of Hepatogastroenterology, University Hospital of Saint-Etienne, Allee Albert Raimond, 42270 Saint-Priest en Jarez, France.

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http://dx.doi.org/10.1177/1756283X16670074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330604PMC
January 2017

Difficult endoscopic diagnosis of a pancreatic plasmacytoma: Case report and review of literature.

World J Clin Oncol 2017 Feb;8(1):91-95

Nicolas Williet, Olivier Dumas, Leslie Rinaldi, Xavier Roblin, Jean-Marc Phelip, Department of Gastroenterology, University Hospital of Saint Etienne, 42270 Saint-Priest en Jarez, France.

A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis. Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later. This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission. A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography. In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search.
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http://dx.doi.org/10.5306/wjco.v8.i1.91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309718PMC
February 2017

The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker.

Oncotarget 2017 Mar;8(10):16507-16517

Department of Hepato-Gastroenterology, University Hospital of Saint-Etienne, France.

Introduction: Data about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce.

Results: 101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature.

Materials And Methods: All patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression.

Conclusions: EGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.
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http://dx.doi.org/10.18632/oncotarget.14961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369981PMC
March 2017

Development and Internal Validation of a Model Using Fecal Calprotectin in Combination with Infliximab Trough Levels to Predict Clinical Relapse in Crohn's Disease.

Inflamm Bowel Dis 2017 01;23(1):126-132

*Department of Gastroenterology, University Hospital of Saint Etienne, France; †Mathematic Unit, University Claude Bernard, Lyon, France; ‡Department of Radiology, University Hospital of Saint Etienne, France; §Department of Gastroenterology, CHU, Lyon Sud, Lyon, France; ‖Department of Gastroenterology and Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-les-Nancy, France; and ¶Department of Immunology, University Hospital of Saint Etienne, Saint Etienne, France.

Background: The best noninvasive method predicting clinical relapse remains undetermined in infliximab (IFX)-treated patients with Crohn's disease.

Methods: All patients with CD on IFX maintenance treatment and in clinical remission for at least 16 weeks, between 2011 and 2014, were enrolled in a prospective single-center study. The Crohn's Disease Activity Index (CDAI), fecal calprotectin, C-reactive protein levels, antibodies (ATI), and trough level (TLI) of IFX were measured at every IFX infusion. The best thresholds of TLI (2 versus 3 μg/mL) and calprotectin (50 versus 250 μg/g stools) were identified across four logistic regression models.

Results: One hundred nineteen patients (mean age: 34 ± 12 yrs, mean disease duration: 7.8 yrs) were included. Mean follow-up was 20.4 months, and 17% of the patients were on IFX and azathioprine at inclusion. During follow-up, 37 patients (31.1%) relapsed, 78% within the first 6 months. The clinical characteristics of the relapsed and nonrelapsed patients were similar. After logistic regression, fecal calprotectin >250 μg/g stools (OR: 4.09; 95% CI, 1.01-16.21; P = 0.049) and TLI <2 μg/mL (OR: 14.85; 95% CI, 3.67-60; P < 0.0001) were associated with loss of response. A training cohort of 55 patients was isolated randomly to implement prediction rules for loss of response. The best predictive rules were the combination of a TLI <2 μg/mL and a fecal calprotectin level >250 μg/g stools (78.3%). These rules were validated on a test cohort of 64 patients with an accuracy of 87%, (sensitivity = 0.94, specificity = 0.84, positive predictive value = 0.73, and negative predictive value = 0.97).

Conclusions: In IFX-treated patients with CD in clinical remission, a combination of TLI (<2 μg/mL) and fecal calprotectin (>250 μg/g of stools) is a good model for predicting loss of response. In contrast with previous data, low TLIs ranging from 2 to 3 μg/mL should neither systematically lead to the optimization of IFX use nor a switch in the treatment.
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http://dx.doi.org/10.1097/MIB.0000000000000986DOI Listing
January 2017

Association Between Low Trough Levels of Vedolizumab During Induction Therapy for Inflammatory Bowel Diseases and Need for Additional Doses Within 6 Months.

Clin Gastroenterol Hepatol 2017 Nov 24;15(11):1750-1757.e3. Epub 2016 Nov 24.

Department of Gastroenterology, University of Saint-Etienne, Saint-Etienne, France; EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France.

Background & Aims: We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin α4β7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months.

Methods: We conducted an observational study of 47 consecutive patients with Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All patients were given a 300-mg infusion of vedolizumab at the start of the study, Week 2, Week 6, and then every 8 weeks; patients were also given corticosteroids during the first 4-6 weeks. Patients not in remission at Week 6 were given additional doses of vedolizumab at Week 10 and then every 4 weeks (extended therapy or optimization). Remission at Week 6 of treatment was defined as CD activity score below 150 points for patients with CD and a partial Mayo Clinic score of <3 points, without concomitant corticosteroids, for patients with UC. Blood samples were collected each week and serum levels of vedolizumab and antibodies against vedolizumab were measured using an enzyme-linked immunosorbent assay. Median trough levels of vedolizumab and interquartile ranges were compared using the nonparametric Mann-Whitney test. The primary objective was to determine whether trough levels of vedolizumab measured during the first 6 weeks of induction therapy associated with the need for extended treatment within the first 6 months.

Results: Based on response to therapy at Week 6, extended treatment was required for 30 of the 47 patients (23 patients with CD and 7 patients with UC). At Week 2, trough levels of vedolizumab for patients selected for extended treatment were 23.0 μg/mL (interquartile range, 14.0-37.0 μg/mL), compared with 42.5 μg/mL in patients who did not receive extended treatment (interquartile range, 33.5-50.7; P = .15). At Week 6, trough levels of vedolizumab <18.5 μg/mL were associated with need for extended therapy (100% positive predictive value, 46.2%; negative predictive value; area under the receiver operating characteristic curve, 0.72) within the first 6 months. Among patients who required extended treatment at Week 10, all of those with trough levels of vedolizumab <19.0 μg/mL at Week 6 had achieved clinical remission 4 weeks later (secondary responders).

Conclusions: In a prospective study of patients with CD or UC receiving induction therapy with vedolizumab, low trough levels of vedolizumab at Week 6 (<19.0 μg/mL) are associated with need for additional doses (given at Week 10 and then every 4 weeks). All patients receiving these additional doses achieved a clinical response 4 weeks later.
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http://dx.doi.org/10.1016/j.cgh.2016.11.023DOI Listing
November 2017