Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery.

OBJECTIVES: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial. DESIGN: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis. RESULTS: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/ß Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence. CONCLUSIONS: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

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.

Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study.

BACKGROUND AND AIMS: The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. METHODS: A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. RESULTS: A total of 52 patients [male 65%, Crohn's disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4-7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%-96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%-94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%-100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. CONCLUSIONS: In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

IFNgamma and antibody responses among French nurses during a tuberculosis contact tracing investigation.

STUDY: A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON((R)) TB Gold In-tube, QF-TB-IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital. PATIENTS: Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry. RESULTS: Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case. CONCLUSION: This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.

[Colonic lipoma: case report and literature review]. / Lipome colique : cas clinique et revue de la littérature.

Colonic lipoma is a rare benign tumor infrequently met in clinical practice. We report a case of symptomatic lipoma of the ascending colon in a 61-year-old woman. Diagnosis was suspected on CT scan. Colotomy with lipectomy was performed. The diagnosis was confirmed by histological examination. Reviewing the literature and combining with our experience, we discuss the clinical features, diagnosis and treatment of this uncommon disease.

[Prolonged acute pancreatitis after bone marrow transplantation]. / Une pancréatite aiguë prolongée après allogreffe de moelle.

Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience.

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.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

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.

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

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.

Benefit of infliximab reintroduction after successive failure of infliximab and adalimumab in Crohn's disease.

BACKGROUND: Infliximab [IFX] and adalimumab [ADA] are effective in Crohn's disease [CD] for induction and maintenance therapy. However, high annual rate of discontinuation for loss of response or intolerance may lead to a switch to another anti-tumor necrosis factor agent. Patients with successive failure to IFX and ADA are becoming more frequent. The aim of this study was to assess the efficacy and the tolerance of re-treatment with IFX in CD patients who successively failed IFX and ADA. METHODS: A total of 61 patients with CD who received and discontinued successively IFX and ADA, and who were re-exposed to IFX, were identified in four French tertiary centers and retrospectively analyzed. Clinical data, follow-up and outcome were abstracted from medical records. RESULTS: Median treatment duration after reintroduction was 16 months, and probability of remaining under IFX was 60% and 51%, respectively, at 12 and 24 months. In all 29 patients discontinued the second IFX treatment due to intolerance [13], primary non-response [8], loss of response [7] or patient's wish [1]. Remission was achieved in 42% at week 6-8 after IFX re-induction, and was predictive of better long-term response [p = 0.006]. In multivariate analysis, receiving co-immunosuppression in both first and second IFX treatments [p = 0.04] and shorter interval between first and second IFX treatments [p = 0.017] were independently associated with longer duration of second IFX treatment. CONCLUSION: For CD patients who successively failed IFX and ADA, reintroducing IFX is feasible and often clinically efficient, particularly in patients who received co-immunosuppression during both first and second IFX treatments.

The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab.

BACKGROUND: Optimising infliximab therapy is recommended in inflammatory bowel disease (IBD) patients who lose response to infliximab; however, there are no data on the outcome of ulcerative colitis (UC) patients after doubling the dose. AIM: To determine the efficacy and safety of infliximab dose doubling in UC patients with a loss of response to infliximab. METHODS: From January 2006 to May 2013, we retrospectively reviewed the outcome of the consecutive UC patients who were treated with infliximab dose doubling (10 mg/kg) for loss of response in four French academic centres. The clinical response and remission were assessed. A composite event-free survival analysis was performed using the log-rank test and the Cox model. RESULTS: One hundred and fifty-seven patients [84 males; median age 37. 6 (IQR 28.2-49.4) years] were included. The median follow-up after infliximab dose doubling was 1.8 (1.0-3.1) years. At weeks 8 and 24, 55% and 43% of the patients achieved a clinical response respectively. The probabilities of the event-free survival were 71%, 61% and 55% at 6 months, 1 year and 2 years respectively. In the multivariate analysis, the predictors of infliximab dose doubling failure were the absence of the introduction of an immunomodulator concomitantly to dose doubling, a partial Ulcerative Colitis Disease Activity Index >6, a C-reactive protein level >10 mg/L, a leucocyte count >8000/mm(3) and a haemoglobin level <12.5 g/dL. Adverse events were reported in 12 patients (8%). CONCLUSIONS: Infliximab dose doubling led to short- and long-term event-free survival in UC patients, who had a loss of response to infliximab, in greater than 50% of the cases. The benefits of such a strategy were significantly improved by adding a concomitant immunomodulator.

Prevalence, risk factors, and impact on clinical outcome of extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia: a five-year study.

BACKGROUND: The impact of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) bacteraemia on outcome remains controversial. METHODS: A retrospective analysis of the prevalence, risk factors, clinical features, and outcomes of all ESBL-EC bacteraemia in one French hospital over a 5-year period was performed. A case-control study was undertaken: cases had at least one ESBL-EC bacteraemia and controls a positive non-ESBL-EC bacteraemia. RESULTS: The prevalence of ESBL-EC bacteraemia increased from 5.2% of all positive E. coli blood cultures in 2005 to 13.5% in 2009 (p<0.003). CTX-M represented 70% of ESBL-EC bacteraemia strains, and strains were not clonally related. On adjusted analysis, the only significant risk factor for ESBL-EC bacteraemia was a previous ESBL-EC colonization (odds ratio 11.3, 95% confidence interval 1.2-107; p=0.003). Initial antimicrobial therapy was less frequently adequate in the ESBL-EC group (48% vs. 85%; p=0.003). The presence of ESBL-EC bacteraemia was not associated with a longer hospital stay (p=0.088). Day 30 mortality was high, but not significantly different in the two groups (30% vs. 27%; p=0. 82). CONCLUSION: The prevalence of ESBL-EC bacteraemia has been increasing dramatically. Previous colonization with ESBL-EC was a strong risk factor for ESBL-EC bacteraemia. More inadequate initial antimicrobial therapy was noted in the ESBL-EC group, but mortality and length of hospital stay were not significantly different from those of patients with non-ESBL-EC bacteraemia.