Showing papers by "Javier P. Gisbert published in 2018"

European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease.

Abstract: Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.

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

Abstract: 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.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

Abstract: BACKGROUND Effectiveness of vedolizumab in real world clinical practice is unknown. AIM To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study.

Abstract: SummaryBackground Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). Aim To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. Methods Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). Results One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). Conclusions Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

The Innate Immune System in the Gastrointestinal Tract: Role of Intraepithelial Lymphocytes and Lamina Propria Innate Lymphoid Cells in Intestinal Inflammation.

Abstract: Background The gastrointestinal tract harbors the largest microbiota load in the human body, hence maintaining a delicate balance between immunity against invading pathogens and tolerance toward commensal. Such immune equilibrium, or intestinal homeostasis, is conducted by a tight regulation and cooperation of the different branches of the immune system, including the innate and the adaptive immune system. However, several factors affect this delicate equilibrium, ultimately leading to gastrointestinal disorders including inflammatory bowel disease. Therefore, here we decided to review the currently available information about innate immunity lymphocyte subsets playing a role in intestinal inflammation. Results Intestinal innate lymphocytes are composed of intraepithelial lymphocytes (IELs) and lamina propria innate lymphoid cells (ILCs). While IELs can be divided into natural or induced, ILCs can be classified into type 1, 2, or 3, resembling, respectively, the properties of TH1, TH2, or TH17 adaptive lymphocytes. Noteworthy, the phenotype and function of both IELs and ILCs are disrupted under inflammatory conditions, where they help to exacerbate intestinal immune responses. Conclusions The modulation of both IELs and ILCs to control intestinal inflammatory responses represents a major challenge, as they provide tight regulation among the epithelium, the microbiota, and the adaptive immune system. An improved understanding of the innate immunity mechanisms involved in gastrointestinal inflammation would therefore aid in the diagnosis and further treatment of gastrointestinal inflammatory disorders.

Treatment of Helicobacter pylori infection in 2018

Abstract: Treatment options for the eradication of Helicobacter pylori continue to evolve There have been many guidelines for H pylori treatment published, which may lead to some confusion However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option Sequential therapy is challenging in terms of compliance and is no longer recommended This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H pylori treatment and prevent the inappropriate use of antibiotics

Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases.

Abstract: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a serious, costly, and persistent health problem with an estimated prevalence in Western countries around 0.5% of the general population; its socioeconomic impact is comparable with that for chronic diseases such as diabetes. Conventional treatment involves escalating drug regimens with concomitant side effects followed, in some cases, by surgical interventions, which are often multiple, mainly in Crohn's disease. The goal of finding a targeted gut-specific immunotherapy for IBD patients is therefore an important unmet need. However, to achieve this goal we first must understand how dendritic cells (DC), the most potent antigen present cells of the immune system, control the immune tolerance in the gastrointestinal tract and how their properties are altered in those patients suffering from IBD. In this review, we summarize the current available information regarding human intestinal DC subsets composition, phenotype, and function in the human gastrointestinal tract describing how, in the IBD mucosa, DC display pro-inflammatory properties, which drive disease progression. A better understanding of the mechanisms inducing DC abnormal profile in IBD may provide us with novel tools to perform tissue specific immunomodulation.

Probiotic supplementation with Lactobacillus plantarum and Pediococcus acidilactici for Helicobacter pylori therapy: A randomized, double-blind, placebo-controlled trial

Abstract: Objective To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. Design Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. Results A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (β -0.023, P 0.738). Female gender (P 90% in all cases) between triple and quadruple concomitant therapy. Conclusion Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.

Acute severe ulcerative colitis: State of the art treatment

Abstract: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition. In the present review, we give a broad overview of the state of the art in the management of this condition. A systematic bibliographic search was performed in PubMed. Patient with ASUC should be hospitalized and managed by a multidisciplinary team (gastroenterologist plus surgeon). Intravenous corticosteroids remain the cornerstone of medical therapy. However, about 30% of patients do not respond. After failing 3-5 days of corticosteroids, patients should be considered for either rescue medical therapy or for colectomy. Cyclosporin and infliximab are similarly effective and safe. Cyclosporin should be mainly used as a "bridge" in thiopurine-naive patients. More recently, infliximab has become the most widely used salvage therapy. Third-line salvage therapy with either cyclosporin or infliximab is efficacious in some patients but carries a significant risk of complications. Colectomy is appropriate in case of complications or medical rescue therapy failure.

Serial Tuberculin Skin Tests Improve the Detection of Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease

Abstract: Aim To assess the likelihood of detecting latent tuberculosis infection [LTBI] by the positive conversion of a serial tuberculin skin test [TST] at 1 year in inflammatory bowel disease [IBD] patients with negative baseline two-step TST. Methods In this multicentre prospective cohort study, we evaluated rate and predictors of conversion of TST at 1 year in patients with negative baseline TST. We also evaluated management of patients who had a positive TST at baseline or a conversion at 1 year. In all patients we assessed TB cases occurring during follow-up. Results Of the 192 IBD patients receiving anti-tumour necrosis factor [TNF] and 220 IBD controls not receiving anti-TNF, 35 [8.5%, 95% CI 5.7-11.3] had positive conversion (median TST induration 13 mm, interquartile range [IQR] 9-16). Ten anti-TNF cohort patients [5.2%, 95% CI 2.5-9.5] versus 25 controls [11.4%, 95% CI 7.5-16.3] had TST conversion [p = 0.029]. In multivariate analysis, conversion was associated with smoking habit (odds ratio [OR] 2.19, 95% CI 1.08-3.97; p = 0.028). Anti-TNF-treated patients had a lower conversion rate [OR 0.41, 95% CI 0.20-0.83; p = 0.013]. The likelihood of conversion correlates with fewer immunosuppressive therapies between baseline TST and TST at 1 year [p = 0.042]. One case of active TB [isoniazid-resistant strain] occurred in a patient with positive baseline TST receiving anti-TNF [0.05 events/100 patient-years]. Conclusions Serial TST at 1 year can detect LTBI in IBD patients receiving anti-TNF therapy with negative baseline TST. Serial TST seems to be advisable to reduce the risk of TB cases associated with inability to detect LTBI in pre-treatment screening.

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

Abstract: Background: Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice.Objectives: To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission.Materials and methods: Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up.Results: One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients...

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14.

Abstract: Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow-up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

European Registry on the management of Helicobacter pylori infection (Hp-EuReg): analysis of 2360 patients receiving first-line therapy in Russia.

Abstract: On behalf of the scientific Committee and researchers Hp-EuReg European Registry on the management of Helicobacter pylori infection («Hp-EuReg») - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations. Materials and methods. The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg» in 2013-2017, who were underwent 1st line eradication therapy. Results. The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effectiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clarithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Еradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment. Conclusion. Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.

Validation of the 'United Registries for Clinical Assessment and Research' [UR-CARE], a European Online Registry for Clinical Care and Research in Inflammatory Bowel Disease.

Abstract: Background The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Methods Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. Results For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. Conclusion The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.