Showing papers by "Javier P. Gisbert published in 2019"

Meta-analysis of three-in-one single capsule bismuth-containing quadruple therapy for the eradication of Helicobacter pylori.

Abstract: Background Bismuth-containing quadruple therapy has been suggested as first-line and rescue alternative for Helicobacter pylori eradication. Our objective was to perform a meta-analysis evaluating the efficacy and safety of single capsule Pylera® (bismuth, metronidazole, and tetracycline) plus a proton-pump inhibitor (PPI) in any line of treatment. Methods Studies were selected up to October 2018. Outcomes were eradication and adverse events (AEs) rates pooled using the generic inverse variance method. Results In total, 30 studies (6482 patients) were included in the systematic review. The intention-to-treat (ITT) efficacy was 90% (95% CI: 87%-92%, 21 studies, I2 = 88%) in first-line therapy, 89% (95% CI: 86%-93%, 12 studies, I2 = 78%) in second-line and 82% (95% CI: 78%-87%, nine studies, I2 = 60%) in third-line; with no differences by the type or dosage of PPI used. For metronidazole-resistant infection, the ITT efficacy as first-line therapy was 93% (95% CI: 90%-96%, six studies, I2 = 0%). In second-line therapies where patients had been previously treated with clarithromycin, the ITT efficacy was 90% (95% CI: 87%-93%, 11 studies, I2 = 78%). The overall incidence of AEs was 43% (95% CI: 35%-50%, 24 studies, I2 = 92%) and they were mostly mild. In nearly 3% of the cases, treatment was interrupted due to AEs. Conclusions A 10-day treatment with Pylera® achieved an effective eradication rate of approximately 90% both in first- and second-line therapy. This applies regardless of the type and dose of the PPI, in patients with clarithromycin- or metronidazole-resistant strains, and in those previously treated with clarithromycin.

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus.

Abstract: Background The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. Methods PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. Results In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. Conclusions These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC.

Role of food proteins and bioactive peptides in inflammatory bowel disease

Abstract: Background Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract which precise aetiology remains unknown. Diet is one of the main environmental factors involved in IBD as it modulates both the gut microbiota and the mucosal immune system. The gastrointestinal tract is therefore the main target of bioactive compounds, such as food-derived bioactive peptides. Scope and approach The present review provides an overview on the physiological relevance of food proteins, hydrolysates and peptides in the digestive system and explores the preventive and therapeutic role that they can play in IBD. Findings and insights from studies on cell cultures, animal models and human clinical trials are summarised and discussed. Key findings and conclusions The gastrointestinal mucosa presents unique mechanisms of immune tolerance towards nutrients and commensals under a delicate balance, which is nevertheless dysregulated in IBD. Counteracting this imbalance, dietary peptides carry a range of biological activities that might provide positive impact on gastrointestinal homeostasis. The anti-inflammatory, antioxidant and immunomodulatory properties of peptides from diverse food sources has been broadly evaluated in vitro. Protective mechanism of action through modulation of the pro-/anti-inflammatory and tolerogenic profile of immune responses has been demonstrated in animal models both in resting conditions and in IBD-like inflammation. However, there is still limited evidence in the human setting to support their bioactivity. This review highlights the impact of bioactive peptides in gastrointestinal health and encourages more robust information in clinical trials to ultimately elucidate their role as functional compounds in human IBD.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

Abstract: BACKGROUND There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

Abstract: BACKGROUND AND AIMS The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Protocol of the European Registry on the management of Helicobacter pylori infection (Hp‐EuReg)

Abstract: Introduction Helicobacter pylori selectively infects the human stomach, being the most prevalent chronic infection in the world. H pylori presence causes chronic gastritis in 100% of infected patients and is the major cause of relevant diseases such as atrophic gastritis, peptic ulcer disease, and gastric cancer; it is for this reason that from a public health standpoint, it is considered a high-impact pathogen, responsible of a significant morbidity and mortality. Nowadays, there are consensus and clinical guidelines regarding the infection management at a European level and in most of European countries, but no data have shown the level of implementation of these recommendations. The high costs that this infection carries both socially and to the health system require the continuous and systematic assessment of the diagnostic and treatment strategies, as well as the accessibility to diagnostic methods and most efficient drugs. Aim To register the diagnosis, management strategies, and treatment of H pylori-infected adult patients in the Digestive Services outpatient clinics throughout Europe. Methods Noninterventionist prospective multicentre international Registry promoted by the European Helicobacter and Microbiota Study Group. National Coordinators will select recruiting gastroenterologists in their country that will register the H pylori-related routine clinical practice consultations they receive in an electronic case report form (e-CRF) provided by AEG-REDCap. Variables retrieved will include clinical, diagnostic, treatment, eradication confirmation, and outcome data. The database will allow researchers to perform specific subanalyses after approval by the Scientific Committee of the study.

Review: Treatment of Helicobacter pylori Infection 2019

Abstract: This review summarizes important studies regarding Helicobacter pylori therapy published from May 2018 to May 2019. The main themes that emerge involve studies assessing the efficacy of bismuth-based regimens. While in recent years the efficacy of bismuth-based quadruple therapy as a second-line therapy has been clearly established, there is now substantial evidence that it is the best performing first-line therapy. Antibiotic resistance was again intensely studied this year, and a clear and dramatic increase in resistance is noted for clarithromycin and levofloxacin; most notably, it may not be possible to support these therapies in most regions of the world much longer without testing. The utility of vonoprazan as an alternative to proton-pump inhibitor therapy, especially in resistant and difficult to treat groups, has also been considered in greater detail this year, as well as means of supporting and enhancing adherence to therapy. Several studies showed that the diversity of gut microbiota was significantly altered shortly after H pylori eradication. However, the diversity was restored to pre-treatment state after 2 months in patients treated with triple therapy. More studies are warranted to assess the long-term changes of gut microbiota after H pylori eradication.

'Quality of Care' Standards in Inflammatory Bowel Disease: A Systematic Review.

Abstract: Background Inflammatory bowel disease [IBD] includes chronic, disabling and progressive conditions that need a complex approach and management. Although several attempts have been made to standardize the care of IBD patients, no clear definitions of a global 'standard of care' are currently available. Methods We performed a systematic review of the available literature, searching for all relevant data concerning three main domains of standards of quality of care in IBD patients: structure, process and outcomes. From the literature search, 2394 abstracts were retrieved, and 62 relevant papers were included in the final review. Results Standards of quality of care in IBD include several aspects that can be summarized in three identified domains: structure, process and outcomes. The suggested structure of an IBD Unit includes a multi-disciplinary approach, effective referral processes, improved access using helplines, and departmental guidelines/pathways with identification of measurable quality indicators. Coordinated care models which incorporate a multi-disciplinary approach, structured clinical pathways or processes for the diagnosis, monitoring and treatment of IBD, fast-track recovery from IBD surgery, designated IBD clinics, virtual clinics and telemanagement are currently considered the main standards for process, although supporting data are limited. Several consensus statements on outcomes and quality indicators have been reported, focusing on outcomes in symptoms, function and quality of life restoration, survival and disease control, in addition to effective healthcare utilization. Conclusions The results of this systematic review can provide the basis for general recommendations for standards of quality of care in IBD.

A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection.

Abstract: Background Recurrence remains a challenge in Clostridium difficile infection (CDI), and in this field fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysi...

Clinical Usefulness of Proteomics in Inflammatory Bowel Disease: A Comprehensive Review.

Abstract: The protein domain is probably the most ubiquitously affected in disease, response and recovery, and therefore proteomics holds special promise for biomarker discovery in general, and particularly in inflammatory bowel disease [IBD], i.e. ulcerative colitis and Crohn's disease. Tremendous progress has been made over the past decade in the development and refinement of proteomics technologies. These advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of IBD. The present review examines the current state of IBD proteomics research and its usefulness in clinical practice. We performed a systematic bibliographic search to identify studies investigating the use of proteomics in patients with IBD, and we then summarized the current 'state of the art' in the applications of proteomic technologies in the study of IBD. In particular, in the present review we provide: [1] a brief introduction to proteomics in health and disease; [2] a review of the different stages from biomarker discovery to clinical application; and [3] a comprehensive review of the clinical usefulness and application of proteomics in IBD, including: [a] screening to differentiate IBD from healthy controls; [b] differentiating Crohn's disease from ulcerative colitis; [c] prediction of the behaviour or the IBD course; [d] prediction of IBD response to biological treatment; and [e] monitoring response to treatment. We also review the importance of the type of sample-blood vs intestinal tissue-for the study of proteomics in IBD patients. Finally, we emphasize the current limitations of proteomic studies in IBD.

Increased risk of thiopurine-related adverse events in elderly patients with IBD.

Abstract: BACKGROUND Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases. AIM To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared. RESULTS Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P 60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs. CONCLUSION In elderly IBD patients, thiopurines are associated with an increased risk of non-infectious, non-neoplastic, AEs.

Differences between childhood- and adulthood-onset inflammatory bowel disease: the CAROUSEL study from GETECCU.

Abstract: BACKGROUND Cohort studies comparing the characteristics of childhood-onset and adulthood-onset inflammatory bowel disease (IBD) in the biologics era are scarce. AIM To compare disease characteristics, the use of immunomodulators and biologic agents and the need for surgery between childhood- and adulthood-onset IBD. METHODS Inflammatory bowel disease patients from the ENEIDA registry diagnosed between 2007 and 2017 were included. The childhood-onset cohort comprised patients diagnosed at ≤16 years of age and the adulthood-onset cohort those diagnosed at >16 years. The cumulative incidences of immunosuppressive therapy, biologic therapy and surgery were estimated using Kaplan-Meier curves, compared by the log-rank test. Cox regression analysis was performed to identify potential predictive factors of treatment with immunosuppressants, biologic agents or surgery. RESULTS The adulthood-onset cohort comprised 21 200 patients out of 20 354 (96%) and the childhood-onset cohort 846 (4%). Median follow-up was 54 months in the childhood-onset cohort and 38 months in the adulthood-onset cohort (P < 0.01). Proportions of Crohn's disease, ileocolonic involvement and inflammatory behaviour at diagnosis were higher in the childhood-onset cohort. In the multivariate analysis, after adjusting for sex, type of IBD, extraintestinal manifestations, family history and smoking habit, childhood-onset IBD was associated with higher risk of immunomodulator use (hazard ratio [HR] = 1.2, 95% confidence interval [95% CI] = 1.1-1.2) and higher probability of receiving biologic treatment (HR = 1.2, 95% CI = 1.1-1.3). However, childhood-onset IBD was not associated with higher risk of surgery (HR = 0.9, 95% CI = 0.8-1.2). CONCLUSIONS Childhood-onset IBD has differential characteristics and higher risk of treatment with immunomodulators and biologic agents, compared with adulthood-onset IBD. Nevertheless, paediatric IBD is not associated with higher risk of surgery.

Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study.

Abstract: Background and aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

Abstract: BACKGROUND The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

[European registry Helicobacter pylori (Hp-EuReg): how has clinical practice changed in Russia from 2013 to 2018 years].

Abstract: The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: “Hp-EuReg”) allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. Materials and methods. A comparative analysis of the data entered in the register by the Russian research centers “Hp-EuReg”, in the period from 2013 to 2018, was conducted. Results and discussion. Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. Conclusion. In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.

Immunomodulatory Effect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease

Abstract: Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

Abstract: BACKGROUND AND AIMS To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

Abstract: Background Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. Methods Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. Results In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. Conclusions In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

Correlation Between Anti-TNF Serum Levels and Endoscopic Inflammation in Inflammatory Bowel Disease Patients

Abstract: (a) To evaluate the diagnostic accuracy of anti-TNF trough levels to predict mucosal healing in inflammatory bowel disease (IBD); (b) to determine the best cut-off point to predict mucosal healing in IBD patients treated with anti-TNF. This is a multicenter, prospective study. IBD patients under anti-TNF treatment for at least 6 months that had to undergo an endoscopy were included. Mucosal healing was defined as: Simple endoscopic score for Crohn’s Disease < 3 for Crohn’s disease (CD), Rutgeerts score < i2 for CD in postoperative setting, or Mayo endoscopic score ≤ 1 for ulcerative colitis (UC). Anti-TNF concentrations were measured using SMART ELISAs at trough. A total of 182 patients were included. Anti-TNF trough levels were significantly higher among patients that had mucosal healing than among those who did not. The area under the curve of infliximab for mucosal healing was 0.63 (best cutoff value 3.4 μg/mL), and for adalimumab 0.60 (best cutoff value 7.2 μg/mL). In the multivariate analysis, having anti-TNF drug levels above the cutoff values [odds ratio (OR) 3.1]) and having UC instead of CD (OR 4) were associated with a higher probability of having mucosal healing. Additionally, the need for an escalated dosage (OR 0.2) and current smoking habit (OR 0.2) were also associated with a lower probability of mucosal healing. There was an association between anti-TNF trough levels and mucosal healing in IBD patients; however, the accuracy of the determination of infliximab and adalimumab concentrations able to predict mucosal healing was suboptimal.

Systematic review with meta-analysis: the prevalence of bile acid malabsorption and response to colestyramine in patients with chronic watery diarrhoea and previous cholecystectomy.

Abstract: Background A limited number of small-sized studies suggest that bile acid diarrhoea is frequent in patients with chronic watery diarrhoea and previous cholecystectomy. Aim To perform a systematic review and meta-analysis to assess the prevalence of bile acid diarrhoea in patients with chronic watery diarrhoea and previous cholecystectomy, and their response to colestyramine, including a new consecutive series of patients. Methods MEDLINE and EMBASE were searched up to January 2018. Selected studies included patients with previous cholecystectomy and chronic watery diarrhoea assessed by the 23-seleno-25-homotaurocholic acid (SeHCAT) test. We calculated the pooled rate of bile acid diarrhoea using the inverse double arcsine square root method. Additionally, the medical records of 291 consecutive patients with chronic watery diarrhoea in whom a SeHCAT test was performed were retrospectively reviewed and 74 with previous cholecystectomy were included in the meta-analysis. Results The search strategy identified eight relevant studies, which, together with the data of the present series, comprise 361 individuals. The pooled bile acid diarrhoea rate was 70% (95% CI 56%-82%), and was similar when using cut-offs of 10% or 15%. There was substantial heterogeneity (I2 = 84%). Five studies comprising 166 patients evaluated the effect of colestyramine in patients with bile acid diarrhoea. The pooled colestyramine response rate was 79% (95% CI 63%-91%) with substantial heterogeneity (I2 = 73%). Conclusions Two-thirds of patients with chronic watery diarrhoea and previous cholecystectomy have bile acid diarrhoea. Response to colestyramine in these patients is good.

Spanish primary care survey on the management of Helicobacter pylori infection and dyspepsia: Information, attitudes, and decisions.

Abstract: Introduction Dyspepsia and Helicobacter pylori are two of the most relevant digestive conditions in primary care. Several consensuses on the subject have been published, but the assimilation/implementation of these guidelines is uncertain. Aims and methods To evaluate the attitudes, perceptions, limitations, and adherence to recommendations of Spanish primary care physicians using an open online survey. Responses were anonymously codified. Estimated margin of error was 3.4%. Responses were weighted by province, gender, age, and type of practice. Survey was performed using the AEG-REDCap platform. Results A total of 1445 responses, received between December 2017 and April 2018, were analyzed. Women represented 54%, and the average age was 48 years; 59% were from urban context, 20% from semi-urban, and 21% from rural; 93% provided public practice. Over 40% had read at least one Maastricht consensus (24% Maastricht V), and 34% had attended a course related to H. pylori. 16% reported no direct access to any validated diagnostic method, only 44% to urea breath test, and 33% did not systematically refer to eradication confirmation test. The first-line treatment of choice was standard triple therapy in 56%, followed by concomitant therapy (28%). Only 20% of physicians had optimal adherence to recommendations. Conclusion Even though some improvements from guidelines have been partially incorporated, the level of penetration of recommendations is still poor and delayed. To provide optimal primary care, the barriers for implementation, access to diagnostic tests and to continuous medical education, should be removed. Rigorous dissemination, implementation, and evaluation programs are desired in future consensuses.

EpidemIBD: Rationale and Design of a Large-Scale Epidemiological Study of Inflammatory Bowel Disease in Spain

Abstract: Background:Inflammatory bowel disease (IBD) is associated with a considerable burden to the patient and society. However, current data on IBD incidence and burden are limited because of the paucity...

Biosimilar and interchangeable: Inseparable scientific concepts?

Abstract: As defined by the European Commission, the term interchangeability refers to “the possibility of exchanging one medicine for another that is expected to have the same clinical effect.” In the context of biosimilars the term interchangeability has caused confusion. Likely due to specific regulatory requirements in the United States, physicians sometimes interpret interchangeability as the potential for a biologic to be substituted by a biosimilar at the pharmacy level, without the involvement of a physician. However, interchangeability between a biological reference medicine and a corresponding biosimilar medicine should not be defined by its practical application; whether physician‐driven switch or pharmacist‐driven substitution. Interchangeability, ie, the possibility of safely and effectively changing a reference medicine by its biosimilar, or vice‐versa, in a given patient, should be rather recognized as a scientific concept. In this paper, we review the evidence supporting the assertion that interchangeability is inherent to biosimilarity. In science, a conclusion is reached when a hypothesis is tested by the use of an appropriate experimental approach. The aim of biosimilar development is to replicate an existing biomedicine. Biosimilarity must be substantiated by robust scientific evidence. To generate such evidence, a hypothesis of high similarity between a biosimilar candidate and the original reference medicine should be verified through well‐ established and validated methodologies that aim to identify all the potential relevant physicochemical differences, but are also capable of detecting even clinically meaningless differences. The acceptable difference level between the biosimilar candidate and the reference medicine is determined to a qreat extent by a thorough assessment of multiple batches of the reference biologic. Indeed, no approved biological medicine, whether original or not, is structurally identical to itself, due to an intrinsic batch‐to‐batch variability that can be enhanced by manufacturing changes. Although different batches of reference biological compounds are not identical to each other, they may be considered essentially equal and therapeutically indistinguishable. Therefore, there is a clinically acceptable range of inherent structural heterogeneity for any biological product. As a consequence, many patients have likely been treated with structurally slightly different versions of any given reference biomedicine, which constitutes a de facto switch of insignificant therapeutic concern. The approach used to substantiate biosimilarity represents a refinement of the procedures that have been securely applied for decades to batches of biologics that are subject to manufacturing changes, but also to the very precise discrimination between native and non‐native proteins during the monitoring of

Empirical Helicobacter pylori rescue therapy: an 18‐year single‐centre study of 1200 patients

Abstract: Many changes have been made to the guidelines on rescue treatments for Helicobacter pylori infection due to their poor effectiveness in clinical practice.

Randomised clinical trial: intravenous vs oral iron for the treatment of anaemia after acute gastrointestinal bleeding

Abstract: BACKGROUND Acute gastrointestinal bleeding is prevalent condition and iron deficiency anaemia is a common comorbidity, yet anaemia treatment guidelines for affected patients are lacking. AIM To compare efficacy and safety of intravenous ferric carboxymaltose (FCM) and oral ferrous sulphate (FeSulf) in patients with anaemia secondary to non-variceal gastrointestinal bleeding METHODS: A prospective 42-day study randomised 61 patients with haemoglobin <10 g/dL upon discharge (Day 0) to receive FCM (n = 29; Day 0: 1000 mg, Day 7: 500 or 1000 mg; per label) or FeSulf (n = 32; 325 mg/12 hours for 6 weeks). Outcome measures were assessed on Days 0 (baseline), 7, 21 and 42. The primary outcome was complete response (haemoglobin ≥12 g/dL [women], ≥13 g/dL [men]) after 6 weeks. RESULTS A higher proportion of complete response was observed in the FCM vs the FeSulf group at Days 21 (85.7% vs 45.2%; P = 0.001) and 42 (100% vs 61.3%; P < 0.001). Additionally, the percentage of patients with partial response (haemoglobin increment ≥2 g/dL from baseline) was significantly higher in the FCM vs the FeSulf group (Day 21:100% vs 67.7%; P = 0.001, Day 42:100% vs 74.2%; P = 0.003). At Day 42, normalisation of transferrin saturation to 25% or greater was observed in 76.9% of FCM vs 24.1% of FeSulf-treated patients (P < 0.001). No patient in the FCM group reported any adverse event vs 10 patients in the FeSulf group. CONCLUSION FCM provided greater and faster Hb increase and iron repletion, and was better tolerated than FeSulf in patients with iron deficiency anaemia secondary to non-variceal acute gastrointestinal bleeding.