HIV infection is associated with a less aggressive phenotype of inflammatory bowel disease. A multicenter study of the ENEIDA registry.

BACKGROUND: The coexistence of human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD) is uncommon. Data on the impact of HIV on IBD course and its management is scarce. AIM: To describe the IBD phenotype, therapeutic requirements and prevalence of opportunistic infections (OI) in IBD patients with a coexistent HIV infection. METHODS: Case-control, retrospective study including all HIV positive patients diagnosed with IBD in the ENEIDA registry. Patients with positive HIV serology (HIV-IBD) were compared to controls (HIV seronegative), matched 1:3 by year of IBD diagnosis, age, gender and type of IBD. RESULTS: A total of 364 patients (91 HIV-IBD and 273 IBD controls) were included. In the whole cohort, 58% had ulcerative colitis (UC), 35% had Crohn's disease (CD) and 7% were IBD unclassified. The HIV-IBD group presented a significantly higher proportion of proctitis in UC and colonic location in CD but fewer extraintestinal manifestations than controls. Regarding treatments, non-biological therapies (37.4% vs. 57.9%; P=0.001) and biologicals (26.4% vs. 42.1%; P=0.007), were used less frequently among patients in the HIV-IBD group. Conversely, HIV-IBD patients developed more OI than controls regardless of non-biological therapies use. In the multivariate analysis, HIV infection (OR 4.765, 95%CI 2.48-9.14; P<0.001) and having ≥1 comorbidity (OR 2.445, 95%CI 1.23-4.85; P=0.010) were risk factors for developing OI, while CD was protective (OR 0.372, 95%CI 0.18-0.78;P=0.009). CONCLUSIONS: HIV infection appears to be associated with a less aggressive phenotype of IBD and a lesser use of non-biological therapies and biologicals but entails a greater risk of developing OI.

Long-term risk of delayed postoperative Crohn's disease recurrence in patients with no or mild endoscopic recurrence at first assessment.

BACKGROUND: Early endoscopic evaluation is recommended for assessment of postoperative recurrence (POR) of Crohn's disease (CD) but no further monitoring recommendations are available. AIM: To evaluate the long-term outcome of patients without endoscopic POR at first endoscopic assessment. METHODS: Retrospective four-centre study including consecutive CD patients with ileocolonic resection (ICR) without endoscopic POR (Rutgeerts score i0-i1) at first endoscopic assessment performed within 18 months from ICR. All patients had a clinical follow-up ≥24 months and at least one further endoscopic assessment. Main outcomes were endoscopic, clinical and surgical POR, need for rescue therapy and "delayed POR" (any need for rescue therapy or clinical or surgical POR) during follow-up. RESULTS: Overall, 183 patients were included (79% with risk factors for POR, 44% without postoperative prophylaxis). Endoscopic POR was observed in 42% of patients. Clinical POR-free survival was 89.4% and 81.5% at 3 and 5 years, and delayed POR-free survival was 76.9% and 63.4% at 5 and 10 years, respectively. In multivariate analysis, postoperative prophylaxis (HR .55; 95% CI .325-.942) and active smoking (HR 1.72; 95%CI 1.003-2.962) were independent risk factors for clinical POR, whereas presence of mild endoscopic lesions at index ileocolonoscopy (i1) was the only risk factor for delayed POR (HR 1.824; 95% CI 1.108-3.002). CONCLUSIONS: Long-term risk of POR among patients with no or mild endoscopic lesions at first ileocolonoscopy after surgery is steadily low, being higher among smokers, in the absence of postoperative prophylaxis and when mild endoscopic lesions are observed in the first endoscopic assessment.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

External validation of the SHA2PE score and its comparison to the Oakland score for the prediction of safe discharge in patients with lower gastrointestinal bleeding.

BACKGROUND: The growing incidence of lower gastrointestinal bleeding (LGIB) is leading to a rise in-hospital admissions even though most LGIB episodes are self-limiting. The Oakland and SHA2PE scores were designed to identify patients best suited to outpatient care. Our aim is explore the validity of the SHA2PE score and compare both of these scores in terms of predictiveness of safe discharge. METHODS: Retrospective observational study of LGIB patients admitted to a tertiary hospital between June 2014 and June 2019. Safe discharge was defined as the absence of all the following: blood transfusion, haemostatic intervention, re-bleeding, in-hospital death, and re-admission due to LGIB within 28 days after discharge. RESULTS: From 595 hospital admissions for LGIB, 398 episodes were included. Fifty-four per cent met safe discharge criteria, with these cases being younger, with a lower score in the Charlson's index and significantly higher haemoglobin concentration upon arrival. The performance of both scores was good, with an AUC for the Oakland score of 0.85 (95% CI 0.82-0.89) and of 0.797 (95% CI 0.75-0.84) for the SHA2PE score. The Oakland score performed better in terms of prediction of safe discharge, with a positive predictive value and specificity of 100% when a cut-off value of ≤ 8 points was used; however, only a minority of patients might benefit from its implementation given its low sensitivity. CONCLUSIONS: Almost half of the patients admitted for LGIB met criteria for safe discharge. However, the available indexes only allow for the identification of a small proportion of those patients candidates for outpatient care.

Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

Hepatosplenic T-cell lymphoma and inflammatory bowel disease.

A 48-year-old man with a diagnosis of ulcerative colitis 18 years ago, under immunosuppressive treatment with azathioprine in the last 6 years due to corticosteroid dependence, was admitted to the Emergency Department due to fever of one week's evolution. Blood tests showed thrombocytopenia, CRP 96.9mg/L, ferritin 3021ng/mL and hypertriglyceridemia. Blood and urine cultures were negative. Viral serologies (hepatitis B and C, HIV, parvovirus, CMV, HSV), atypical bacteria (Borrelia, Chlamydia, Coxiella) and screening for latent tuberculosis were also negative. Thoracoabdominal CT scan only showed splenomegaly. The bone marrow aspirate revealed immature lymphoid cells and a hemophagocyte figure, fulfilling the criteria for hemophagocytic syndrome, starting corticosteroid therapy at a dose of 1mg/Kg. Subsequently, the existence of an intrasinusoidal CD3 + CD5- lymphoid infiltrate and a FISH study with isochromosome 7q was reported, a characteristic pattern of hepatosplenic T-cell lymphoma (HSTCL). The study was completed with liver biopsy appreciating a 70% infiltration of T lymphocytes (50% gamma-delta) therefore the diagnosis was confirmed. Chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide) was started with the aim of considering hematopoietic stem cell transplantation. Unfortunately, the patient died 6 months later.

Incidence of herpes zoster in patients with inflammatory bowel disease. / Incidencia de herpes zóster en pacientes con enfermedad inflamatoria intestinal: estudio observacional y retrospectivo en dos hospitales españoles de tercer nivel.

BACKGROUND: Herpes zoster (HZ) is a prevalent disease caused by the reactivation of the varicella-zoster virus (VZV) and associated with chronic morbidity, particularly with post-herpetic neuralgia (PHN). Inflammatory bowel disease (IBD) has been associated with an increased risk of HZ, mainly when immunosuppressive treatment (IMT) is used. However, studies assessing the risk of HZ in IBD are scarce. AIMS: To evaluate the incidence rate and risk factors of HZ in IBD. METHODS: Retrospective study in IBD patients with a positive VVZ serology from two referral hospitals from the area of Barcelona. Diagnosis of HZ and its clinical features were recorded. RESULTS: A total of 398 IBD patients with a positive IgG-VVZ serology were identified. Fifty-eight percent of the patients received IMT (46.5% immunosuppressants monotherapy, 20.6% biologics monotherapy and, 32.7% combination therapy). After a median follow-up of 71 months (IQR 41.5-138.0), 17 (4.3%) patients developed HZ (cumulative incidence of 5.2 per 1000 person-year), 12 of them (70.6%) while receiving IMT. Median age at HZ episode was 38 years (IQR 27.5-52.5). Two (11%) developed PHN. Biological therapy was the only risk factor for developing HZ (OR 3.8 IC 95% 1.3-11.5; p=0.018). CONCLUSIONS: HZ is quite prevalent in IBD, occurring at early ages and particularly among patients using IMT. NPH appears to occur in a notable proportion of cases.

Perception of the impact of intravenous biological treatment on the work and professional environment in patients with inflammatory bowel disease. / Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). / Impacto de la mesalazina en la respuesta a la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal. Resultados de un estudio prospectivo multicéntrico de GETECCU (VACOVEII).

OBJECTIVE: The recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Mesalazine dose modification based on faecal calprotectin levels in patients with ulcerative colitis in clinical remission. / Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica.

BACKGROUND: Faecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. METHODS: Retrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. RESULTS: A total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36µg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524µg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. CONCLUSIONS: Mesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

Impact of left atrial appendage closure in patients on anticoagulation for atrial fibrillation and recurrent or chronic gastrointestinal bleeding.

BACKGROUND: Oral anticoagulation in non-valvular atrial fibrillation is associated with an increased risk of bleeding, particularly gastrointestinal bleeding, leading to treatment withdrawal in up to 50% of patients and putting them at risk of embolic events. Left atrial appendage closure (LAAC) can be an alternative to chronic anticoagulation. We aim to describe the impact of LAAC in patients with gastrointestinal bleeding (GIB) or chronic iron deficiency anaemia (CIDA) on healthcare resources consumption. METHODS: Observational retrospective study of patients who underwent LAAC for GIB or CIDA at a single centre. RESULTS: Nineteen patients with a median age of 74 years and a median Charlson score of six points were included in the study. Angiodysplasias were the most frequent cause of GIB or CIDA. The procedural success rate of LAAC was 100% with a median anticoagulant and antiplatelet treatment duration of 92 days. One year after the LAAC, we found a significant improvement in the lowest haemoglobin concentration and a reduction in the number of red blood cells transfusion, hospital admissions due to GIB and CIDA and the number of endoscopic examinations. One patient died due to a pulmonary thromboembolism. No deaths related to GIB were observed. CONCLUSIONS: LAAC seems to be a safe and effective alternative to anticoagulation in patients with GIB or CIDA.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

A booster dose of SARS-COV-2 vaccine improves suboptimal seroconversion rates in patients with inflammatory bowel disease. Results of a prospective multicenter study of GETECCU (VACOVEII study).

BACKGROUND: The response to SARS-CoV-2 vaccination decreases in inflammatory bowel disease (IBD) patients, specially under anti-TNF treatment. However, data on medium-term effectiveness are limited, specially using new recommended seroconversion rate (>260BAU/mL). Our aim was to evaluate the 6-month>260 BAU-seroconversion rate after full vaccination and after booster-dose. METHODS: VACOVEII is a Spanish multicenter, prospective study promoted by GETECCU. IBD patients full vaccinated against SARS-CoV-2 and without previous COVID-19 infection, treated or not with immunosuppressants, were included. The booster dose was administered 6 months after the full vaccination. Seroconversion was set at 260BAU/mL, according to most recent recommendations and was assessed 6 months after the full vaccination and 6 months after booster-dose. RESULTS: Between October 2021 and March 2022, 313 patients were included (124 no treatment or mesalazine; 55 immunomodulators; 87 anti-TNF; 19 anti-integrin; and 28 ustekinumab). Most patients received mRNA-vaccines (86%). Six months after full vaccination, overall seroconversion rate was 44.1%, being significantly lower among patients on anti-TNF (19.5%, p<0.001) and ustekinumab (35.7%, p=0.031). The seroconversion rate after booster was 92%. Again, anti-TNF patients had a significantly lower seroconversion rate (67%, p<0.001). mRNA-vaccine improved seroconversion rate (OR 11.720 [95% CI 2.26-60.512]). CONCLUSION: The full vaccination regimen achieves suboptimal response in IBD patients, specially among those anti-TNF or ustekinumab. The booster dose improves seroconversion rate in all patients, although it remains limited in those treated with anti-TNF. These results reinforce the need to prioritize future booster doses in patients on immunosuppressants therapy, specially under anti-TNF, and using mRNA-vaccines.

Effect of rifaximin on infections, acute-on-chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA-AH).

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. METHODS: This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end-stage liver disease (MELD). We evaluated bacterial infections, liver-related complications, mortality and liver function tests after 90 days. RESULTS: Twenty-one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute-on-chronic liver failure (ACLF) linked to infections within the treatment group. Liver-related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. CONCLUSIONS: Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.

Treatment Adherence and Clinical Outcomes of Patients with Inflammatory Bowel Disease on Biological Agents During the SARS-CoV-2 Pandemic.

BACKGROUND: The outbreak of COVID19 evolved rapidly into a global pandemic, forcing hospitals, including inflammatory bowel disease (IBD) referral units, to change their practices to ensure quality of care. AIMS: To describe the clinical outcomes and the fulfilment of the treatment schedule of patients with IBD treated with biological agents in a single-center of a red-zone of the pandemic, and to report the patients' perceptions about COVID-19 and the measures adopted at our center. METHODS: Therapeutic adherence and clinical outcomes were collected for all patients undergoing treatment with intravenous biologicals and subcutaneous biologicals at our center. A telephone survey was also performed to assess these patients' perceptions of the COVID pandemic and the related measures adopted at their IBD unit. RESULTS: A total of 234 patients were included (117 on intravenous and 117 on subcutaneous biologicals). Only 10% of patients postponed intravenous infusions intentionally and 5% postponed the collection of subcutaneous biologicals at the hospital pharmacy. Only five confirmed COVID-19 cases were registered (2.1%), all of them of mild severity. One hundred and fifty-five patients participated in the survey (77 on intravenous and 78 on subcutaneous drugs). Fear of going to the hospital was the most common reason for postponing biological administrations. Among those on combination therapy, only 7% admitted to have withdrawn immunosuppressants. CONCLUSIONS: Adherence to intravenous and subcutaneous biological therapies during the pandemic was high in a single-center cohort of IBD patients even though the cumulative incidence of confirmed COVID-19 was low.

Impact of immunosuppressants on SARS-CoV-2 infection in elderly patients with inflammatory bowel disease.

BACKGROUND: Older age has been reported as a risk factor for severe SARS-CoV-2 disease (COVID-19). The impact of immunosuppressants (IMS) on COVID-19 is still under debate. AIM: To describe the incidence and severity of COVID-19 in elderly patients with inflammatory bowel disease (IBD) in relation to the use of IMS. METHODS: IBD patients over 65 years of age were selected and grouped in terms of IMS use. Confirmed COVID-19, adherence to IST, comorbidities and concomitant non-IBD-related treatments between 1st of March 2020 to 1st of March 2021 were recorded. RESULTS: Out of 418 patients included, 89 (21.3%) were on IMS. Thirty-two patients (7.7%) had COVID-19, 7 of whom were on IMS (7.6% not on IMS vs. 7.9% on IMS; P = 0.933) and 7 (22%) patients died. CONCLUSIONS: Incidence of COVID-19 among elderly IBD patients was similar to that reported in the background population, regardless of the use of IMS.

Spacing the Administration Interval of Anti-TNF Agents: A Valid Strategy for Patients with Inflammatory Bowel Disease?

BACKGROUND: Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). AIM: To evaluate the outcomes of IBD patients treated with this strategy. METHODS: Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. RESULTS: Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. CONCLUSIONS: Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.

Efficacy and safety of endoscopic balloon dilation in inflammatory bowel disease: results of the large multicenter study of the ENEIDA registry.

BACKGROUND: There is no information regarding the outcome of Crohn's disease (CD) patients treated with endoscopic balloon dilation (EBD) in non-referral hospitals, nor on the efficacy of EBD in ulcerative colitis (UC). We report herein the results of the largest series published to date. AIM: To assess the efficacy and safety of EBD for inflammatory bowel disease (IBD) stenosis performed in 19 hospitals with different levels of complexity and to determine factors related to therapeutic success. METHODS: We identified IBD patients undergoing EBD in the ENEIDA database. Efficacy of EBD was compared between CD and UC and between secondary and tertiary hospitals. Predictive factors of therapeutic success were assessed with multivariate analysis. RESULTS: Four-hundred dilations (41.2% anastomotic) were performed in 187 IBD patients (13 UC/Indeterminate colitis). Technical and therapeutic success per dilation was achieved in 79.5% and 55.3%, respectively. Therapeutic success per patient was achieved in 78.1% of cases (median follow-up: 40 months) with 49.7% requiring more than one dilation. No differences related to either diagnosis or hospital complexity was found. Technical success [OR 4.12 (95%CI 2.4-7.1)] and not receiving anti-TNF at the time of dilation [OR 1.7 (95% CI 1.1-2.6)] were independently related to therapeutic success per dilation. A stricture length ≤ 2 cm [HR 2.43 (95% CI 1.11-5.31)] was a predictive factor of long-term success per patient. The rate of major complications was 1.3%. CONCLUSIONS: EBD can be performed with similar efficacy and safety in hospitals with differing levels of complexity and it might be a suitable treatment for UC with short stenosis. To achieve a technical success and the short length of the stenosis seem to be critical for long-term therapeutic success.