Evaluation of the transition from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease. / Valoración de la transición de vedolizumab intravenoso a subcutáneo en pacientes con enfermedad inflamatoria intestinal.

AIMS: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc). METHODS: An observational, prospective, single-center cohort study was performed. Patients with inflammatory bowel disease and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. RESULTS: Forty-three patients were included, 12 of them (27.9%) chose to transition to sc formulation. All included patients remained in remission during follow-up. At week 16 no significant differences were found in terms of calprotectin levels in patients on iv treatment (mean 146.6±SD 45.9) vs. sc (159.26±53.9) (p=0.9). Vedolizumab serum levels at week 16 were higher in the sc group (22,364.3±5141.6) vs. iv (11,425.9±1514.2) (p=0.009). At week 16, 9 (75%) of the patients in the sc group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. Four patients (12.9%) in the iv group and 2 (16.6%) in the sc group presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. CONCLUSION: In our experience, vedolizumab sc is a convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.

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.

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Intensification with Intravenous Ustekinumab in Refractory Crohn's Disease.

BACKGROUND: The rates of clinical and biochemical responses in Crohn's disease (CD) patients treated with intravenous (IV) ustekinumab (UST) intensification are scarcely described. METHODS: Patients with diagnosis of CD who were under intensified IV ustekinumab treatment (130 mg every 4 weeks) were retrospectively included, evaluating the clinical and biochemical response 12 weeks after the change in treatment regimen (switch from SC to IV), as well as the serum levels of the drug. RESULTS: Twenty-seven patients, all of whom had transitioned to intensified intravenous ustekinumab treatment due to a secondary loss of response to the drug, were included in the retrospective analysis. At the baseline visit, prior to changing IV UST, differences in levels were observed between intensified and non-intensified patients (7216 vs. 2842 ng/mL, p = 0.00005). However, no significant differences were found between these two groups 12 weeks after IV intensification (7949 vs. 7937 ng/mL; p = 0.99). In patients with previous intensified UST SC, a decrease in fecal calprotectin was observed 12 weeks after starting IV intensification, going from a mean of 1463 ug/g to 751 ug/g, although the differences were not significant (p = 0.14). CONCLUSION: In our experience, intensifying treatment with IV UST leads to clinical and biochemical improvements in CD patients with a secondary loss of response to SC maintenance with this drug, and an increase in drug levels was observed 12 weeks after IV UST intensification.

Selective granulocyte-monocyte apheresis during induction with vedolizumab in moderate-severe ulcerative colitis: Experience in a tertiary hospital.

AIM: Granulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate-severe UC and incomplete response to steroids. PATIENTS AND METHODS: Single-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded. RESULTS: The study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4-5; 3-10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39-74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378µg/g (IQR: 924-5778µg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3-113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed. CONCLUSIONS: GMA+VDZ during induction can be effective and safe in selected patients with moderate-severe UC and partial response to steroids.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

Human intestinal spirochetosis: an entity associated with sexual transmitted infections.

INTRODUCTION: Human intestinal spirochetosis (HIE) is a poorly studied clinical entity with variable clinical manifestations. However, in recent years it has gained special relevance because an increasing number of cases have been described in people living with HIV (PWH) and in patients with a history of sexually transmitted infections (STI) or immunosuppression. METHODS: Retrospective review of all HIE cases identified in a tertiary level hospital (Hospital Universitario la Paz, Madrid) between 2014 and 2021. RESULTS: 36 Cases of HIE were identified. Most cases corresponded to males (94%) with a median age of 45 years. 10 patients (29.4%) were PWH and 20 (56%) were men who had sex with men. Although the clinical manifestations were very heterogeneous, the most frequent was chronic diarrhea (47%), and up to 25% of the subjects had clinical proctitis. 39% percent of patients had been diagnosed with an STI in the previous two years, this characteristic being more frequent in PWH (90% vs. 28%; p < 0.01) than in patients without HIV infection. The STI most frequently associated with a diagnosis of HIE was syphilis (31%). CONCLUSION: HIE is frequently diagnosed with other STIs and affects mostly men who have sex with men, which supports that this entity could be considered as a new STI.

Serologic response to COVID-19 vaccines in patients with inflammatory bowel disease: a prospective study.

BACKGROUND AND AIMS: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. METHODS: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. RESULTS: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. CONCLUSION: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious.

Serologic response to COVID-19 vaccines in patients with inflammatory bowel disease: a prospective study

Background and aims: response to the SARS-CoV-2 vaccine can be altered in patients with immune-mediated diseases, such as inflammatory bowel disease, and in patients under immunosuppressive treatment. The aims of this study were to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease, to analyze the influence of immunosuppressive drugs on response, and to describe any adverse events in this population. Methods: this was a prospective study that included adult patients with inflammatory bowel disease. Baseline characteristics, concomitant treatments and previous COVID-19 symptoms were collected. Patients underwent serological testing before the first and after the second vaccine dose. Results: a total of 265 patients were consecutively included. Patients received one of the following vaccines: messenger RNA vaccines from Pfizer/BioNTech and Moderna; and adenovirus vaccines from AstraZeneca and Janssen. All adverse events were mild, and the most frequent was injection site pain in 141 (86 %) patients. The seroconversion rate according to the treatment that patients were receiving was: 100 % for those without treatment, 92.5 % for patients treated with mesalazine, 90.3 % for those receiving immunomodulators, 88.9 % for patients with biological monotherapy and 92.5 % for patients on combined treatment. The generation of antibodies according to the vaccine administered was: Pfizer 92.9 %, Moderna 93.3 %, AstraZeneca 98.4 %, and Janssen 12.5 %. Conclusion: the antibody response after vaccination against SARS-CoV-2 is high in patients with inflammatory bowel disease. However, patients treated with immunosuppressive or biologic drugs had a lower response. Adverse events were frequent, but not serious (AU)