Evaluation of genetic variants associated with the risk of thiopurine-related pancreatitis: a case control study from ENEIDA registry.

BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: 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, 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.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.

Subclinical bowel inflammation increases healthcare resources utilization and steroid use before diagnosis of inflammatory bowel disease.

BACKGROUND: Previous data support that the inflammatory process underlying ulcerative colitis (UC) and Crohn's disease (CD) can start years before the diagnosis. The aim of this study was to determine if patients with an incidental diagnosis of UC or CD demonstrate an increase in healthcare utilization in the years preceding the symptomatic onset of the disease. METHODS: We performed a multicenter, retrospective, hospital-based, case-control study. Patients with an incidental diagnosis of UC or CD during the colorectal cancer screening program at 9 hospitals were included. Cases were matched 1:3 and compared separately with two control populations: one including healthy non-IBD subjects adjusted by gender, age, and date, excluding those with visits to Gastroenterology; and a second control cohort of UC/CD patients with symptomatic onset. RESULTS: A total of 124 patients with preclinical inflammatory bowel disease (IBD) were included (87 UC, 30 CD, 7 IBD unclassified; median age 56 years). Patients with preclinical IBD showed an increase in the number of visits to Primary Care up to 3 and 5 years before diagnosis (aIRR 1.59, 95% CI [1.37-1.86], p = 0.001; aIRR 1.43, 95% CI [1.24-1.67], p = 0.01) and more frequent use of steroids (aOR 2.84, 95% CI [1.21-6.69], p = 0.03; aOR 2.25, 95% CI [1.06-4.79], p = 0.04) compared to matched non-IBD healthy controls, respectively. In contrast, patients with a symptomatic onset visited Primary Care less frequently, but they had an increase in the number of visits to Emergency Department, specialist care, sick-leaves, CT/ultrasound examinations, and use of antibiotics or systemic steroids. CONCLUSIONS: There is an increased need for medical assistance and use of systemic steroids during the presymptomatic phase of IBD. These results will help in establishing new tools for early identification of IBD in the future.

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

BACKGROUND: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice. METHODS: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. RESULTS: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). CONCLUSIONS: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Extraintestinal Manifestations in Patients with Inflammatory Bowel Disease: Study Based on the ENEIDA Registry.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. AIMS: Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. METHODS: Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. RESULTS: The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease, p < 0.001), gender (female, p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. CONCLUSIONS: One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Antitumor Necrosis Factor Agents to Treat Endoscopic Postoperative Recurrence of Crohn's Disease: A Nationwide Study With Propensity-Matched Score Analysis.

INTRODUCTION: Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR. METHODS: Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively. RESULTS: A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis. DISCUSSION: In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.

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

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.

Acute infection due to Mycobacterium marinum in a patient with ulcerative colitis and metabolic syndrome on infliximab therapy / Infección aguda por Mycobacterium marinum en un paciente con colitis ulcerosa y síndrome metabólico bajo tratamiento con infliximab

No disponible

Methotrexate Pneumonitis in Crohn's Disease: A Rare Case Report and Review of Literature / Neumonitis por metotrexato en la enfermedad de Crohn: un caso clínico inusual y revisión de la literatura

No disponible

Adalimumab treatment of anti-TNF-naïve patients with ulcerative colitis: Deep remission and response factors.

BACKGROUND: Adalimumab is the second tumour necrosis factor antagonist (anti-TNF) adopted for the treatment of ulcerative colitis. Clinical data from naïve patients are scarce. AIM: Examine the response to adalimumab in TNF-antagonist-naïve patients. METHODS: This multicentre, observational, prospective study was conducted using a cohort of consecutive patients with ulcerative colitis. Clinical remission, mucosal healing and deep remission were examined employing the Mayo Score and Mayo Endoscopic Score. Clinical response was assessed using the Partial Mayo Score. RESULTS: Of 53 individuals included in this study, 49.1% of patients were in clinical remission at week 8 and 60.3%, at week 52. Clinical response was observed in 84.9% and 69.8%, respectively. Mucosal healing was found in 62.3% and 67.9% of the patients, and 43.4% and 58.4% showed deep remission at week 8 and 52, respectively. After a year, 71.7% of the patients continued the adalimumab treatment. Adverse effects were observed in 28.3% of patients. Multivariate analysis showed that the long-term factor predictive of response at week 52 was the response in week 8 (expressed as Mayo Score; OR 0.66; 95% IC 0.1-0.67, p < 0.006). CONCLUSIONS: Adalimumab treatment of ulcerative colitis is effective; the results are better in clinical practice and in patients naïve to anti-TNF.

Prevalence of Malnutrition and Nutritional Characteristics of Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.

Colitis cystica profunda: A report of 2 cases with a 15-year follow-up / Colitis quística profunda: informe de 2 casos con 15 años de seguimiento

No disponible

Derrame pleural de predominio derecho secundario a fístula pancreatopleural en paciente con pancreatitis crónica asintomática / Right pleural effusion secondary to a pancreaticopleural fistula in a patient with asymptomatic chronic pancreatitis

No disponible

Combined liver and kidney transplant in a patient with budd-Chiari syndrome secondary to autosomal dominant polycystic kidney disease associated with polycystic liver disease: report of a case with a 9-year follow-up.

Polycystic liver disease (PLD) is a hereditary disease inherited by autosomal dominant trait that occurs as a frequent extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). We report a case of a 59-year-old woman diagnosed with ADPKD associated with PLD. End-stage chronic renal failure with a secondary Budd-Chiari syndrome developed during the patient's clinical course. She underwent combined liver and kidney transplantation, with a successful response over a 9-year follow-up period.