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 assesment, 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 analysed. 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.

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.

Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011). CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

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.

Incidence and Course of Joint Inflammation Associated with Inflammatory Bowel Disease in Patients Undergoing Treatment with Vedolizumab/Ustekinumab: The VEDUSTAR Study.

BACKGROUND: The role of ustekinumab (UST) and vedolizumab (VDZ) in the extraintestinal joint manifestations of inflammatory bowel disease (IBD) remain unclear, and most existing studies are retrospective. The aim of this prospective study was to analyze the incidence of new-onset joint disease or the worsening of pre-existing IBD-associated joint disease in patients treated with UST and VDZ. METHODS: The study population comprised IBD patients with previous spondyloarthritis (SpA) or new-onset arthropathy undergoing treatment with VDZ or UST. RESULTS: Eighty patients were referred to rheumatology because of previous SpA or onset of symptoms. Most patients (90%) were anti-TNF experienced. Two patients with previous SpA (2/22; 9%) experienced a flare-up (one with UST and one with VDZ), and two patients with VDZ developed SpA during follow-up (2/58; 3%). Only one of these four patients did not have gastrointestinal symptoms, and VDZ was discontinued because of joint symptoms. The other three patients had concomitant intestinal activity, and treatment was not discontinued. CONCLUSION: Our experience shows that treatment with UST and VDZ did not worsen joint disease in patients with SpA. Most remained stable or improved. In addition, poor control of IBD in patients with joint flare-ups could be the main cause of worsening SpA.

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.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

Diffuse large B-cell lymphoma and gastrointestinal Kaposi's sarcoma: a rare cause of upper gastrointestinal bleeding.

A 49-year-old man with a history of human immunodeficiency virus (HIV) infection, in a state of advanced immunosuppression and current antiretroviral therapy initiation. He was admitted to the hematology department after diagnosis of diffuse large B-cell lymphoma (DLBCL) associated with Epstein-Barr virus (EBV), disseminated cytomegalovirus (CMV) infection and cutaneous Kaposi's sarcoma (KS). During admission, he presented an episode of melena with anemization, so an urgent gastroscopy was performed. In the stomach there were multiple erythematous lesions, large and elevated, suggestive of subepithelial origin. Some of them presented an umbilicated center and other were ulcerated, covered with fibrin. The bulb and second duodenal portion showed similar involvement, large violaceous ulcerated lesions. Biopsies were taken and the anatomopathological diagnosis of the duodenal lesions was KS and of the gastric lesions KS and DLBCL associated with EBV. KS is an endothelial tumor associated with HIV. The stomach is the gastrointestinal organ most frequently affected and the typical endoscopic findings are nodular lesions. The stomach is the most common site of extranodal involvement in DLBCL. In both pathologies, the manifestation as upper gastrointestinal bleeding is exceptional and endoscopic biopsies can confirm the diagnosis.

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.

Epidemiological, Clinical, Patient-Reported and Economic Burden of Inflammatory Bowel Disease (Ulcerative colitis and Crohn's disease) in Spain: A Systematic Review.

INTRODUCTION: This study describes the epidemiological, clinical, patient-reported and economic burden of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), in Spain. METHODS: A systematic review was performed of observational studies reporting the epidemiological, clinical, patient-reported and economic burden of IBD in the Spanish population, from 2011 to 2021. Original articles and conference abstracts published in English or Spanish were eligible. RESULTS: A total of 45 publications were included in the review. The incidence of IBD in adults ranged from 9.6 to 44.3 per 100,000 inhabitants (4.6 to 18.5 for CD and 3.4 to 26.5 for UC). The incidence increased between 1.5- and twofold from 2000 to 2016 (regionally). Up to 6.0% (CD) and 3.0% (UC) IBD-associated mortality was reported. Disease onset predominantly occurs between 30 and 40 years (more delayed for UC than CD). Most frequently reported gastrointestinal manifestations are rectal bleeding in UC and weight loss in CD. Extraintestinal manifestations (EIM) have been described in up to 47.4% of patients with CD and 48.1% of patients with UC. Psychiatric comorbidities were frequently reported in both CD and UC (depression up to 20% and anxiety up to 11%). Reduced health-related quality of life (HRQoL) compared to the general population was reported. Significant symptomatology was associated with high levels of anxiety, depression, stress and lower HRQoL. Main healthcare resources reported were emergency department visits (24.0%), hospitalization (14.7%), surgery (up to 11%) and use of biologics (up to 60%), especially in CD. Direct and indirect annual costs per patient with UC were €1754.1 and €399.3, respectively. CONCLUSION: Patients with CD and UC present a high disease burden which negatively impacts their HRQoL, leading to elevated use of resources.

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.

Randomized clinical trial evaluating three low-volume preparations for colonoscopy in outpatients with Inflammatory Bowel Disease: the EII-PREP trial.

BACKGROUND: Data regarding bowel preparation in patients with Inflammatory Bowel Disease (IBD) are scarce. AIM: To compare efficacy, safety, and tolerability of low-volume preparations in patients with IBD. METHODS: Single-center, randomized, prescriber, and colonoscopist-blinded clinical trial. IBD outpatients undergoing colonoscopy were randomized 1:1:1 to receive 1 Liter-polyethylene glycol-ascorbate (1L-PEG), 2 Liters-PEG, or sodium picosulfate (SP). The primary endpoint was percentage of quality cleansing assessed via the Boston Bowel Preparation Scale (BBPS ≥6, segments ≥2). Secondary endpoints were total high quality cleansing (BBPS 8 or 9), high-quality segmental BBPS (≥2), and patients' tolerability, symptoms, and satisfaction, assessed by questionnaires. Safety was monitored by adverse event reporting, laboratory evaluation at colonoscopy, and telephonic follow-up. RESULTS: Ninety-two patients were included (33 1L-PEG, 28 2L-PEG, and 31 SP). No significant differences between preparations were observed in quality or high-quality total BBPS or high-quality segmental BBPS. Complete intake of the solution was higher for SP (p = 0.006) and lower for 1L-PEG (p = 0.02) compared to 2L-PEG intake (p = 0.55). Clinically irrelevant hyponatremia was higher in the SP group (p < 0.0001). SP instructions were easier to understand from patient's point of view (p = 0.01). Willingness to retake was higher with SP (p < 0.0001) and less for 1L-PEG (p < 0.0001). No serious adverse events were reported. CONCLUSIONS: We observed no differences in efficacy between low-volume preparations in patients with IBD. Complete intake was higher for SP and lower for 1L-PEG. SP and 2L-PEG instructions were better understood and graded, and SP was more likely to be retaken. Willingness to retake was lower for 1L-PEG. No serious adverse events were reported. SUMMARY: No differences in terms of efficacy were regarded in this clinical trial comparing low-volume preparations for colonoscopy in patients with IBD: however, Sodium Pisoculfate is better tolerated and accepted from patient's point of view. No serious adverse events were reported.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Influence of biologic therapy on cardiovascular risk factors in patients with inflammatory bowel disease. / Influencia del tratamiento biológico en los factores de riesgo cardiovascular de los pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Chronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age. OBJECTIVE: To describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity. PATIENTS AND METHODS: It is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission. RESULTS: A total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab. The changes in blood glucose levels are [86.31mg/dL (84.57-88.06) vs. 89.25mg/dL (87.54-90.96), P=.001] for those treated with antiTNFα and [86.52mg/dL (83.48-89.55) vs. 89.44mg/dL (85.77-93.11), P=.11] in the other group. In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40mg/dL (164.97-173.83) vs. 177.40mg/dL (172.75-182.05) at one year of treatment, P=<.001], those of HDL [50.22mg/dL (48.39-52.04) vs. 54.26mg/dL (52.46-56.07), P=<.001] and those of triglycerides [114.77mg/dL (106.36-123.18) vs. 121.83mg/dL (112.11-131.54), P=.054]. Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39kg (69.53-73.25) vs. 72.87kg (71.05-74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59kg (64.10-71.08) vs. 69.43kg (65.65-73.04), P=.003]. Concerning CVE, no significant differences were observed neither according to the drug used (p=0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46). CONCLUSIONS: Our results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients.

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)

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case-Control Study (COVID-19-EII).

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.

Correction: Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885.

The authors wish to make the following corrections to this paper [...].

Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.

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.