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.

Trastorno por déficit de atención e hiperactividad: perfil neuropsicológico y estudio de su impacto en las funciones ejecutivas y académicas / Attention deficit hyperactivity disorder: Neuropsychological profile and study of its impact on executive functions and academic performance

Introducción: El objetivo del presente estudio es describir el perfil neuropsicológico de los pacientes con trastorno por déficit de atención con hiperactividad (TDAH) y su impacto en las funciones ejecutivas y académicas. Pacientes y métodos: Se realizó un estudio analítico, observacional y retrospectivo. La muestra estuvo compuesta por 24 sujetos con diagnóstico de TDAH (6-15 años) sin tratamiento farmacológico y 24 controles (7-15 años) sin TDAH. Se realizó una evaluación neuropsicológica completa que abarcase los principales dominios cognitivos, así como la evaluación mediante cuestionarios a padres y profesores del funcionamiento ejecutivo y sintomatología psicopatológica. Resultados: El perfil cognitivo del grupo con TDAH se caracteriza por presentar puntuaciones globales (incluidas funciones ejecutivas y habilidades académicas) dentro del rango de la normalidad (puntuaciones z entre −1 y 1), aunque significativamente menores que las del grupo. Más de la mitad de los sujetos (58%) con TDAH presentan trastornos específicos de aprendizaje de manera comórbida. Por otro lado, los profesores tienden a informar de más dificultades de tipo ejecutivo cuando los sujetos son varones. Conclusiones: En nuestro grupo de estudio los pacientes diagnosticados con TDAH se caracterizan por presentar un rendimiento cognitivo dentro de la normalidad, aunque con menores puntuaciones que los controles. Los cuestionarios de conducta proporcionan información muy valiosa sobre el funcionamiento en entornos fuera de la consulta, pero pueden presentar sesgos al predominar los síntomas externalizantes. La evaluación neuropsicológica es una herramienta útil que puede facilitar el diagnóstico del TDAH y dar una respuesta eficaz a las características y a las necesidades de los pacientes y sus familias.(AU)

Introduction: The aim of the study was to describe the neuropsychological profile of patients with attention deficit hyperactivity disorder (ADHD) and the impact of the disorder on executive functioning and academic performance. Patients and methods: We conducted a retrospective observational and analytical study. The sample consisted of 24 children with a diagnosis of ADHD (aged 6-15 years) without pharmacological treatment and 24 controls without ADHD (aged 7-15 years). A comprehensive neuropsychological evaluation was carried out, encompassing major cognitive domains, in addition to assessment of executive functioning and psychopathological symptoms through the administration of questionnaires to parents and teachers. Results: The cognitive profile of the ADHD group was characterized by overall scores (including executive functions and academic abilities) in the normal range (z scores between −1 and 1), although significantly lower compared to the control group. Over half of the patients with ADHD (58%) had associated specific learning disorders. Furthermore, teachers tended to report executive function difficulties more frequently in male students. Conclusions: In the study sample, the group of patients with ADHD exhibited cognitive performance within the normal range, although with lower scores compared to controls. Behavioural rating scales provide valuable information about functioning outside the clinic, but may yield biased results on account of the focus on externalising symptoms. The neuropsychological evaluation is a useful tool that can facilitate the diagnosis of ADHD and an effective response to the needs and characteristics of patients and families.(AU)

Attention deficit hyperactivity disorder: Neuropsychological profile and study of its impact on executive functions and academic performance.

INTRODUCTION: The aim of the study was to describe the neuropsychological profile of patients with attention deficit hyperactivity disorder (ADHD) and the impact of the disorder on executive functioning and academic performance. PATIENTS AND METHODS: We conducted a retrospective observational and analytical study. The sample consisted of 24 children with a diagnosis of ADHD (aged 6-15 years) without pharmacological treatment and 24 controls without ADHD (aged 7-15 years). A comprehensive neuropsychological evaluation was carried out, encompassing major cognitive domains, in addition to assessment of executive functioning and psychopathological symptoms through the administration of questionnaires to parents and teachers. RESULTS: The cognitive profile of the ADHD group was characterized by overall scores (including executive functions and academic abilities) in the normal range (z scores between -1 and 1), although significantly lower compared to the control group. Over half of the patients with ADHD (58%) had associated specific learning disorders. Furthermore, teachers tended to report executive function difficulties more frequently in male students. CONCLUSIONS: In the study sample, the group of patients with ADHD exhibited cognitive performance within the normal range, although with lower scores compared to controls. Behavioural rating scales provide valuable information about functioning outside the clinic, but may yield biased results on account of the focus on externalising symptoms. The neuropsychological evaluation is a useful tool that can facilitate the diagnosis of ADHD and an effective response to the needs and characteristics of patients and families.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naïve Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.

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.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Clinical Presentation, Management, and Evolution of Lymphomas in Patients with Inflammatory Bowel Disease: An ENEIDA Registry Study.

An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of GETECCU. We identified 52 patients (2.4 cases of lymphoma/1000 patients with IBD; 95% CI 1.8-3.1). Thirty-five were men (67%), 52% had ulcerative colitis, 60% received thiopurines, and 38% an anti-TNF drug before lymphoma diagnosis. Age at lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17) than in those patients not treated with these drugs (63 ± 12; p < 0.05). Five cases had relapse of lymphoma (1.7 cases/100 patient-years). Nine patients (17%) died after 19 months (IQR 0-48 months). Relapse and mortality were not related with the type of IBD or lymphoma, nor with thiopurines or biologic therapies. In conclusion, most IBD patients had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. Relapse and mortality of lymphoma were not related with these therapies.

Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

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.

Serological response to vaccines against SARS-CoV-2 in patients with inflammatory bowel disease. / Respuesta serológica a las vacunas frente a SARS-CoV-2 en pacientes con enfermedad inflamatoria intestinal.

OBJECTIVE: To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. METHODS: Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). RESULTS: 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P<.001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.9-7.0; P<.001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P=.9). CONCLUSIONS: One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases.

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.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Effects of guided exploration on reaching measures of auditory peripersonal space.

Despite the recognized importance of bodily movements in spatial audition, few studies have integrated action-based protocols with spatial hearing in the peripersonal space. Recent work shows that tactile feedback and active exploration allow participants to improve performance in auditory distance perception tasks. However, the role of the different aspects involved in the learning phase, such as voluntary control of movement, proprioceptive cues, and the possibility of self-correcting errors, is still unclear. We study the effect of guided reaching exploration on perceptual learning of auditory distance in peripersonal space. We implemented a pretest-posttest experimental design in which blindfolded participants must reach for a sound source located in this region. They were divided into three groups that were differentiated by the intermediate training phase: Guided, an experimenter guides the participant's arm to contact the sound source; Active, the participant freely explores the space until contacting the source; and Control, without tactile feedback. The effects of exploration feedback on auditory distance perception in the peripersonal space are heterogeneous. Both the Guided and Active groups change their performance. However, participants in the Guided group tended to overestimate distances more than those in the Active group. The response error of the Guided group corresponds to a generalized calibration criterion over the entire range of reachable distances. Whereas the Active group made different adjustments for proximal and distal positions. The results suggest that guided exploration can induce changes on the boundary of the auditory reachable space. We postulate that aspects of agency such as initiation, control, and monitoring of movement, assume different degrees of involvement in both guided and active tasks, reinforcing a non-binary approach to the question of activity-passivity in perceptual learning and supporting a complex view of the phenomena involved in action-based learning.

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.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-×¥-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Association of golimumab trough concentrations during maintenance with clinical, biological, endoscopic and histologic remission in patients with ulcerative colitis.

BACKGROUND: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. AIMS: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 µg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] µg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. CONCLUSIONS: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.

Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.

Cost-effectiveness analysis of ferric carboxymaltose versus iron sucrose for the treatment of iron deficiency anemia in patients with inflammatory bowel disease in Spain.

Background: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD) and can result in reduced quality of life and increased healthcare costs. IDA is treated with iron supplementation, commonly with intravenous iron formulations, such as ferric carboxymaltose (FCM), and iron sucrose (IS). Methods: This study assessed the cost-effectiveness of FCM compared with IS, in terms of additional cost per additional responder in patients with IDA subsequent to IBD in the Spanish setting. An economic model was developed to assess the additional cost per additional responder, defined as normalization or an increase of ⩾2 g/dl in hemoglobin levels, for FCM versus IS from a Spanish healthcare payer perspective. Efficacy inputs were taken from a randomized controlled trial comparing the two interventions (FERGIcor). Costs of treatment were calculated in 2021 Euros (EUR) using a microcosting approach and included the costs of intravenous iron, healthcare professional time, and consumables. Cost-effectiveness was assessed over one cycle of treatment, with a series of sensitivity analyses performed to test the robustness of the results. Results: FCM was more effective than IS, with 84% of patients achieving a response compared with 76%. When expressed as number needed to treat, 13 patients would need to switch treatment from IS to FCM in order to achieve one additional responder. Costs of treatment were EUR 323 with FCM compared with EUR 470 with IS, a cost saving of EUR 147 with FCM. Cost savings with FCM were driven by the reduced number of infusions required, resulting in a reduced requirement for healthcare professional time and use of consumables compared with the IS arm. Conclusion: The present analysis suggests that FCM is less costly and more effective than IS for the treatment of IDA subsequent to IBD in Spain and therefore was considered dominant.