Explore the vast range of titles available.

Background: Therapeutic drug monitoring of adalimumab (ADA) is still controversial. Objectives: To study the association between ADA trough levels in the early stages of treatment with biological remission (BR) and drug survival in Crohn’s disease (CD). Design: Retrospective cohort study. Methods: Patients treated with ADA with available trough levels at weeks 2 and 6 (after the first induction and maintenance dose, respectively) were included. Fecal calprotectin (Fcal) and C-reactive protein (CRP) were registered at baseline, week 24, and week 52. BR was defined as Fcal <200 µg/g and CRP <5 mg/dl. Treatment survival and the need for dose escalation were assessed at week 52. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of ADA cutoff levels for BR. Quartile-specific comparisons were performed to evaluate differences in the proportion of patients achieving BR at weeks 24 and 52, drug survival, and dose escalation. Results: In all, 112 patients were included. ADA trough levels at week 6 were higher in patients achieving BR at week 24 (12.32 μg/ml vs 10.3 μg/ml, p = 0.0008), week 52 (12.3 μg/ml vs 10.8 μg/ml, p = 0.035), and in patients with 1-year treatment persistence (12.17 μg/ml vs 9.7 μg/ml, p = 0.03), but lower in patients requiring maintenance intensification (9.7 μg/ml vs 12.2 µg/ml, p < 0.0001). ADA week 6 trough levels >12.27 μg/ml predicted BR at week 24 with 79.7% specificity and 79.5% positive predictive value. Patients in the third quartile (Q3) and fourth quartile (Q4) of ADA levels at week 6 exhibited higher rates of BR at week 24, BR at week 52, 1-year drug survival, and less need for dose escalation (all p-values <0.05). In logistic regression, Q3 and Q4 of week 6 levels were significantly associated with BR at week 24 (p = 0.02 and p = 0.001); and week 6 Q4 with BR at week 52 (p = 0.02), treatment persistence (p = 0.03), and lower dose escalation (p = 0.004). ADA trough levels at week 2 did not show similar associations. Conclusion: ADA trough levels at week 6 are associated with BR at weeks 24 and 52, drug survival, and need for dose escalation in CD. However, ADA concentrations at week 2 failed to yield similar results. Plain language summary Early monitoring of adalimumab levels improves outcomes in Crohn’s disease This study investigated whether early monitoring of adalimumab (ADA) levels in patients with Crohn’s disease (CD) could predict remission and improve treatment success. We aimed to identify the best timepoint and threshold for ADA monitoring, hypothesizing that early induction (week 2) and early maintenance levels (week 6) would correlate with long-term remission. CD is a chronic condition causing significant health issues, including inflammation and complications requiring surgery. Biological remission, measured through biomarkers like fecal calprotectin and C-reactive protein, is a key treatment goal. Understanding how ADA levels predict remission could improve treatment strategies and benefit a wide range of patients. We analyzed data from 112 CD patients treated with ADA. ADA levels were measured at weeks 2 and 6, and remission was assessed at weeks 24 and 52. We examined the association between ADA levels and treatment outcomes, such as dose adjustments and treatment persistence. We found that ADA levels at week 6 were significantly associated with achieving remission at weeks 24 and 52. Patients with ADA levels above 12.27 μg/ml at week 6 were more likely to remain in remission, avoid dose escalation, and continue treatment successfully. However, ADA levels at week 2 did not predict these outcomes. This research highlights the importance of early ADA monitoring during maintenance rather than induction. By identifying an optimal time and threshold for monitoring, this study offers a potential strategy to personalize treatments, reduce complications, and improve long-term outcomes for CD patients. These findings emphasize the need for further research to refine therapeutic monitoring guidelines.

Crohn's disease (CD) is a disabling inflammatory disorder with highly variable response to biologic therapies. Despite the availability of multiple biologic agents, a significant proportion of patients experience primary non-response, while others initially respond but subsequently develop secondary loss of response, leading to sequential treatment failures and increased healthcare burden. The disease course and response to treatment are remarkably heterogeneous among patients, and a better understanding of the personalised pathways affected is required. Identifying early biomarkers of treatment efficacy is crucial for improving patient outcomes and reducing unnecessary healthcare costs. In this study, we comprehensively analysed T cell subpopulations in blood and lamina propria, together with serum cytokine profiles, in CD patients receiving the IL-12/IL-23 inhibitor ustekinumab. The most remarkable findings were observed in peripheral blood. At week 24, good responders showed decreased Th1, increased Th2, and reduced IL-17A serum levels compared with non-responders. Importantly, elevated IL-12/IL-23 serum levels at week 8 associated with favourable clinical and endoscopic outcomes, suggesting effective pathway blockade. These findings support the measurement of serum IL-12/IL-23 at week 8 as a simple, early predictor of ustekinumab response in CD, potentially guiding personalised treatment strategies and ultimately long-term response.

Background: Perianal Crohn’s disease (PD) remains a major therapeutic challenge, with heterogeneous responses to anti-TNF therapy and limited real-world data on predictors of long-term outcomes. This study aimed to evaluate clinical and radiological response to anti-TNF therapy initiated exclusively for PD and to identify factors associated with treatment response. Methods: A retrospective study was conducted in a cohort of 65 patients with PD treated with anti-TNF. The primary endpoint was clinical response assessed at weeks 24, 52, and 60 months. It was defined as a ≥50% reduction in drainage, and remission as complete absence of drainage. Radiological response was assessed by magnetic resonance imaging at the same time points whenever feasible. Multivariate logistic regression analyses were performed to identify independent predictors of response. Results: At week 24, 84.6% of patients achieved a clinical response, while radiological response was observed in 30.8%. At week 52, clinical and radiological response rates were 80.0% and 52.3%, respectively. At 60 months, 61.5% maintained clinical response and 46.1% radiological response. Among patients who responded at week 24, 90.7% maintained response at week 52, with a secondary loss of response rate of 9.3%. Multivariate analysis identified absence of antineutrophil cytoplasmic antibodies (ANCA) as an independent predictor of clinical response at week 52 (OR 0.06, 95% CI 0.006–0.59; p = 0.01). No significant associations were observed between anti-TNF serum levels and clinical or radiological outcomes. Conclusions: In this real-world cohort of patients initiating anti-TNF exclusively for PD, early response (week 24) emerged as a potential marker of long-term outcomes, highlighting the importance of early reassessment and individualized therapeutic strategies.

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.

BackgroundThe outbreak of COVID-19 has rapidly evolved into a pandemic that has represented a challenge to health systems worldwide. Inflammatory bowel disease (IBD) units have been forced to change their practices to address the disease and to ensure the quality of care.MethodsWe conducted a national survey among IBD gastroenterologist members of the Spanish Working Group on Crohn’s Disease and Colitis regarding changes of practice, IBD treatments, and diagnosis and treatment of COVID-19.ResultsWe received 54 answers from Spanish hospitals. One hundred percent of the IBD units rescheduled onsite visits to telematic consultation, and elective endoscopic and surgical procedures were delayed. Protective measures were also taken in the infusion units (100% of health centers) and hospital pharmacies, with 40.7% sending subcutaneous medications to patients. No switching between intravenous and subcutaneous anti-tumor necrosis factor drugs were made. We also found that 96.1% of IBD units advised their patients to maintain treatment if they were asymptomatic for COVID-19. For patients with COVID-19 symptoms, 92.6% of IBD units referred them to primary care or the emergency department. In addition, 7.5% of IBD units made a COVID-19 diagnosis through polymerase chain reaction and/or chest x-ray.Modifications in IBD treatment and treatment recommended for COVID-19 are also discussed.ConclusionsWe report a representative national survey of changes made in the structure, diagnosis of COVID-19, and modifications in IBD treatments within IBD units.Because of the COVID-19 pandemic, IBD units have been forced to adapt their practices to address the disease. A nationwide questionnaire was conducted among IBD units regarding measures taken in terms of organization, IBD treatment, and management of patients with COVID-19 symptoms.

Does celiac disease influence the course of inflammatory bowel disease? What was already known? Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, and celiac disease, are digestive disorders caused by an abnormal immune response. Both conditions share some genetic and environmental risk factors and can sometimes occur in the same person. However, it was unclear whether having celiac disease in addition to IBD could make IBD more severe or change its course. What did we want to study? We aimed to compare the course of IBD in patients who also had celiac disease with that of patients with IBD alone, to determine whether the coexistence of both conditions influenced the type of IBD, its severity, or the treatments required. How was the study performed? We conducted a multicenter study including 66 patients with both IBD and celiac disease and compared them with 132 similar patients with IBD without celiac disease. The groups were matched by sex, type of IBD, and year of diagnosis. Medical records were reviewed to collect information on disease extent, symptoms outside the intestine, treatments received, need for surgery, development of cancer, and survival. What did we find? No important differences were observed between patients with and without celiac disease. Both groups showed similar IBD characteristics, including disease extent and behavior. There were also no differences in complications such as perianal disease, use of immunosuppressive or biologic drugs, need for surgery, development of tumors, or mortality. What do these results mean? Having celiac disease in addition to IBD does not appear to worsen the course of IBD or modify its natural history. This information can help reassure patients and clinicians that the coexistence of celiac disease is unlikely to negatively affect IBD outcomes.

Inflammatory bowel disease (IBD) and celiac disease (CeD) are immune-mediated digestive disorders with shared genetic, immunological, and environmental risk factors. This study aimed to assess whether the coexistence of CeD and IBD is associated with a differential IBD disease course. Multicenter case-control study. This study included patients with both CeD and IBD, and controls with IBD alone in a 1:2 ratio, matched by sex, IBD type, and year of diagnosis. CeD was diagnosed based on a Marsh score >1. Data on IBD phenotype and treatment, mortality and neoplasm development were collected from medical records. The study included 66 celiac-IBD patients (30 ulcerative colitis, 6 indeterminate colitis, 30 Crohn's disease; mean age 30 ± 14 years) and 132 non-celiac-IBD patients (68 ulcerative colitis, 4 indeterminate colitis, 60 Crohn's disease; mean age 32 ± 14 years). Among patients with CeD, Marsh type 3 was the most frequently observed lesion. No significant differences were observed between celiac and non-celiac-IBD patients in terms of IBD extension, extraintestinal manifestations, or coexisting autoimmune diseases. Similarly, no differences were found in outcomes including perianal disease, use of mesalamine, immunomodulators, biologics, need for surgery, or development of neoplasms. No deaths occurred in either group. In this large multicenter cohort, the concurrent diagnosis of CeD and patients with IBD was not associated with a different IBD phenotype or worse outcomes compared to non-celiac-IBD patients. The coexistence of CeD does not appear to alter the natural history of IBD.

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.

Background: Malnutrition and suboptimal diet quality are common, yet under-recognized, in inflammatory bowel disease (IBD) and are associated with worse clinical outcomes and lower quality of life. Digital tools may facilitate continuous, personalized nutritional support, but evidence in IBD remains limited. The aim of this study was to evaluate the impact of a nutritional intervention based on a mobile application (Nootric®) on nutritional status, diet quality, and malnutrition risk in patients with IBD undergoing stable follow-up. Methods: We conducted a prospective longitudinal cohort study without a control group including 151 adult patients with Crohn’s disease or ulcerative colitis under stable follow-up in a tertiary IBD unit. Participants used a structured digital nutritional support program through the Nootric® app for 24 weeks, supervised by dietitians and the IBD team. Clinical activity, biochemical markers (C-reactive protein, fecal calprotectin), nutritional biomarkers (albumin, prealbumin, micronutrients), body mass index (BMI), malnutrition risk (self-administered Malnutrition Universal Screening Tool, MUST), and diet quality (PREDIMED and an expanded “Nootric score”) were assessed at baseline, 12 weeks, and 24 weeks. Analyses focused on patients with adequate adherence. Results: Of the 151 included IBD patients, 110 maintained stable app use. Mean albumin increased from 4.38 to 4.49 g/dL at 24 weeks (p = 0.003), and prealbumin from 24.9 to 26.1 mg/dL (p = 0.047), despite the absence of overt protein–calorie malnutrition at baseline. Patients with obesity achieved a mean weight loss of approximately 6% of baseline body weight. Diet quality improved significantly, with higher Nootric score and a positive correlation between app use intensity and increased score. Malnutrition risk according to the MUST scale improved in more adherent patients, while clinical and biochemical disease activity remained stable overall. Conclusions: A mobile app-based nutritional program supervised by dietitians was feasible, well accepted, and associated with improved nutritional markers, diet quality, and malnutrition risk, supporting its role as a complementary component of IBD care.

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.