Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

BACKGROUND: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. METHODS: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. RESULTS: We included 101 children with a mean age at diagnosis of 12.8 ±â€…2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. CONCLUSIONS: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Tofacitinib, widely reported in adult ulcerative colitis, has very limited pediatric data. This international collaboration is the largest pediatric study on the efficacy and safety of tofacitinib to date, providing important supportive data to clinicians and regulators.

Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND OBJECTIVES: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. METHODS: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. RESULTS: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 µg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. CONCLUSION: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Transcultural adaptation and validation of IMPACT-III and IMPACT-III-P in Spanish families: a multicenter study from SEGHNP.

IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform a transcultural adaptation and validation for the Spanish context. Translation, back-translation, and evaluation of the questionnaires were performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett's sphericity test (p-value < 0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser's criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, and CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92). CONCLUSION: The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families. WHAT IS KNOWN: • IMPACT-III and parent-proxy IMPACT-III (IMPACT-III-P) are useful questionnaires for assessing health-related quality of life (HRQoL) in pediatric inflammatory bowel disease (p-IBD) patients and their parents/caregivers and have been translated and validated in several countries. • To date, no transcultural adaptation and validation of these questionnaires have been published for Spanish patients with p-IBD and their families. WHAT IS NEW: • This is the first transcultural adaptation and validation of IMPACT-III and IMPACT-III-P for Spanish p-IBD families. • These are valid and reliable instruments for assessing HRQoL in Spanish families of patients with p-IBD.

Assessment of the length of sick leave in patients with inflammatory bowel disease. / Evaluación de la duración de la baja laboral en pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic disorder that can lead to periods of work-related temporary disability (TD), which may result in the need for permanent disability. The objective was to assess the impact of IBD on patients' temporary disability by analyzing periods, duration, and causes. It also investigates risk factors influencing the severity, frequency, and duration of flare-ups and associated complications in IBD patients. METHOD: The study includes patients aged 18 to 65, with at least 1 day of TD in 2019 (Pre-COVID), referred or not by UMEVI, due to reasons related to IBD. RESULTS: A total of 172 patients were included, and in all cases, TD was associated with IBD. TD was higher in patients over 30 years old, with anxious depressive disorder, who required hospitalization and did not receive prednisone treatment (p<0.05). TD duration was longer in patients belonging to the Special Regime for Self-Employed Workers (RETA): 67 days (IQR: 22-160) versus the General Regime (RG): 33 days (IQR: 8-110), with no statistically significant difference (p=0.120). The mean cost (€) per worker in this series was €745.5 (IQR: 231-2608.2). CONCLUSIONS: IBD has a significant impact on patients' temporary work disability. The duration of TD was longer in patients older than 30 years, with anxious-depressive disorder, who required hospital admission and did not receive steroid treatment.

Blood gene expression biomarkers of response to anti-TNF drugs in pediatric inflammatory bowel diseases before initiation of treatment.

BACKGROUND/AIMS: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment. METHODS: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. RESULTS: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR = 2.3 ×10-7) as the most significant biological processes, and hemoglobin binding (FDR = 0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR = 0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). CONCLUSIONS: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.

Dietary Interventions in Ulcerative Colitis: A Systematic Review of the Evidence with Meta-Analysis.

(1) Background: Ulcerative colitis (UC) is a chronic colon inflammation caused by genetic and environmental factors, including diet. This systematic review and meta-analysis aims to assess the impact of diet on UC management in children and adults (2) Methods: A comprehensive search across databases yielded relevant studies, and risk of bias in randomized controlled trials (RCTs) was assessed using the Cochrane Risk of Bias tool. This study was conducted in conformity to the 2020 PRISMA guidelines. The certainty of evidence for outcomes was evaluated using GRADE methodology. Meta-analysis was performed using Review Manager software version 5.4. (3) Results: Fourteen RCTs were included, results indicated higher clinical response, remission, and endoscopic remission rates in diet-treated groups. Carrageenan-free, anti-inflammatory, and cow milk protein elimination diets showed no significant advantages in maintaining clinical remission. However, a study involving fermented cow milk with bifidobacterial demonstrated favorable outcomes. Overall, pooled analysis leaned in favor of dietary intervention for sustaining clinical remission; (4) Conclusions: The relationship between diet and UC is an evolving terrain that demands deeper exploration. This systematic review and meta-analysis highlight the evolving relationship between diet and UC, necessitating further exploration. While understanding grows, adopting personalized dietary approaches could alleviate symptoms, and support a more positive disease trajectory.

Spanish Pediatricians' Positions Regarding Prevention, Diagnosis, Nutritional Management, and Challenges in Cow's Milk Protein Allergy.

Management of cow's milk protein allergy (CMPA) can vary depending on the experience and area of expertise of the clinician responsible for the patient's follow-up, which may or may not align with the recently published literature. To analyze the perspectives of Spanish pediatricians on this topic, a survey was conducted. The survey aimed to determine the current opinions and attitudes of 222 primary care and hospital pediatricians toward CMPA prevention and nutritional management. Participating pediatricians completed the questionnaire, providing insights into their daily clinical practices, including access to testing, attitudes with respect to various aspects of CMPA diagnosis, prevention, oral food challenges, and treatment. The findings revealed that pediatricians generally agree on the use of extensively hydrolyzed formulas (eHFs) to prevent CMPA in high-risk atopic children, despite limited evidence supporting the widespread use of this practice. However, consensus was lacking regarding the utility of formulas with prebiotics and probiotics for expediting tolerance development. In most cases, pediatricians preferred eHFs for the nutritional management of CMPA, followed by hydrolyzed rice formulas (HRFs), with amino-acid-based formulas (AAFs) being the third option. Certain issues remained controversial among pediatricians, such as prevention methods, symptom assessment, and the role of probiotics. These variations in management approaches reflect the influence of clinician experience and area of expertise, underscoring the need for standardized guidelines in this field.

Polymorphisms indicating risk of inflammatory bowel disease or antigenicity to anti-TNF drugs as biomarkers of response in children.

Few genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Phase angle as a marker of outcome in hospitalized pediatric patients. A systematic review of the evidence (GRADE) with meta-analysis.

Phase angle (PhA) is a valuable tool for evaluating the nutritional and inflammatory status, which can accompany acute and severe disorders. PhA is a cellular health biomarker, whose value is particularly substantial due to the negative consequences of these situations in the pediatric population. Relevant literature was collected with the aim of comprehensively analysing the evidence on the association between an altered PhA can serve as a predictive-marker for mortality and poor-outcomes in at-risk-pediatric patients. Understanding this relationship could have significant implications for identifying high-risk individuals and implementing timely interventions. A systematic review with meta-analysis was conducted in the primary electronic databases from inception until January 2023. Overall, four studies with a total of 740 patients were eligible for our analysis. Evidence demonstrates that PhA is associated with nutritional status, reflecting undernutrition and changes in body composition related to illness. This review suggests that PhA can indeed be used as an indicator of nutritional status and a tool for predicting prognosis, including mortality and poor-outcomes, in hospitalized pediatric patients. A low PhA was associated with a significant mortality risk [RR:1.51;95%CI (1.22-1.88),p = 0.0002;I2 = 0%,(p = 0.99)] and an increased complications risk [OR:8.17;95%CI (2.44-27.4),p = 0.0007;I2 = 44%,(p = 0.18)]. These findings highlight the importance of taking a comprehensive approach to clinical nutrition, integrating multiple evaluation aspects to establish an accurate diagnosis and personalized therapeutic plans. While PhA emerges as a valuable tool for assessing the risk of malnutrition and as a prognostic-indicator for poor-outcomes in pediatric patients. Further future studies are needed to focus on investigating this relationship in larger and diverse population to strengthen the evidence base.

Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet.

Celiac disease (CD) is included in the group of complex or multifactorial diseases, i.e., those caused by the interaction of genetic and environmental factors. Despite a growing understanding of the pathophysiological mechanisms of the disease, diagnosis is still often delayed and there are no effective biomarkers for early diagnosis. The only current treatment, a gluten-free diet (GFD), can alleviate symptoms and restore intestinal villi, but its cellular effects remain poorly understood. To gain a comprehensive understanding of CD's progression, it is crucial to advance knowledge across various scientific disciplines and explore what transpires after disease onset. Metabolomics studies hold particular significance in unravelling the complexities of multifactorial and multisystemic disorders, where environmental factors play a significant role in disease manifestation and progression. By analyzing metabolites, we can gain insights into the reasons behind CD's occurrence, as well as better comprehend the impact of treatment initiation on patients. In this review, we present a collection of articles that showcase the latest breakthroughs in the field of metabolomics in pediatric CD, with the aim of trying to identify CD biomarkers for both early diagnosis and treatment monitoring. These advancements shed light on the potential of metabolomic analysis in enhancing our understanding of the disease and improving diagnostic and therapeutic strategies. More studies need to be designed to cover metabolic profiles in subjects at risk of developing the disease, as well as those analyzing biomarkers for follow-up treatment with a GFD.

The Importance of an Early Evaluation after Establishing a Gluten-Free Diet in Children with Celiac Disease.

A gluten-free diet (GFD) is the only treatment available for celiac disease (CD); hence, it is important to ensure correct adherence to the diet and adequate monitoring of the diet. The present study aims to assess the importance of an early follow-up of celiac patients after diagnosis of the disease, identify the role of stool gluten immunogenic peptides (GIPs) in the assessment of GFD adherence, and analyze possible nutritional imbalances or deficiencies in the GFD. This is a cross-sectional study carried out in pediatric patients with newly diagnosed CD in a tertiary hospital in Spain. Of the 61 patients included, 14% had positive stool GIPS at 4 months after CD diagnosis, Among them, 88% had negative stool GIPS at 9 months after diagnosis, following dietary advice. We found nutritional deficiencies in the GFD, such as vitamin D (with only 27% of patients with adequate intakes), folate, calcium, magnesium, and fiber. Similarly, we found imbalances: excess protein and fat intakes and a high percentage of total daily energy intake came from ultra-processed foods (UPF). These findings emphasize the importance of early follow-up of children after diagnosis of CD. It is also crucial to identify patients with poor GFD compliance based on stool GIPS and analyze GFD nutritional imbalances and deficits. Our findings may contribute to the development of specific strategies for the early follow-up of patients with CD, including appropriate nutritional counselling.

Celiac Disease Is a Risk Factor for Mature T and NK Cell Lymphoma: A Mendelian Randomization Study.

Celiac disease (CeD) is an immune-mediated disorder triggered by gluten ingestion that damages the small intestine. Although CeD has been associated with a higher risk for cancer, the role of CeD as a risk factor for specific malignancies, such as enteropathy-associated T-cell lymphoma (EATL), remains controversial. Using two-sample Mendelian randomization (2SMR) methods and the summarized results of large genome-wide association studies from public repositories, we addressed the causal relationship between CeD and eight different malignancies. Eleven non-HLA SNPs were selected as instrumental variables (IVs), and causality estimates were obtained using four 2SMR methods: random-effects inverse variance-weighted, weighted median estimation, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO). We identified a significant causal relationship between CeD and mature T/NK cell lymphomas. Under a multivariate Mendelian randomization model, we observed that the causal effect of CeD was not dependent on other known lymphoma risk factors. We found that the most instrumental IV was located in the TAGAP locus, suggesting that aberrant T cell activation might be relevant in the T/NK cell malignization process. Our findings provide new insights into the connection between immune imbalance and the development of severe comorbidities, such as EATL, in patients with CeD.

Impact of the COVID-19 pandemic on the digitization of routine pediatric practice in Spain: A nationwide survey study.

Introduction: The COVID-19 pandemic forced a change in the working dynamics of all healthcare professionals, leading to the sudden introduction of telemedicine. Although until that moment telemedicine applications had been described in the paediatric age, their use was anecdotal. Objective: To analyse the experience of Spanish paediatricians after the forced digitization of consultations due to the pandemic. Methods: A cross-sectional survey-type study was designed to obtain information from Spanish paediatricians about the changes that took place in the usual clinical practice. Results: 306 health professionals participated in the study Most of them agreed on the use of the internet and social networks during the pandemic, referring to mail or WhatsApp® as usual channels of communication with their patients' families. There was a great agreement among paediatricians that the evaluation of newborns after hospital discharge and establishing methodologies that allow childhood vaccination and the identification of subsidiary patients for face-to-face evaluation were necessary although the limitations of the lockdown. The idea that telephone and digital consultations have optimized the consultation time and that they will probably continue after the end of the pandemic was generally accepted. No changes in adherence to breastfeeding or the start of complementary feeding were referred to, but an increase in the duration of breastfeeding and the appearance of frequent hoaxes in social networks concerning infant feeding were found. Conclusions: It is necessary to analyse the impact of telemedicine in paediatric consultations during the pandemic to evaluate its effectiveness and quality to maintain it in routine paediatric practice.

La monitorización proactiva de niveles de anti-TNF mejora el seguimiento de los pacientes pediátricos con enfermedad de Crohn / Proactive monitoring of anti-TNF agents improves follow-up of paediatric patients with Crohn disease

Introducción y objetivos: La incidencia de la enfermedad inflamatoria intestinal pediátrica ha aumentado en las últimas décadas. El objetivo del presente estudio fue evaluar el papel de la monitorización proactiva y en serie de los niveles de fármacos anti-TNF (factor de necrosis tumoral) para mantener la remisión clínica y la curación mucosa durante el seguimiento de pacientes pediátricos con enfermedad de Crohn (EC). Método: Estudio prospectivo que incluye a todos los pacientes diagnosticados de EC y tratados con adalimumab o infliximab entre mayo de 2015 y noviembre de 2020, en los que se ha realizado una monitorización seriada y proactiva de los niveles de anti-TNF. Resultados: Se incluyeron treinta pacientes, 21 varones (70%). La edad en el momento del diagnóstico fue de 11,3±2,0 años, la edad en el momento de iniciar el anti-TNF fue de 12,6±1,9 años con un tiempo medio de seguimiento de 27,1±9,1 meses. Se consideró remisión clínica si weighted Pediatric Crohn's Disease Activity Index (wPCDAI)<12,5 puntos y curación mucosa si el índice Mucosal Inflammation Non-invasive Index (MINI)<8. Durante el seguimiento, el paciente estuvo en remisión clínica en el 87,1% de las visitas, el 11,4% presentó enfermedad leve, el 1,5% enfermedad moderada y se asumió curación mucosa en el 83% de las visitas. Las tasas de remisión clínica y mucosa tras 1, 2 y 3 años de seguimiento fueron del 83,3%, 95,8%, 92,8% y 86,7%, 87,5% y 85,7%, respectivamente. Conclusiones: La monitorización proactiva y seriada de los niveles séricos de anti-TNF podría permitir al paciente mantener la remisión clínica y la curación mucosa durante el seguimiento, optimizando individualmente la dosis requerida y minimizando la pérdida secundaria de respuesta. (AU)

Introduction and aims: The incidence of paediatric inflammatory bowel disease has increased in recent decades. The aim of the present study was to evaluate the role of proactive and serial monitoring of tumour necrosis factor (TNF) inhibitor levels to maintain clinical remission and mucosal healing in the followup of paediatric patients with Crohn disease (CD). Method: Prospective study that included all patients diagnosed with CD and treated with adalimumab or infliximab between May 2015 and November 2020 who underwent serial and proactive monitoring of TNF inhibitor levels. Results: The study included 30 patients, 21 male (70%). The mean age at diagnosis was 11.3 years (SD, 2.0), the mean age at initiation of TNF inhibitors was 12.6 years (SD, 1.9) with a mean duration of follow-up of 27.1±9.1 months. Clinical remission was defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) of less than 12.5 and mucosal healing as a Mucosal Inflammation Non-invasive Index (MINI) of less than 8. During the follow-up, patients were in clinical remission in 87.1% of the visits, presented with mild disease in 11.4% and with moderate disease in 1.5%, and mucosal healing was assumed in 83% of the visits. The rates of clinical remission and mucosal healing at 1, 2, and 3 years of follow-up were 83.3%, 95.8%, 92.8%, and 86.7%, 87.5% and 85.7%, respectively. Conclusions: Proactive and serial monitoring of serum TNF inhibitor levels may make it possible for patients to maintain clinical remission and mucosal healing in the maintenance phase, with individualised optimization of the required dosage and minimization of secondary loss of response. (AU)

Proactive monitoring of anti-TNF agents improves follow-up of paediatric patients with Crohn disease.

INTRODUCTION AND AIMS: The incidence of paediatric inflammatory bowel disease has increased in recent decades. The aim of the present study was to evaluate the role of proactive and serial monitoring of tumour necrosis factor (TNF) inhibitor levels to maintain clinical remission and mucosal healing in the follow-up of paediatric patients with Crohn disease (CD). METHODS: Prospective study that included all patients diagnosed with CD and treated with adalimumab or infliximab between May 2015 and November 2020 who underwent serial and proactive monitoring of TNF inhibitor levels. RESULTS: The study included 30 patients, 21 male (70%). The mean age at diagnosis was 11.3 years (SD, 2.0), the mean age at initiation of TNF inhibitors was 12.6 years (SD, 1.9) with a mean duration of follow-up of 27.1 ±â€¯9.1 months. Clinical remission was defined as a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) of less than 12.5 and mucosal healing as a Mucosal Inflammation Non-invasive Index (MINI) of less than 8. During the follow-up, patients were in clinical remission in 87.1% of the visits, presented with mild disease in 11.4% and with moderate disease in 1.5%, and mucosal healing was assumed in 83% of the visits. The rates of clinical remission and mucosal healing at 1, 2, and 3 years of follow-up were 83.3%, 95.8%, 92.8%, and 86.7%, 87.5% and 85.7%, respectively. CONCLUSIONS: Proactive and serial monitoring of serum TNF inhibitor levels may make it possible for patients to maintain clinical remission and mucosal healing in the maintenance phase, with individualised optimization of the required dosage and minimization of secondary loss of response.