Drug-related adverse events necessitating treatment discontinuation in pediatric inflammatory bowel disease patients.

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. METHODS We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments and related AE. We analysed the frequency, type, and risk factors for AE necessitating drug discontinuation. RESULTS A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn's disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least one drug-related AE that required drug cessation. Immunomodulators (methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)) followed by tumor necrosis factor (TNF)-alpha antagonists (adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)) accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE (OR = 2.50, 95%CI [1.50-4.17]) in all pediatric IBD patients. CONCLUSIONS Drug-related AE necessitating discontinuation are common in pediatric and adolescent inflammatory bowel disease patients. Caution needs to be taken in the case of concomitant drug use

Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort

INTRODUCTION Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). METHODS Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). RESULTS A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. CONCLUSIONS As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients

The Use of 5-Aminosalicylic Acid in Children and Adolescents With Inflammatory Bowel Disease

BACKGROUND In ulcerative colitis (UC) 5-aminosalicylic acid (5-ASA) is recommended as primary therapy for mild to moderate disease. Topical 5-ASA has been proven especially effective. In Crohn's disease (CD) the evidence for a beneficial role of 5-ASA is weak. We investigated the use of topical and systemic 5-ASA therapy in children and adolescents with inflammatory bowel disease. MATERIALS AND METHODS Data of patients younger than 18 years, registered between April 2008 and December 2015 in the Swiss Inflammatory Bowel Disease Cohort, were analyzed. RESULTS Three hundred twenty pediatric inflammatory bowel disease patients were included; 189 with CD and 131 with UC. Over one third of UC patients [51 (39%)] received topical 5-ASA therapy and 43 (33%) received combination therapy during their disease course. UC patients with left-sided colitis or proctitis were more likely to receive topical or combination therapy as compared with patients with pancolitis (P<0.001 and <0.001, respectively). An increase in the use of topical 5-ASA therapy in UC patients was noted over time from 5% to 38%. Forty-seven percent of CD patients were treated with oral 5-ASA during their disease course. The usage was stable over time at approximately 15% to 20%. CONCLUSIONS In recent years a very positive trend showing an increase in topical 5-ASA therapy in children and adolescents with UC has been observed. However topical therapy is still used with relative low frequency, especially in patients with a more extensive disease. Conversely, despite weak evidence supporting 5-ASA use in CD patients it has been frequently prescribed. Physicians should continue to encourage their UC patients to use topical therapy

Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease: Prevalence, Presentation, and Anti-TNF Treatment.

There is a paucity of data on extraintestinal manifestations (EIM) and their treatment in pediatric patients with inflammatory bowel disease (IBD). Since 2008, the Pediatric Swiss IBD Cohort Study has collected data on the pediatric IBD population in Switzerland. Data on 329 patients were analyzed retrospectively. A total of 55 patients (16.7%) experienced 1-4 EIM (39 Crohn disease, 12 ulcerative colitis, and 4 IBD-unclassified patients). At IBD onset, presence of EIM was more frequent than in the adult population (8.5% vs 5.0%, P = 0.014). EIM were more frequent in Crohn disease when compared to ulcerative colitis/IBD-unclassified (22.5% vs 10.3%, P = 0.003). The most prevalent EIM were peripheral arthritis (26/329, 7.9%) and aphthous stomatitis (24/329, 7.3%). Approximately 27.6% of all EIM appeared before IBD diagnosis. Median time between IBD diagnosis and occurrence of first EIM was 1 month (-37.5-149.0). Thirty-one of the 55 patients (56.4%) were treated with 1 or more anti-tumor necrosis factor (TNF) agents. IBD patients with EIM were more likely to be treated with anti-TNF compared to those without (56.4% vs 35.0%, P = 0.003). Response rates to anti-TNF depended on underlying EIM and were best for peripheral arthritis (61.5%) and uveitis (66.7%). In a cohort of pediatric patients with IBD, EIM were frequently encountered. In up to 30%, EIM appeared before IBD diagnosis. Knowledge of these findings may translate into an increased awareness of underlying IBD, thereby decreasing diagnostic delay. Anti-TNF for the treatment of certain EIM is effective, although a substantial proportion of new EIM may present despite ongoing anti-TNF therapy

Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort.

BACKGROUND AND AIM Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort. PATIENTS AND METHODS A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine). RESULTS A total of 3192 patients were analyzed, of whom 1792 (56.1%) had Crohn's disease, 1322 (41.4%) had ulcerative colitis, and 78 (2.5%) had IBD unclassified. Of 3138 patients treated with IBD drugs, 2129 (67.8%) presented with one or several drug-related side effects necessitating drug cessation. We found a significant positive correlation between the number of concomitantly administered IBD drugs and the occurrence of side effects requiring drug cessation (P<0.001). Logistic regression modeling identified Crohn's disease diagnosis [odds ratio (OR)=1.361, P=0.017], presence of extraintestinal manifestations (OR=2.262, P<0.001), IBD-related surgery (OR=1.419, P=0.006), and the increasing number of concomitantly used IBD drugs [OR=2.007 (P<0.001) for two concomitantly used IBD drugs; OR=3.225 (P<0.001) for at least three concomitantly used IBD drugs] to be associated significantly with the occurrence of IBD drug-related adverse events that necessitated treatment cessation. CONCLUSION Physicians should keep in mind that the number of concomitantly administered IBD drugs is the main risk factor for drug-related adverse events necessitating treatment cessation

Calprotectine en pédiatrie

Les douleurs abdominales sont un motif de consultation fréquent en pédiatrie, tant en consultation de pédiatrie générale qu’en gastroentérologie pédiatrique et constituent un réel défi diagnostic pour les pédiatres traitants. Dans la majorité des cas, il s’agit de douleurs fonctionnelles. Cependant des maladies organiques, en premier lieu les maladies intestinales chroniques inflammatoires (MICI) peuvent causer ces douleurs et un diagnostic précoce ainsi que l’initiation d’un traitement adéquat sont d’intérêt capital pour le patient. La mesure de la calprotectine fécale, méthode élégante car non invasive, peut aider à la discrimination des différentes étiologies des douleurs abdominales