Onset Inflammatory Bowel Disease Research Articles

Pyoderma gangrenosum in a patient with onset of inflammatory bowel diseases

The course of inflammatory bowel diseases can be complicated by damage to almost all organs and systems, including the eyes, skin, lungs, kidneys, liver, as well as hematopoietic organs and the cardiovascular system. In this case, skin diseases are most often affected, and skin extraintestinal manifestations occur in more than 10% of patients with inflammatory bowel disease. Among the cutaneous extraintestinal manifestations, the second place in prevalence after erythema nodosum is occupied by pyoderma gangrenosum - neutrophilic dermatosis, an idiopathic disease, most often associated with systemic immune-inflammatory conditions, such as rheumatoid arthritis, hemoblastoses or intestinal diseases. Also, this disease is one of the components of such genetically determined syndromes as PAPA, PASH, PAPASH and SAPHO. Difficulties in diagnosing and detecting this condition are due to the lack of a standardized approach to the appointment of these patients, the achievement of the results of randomized trials, and the identification of the reliability of the reliability of drug therapy for pyoderma gangrenosum. This article presents a review of the literature and, as a clinical manifestation, an observation in patients with the onset of inflammatory bowel disease complicated by pyoderma gangrenosum was identified.

Anti-CD20-Triggered Crohn’s-Like Disease with Severe Perianal Involvement in a Patient with Multiple Sclerosis: Case Report, Review of the Literature, and Potential Therapeutic Approach

This case report describes a 38-year-old female patient with a 3-year history of multiple sclerosis who developed rituximab-induced pancolitis, possibly representing a new onset of inflammatory bowel disease. The patient presented with bloody diarrhea, epigastric pain, fever, and general malaise. Laboratory testing revealed elevated acute inflammation markers, and endoscopy showed deep ulcerations and severe perianal disease. The patient was treated effectively with corticosteroids. Monthly doses of ustekinumab have been administered during follow-up due to perianal disease that has remitted. Rituximab was discontinued and ozanimod was initiated with clinical and analytical stability to date.

Increased risk of obstructive lung disease in inflammatory bowel disease: A population-based cohort study.

Inflammatory bowel disease (IBD) is associated with disease manifestations in organs other than the gastrointestinal tract. In this study, we aimed to estimate the odds of obstructive lung disease (OLD) before IBD onset and the risk of OLD after IBD onset. In a nationwide population-based Danish cohort study from 1999 to 2018, individuals with IBD and OLD were identified using the Danish registries. Between 2003 and 2013, 24,238 individuals with IBD were identified and matched 1:10 with non-IBD individuals. Logistic regression was used to estimate the prevalence odds ratio for OLD before IBD onset. Time-to-event analysis was performed to explore the risk of OLD after IBD onset. In a sensitivity analysis, the time-to-event analysis was repeated using the composite outcome OLD and the separate outcomes, chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis. Individuals with IBD were 60% more likely to have OLD before onset (adjusted odds ratio: 1.60, 95% confidence interval [CI]: 1.53-1.67). Furthermore, their risk of OLD was more than 40% higher after IBD diagnosis (adjusted hazard ratio [aHR]: 1.43, 95% CI: 1.37-1.49). The sensitivity analysis increased the risk to 60% (aHR: 1.63, 95% CI: 1.53-1.73). Similar results were found for COPD and asthma separately, whereas the risk of bronchiectasis increased more than 2-fold (aHR: 2.44, 95% CI: 1.91-3.11). The odds of OLD before- and the risk following an IBD diagnosis were increased. We encourage physicians to be vigilant of pulmonary symptoms in persons with IBD and gastrointestinal symptoms in individuals with OLD.

Environmental Exposure to Trace Elements and Heavy Metals Preceding the Clinical Onset of Inflammatory Bowel Disease.

The immune dysregulation underlying inflammatory bowel disease (IBD) can start years before the diagnosis, but the role of triggering factors and environmental exposures during this period is still uncertain. This single-center case-control study included asymptomatic subjects with an incidental diagnosis of IBD during the colorectal cancer screening program. Twenty-two minerals and 17 metals were determined at diagnosis in hair samples and compared 1:2 to healthy controls. Six patients with preclinical IBD (3 ulcerative colitis, 67% left-sided; 3 Crohn's disease, 100% ileal, 67% inflammatory behavior) and 13 healthy non-IBD controls were included. No relevant occupational exposures were identified. We found statistically significant higher levels of sodium, potassium, and boron among cases compared to controls; while lower levels of zinc, uranium, copper, and germanium were observed. A range of environmental exposures can be identified during the preclinical phase of IBD, but their relationship with the symptomatic onset and disease progression should be further explored.

Recent clinical evidence on nutrition, novel pharmacotherapy, and vaccination in inflammatory bowel diseases.

Inflammatory bowel diseases (IBD), which enclose Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory ailments. Their specific pathogenesis is not completely clarified, the worldwide incidence and prevalence of IBD has been steadily growing, and there is still not a definitive cure. The management of IBD has become more and more targeted, with specific immune mediators identified to be involved in its pathogenesis. Vedolizumab, a humanised monoclonal antibody binding specifically to the α4β7 integrin, is a gut-selective immunosuppressive biologic drug administered for both CD and UC. With the same indications as vedolizumab, ustekinumab is a fully human IgG1κ monoclonal antibody binding with specificity to the shared p40 protein subunit of human cytokines interleukin (IL)-12 and IL-23. Several selective IL-23p19 monoclonal antibodies (risankizumab, mirikizumab, and guselkumab) have also revealed admirable efficacy and safety in IBD patients. Nutrition is a very important environmental factor associated with the onset and progression of IBD, and the Western diet is considered to contribute to the development of IBD. In this narrative review, our aim is to present an overview of the main results from recent clinical studies on IBD regarding diet, new drug treatments, and also vaccination.

Le malattie infiammatorie croniche intestinali: aspetti genetici (II parte)

In recent years, many evidences have shown the importance of genetics in inflammatory bowel disease (IBD). It is well known that from an etiopathogenetic point of view, IBDs are multifactorial diseases, likely due to a complex interaction between genetic predisposition, intestinal microbiota, and other environmental factors. Regarding genetic factors, these, in terms of IBD-associated gene variants, are believed to influence only 20% of cases. Conversely, in recent years, there is increasing evidence of a role of epigenetic modifications associated with environmental modifiers underlying the onset of IBD and its recurrence. In particular, the role of DNA methylation and noncoding RNAs in disease expression, relapse, and tumor complications appears increasingly clear.

Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

ObjectiveIn this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment. MethodsThe study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study. ResultsOf the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04–67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months. ConclusionOur study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings.

Studying zonulin levels in patients with inflammatory bowel disease and peripheral arthritis

BACKGROUND: Currently, disruption of the barrier function of the intestinal mucosa is considered one of the key mechanisms in the pathogenesis of extraintestinal manifestations of inflammatory bowel diseases, especially damage to the musculoskeletal system.
 AIM: To study the relationship between the level of zonulin in blood serum and the parameters of the immune status in patients with inflammatory bowel diseases in combination with peripheral arthritis.
 MATERIALS AND METHODS: 97 patients with ulcerative colitis and Crohn’s disease have been examined, with peripheral arthritis verified in 47 patients; the control group included 50 patients without peripheral arthritis. Zonulin, tumor necrosis factor α, interleukin-1β, -10, -17A, -23 were determined in blood serum using standard kits for direct enzyme immunoassay.
 RESULTS: Patients with peripheral arthritis were younger with an earlier onset of inflammatory bowel diseases (p 0.001). When assessing the concentration of serum zonulin in the patients with and without arthritis, no significant differences have been found. In the patients with peripheral arthritis, zonulin concentration directly correlated with the level of interleukin-17A (r = 0.323; p = 0.039), interleukin-23 (r = 0.321; p = 0.041).
 CONCLUSIONS: According to the data obtained, the use of zonulin as a marker of peripheral arthritis in inflammatory bowel diseases is not recommended. Nevertheless, the correlation of zonulin and the concentrations of interleukin-17А and -23 demonstrates its role in the regulation of mucosal immunity in the development of extraintestinal manifestations of inflammatory bowel diseases.

Oat Peptides Alleviate Dextran Sulfate Sodium Salt-Induced Colitis by Maintaining the Intestinal Barrier and Modulating the Keap1-Nrf2 Axis.

The prevalence of inflammatory bowel disease (IBD) is progressively rising each year, emphasizing the significance of implementing rational dietary interventions for disease prevention. Oats, being a staple agricultural product, are abundant in protein content. This study aimed to investigate the protective effects and underlying mechanisms of oat peptides (OPs) in a mouse model of acute colitis induced by dextran sulfate sodium salt (DSS) and a Caco-2 cell model. The findings demonstrated that intervention with OPs effectively mitigated the symptoms associated with DSS-induced colitis. The physicochemical characterization analysis demonstrated that the molecular weight of the OPs was predominantly below 5 kDa, with a predominant composition of 266 peptides. This study provides further evidence of the regulatory impact of OPs on the Keap1-Nrf2 signaling axis and elucidates the potential role of WGVGVRAERDA as the primary bioactive peptide responsible for the functional effects of OPs. Ultimately, the results of this investigation demonstrate that OPs effectively mitigate DSS-induced colitis by preserving the integrity of the intestinal barrier and modulating the Keap1-Nrf2 axis. Consequently, these findings establish a theoretical foundation for the utilization of OPs as dietary supplements to prevent the onset of IBD.

Фактори ризику виникнення запальних захворювань кишечника в дітей раннього віку

In recent decades, there has been a rapid increase in the incidence of inflammatory bowel diseases in the children's population, especially in the age group under 6 years old. Risk factors significantly affect the reactive response of the child's organism and the probability of a pathology occurrence. Purpose - to analyze risk factors for the development of inflammatory bowel diseases with very early onset in children. Materials and methods. The anamnestic data of 78 examined patients with inflammatory bowel diseases - 17 patients with inflammatory bowel diseases with a very early onset and 61 children with inflammatory bowel disease that debuted over 6 years of age - were studied in detail retrospectively. Results. The anamnestic risk factors that were significantly more often observed in patients with inflammatory bowel diseases with a very early onset compared to children with inflammatory bowel diseases with an onset after 6 years of age included: spontaneous abortion in patients' mothers anamnesis, autoimmune diseases in relatives, the presence of concomitant autoimmune diseases in patients, early introduction of artificial feeding and the presence of an infectious disease just before the onset of inflammatory bowel disease. Conclusions. Taking into account the identified risk factors of inflammatory bowel diseases with a very early onset will ensure the improvement of prevention and early diagnosis of this gastrointestinal disease in young children. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the work. The informed consent of the children’s parents was obtained for the conducting the studies. No conflict of interests was declared by the authors.

Effect of ileostomy on the clinical outcomes of children with very early onset inflammatory bowel disease

To explore the effect of ileostomy on clinical outcomes of children with very early onset inflammatory bowel disease(VEO-IBD). The clinical data of 11 children with VEO-IBD who underwent ileostomy in the Department of Gastroenterology of the Affiliated Children's Hospital of Zhengzhou University from January 2016 to December 2022 were retrospectively analyzed, and the clinical characteristics and outcomes were analyzed. A total of 11 cases were included, including 7 males and 4 females, aged 3.0 (0.9, 8.0) months. The main clinical manifestations were fever and diarrhea, with L2 type the main lesion site (according to the Paris classification of childhood Crohn's disease). There were 7 cases of gene type interleukin (IL)-10RA. After VEO-IBD ileostomy, the disease site, incidence of growth disorders, the weighted children's Crohn's disease activity index, the simplified endoscopic score of Crohn's disease, and severe mucosal inflammation activity rate were all lower than those before ileostomy (all P<0.05). The postoperative inflammatory indicators and factors were lower than those before ileostomy (all P<0.05). The mucosal barrier indicators after ileostomy were increased than before (all P<0.05). The nutritional evaluation indicators after ileostomy were improved (P<0.05). Ileostomy can reduce inflammatory response of VEO-IBD, improve intestinal mucosal barrier, reduce disease activity, and improve nutritional status.

Body Surface Area-Based Dosing of Infliximab is Superior to Standard Weight-Based Dosing in Children With Very Early Onset Inflammatory Bowel Disease

Children with very early onset inflammatory bowel disease (VEO-IBD) are uniquely at risk of inadequate infliximab (IFX) exposure. We studied the association between standard body weight (BW)-based and body surface area (BSA)-based dosing strategies and outcomes. We identified VEO-IBD patients treated with IFX before 9 years at a single center. Patients were separated into those that received a BSA-based dose (200 mg/m2) and standard BW dosing (5 mg/kg). IFX drug levels, dose intensification, time on steroids, and long-term outcomes were compared. Receiver operator characteristic curves determined the optimal BW- and BSA-based dose to achieve a trough ≥10 μg/ml at dose 4 (IFX#4). Forty-three children with VEO-IBD were identified. Receiver operator characteristic curves demonstrated optimal BW- and BSA-based doses to achieve IFX trough ≥10 μg/ml at IFX#4 were 7.5 mg/kg and 180mg/m2. Children were classified to standard BW dosing (22/43) and BSA dosing (10/43). IFX#4 trough was significantly higher in those who received BSA dosing (BSA 18.6 μg/ml [interquartile range 10.8-28.1] vs BW 5.1 μg/ml [interquartile range 2.6-10.7], P= .04). BSA dosing was more likely to achieve a target drug level >10μg/ml at IFX#4 (BSA 70% vs BW 18%, P= .02). BW dosing was associated with a greater likelihood of dose escalation (BW 82% vs BSA 30%, P < .01) and a shorter time to first escalation. BSA dosing was associated with shorter time spent on steroids (P= .02). Young children require higher IFX dosing to achieve adequate drug exposure. Our data support the use of a BSA-based dose of 200 mg/m2 or, if a BW-based approach is used, 7.5 mg/kg. BSA dosing allows the use of a consistent dose over the age and weight spectrum.

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study

BackgroundVery early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AimsThis study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. MethodsA retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. ResultsA total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. ConclusionsEndoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.

Body Mass Index Profile of Adult Patients with Inflammatory Bowel Disease in a Multicenter Study in Northeastern Brazil.

Inflammatory bowel disease (IBD) is a disease of increasing prevalence in developing countries. Obesity has emerged as a potential risk for IBD; however, the data in the literature are conflicting, and relevant studies in Brazil are limited. Here, we report body mass index profile (BMI) of patients with IBD treated at reference centers in three states of northeastern Brazil. Observational descriptive study conducted from January 2021 through December 2021 in patient with IBD. Of 470 patients with IBD, 194 (41%) were classified as normal weight, 42 (9%) as underweight, 155 (33%) as overweight, and 79 (17%) as obese; CD patients were significantly more likely to be underweight than UC patients (p=0.031)Overweight patients were older (median age: 47 years) than normal-weight and underweight patients at diagnosis (38.5 and 35.5 years, respectively [p<0.0001]). IBD onset and diagnosis among overweight and obese individuals were associated with older age. More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD, irrespective of nutritional status. There was a higher frequency of compatible symptoms with axial joint inflammation among obese patients (p=0.005) and a lower frequency of compatible symptoms with peripheral joint inflammation in underweight patients (p=0.044) than in patients of normal weight. No significant difference in the frequency of different drug or surgical treatments was observed among the groups. Despite the predominance of overweight and obesity in patients with IBD, no differences in the patterns of disease were seen between the overweight and normal-weight groups; however, obesity was associated with IBD onset in older adults and a higher frequency compatible symptom with axial joint inflammation. These data reinforce the importance of monitoring the nutritional status of IBD patients and the need for a multidisciplinary approach, as recommended in the current guidelines.

Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives.

Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD). Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next-generation sequencing (NGS) for AS events in IBD have been also discussed. Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis-associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro-fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third-generation sequencing (TGS), single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), will be desired with great expectations. To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

The Role of Mitochondrial in Intestinal Epithelial Barrier Dysfunction during Inflammatory Bowel Disease

Inflammatory bowel diseases are widely spread in industrial countries with every 20th citizen being affected. Dysregulation of epithelial barrier function is considered to play a key role in the development of inflammatory bowel diseases. Intestinal epithelium permeability depends mostly on the condition of intercellular contacts and epithelial cells' renewal ability. Mitochondria participate in the regulation of various intracellular processes besides performing the energetic function. Recent data indicate the potential role of mitochondria in intestinal epithelial barrier regulation and inflammatory bowel diseases onset. Mitochondrial dysfunction may be one of the reasons for disruption of the structure of tight junctions and the cytoskeleton of intestinal epithelial cells, as well as a decrease in the ability of the epithelial lining to self-renewal. All this leads to a decrease in the barrier function of the intestinal epithelium and the development of inflammatory bowel diseases. Nevertheless, the mechanisms of these processes are still unclear and further research is required.

Pediatric inflammatory bowel diseases, features of the disease course: a clinical case of complicated course of ulcerative colitis

The article is devoted to one of the urgent problems of pediatric gastroenterology – inflammatory bowel diseases (IBD), which currently include ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD is inferior to other gastroenterological diseases, but according to the severity of the course, the frequency of complications and the level of mortality, IBD occupy one of the leading places in the structure of diseases of the gastrointestinal tract. The problem of IBD constantly attracts the attention of doctors of various specialties – pediatricians, gastroenterologists, surgeons and others. This is due to an increase in the incidence of this pathology, a variety of clinical manifestations, including extra-intestinal manifestations, faced by doctors of various specialties. In childhood, there is more often a greater prevalence of the lesion, a less specific and erased picture, there is an impact on the physical development of the child. The article provides information on the prevalence, significant factors in the development of the disease; research data revealing the relationship between taking med ications and the risk of IBD onset. The problems of the pathogenesis of the disease, the significance of the genetic status in the development of CD and UC are described. The article presents data on the features of the clinical picture of UC in childhood, recommendations for the primary diagnosis of IBD, including modern laboratory and instrumental research methods. The article also describes the recommended international criteria for assessing the severity of IBD and the problems of differential diagnosis. As a demonstration, the authors’ own observations are presented. The clinical example describes an atypical case of UC in a teenager, occurring with the involvement of the cardiovascular, bronchopulmonary and urinary systems with the development of polyserositis. Early diagnosis of IBD is necessary to prevent disability of patients, ensure further development of the child, improve the quality of life.

Inflammatory Bowel Disease in Adults and Elderly: The Use of Selected Non-IBD Medication Examined in a Nationwide Cohort Study.

Real-world data on medications used for conditions other than inflammatory bowel disease (IBD) are sparse. We examined how the onset of IBD affects the prescription pattern of selected non-IBD medication and the risk of becoming an incident user. This nationwide cohort study utilized data from Danish health registers. We included incident patients with young adult-onset IBD (18-39 years of age), adult-onset IBD (40-59 years of age), and elderly-onset IBD (60+ years of age), from 1998 to 2018 and followed all for 3 years. We examined redeemed prescriptions before and after the onset of IBD and estimated the risk of becoming a user of non-IBD medications using logistic regression models. We identified 36165 patients, 16 771 (46%) with young adult onset, 10615 (29%) with adult onset, and 8779 (24%) with elderly onset. The onset of IBD increased the use of antidepressants, antipsychotics, sedatives/hypnotics, opioids, nonopioid analgesics, antidiabetics, and proton pump inhibitors, even in patients with no other underlying comorbid diseases. The adjusted odds ratio for using antidepressants 1 year after the onset of IBD in elderly was 1.50 (95% confidence interval [CI], 1.14-1.82), in opioids 1.69 (95% CI, 1.45-1.95), in nonopioid analgesics 2.10 (95% CI, 1.77-2.48), in cardiovascular medication 2.20 (95% CI, 1.86-2.61), and in proton pump inhibitors 1.51 (95% CI, 1.31-1.74) compared with adults. In all 3 age groups, the proportions of patients with redeemed prescriptions for several groups of non-IBD medication were significantly increased after the IBD diagnosis compared with before. The risk of becoming an incident user for several groups of non-IBD medication was increased in elderly patients.

Efficacy and Safety of Anti-Tumor Necrosis Factor Alpha in Very Early Onset Inflammatory Bowel Disease.

Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD. Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression. In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed. Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.