Studies showing a substantial frequency of dermatologic complications in paediatric Crohn’s disease (CD) patients on anti-tumour necrosis factor (TNF) therapy preferentially include patients treated ...with infliximab. We aimed to identify risk factors for the cumulative incidence of skin complications in a paediatric cohort receiving either adalimumab or infliximab and found an association between current skin complications and the patient’s current clinical condition. This study retrospectively evaluated dermatologic complications in an inception cohort of 100 paediatric CD patients receiving the first anti-TNF (Motol PIBD cohort). Patient data were collected every 3 months. The lesions were classified as psoriatic, atopic dermatitis, or others. We used Cox regression to evaluate the association between predefined variables and the time to complication and a generalised linear mixed model to assess the association between the patient’s current condition and the occurrence of complications. Among the 89 included children, 35 (39%) presented with dermatologic lesions. The only predictor associated with any complication was infliximab (versus adalimumab) therapy (hazard ratio HR: 2.07; 95% confidence interval CI: 1.03–4.17;
p
= 0.04). Infliximab therapy (HR: 5.5; 95%CI: 1.59–19.06;
p
= 0.01) and a family history of atopy (HR: 3.4; 95%CI 1.35–8.57,
p
= 0.002) were associated with early manifestation of atopic dermatitis. Lower C-reactive protein levels (odds ratio OR, 0.947; 95% CI, − 0.898 to 0.998;
p
= 0.046) and infliximab (versus adalimumab) were associated with the occurrence of any dermatologic complications (OR, 5.93; 95% CI, 1.59–22.07;
p
= 0.008).
Conclusion
: The frequency of skin complications seems high in paediatric CD patients treated with anti-TNF and is even higher in those treated with infliximab.
What is Known:
•
The dermatologic complications occur during treatment with anti-tumour necrosis factor
.
•The frequency of skin complications in paediatric patients with Crohn’s disease is high
.
What is New:
•
Infliximab (vs. adalimumab) was identified as a strong risk factor for the cumulative incidence of skin complications
.
•Lower C-reactive protein levels were associated with the current occurrence of dermatologic complications
.
Two antitumor necrosis factor therapies (infliximab IFX and adalimumab ADA) have been approved for the treatment of pediatric Crohn's disease (CD) but have not been compared in head-to-head trials. ...The aim of this study was to compare the efficacy and safety of ADA and IFX by propensity score matching in a prospective cohort of pediatric patients with luminal CD and at least a 24-month follow-up.
Among 100 patients, 75 met the inclusion criteria, and 62 were matched by propensity score. We evaluated time to treatment escalation as the primary outcome and primary nonresponse, predictors of treatment escalation and relapse, serious adverse events, pharmacokinetics, and effect of concomitant immunomodulators as secondary outcomes.
There was no difference between ADA and IFX in time to treatment escalation (HR = 0.63 95% CI 0.31-1.28 P = 0.20), primary nonresponse (P = 0.95), or serious adverse events. The median (interquartile range) trough levels at the primary outcome were 14.05 (10.88-15.40) and 6.15 (2.08-6.58) µg/mL in the ADA and IFX groups, respectively. On a multivariate analysis, the combination of anti-Saccharomyces cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity was a strong independent predictor of treatment escalation (HR 5.19, 95% CI 2.41-11.18, P < 0.0001). The simple endoscopic score for CD, L3 disease phenotype, and use of concomitant immunomodulators for at least the first 6 months revealed a trend toward significance on a univariate analysis.
Propensity score matching did not reveal substantial differences in efficacy or safety between ADA and IFX. The anti-S. cerevisiae antibody negativity and antineutrophil cytoplasmic antibody positivity combination is a strong predictor of treatment escalation.
Exclusive enteral nutrition (EEN) has been recommended as the first-line therapy in children with active Crohn disease (CD). The primary aim of our study was to determine whether it is possible to ...use the difference between basal fecal calprotectin (F-CPT) and the value at week 2 of EEN to predict clinical response at week 6. We prospectively collected stool samples for F-CPT analysis and clinical and laboratory parameters during EEN from 38 pediatric patients (28 boys, median age 12.8 years) with newly diagnosed active luminal CD. The difference between F-CPT concentrations before EEN and at week 2 did not predict clinical non-response at week 6 (OR 0.9996 95% CI 0.9989–1.0002,
p
= 0.18); however, it predicted patients who did not achieve clinical remission at week 6 (OR 0.9993, 95% CI 00.9985–0.9998,
p
= 0.006) with sensitivity of 58%, and specificity of 92% for cut-off of F-CPT increase by 486 μg/g.
Conclusions
: An early decrease in F-CPT levels in children with newly diagnosed active luminal CD did not predict clinical response at week 6 of EEN induction therapy, and clinical remission was predicted with low accuracy. Therefore, F-CPT cannot be used as a predictor to select the patients in whom EEN should be terminated.
What is Known:
•
The fecal calprotectin (F-CPT) is an important marker of intestinal inflammation.
•
Approximately 25% of pediatric patients with Crohn disease (CD) do not achieve clinical remission, and there is still no sufficient predictor of response to exclusive enteral nutrition (EEN) treatment.
What is New:
•
The difference between the F-CPT concentrations before EEN treatment and at week 2 did not predict clinical response to treatment at week 6, even if it predicted clinical remission, however, with low accuracy. F-CPT is not a suitable predictor to select the patients for discontinuing of EEN induction therapy.
Current studies indicate a link between the intake of exclusive enteral nutrition (EEN) and the induction of complex changes in the intestinal microbiota, as well as the clinical improvement of ...Crohn's disease (CD). The first aim of this study was to test the ability of various commensal bacterial strains (
= 19) such as bifidobacteria, lactobacilli, and
to grow on three different polymeric EN
. Tested EN formulas were found to be suitable growth media for tested commensals. Furthermore, the counts of these bacteria and total counts of anaerobic bacteria in the fecal samples of children with CD (
= 15) before and after 6 weeks of EEN diet administration were determined using cultivation on selective media. The counts of cultivable commensal bacteria in the fecal samples of CD children were not significantly affected by EEN. However, tested bacteria showed some individual shifts in counts before and after EEN therapy. Moreover, cultured bifidobacteria were found to be in reduced counts in CD children. Therefore, the application of bifidogenic prebiotic compounds to EN for CD patients might be considered.
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•Enteral nutrition (EN) formulas contain variable nutrient and prebiotic compounds.•Cultivable commensal bacteria of faecal microbiota are able to use EN formulas like growth media in ...vitro.•Composition differences of EN formulas affecting individual microbial shift and metabolite profile after cultivation.•Functional components should be personalised based on individual host microbiota.
Enteral nutrition (EN) formulas of polymeric type ordinarily have similar content of intact macronutrients but may vary in prebiotic saccharides and micronutrients. These components can play an important role in the intestinal microbiota modulation. The aim of this study was to investigate microbial changes of faecal samples after their in vitro anaerobic cultivation in four polymeric EN formulas using plate technique method, metabolite analysis, and microbiota profiling using 16S rRNA sequencing. Detected cultivable commensal groups (bifidobacteria, lactobacilli, Escherichia coli) in faecal samples of donors were able to grow in EN formulas. However, their counts varied depending on the individual donor and the type of EN formula. Similar trend was found in detected metabolites such as acetate, lactate, and butyrate. Also, taxonomic composition and diversity of original and cultivated faecal microbiota of one individual on different EN formula indicate a possible effect of the prebiotics and micronutrients to modulate gut microbiota.
Mutations in the Sterile alpha motif domain containing 9 (
) gene have been described in patients with severe multisystem disorder, MIRAGE syndrome, but also in patients with bone marrow (BM) failure ...in the absence of other systemic symptoms. The role of hematopoietic stem cell transplantation (HSCT) in the management of the disease is still unclear. Here, we present a patient with a novel mutation in
(c.2471 G>A, p.R824Q), manifesting with prominent gastrointestinal tract involvement and immunodeficiency, but without any sign of adrenal insufficiency typical for MIRAGE syndrome. He suffered from severe CMV (cytomegalovirus) infection at 3 months of age, with a delayed development of T lymphocyte functional response against CMV, profound T cell activation, significantly reduced B lymphocyte counts and impaired lymphocyte proliferative response. Cultured T cells displayed slightly lower calcium flux and decreased survival. At the age of 6 months, he developed severe neutropenia requiring G-CSF administration, and despite only mild morphological and immunophenotypical disturbances in the BM, 78% of the BM cells showed monosomy 7 at the age of 18 months. Surprisingly, T cell proliferation after CD3 stimulation and apoptosis of the cells normalized during the follow-up, possibly reflecting the gradual development of monosomy 7. Among other prominent symptoms, he had difficulty swallowing, requiring percutaneous endoscopic gastrostomy (PEG), frequent gastrointestinal infections, and perianal erosions. He suffered from repeated infections and periodic recurring fevers with the elevation of inflammatory markers. At 26 months of age, he underwent HSCT that significantly improved hematological and immunological laboratory parameters. Nevertheless, he continued to suffer from other conditions, and subsequently, he died at day 440 post-transplant due to sepsis. Pathogenicity of this novel
mutation was confirmed experimentally. Expression of mutant
caused a significant decrease in proliferation and increase in cell death of the transfected cells.
We describe a novel
mutation in a patient with prominent gastrointestinal and immunological symptoms but without adrenal hypoplasia. Thus, SAMD9 mutations should be considered as cause of enteropathy in pediatric patients. The insufficient therapeutic outcome of transplantation further questions the role of HSCT in the management of patients with
mutations and multisystem involvement.
Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D ...supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD.
This was a prospective observational study of 55 patients (aged 5-19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0-16.0) months of daily substitution of 2000 IU of cholecalciferol.
Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14-0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32-0.85, P < 0.0001, respectively) but not with the Strength-Strain Index or maximal muscle force (Fmax).
We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.
Objectives:
We prospectively compared the postvaccination immunity to messenger ribonucleic acid BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine of our pediatric ...patients over 12 years old with inflammatory bowel disease (IBD) to that of healthy controls and looked for predictors of its robustness.
Methods:
Anti‐receptor binding domain, anti‐spike S2, and anti‐nucleocapsid immunoglobin‐G (IgG) and immunoglobin‐A levels were measured in 139 pediatric patients with IBD 65 fully vaccinated (2 doses), median age 16.3, interquartile range (IQR) 15.2–17.8 years, median time from vaccination (IQR) 61.0 (42.0–80.0) days and 1744 controls (46, 37–57 years) using microblot array.
Results:
All IBD and control patients developed positive anti‐receptor binding domain IgG antibodies at comparable titers. The proportion of observations with positive anti‐spike S2 IgG was higher in patients with IBD than in controls 63% vs 21%, odds ratio 2.99 (1.51–5.90), as was its titer median (IQR) 485 (92–922) vs 79 33–180 IU/mL. Anti‐receptor binding domain and anti‐spike S2 IgG levels were associated with IBD status. We found an association between anti‐spike S2 IgG levels and time since vaccination (β −4.85, 95% CI −7.14 to 2.71, P = 0.0001), history of SARS‐CoV‐2 polymerase chain reaction positivity (206.76, 95% CI 39.93–374.05, P = 0.0213), and anti‐tumor necrosis factor treatment (−239.68, 95% CI −396.44–83.55, P = 0.0047). Forty‐three percent of patients reported vaccination side effects (mostly mild). Forty‐six percent of observations with positive anti‐nucleocapsid IgG had a history of SARS‐CoV‐2 infection.
Conclusions:
Patients with IBD produced higher levels of postvaccination anti‐spike S2 antibodies than controls. Previous SARS‐CoV‐2 infection is associated with higher production of postvaccination antibodies and anti‐tumor necrosis factor treatment with lower production.
Background
The duration of remission has been shown to be longer in patients initially treated with exclusive enteral nutrition (EEN) compared to corticosteroids (CS). However, no published studies ...required concurrent immunomodulator 6-mercaptopurine or azathioprine (AZA) use at the time of diagnosis.
Aims
The aims of this retrospective study were to compare the duration of remission between patients initially treated with AZA in combination with CS or EEN and identify predictors of early relapse in these patients.
Methods
Data from 65 newly diagnosed children with CD in clinical remission on either EEN or CS and commencing AZA at diagnosis were included. We compared duration of remission using physician global assessment and carried out Cox regression analysis to identify predictors of early relapse. Patients were followed up to the time of first relapse or for at least 12 months.
Results
There were no differences in the duration of remission between patients initially treated with EEN or CS (
p
= 0.978). We identified younger age at diagnosis hazard ratio (HR) 0.87, 95 CI 0.78–0.98,
p
= 0.016, lower height
Z
score at diagnosis (HR 0.61, 95 CI 0.44–0.85,
p
= 0.003), involvement of the upper gastrointestinal tract (HR 2.69, 95 CI 1.27–5.66,
p
= 0.009), and elevated platelet count at remission (HR 1.004, 95 CI 1.001–1.008,
p
= 0.021) as independent predictors of early relapse.
Conclusions
Neither induction regime demonstrated longer duration of remission of CD in patients treated with immunomodulators since the time of diagnosis.
BACKGROUNDWe aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD).METHODSThe Czech National Prospective Registry of Biologic and ...Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability.RESULTSAmong the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410).CONCLUSIONSGiven the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable.IMPACTOur study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.
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