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1.
Eur J Pediatr ; 180(9): 3001-3008, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33876264

RESUMO

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.


Assuntos
Doença de Crohn , Inibidores do Fator de Necrose Tumoral , Criança , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa
2.
Dig Dis ; 36(1): 40-48, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28817809

RESUMO

BACKGROUND: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. SUMMARY: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.


Assuntos
Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Adolescente , Área Sob a Curva , Biomarcadores/metabolismo , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Criança , Doença de Crohn/sangue , Fezes/química , Feminino , Humanos , Inflamação/patologia , Infliximab/administração & dosagem , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Curva ROC , Indução de Remissão , Falha de Tratamento
3.
Eur J Pediatr ; 177(11): 1685-1693, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30128744

RESUMO

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.


Assuntos
Doença de Crohn/terapia , Nutrição Enteral/efeitos adversos , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Biomarcadores/análise , Criança , Doença de Crohn/metabolismo , Feminino , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
4.
Eur J Pediatr ; 177(11): 1695, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30280223

RESUMO

This article was originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above. The original article was corrected.

5.
J Pediatr Gastroenterol Nutr ; 65(2): 207-211, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28248209

RESUMO

OBJECTIVES: Intestinal surgery is an important part of Crohn disease (CD) treatment in children. The aim of the present study was to compare the rate of endoscopic recurrence at the sixth month after ileocecal resection (ICR) in children with CD treated with azathioprine between patients who received prior antitumor necrosis factor alpha (anti-TNF-α) therapy and those who were not administered this therapy. Moreover, we tried to identify the potential risk factors for disease recurrence and describe the schedule of long-term follow-up after surgery. METHODS: We prospectively collected data from pediatric patients with CD, who underwent ICR between October 2011 and June 2015 at our hospital and were treated with azathioprine monotherapy after ICR. We evaluated the endoscopic recurrence (Rutgeerts score) at the sixth month after ICR in all included patients. RESULTS: Among 21 included patients, 13 achieved endoscopic remission (Rutgeerts score < i2) at the sixth month after ICR. No difference was found between patients who received prior anti-TNF-α therapy and those who did not. We did not find any clinically relevant factors associated with endoscopic recurrence rate at the sixth month. CONCLUSIONS: Prior anti-TNF-α therapy does not seem to be a strong risk factor for endoscopic recurrence within 6 months after ICR. Further studies on large sample of patients are needed to identify potential predictors of disease recurrence.


Assuntos
Adalimumab/uso terapêutico , Azatioprina/uso terapêutico , Ceco/cirurgia , Doença de Crohn/tratamento farmacológico , Íleo/cirurgia , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Adolescente , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Colonoscopia , Terapia Combinada , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgia , Feminino , Seguimentos , Gastroscopia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Adulto Jovem
6.
Dig Dis Sci ; 61(7): 2041-50, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26971092

RESUMO

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.


Assuntos
Corticosteroides/uso terapêutico , Azatioprina/uso terapêutico , Doença de Crohn/dietoterapia , Doença de Crohn/tratamento farmacológico , Nutrição Enteral , Adolescente , Azatioprina/administração & dosagem , Criança , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Recidiva , Estudos Retrospectivos
7.
Dig Dis Sci ; 60(11): 3399-407, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26091801

RESUMO

BACKGROUND: Young age and thiopurine therapy are risk factors for lymphoproliferative disease among patients with inflammatory bowel disease (IBD). AIMS: The aims of this study were to evaluate the prevalence of seropositivity for the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) among children and adolescents with IBD, to assess the viral load of EBV, CMV, and BK and JC polyomaviruses (BKV, JCV) in these patients, and to assess the influence of different therapeutic regimens on seroprevalence and viral load. METHODS: Children who had been followed in our center were tested for EBV, CMV, BKV, and JCV in a cross-sectional study. One hundred and six children were included who had Crohn's disease (68%), ulcerative colitis (29%), and unclassified IBD (3%). RESULTS: We found that 64% of patients were EBV seropositive. The proportion of EBV seropositive patients increased during childhood. Azathioprine therapy (p = 0.003) was associated with EBV seropositivity in a multiple logistic regression model, after adjusting for gender, age, and disease activity at determination. We found a significant association between the number of polymerase chain reaction copies and infliximab dose (p = 0.023). We did not find any significant association between CMV serology and CMV, BKV, or JCV viral load, or any other therapeutic regimen or clinical characteristics. CONCLUSIONS: Treatment with azathioprine appears to be a risk factor for early EBV seropositivity in children with IBD, and the infliximab dose was associated with a higher EBV viral load.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Imunossupressores/efeitos adversos , Infecções Oportunistas/epidemiologia , Infecções por Polyomavirus/epidemiologia , Adolescente , Fatores Etários , Azatioprina/efeitos adversos , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/imunologia , Estudos Transversais , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , República Tcheca/epidemiologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Infliximab/efeitos adversos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Testes Sorológicos , Carga Viral
8.
J Pediatr Gastroenterol Nutr ; 58(3): 320-4, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24126833

RESUMO

BACKGROUND: Interferon-γ release assay (IGRA) is widely used for screening of latent tuberculosis (TB) before and during biological therapy (BT). An indeterminate result of IGRA represents a limitation in the management of inflammatory bowel disease (IBD). Data on factors influencing IGRA results are scarce in children. The aim of the study was to identify factors influencing IGRA results in children with IBD. METHODS: Seventy-two children with IBD (59 Crohn disease, 11 ulcerative colitis, 2 IBD-unclassified) indicated for BT were tested for TB infection (history, TB skin test, chest radiograph, IGRA; QuantiFERON-TB Gold in tube [QFT]) and consecutively retested using QFT in 1-year intervals. RESULTS: We recorded 165 results of QFT (3% positive, 87% negative, and 10% indeterminate results). During follow-up we identified 4 conversions of negative QFT to positivity (3%) and 4 reversions (4%). Patients with indeterminate results of QFT had significantly lower actual weight-for-height z score (P = 0.022), higher platelet count (P = 0.00017), and lower levels of serum albumin (P = 0.015) compared with patients with positive or negative QFT. Indeterminate QFT was associated with corticosteroid treatment, BT, and disease activity, but not with treatment by immunomodulators. In a subanalysis of patients with Crohn disease alone, Pediatric Crohn's Disease Activity Index was identified as single independent risk factor for indeterminate results (P = 0.00037). CONCLUSIONS: Although corticosteroid treatment is traditionally considered to be the main risk factor for indeterminate results of IGRA, the disease activity of IBD has even more profound effects on the results.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Testes de Liberação de Interferon-gama , Interferon gama/metabolismo , Tuberculose Latente/diagnóstico , Teste Tuberculínico , Adolescente , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Peso Corporal , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Doença de Crohn/complicações , Doença de Crohn/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Tuberculose Latente/complicações , Tuberculose Latente/metabolismo , Masculino , Contagem de Plaquetas , Fatores de Risco , Albumina Sérica/metabolismo
9.
Paediatr Drugs ; 26(6): 659-672, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39215954

RESUMO

BACKGROUND AND AIMS: Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review (SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. METHODS: We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. RESULTS: Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patients undergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. CONCLUSION: Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.


Assuntos
Doença de Crohn , Recidiva , Humanos , Doença de Crohn/cirurgia , Doença de Crohn/prevenção & controle , Criança , Íleo/cirurgia , Ceco/cirurgia , Prevenção Secundária/métodos , Complicações Pós-Operatórias/prevenção & controle
10.
Eur J Pediatr ; 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24233405

RESUMO

The aim of this study was to assess the accuracy of serological tests in combination with clinical symptoms for diagnosing celiac disease (CD) according to the new proposed European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. We retrospectively assessed children and adolescents aged 16 months -19 years who were examined for suspicion of CD (n = 345). Evaluation of clinical symptoms and the presence of tissue transglutaminase (anti-TG-IgA) and endomysial antibodies (EMA-IgA) as well as intestinal biopsies was performed in all patients. Human leukocyte antigens (HLAs) were not included. Among 345 biopsied children, 213 (62 %) children had anti-TG titers >10 times the upper limit of normal (ULN) and positive EMA antibodies. Ninety-nine (29 %) children also had symptoms suggestive of CD in addition to EMA positivity and elevated titers of anti-TG >10 times the ULN. In patients who were asymptomatic, but positive for EMA, and had anti-TG antibodies >10 times the ULN, the specificity of tests for Marsh 2-3 was only 85 %, while in symptomatic patients with the same antibodies levels, the specificity was 99 %. Conclusion: Our results reveal that intestinal biopsies could be omitted in 28 % of patients when the new ESPGHAN guidelines are applied. Due to high accuracy of serological tests in combination with clinical symptoms for diagnosis of CD, the new guideline seems to be applicable even without the use of HLA testing.

11.
Clin Transl Gastroenterol ; 13(5): e00490, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363628

RESUMO

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.


Assuntos
Doença de Crohn , Adalimumab/efeitos adversos , Anticorpos Anticitoplasma de Neutrófilos , Criança , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Humanos , Fatores Imunológicos , Infliximab/uso terapêutico , Pontuação de Propensão , Estudos Prospectivos , Resultado do Tratamento
12.
Artigo em Inglês | MEDLINE | ID: mdl-34446936

RESUMO

AIM: Detection of possible predictive factors of endoscopic recurrence after ileocecal resection in Crohn's disease could be very beneficial for the individual adjustment of postoperative therapy. The aim of this study was to verify, whether immunohistochemical detection of calprotectin in resection margins is useful in diagnostics of endoscopic recurrence. METHODS: In this study we included pediatric patients with Crohn's disease who underwent ileocecal resection, regardless of pre-operative or post-operative therapy (n=48). We collected laboratory, clinical, surgical, endoscopic and histopathological data at the time of surgery and at 6 months after surgery. The immunohistochemical staining of calprotectin antigen was performed on all paraffin blocks from the resection margins. RESULTS: Out of 48 patients 52% had endoscopic recurrence in the anastomosis (defined by Rutgeerts score) within 6 months after surgery. The number of cells positive for calprotectin in the proximal resection margin was negatively associated with recurrence (P=0.008), as was the elevated level of total calprotectin (from both resection margins). There was no correlation of calprotectin in distal resection margin and endoscopic recurrence. Fecal calprotectin over 100 ug/g (P=0.0005) and high CRP (P<0.001) at 6 months after ileocecal resection and peritonitis (P=0.048) were associated with endoscopic recurrence. CONCLUSION: Approximately half of the patients developed endoscopic recurrence within 6 months after ileocecal resection. The predictive value of tissue calprotectin is questionable, as it is negatively associated with endoscopic recurrence. There are other potentially useful predictors, such as CRP and fecal calprotectin at 6 months after resection and the presence of peritonitis.


Assuntos
Doença de Crohn , Peritonite , Biomarcadores , Criança , Colonoscopia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Fezes , Humanos , Complexo Antígeno L1 Leucocitário , Margens de Excisão , Recidiva
13.
Paediatr Drugs ; 23(2): 183-194, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33709340

RESUMO

BACKGROUND: The additional value of azathioprine concomitant treatment on infliximab pharmacokinetics in children is not well described yet. AIMS: In the present study, we aimed to describe the relationship between thiopurine metabolite levels, infliximab trough levels, anti-IFX antibody formation, and clinical and laboratory markers of disease activity in pediatric patients with Crohn's disease, and to assess non-adherence. METHODS: Data were collected prospectively during repeated visits from pediatric patients followed for Crohn's disease in two Czech pediatric inflammatory bowel disease centers between January 2016 and June 2017. Thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine) were measured by high-performance liquid chromatography. Infliximab trough levels and anti-IFX antibody serum levels were measured routinely by ELISA. The risk of loss of response to infliximab therapy was also assessed. RESULTS: A significant association between infliximab serum levels and 6-thioguanine erythrocyte levels was observed when tested as categorical variables (63 patients, 321 observations). To predict infliximab levels > 5 µg/mL, we propose a 6-thioguanine cutoff of 278 pmol/8 × 108 erythrocytes (sensitivity, 0.799; specificity, 0.347). A higher loss-of-response-to-infliximab rate (tested in a subgroup of 51 patients) was observed in patients with undetectable 6-thioguanine levels than in those with detectable levels (p = 0.026). Non-adherence to azathioprine therapy was suspected in 20% of patients. CONCLUSION: Thiopurine metabolite monitoring in pediatric patients with Crohn's disease is useful when optimizing combination therapy. Pediatric patients with undetectable 6-thioguanine levels are more likely to lose response to infliximab therapy. When targeting optimal infliximab levels, the 6-thioguanine cutoff levels in children appear to be higher than in adults.


Assuntos
Azatioprina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Adolescente , Biomarcadores , Criança , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Estudos Longitudinais , Masculino , Mercaptopurina/análogos & derivados , Mercaptopurina/análise , Estudos Prospectivos
14.
Inflamm Bowel Dis ; 25(4): 789-796, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30239799

RESUMO

BACKGROUND: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children. METHODS: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. RESULTS: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). CONCLUSIONS: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.


Assuntos
Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Doenças Inflamatórias Intestinais/imunologia , Infliximab/administração & dosagem , Masculino , Mães , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Prognóstico
15.
Inflamm Bowel Dis ; 23(4): 514-523, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28267045

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Doenças Inflamatórias Intestinais/terapia , Força Muscular/efeitos dos fármacos , Adolescente , Osso Esponjoso/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Masculino , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Inflamm Bowel Dis ; 23(5): 791-797, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28426458

RESUMO

BACKGROUND: The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNFα) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNFα agent postoperatively. METHODS: Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNFα agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNFα pharmacodynamic failure and those with no preoperative anti-TNFα treatment. RESULTS: A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNFα initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNFα initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNFα treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNFα treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNFα treatment. CONCLUSIONS: Pediatric patients with Crohn's disease who failed anti-TNFα therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNFα naive patients.


Assuntos
Colectomia/métodos , Doença de Crohn/terapia , Fármacos Gastrointestinais/administração & dosagem , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Terapia Combinada , Feminino , Humanos , Masculino , Período Pós-Operatório , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento
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