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1.
Aliment Pharmacol Ther ; 60(6): 765-777, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38997818

RESUMO

BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.


Assuntos
Biomarcadores , Colite Ulcerativa , Neurotoxina Derivada de Eosinófilo , Fezes , Complexo Antígeno L1 Leucocitário , Peroxidase , Humanos , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Masculino , Fezes/química , Adulto , Estudos Prospectivos , Complexo Antígeno L1 Leucocitário/análise , Pessoa de Meia-Idade , Peroxidase/metabolismo , Colite Ulcerativa/diagnóstico , Neurotoxina Derivada de Eosinófilo/análise , Neurotoxina Derivada de Eosinófilo/metabolismo , Doença de Crohn/diagnóstico , Proteína Catiônica de Eosinófilo/análise , Proteína Catiônica de Eosinófilo/metabolismo , Adulto Jovem , Doenças Inflamatórias Intestinais/diagnóstico , Estudos de Casos e Controles , Curva ROC , Progressão da Doença , Valor Preditivo dos Testes
2.
Surgery ; 174(2): 144-151, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37263879

RESUMO

BACKGROUND: Obesity is becoming more prevalent in patients with inflammatory bowel disease. Although bariatric surgery is an effective treatment for obesity, questions remain regarding its safety and effectiveness for patients with inflammatory bowel disease. The aim of this study was to evaluate the safety and effectiveness of bariatric surgery in patients with inflammatory bowel disease. METHOD: This registry-based, propensity-matched cohort study included all patients who had primary Roux-en-Y gastric bypass or sleeve gastrectomy in Sweden from January 2007 to June 2020 who had an inflammatory bowel disease diagnosis and matched control patients without an inflammatory bowel disease diagnosis. The study included data from the Scandinavian Obesity Surgery Registry, the National Patient Register, the Swedish Prescribed Drugs Register, the Total Population Register, and the Education Register from Statistics Sweden. RESULTS: In total, 71,093 patients who underwent bariatric surgery, including 194 with Crohn's disease and 306 with ulcerative colitis, were 1:5 matched to non-inflammatory bowel disease control patients. The patients with Crohn's disease had a higher readmission rate within 30 days (10.7% vs 6.1%, odds ratio = 1.84, 95% confidence interval 1.02-3.31) than the control patients, with no significant difference between the surgical methods. The patients with ulcerative colitis had a higher risk for serious postoperative complications after Roux-en-Y gastric bypass (8.0% vs 3.7%, odds ratio = 2.64, 95% confidence interval 1.15-6.05) but not after sleeve gastrectomy compared to control patients (0.8% vs 2.3%). No difference was observed in postoperative weight loss or postoperative health-related quality of life. CONCLUSION: Sleeve gastrectomy appears to be a safe and effective treatment for obesity in patients with inflammatory bowel disease, whereas Roux-en-Y gastric bypass was associated with a higher risk for postoperative complications in patients with ulcerative colitis.


Assuntos
Cirurgia Bariátrica , Colite Ulcerativa , Doença de Crohn , Derivação Gástrica , Doenças Inflamatórias Intestinais , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos de Coortes , Doença de Crohn/cirurgia , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Qualidade de Vida , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/cirurgia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Resultado do Tratamento , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Sistema de Registros , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
3.
Dig Dis Sci ; 68(7): 3119-3128, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36929241

RESUMO

BACKGROUND: There are little data on positioning biologics in Crohn's disease (CD). AIMS: We aimed to assess the comparative effectiveness and safety of ustekinumab vs tumour necrosis factor-alpha (anti-TNF) agents after first-line treatment with anti-TNF in CD. METHODS: We used Swedish nationwide registers to identify patients with CD, exposed to anti-TNF who initiated second-line biologic treatment with ustekinumab or second-line anti-TNF therapy. Nearest neighbour 1:1 propensity score matching (PSM) was used to balance the groups. The primary outcome was 3-year drug survival used as a proxy for effectiveness. Secondary outcomes included drug survival without hospital admission, CD-related surgery, antibiotics, hospitalization due to infection and exposure to corticosteroids. RESULTS: Some 312 patients remained after PSM. Drug survival at 3 years was 35% (95% CI 26-44%) in ustekinumab compared to 36% (95% CI 28-44%) in anti-TNF-treated patients (p = 0.72). No statistically significant differences were observed between the groups in 3-year survival without hospital admission (72% vs 70%, p = 0.99), surgery (87% vs 92%, p = 0.17), hospital admission due to infection (92% vs 92%, p = 0.31) or prescription of antibiotics (49% vs 50%, p = 0.56). The proportion of patients continuing second-line biologic therapy did not differ by reason for ending first-line anti-TNF (lack of response vs intolerance) or by type of first-line anti-TNF (adalimumab vs infliximab). CONCLUSION: Based on data from Swedish routine care, no clinically relevant differences in effectiveness or safety of second-line ustekinumab vs anti-TNF treatment were observed in patients with CD with prior exposure to anti-TNF.


Assuntos
Produtos Biológicos , Doença de Crohn , Humanos , Ustekinumab/efeitos adversos , Doença de Crohn/patologia , Fator de Necrose Tumoral alfa , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Adalimumab/efeitos adversos , Infliximab/efeitos adversos , Fatores Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Necrose , Resultado do Tratamento
4.
J Crohns Colitis ; 17(6): 919-932, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-36694402

RESUMO

Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Doença de Crohn/complicações , Glicômica , Doenças Inflamatórias Intestinais/complicações , Biomarcadores , Polissacarídeos
5.
J Crohns Colitis ; 17(5): 722-727, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-36455965

RESUMO

BACKGROUND: Idiopathic thrombocytopaenic purpura [ITP] is an acquired haematological disorder with an incidence of 1-6 per 100 00/year. ITP and inflammatory bowel disease [IBD] comorbidity has been reported in the literature, but insights regarding the course, outcome and optimal management are limited by its rarity. The current study aimed to evaluate the clinical presentation and outcome of ITP in patients with IBD. METHODS: This multicentre retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports [CONFER] project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardized collection form. RESULTS: This report includes 32 patients with concurrent ITP and IBD: ten were females, and the median age was 32.0 years (interquartile range [IQR] 20.5-39.5). Fourteen patients had a diagnosis of Crohn's disease [CD] and the other 18 ulcerative colitis [UC]. The diagnosis of IBD preceded the ITP in 26 patients (median time between diagnoses was 7.0 years [IQR, 1.5-9.5]). Among those patients, 17 were in clinical remission at ITP diagnosis. Thirteen patients were treated with mesalamine, four with oral corticosteroids, one with rectal corticosteroids, two with azathioprine and five with anti-tumour necrosis factor agents. The median platelet count was 35 000/microliter [IQR, 10 000-70 000]. Eight patients had rectal bleeding, 13 had skin purpura, three had epistaxis, six had mucosal petechiae and 13 were asymptomatic. Regarding ITP treatment, 19 were treated with corticosteroids, one with anti-RhD immunoglobulin, 12 with intravenous immunoglobulins [IVIGs], four with thrombopoietin, three with rituximab and six patients eventually required splenectomy. Ten patients needed no treatment directed to the ITP. Three patients required colectomy during long-term follow-up, due to IBD or cancer but not to massive bleeding as a complication of ITP. One of eight patients who presented with rectal bleeding required splenectomy, and none required urgent colectomy. Two patients died during the follow-up, one of them due to bleeding complications located in the upper gastrointestinal tract. Median follow-up time was 6.5 years [IQR, 3-10]. With long-term follow-up, all patients had platelet counts above 50 000/microliter, and 24 were in IBD clinical remission. CONCLUSION: Most ITP cases in this series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients followed an expected course, including response to medical therapy and low rates of splenectomy.


Assuntos
Doenças Inflamatórias Intestinais , Púrpura Trombocitopênica Idiopática , Feminino , Humanos , Adulto , Masculino , Estudos Retrospectivos , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Azatioprina/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Corticosteroides/uso terapêutico
6.
J Crohns Colitis ; 17(2): 170-184, 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36029471

RESUMO

BACKGROUND: Epigenetic alterations may provide valuable insights into gene-environment interactions in the pathogenesis of inflammatory bowel disease [IBD]. METHODS: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 Crohn's disease [CD], 161 ulcerative colitis [UC], 28 IBD unclassified [IBD-U)] with covariates of age, sex and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using the Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. RESULTS: A total of 137 differentially methylated positions [DMPs] were identified in IBD, including VMP1/MIR21 [p = 9.11 × 10-15] and RPS6KA2 [6.43 × 10-13], with consistency seen across Scandinavia and the UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 [p = 1.53 × 10-15]. Age acceleration is seen in IBD [coefficient 0.94, p < 2.2 × 10-16]. Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r = -0.32, p = 3.64 × 10-7 vs non-IBD r = -0.14, p = 0.77]. Multi-omic integration of the methylome, genome and transcriptome also implicated specific pathways that associate with immune activation, response and regulation at disease inception. At follow-up, a signature of three DMPs [TAP1, TESPA1, RPTOR] were associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 [CI: 2.14-12.56], logrank p = 9.70 × 10-4). CONCLUSION: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Epigenoma , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/genética , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Epigênese Genética , Fatores Biológicos , Proteínas de Membrana/genética
7.
Clin Exp Gastroenterol ; 15: 5-25, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185343

RESUMO

BACKGROUND: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls. METHODS: Altogether, 323 subjects were included: Crohn's disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome. RESULTS: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn's disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn's disease and ulcerative colitis (>2.6 normalized enrichment scores <-1.8). Gene expression signatures of Crohn's disease and ulcerative colitis did not predict time for treatment escalation (p = 0.175). No significant association was found between gene expression signatures and anti-TNF response. CONCLUSION: Non-inflamed samples are probably superior to inflamed samples when exploring gene expression signatures in IBD and might reveal underlying mechanisms central for disease initiation. The gene expression signatures of the control groups were related to if they were symptomatic or not, which may have important implications for future study designs.

8.
J Crohns Colitis ; 16(8): 1255-1268, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35212366

RESUMO

AIM: To assess the pathobiological and translational importance of whole-blood transcriptomic analysis in inflammatory bowel disease [IBD]. METHODS: We analysed whole-blood expression profiles from paired-end sequencing in a discovery cohort of 590 Europeans recruited across six countries in the IBD Character initiative (newly diagnosed patients with Crohn's disease [CD; n = 156], ulcerative colitis [UC; n = 167], and controls [n = 267]), exploring differential expression [DESeq2], co-expression networks [WGCNA], and transcription factor involvement [EPEE, ChEA, DoRothEA]. Findings were validated by analysis of an independent replication cohort [99 CD, 100 UC, 95 controls]. In the discovery cohort, we also defined baseline expression correlates of future treatment escalation using cross-validated elastic-net and random forest modelling, along with a pragmatic ratio detection procedure. RESULTS: Disease-specific transcriptomes were defined in IBD [8697 transcripts], CD [7152], and UC [8521], with the most highly significant changes in single genes, including CD177 (log2-fold change [LFC] = 4.63, p = 4.05 × 10-118), MCEMP1 [LFC = 2.45, p = 7.37 × 10-109], and S100A12 [LFC = 2.31, p = 2.15 × 10-93]. Significantly over-represented pathways included IL-1 [p = 1.58 × 10-11], IL-4, and IL-13 [p = 8.96 × 10-9]. Highly concordant results were obtained using multiple regulatory activity inference tools applied to the discovery and replication cohorts. These analyses demonstrated central roles in IBD for the transcription factors NFE2, SPI1 [PU.1], CEBPB, and IRF2, all regulators of cytokine signalling, based on a consistent signal across cohorts and transcription factor ranking methods. A number of simple transcriptome-based models were associated with the need for treatment escalation, including the binary CLEC5A/CDH2 expression ratio in UC (hazard ratio = 23.4, 95% confidence interval [CI] 5.3-102.0). CONCLUSIONS: Transcriptomic analysis has allowed for a detailed characterisation of IBD pathobiology, with important potential translational implications.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Proteína beta Intensificadora de Ligação a CCAAT , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Humanos , Doenças Inflamatórias Intestinais/genética , Fator Regulador 2 de Interferon/genética , Lectinas Tipo C , Receptores de Superfície Celular/genética , Fatores de Transcrição/genética , Transcriptoma
9.
J Crohns Colitis ; 16(7): 1097-1109, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35022690

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways. METHODS: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve [n = 110] and treatment-exposed [n = 177] IBD patients as well as symptomatic [n = 65] and healthy controls [n = 95]. RESULTS: Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, IL1B was identified as the central gene. Levels of co-expression among IL1B and chemosensing receptor [CXCR1/2 and FPR1/2] genes were reduced in the blood of IBD patients when compared with healthy controls. CONCLUSIONS: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , MicroRNAs , Humanos , Doenças Inflamatórias Intestinais/metabolismo , MicroRNAs/genética , Ativação de Neutrófilo/genética , RNA Mensageiro/genética , Transcriptoma
10.
J Crohns Colitis ; 16(3): 430-435, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-34498037

RESUMO

BACKGROUND: Orofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn's disease [CD]. We aimed to characterise this relationship and the management options in the biologic era. METHODS: This multicentre case series was supported by the European Crohn's and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form. RESULTS: This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs. CONCLUSIONS: OFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.


Assuntos
Doença de Crohn , Granulomatose Orofacial , Adulto , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Granulomatose Orofacial/diagnóstico , Granulomatose Orofacial/tratamento farmacológico , Granulomatose Orofacial/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Ustekinumab/uso terapêutico
11.
Scand J Gastroenterol ; 56(11): 1304-1311, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34415803

RESUMO

OBJECTIVES: Clinical trials demonstrated that golimumab is effective in anti-TNF naïve patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. MATERIALS AND METHODS: This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore ≥2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by ≥3 points or 30% from baseline) and remission (defined as a Mayo score of ≤2 with no individual subscores >1). RESULTS: Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p < .01) and the faecal calprotectin decreased from 862 (335-1759) µg/g to 90 (34-169) µg/g (p < .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5‒1188.9). CONCLUSIONS: The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.


Assuntos
Colite Ulcerativa , Anticorpos Monoclonais , Colite Ulcerativa/tratamento farmacológico , Humanos , Estudos Prospectivos , Suécia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
12.
Gastroenterology ; 161(5): 1526-1539.e9, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34298022

RESUMO

BACKGROUND & AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. METHODS: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. CONCLUSIONS: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.


Assuntos
Proteínas Sanguíneas/análise , Colite Ulcerativa/sangue , Mediadores da Inflamação/sangue , Proteoma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL11/sangue , Quimiocina CCL2/sangue , Quimiocina CXCL11/sangue , Quimiocina CXCL9/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Feminino , Humanos , Masculino , Metaloproteinase 10 da Matriz/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteômica , Reprodutibilidade dos Testes , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/sangue , Regulação para Cima , Adulto Jovem
13.
United European Gastroenterol J ; 8(8): 949-960, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32715989

RESUMO

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/terapia , Mesalamina/uso terapêutico , Adulto , Fatores Biológicos/uso terapêutico , Colectomia/estatística & dados numéricos , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Progressão da Doença , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Europa (Continente) , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Fatores Imunológicos/uso terapêutico , Quimioterapia de Manutenção/métodos , Quimioterapia de Manutenção/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
14.
Eur J Gastroenterol Hepatol ; 30(11): 1297-1303, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30134383

RESUMO

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Criança , Europa (Continente)/epidemiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/sangue , Fumar/epidemiologia , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto Jovem
15.
Scand J Gastroenterol ; 52(6-7): 722-729, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28362144

RESUMO

OBJECTIVES: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. MATERIALS AND METHODS: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). RESULTS: Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48). CONCLUSION: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Estudos de Coortes , Fezes/química , Feminino , Humanos , Estimativa de Kaplan-Meier , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros , Suécia , Resultado do Tratamento
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