RESUMO
OBJECTIVE: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy). DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively). CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal. TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.
RESUMO
INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.
Assuntos
Produtos Biológicos , Colectomia , Colite Ulcerativa , Piperidinas , Complicações Pós-Operatórias , Pirimidinas , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Tromboembolia Venosa/epidemiologia , Reoperação/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , IdosoRESUMO
BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients. METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected. RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index. CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.
Assuntos
Doença de Crohn , Feminino , Humanos , Proteína de Matriz Gla , Constrição Patológica , Envelhecimento , Complexo Antígeno L1 LeucocitárioRESUMO
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.
Assuntos
Expossoma , Doenças Inflamatórias Intestinais , Animais , Epigenoma , Inflamação/genética , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Modelos AnimaisRESUMO
OBJECTIVES: To compare dynamic contrast-enhanced (DCE)-MRI parameters in affected and unaffected segments of CD patients with those of a control group, and to assess the correlation between DCE-MRI parameters and clinical index of activity (HBI) as well as biomarkers (CRP and faecal calprotectin). METHODS: We performed a single-center prospective study of CD patients and control subjects who underwent DCE-MRI. Regions of interest were drawn in segments and the program (Olea Medical - Canon) provided values for transfer constant (Ktrans), fractional volume of extravascular-extracellular space (Ve), slope of enhancement (SoE), time to maximum enhancement (TME), maximum enhancement (ME) and enhancement ratio (ER) which were determined and compared. RESULTS: Fifteen CD patients (mean age 42 years; 10 women) and 7 healthy subjects (mean age 40.4 years; 6 women) were included. Paired comparisons of affected and unaffected segments in CD showed a significant increase of all parameters in affected segments, except for ER and TME. When comparing to controls, the affected segments did not show any significant difference, while a significant decrease in most of the parameters (except for ER and TME) was observed when comparing unaffected segments of CD patients to controls. In CD, significant correlations between DCE-MRI parameters and biomarkers (CRP, faecal calprotectin) were more frequent in unaffected segments than in affected segments. CONCLUSIONS: Significant differences in perfusion parameters were observed between affected and unaffected segments of CD patients and between unaffected segments and those of control subjects. This suggests complex perfusion changes in both unaffected and affected intestinal segments in CD.
Assuntos
Doença de Crohn , Adulto , Meios de Contraste , Doença de Crohn/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Perfusão , Estudos ProspectivosRESUMO
BACKGROUND AND AIMS: Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients. METHODS: We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded. RESULTS: Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline. CONCLUSION: Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.
We studied the abnormalities found by confocal endomicroscopy in patients with chronic inflammatory disease in deep endoscopic remission under immunosuppressive treatment. Relapse was not associated with the abnormalities found, which, although numerous, remain of unknown significance.
Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Endoscopia , Fator de Necrose Tumoral alfa/uso terapêutico , Necrose , Indução de RemissãoRESUMO
BACKGROUND: While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission. METHODS: We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate. RESULTS: A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036). CONCLUSION: Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not).
Assuntos
Colite Ulcerativa , Piperidinas , Pirimidinas , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Estudos Retrospectivos , Estudos de Coortes , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.
Assuntos
Doença de Crohn , Proteoma , Úlcera , Humanos , Doença de Crohn/sangue , Masculino , Proteoma/análise , Proteoma/metabolismo , Feminino , Adulto , Úlcera/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Íleo/metabolismo , Íleo/patologiaRESUMO
Inflammatory bowel diseases (IBD) encompass two main entities including ulcerative colitis and Crohn's disease. Although having a common global pathophysiological mechanism, IBD patients are characterized by a significant interindividual heterogeneity and may differ by their disease type, disease locations, disease behaviours, disease manifestations, disease course as well as treatment needs. Indeed, although the therapeutic armamentarium for these diseases has expanded rapidly in recent years, a proportion of patients remains with a suboptimal response to medical treatment due to primary non-response, secondary loss of response or intolerance to currently available drugs. Identifying, prior to treatment initiation, which patients are likely to respond to a specific drug would improve the disease management, avoid unnecessary side effects and reduce the healthcare expenses. Precision medicine classifies individuals into subpopulations according to clinical and molecular characteristics with the objective to tailor preventative and therapeutic interventions to the characteristics of each patient. Interventions would thus be performed only on those who will benefit, sparing side effects and expense for those who will not. This review aims to summarize clinical factors, biomarkers (genetic, transcriptomic, proteomic, metabolic, radiomic or from the microbiota) and tools that could predict disease progression to guide towards a step-up or top-down strategy. Predictive factors of response or non-response to treatment will then be reviewed, followed by a discussion about the optimal dose of drug required for patients. The time at which these treatments should be administered (or rather can be stopped in case of a deep remission or in the aftermath of a surgery) will also be addressed. IBD remain biologically complex, with multifactorial etiopathology, clinical heterogeneity as well as temporal and therapeutic variabilities, which makes precision medicine especially challenging in this area. Although applied for many years in oncology, it remains an unmet medical need in IBD.
RESUMO
INTRODUCTION: Ustekinumab is a humanized monoclonal antibody, targeting the p40 subunit common to both human interleukin 12 and 23, approved by the European Medicines Agency and US Food and Drug Administration for the treatment of moderate-to-severe ulcerative colitis. AREAS COVERED: In this review, the results of the phase 3 UNIFI and the real-world studies assessing the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis are discussed, as well as limitations of these studies. Predictive factors of response, the interest of therapeutic drug monitoring and the positioning of ustekinumab in specific situations are also addressed. Finally, in the light of data presented, the positioning of ustekinumab in the therapeutic algorithm of ulcerative colitis will also be considered. EXPERT OPINION: Ustekinumab has been shown to be effective to induce and maintain clinical, endoscopic and histologic remission in moderate-to-severe ulcerative colitis both in phase 3 and real-world studies, with a favorable safety profile. Overall, its favorable risk-benefit ratio, its efficacy on extra-intestinal manifestations and in biologics failure patients make ustekinumab an ideal candidate as first, second, or third-line therapy in ulcerative colitis.
Assuntos
Colite Ulcerativa , Ustekinumab , Humanos , Adulto , Ustekinumab/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Interleucina-12/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
In Crohn's disease, the treat-to-target strategy has been greatly encouraged and has become a standard of care. In this context, defining the target [remission] constitutes a major stake and is fuelling the literature. Currently, clinical remission [symptom control] is no longer the only objective of treatments since it does not allow to closely control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target clearly represented progress but this examination remains invasive, costly, not well accepted by patients and does not allow tight control of disease activity. More fundamentally, morphological techniques [e.g. endoscopy, histology, ultrasonography] are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggests that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalization of inflammatory markers [C-reactive protein and faecal calprotectin]: absence of biological signs associated with the risk of short-term relapse and mid-/long-term relapse. The risk of short-term relapse seems essentially to be characterized by a persistent inflammatory state while the risk of mid-/long-term relapse implies a more heterogeneous biology. We discuss the value of our proposal [guiding treatment maintenance, escalation or de-escalation] but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Proteína C-Reativa/análise , Endoscopia Gastrointestinal , Recidiva , Indução de RemissãoRESUMO
BACKGROUND: Treatment choices for patients with inflammatory bowel disease (IBD) are based on the balance between risks and benefits. Our AI was to compare the perspectives of patients and physicians in evaluating the risks and benefits before initiating therapy for IBD. METHODS: An anonymous survey was conducted between March and August 2022. All patients with confirmed IBD and all physicians who attended an IBDscope webinar were invited to participate. RESULTS: In total, 367 patients and 146 physicians participated. For most patients (71.4%) and physicians (89.0%), efficacy and safety were equally important. Clinical improvement and clinical remission were the most relevant outcomes for patients (90.9 and 88.4), while clinical remission and endoscopic remission were for physicians (90.0 and 87.6). The main factors in the benefit-risk assessment were quality of life (95.1%), disease activity (87.5%), and presence of comorbidities (84.5%) for patients, and presence of comorbidities (99.3%), disease activity (97.9%), and prior failure to biologics/small molecules (96.6%) for physicians. Based on patients' and physicians' opinions, the risk of serious infections, malignancies, cardiovascular events, death, relapse, all infections, surgery, and hospitalization should be included in the benefit-risk assessment. CONCLUSION: Physicians and patients have different priorities in evaluating the benefit-risk balance of a new therapy.
RESUMO
BACKGROUND AND AIM: In view of their frequent onset during childbearing years, the impact of inflammatory bowel diseases [IBD] on reproductive health is of important concern to young women and to the IBD physician. This study aims to assess the fertility and assisted reproductive technologies outcomes in non-surgically treated IBD females. METHODS: A systematic review was conducted using MEDLINE, SCOPUS, and EMBASE [until March 2022] to identify studies assessing fertility and assisted reproductive technologies outcomes in women with non-operated IBD, compared with non-IBD patients. Two reviewers independently selected studies, assessed risk of bias, and extracted study data. RESULTS: A total of 14 studies encompassing 18 012 patients with ulcerative colitis [UC] and 14 353 patients with Crohn's disease [CD] were included for analysis. The fertility rate in UC patients and in the general population was comparable, but UC patients tended to have fewer children, mainly by choice. On the contrary, the fertility of CD patients appeared to be reduced. Although a deliberate component cannot be not excluded, the disease itself could affect fertility. Disease activity was associated with reduced fertility in both UC and CD patients. In CD, the colonic involvement of the disease and perianal damage could be associated with subfertility, but data are less consistent. According to the only study reporting the assisted reproductive technologies outcomes, pregnancy rates after in vitro fertilization in subfertile non-operated UC patients and non-IBD patients were similar. CONCLUSIONS: There is low-quality evidence from observational studies that patients with CD and relapsing UC may have impaired fertility. After assisted reproductive technologies, pregnancy rates of subfertile non-operated UC patients were similar to those of the general population, although this observation requires further scrutiny in larger studies that should include UC and CD patients.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Gravidez , Criança , Humanos , Feminino , Doenças Inflamatórias Intestinais/terapia , Fertilidade , Colite Ulcerativa/terapia , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/terapia , Doença de Crohn/epidemiologia , Técnicas de Reprodução AssistidaRESUMO
The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.
RESUMO
INTRODUCTION: Crohn's disease (CD) mostly affects the terminal ileum and ileocecal region and up to 80% of patients end up requiring surgery. Previously reserved for complicated or refractory forms, surgery is now considered as an alternative to medical treatment in localized ileocecal disease. AREAS COVERED: This review examines factors associated with response to medical treatment and those associated with the need for surgery in ileocecal CD to identify the patients' profile for whom pharmacotherapy might be enough. Factors associated with the recurrence and the postoperative complications are also reviewed to help the clinician identify patients for whom medical therapy might be preferred. EXPERT'S OPINION: LIR!C study long-term follow-up data show that 38% of infliximab-treated patients were still treated with infliximab at the end of their follow-up, while 14% had switched to another biologic or had received immunomodulator or corticosteroid and 48% had CD-related surgery. Only the combination with an immunomodulator was associated with a greater likelihood of continuing infliximab. Patients with ileocecal CD for whom pharmacotherapy might be sufficient are probably those with no risk factors for CD-related surgery.In addition, patients with high risk of recurrence or of post-operative complications may benefit more from medical treatment than from surgery.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Infliximab/uso terapêutico , Resultado do Tratamento , Íleo/cirurgia , Fatores Imunológicos/uso terapêutico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) can affect patients during their childbearing years. Literature evidence is scarce regarding the level of knowledge among health care professionals (HCPs) and patients about the impact of IBD on fertility. The aim of this survey was to investigate HCPs' and patients' knowledge on fertility, pregnancy, and sexual function, to evaluate how HCPs approach this topic and to report patients' reproductive outcomes. METHODS: Subjects were invited to anonymously complete an online questionnaire collecting data on demographics, patients' disease characteristics, Crohn's and colitis pregnancy-specific disease-related knowledge (CCPKnow), family planning, reason of childlessness, pregnancy outcomes, need for assisted reproductive technology, impact on sexual function, and availability of patients' information regarding IBD and pregnancy. RESULTS: A total of 257 HCPs from 40 countries and 793 patients (615 females, 176 males and 2 who preferred not to disclose their gender; 396 (50%) with ulcerative colitis, 381 (48%) with Crohn's disease, 14 (1.8%) with undetermined IBD) from 4 countries completed the survey. In total, 98.4% of HCPs had good or very good pregnancy-specific knowledge according to CCPKnow score, compared to only 29.3% of patients. Of the women surveyed, 56.3% had no children (14.1% due to a voluntary choice). A total of 427 pregnancies and 401 live births were reported in 266 women. Twenty-four pregnancies (5.6%) in 22 women required assisted reproductive technologies (ART). There were no more complications in pregnancies resulting from ART compared with spontaneous conception (5/24; 20.8% vs 81/401; 20.2%). Three quarters of IBD patients (75.6%) had breastfed. An impaired sexual function was found in one-fifth (21.9%) of men with IBD, while two-thirds (66.1%) of the women reported sexual function impairment. Surprisingly, 63% of patients reported not having received any information about IBD and pregnancy, and only 10% of patients had received information from their IBD specialist. In addition, 42.1% and 36% of HCPs had already referred a patients to a medically assisted reproduction center to receive general information about their reproductive health and about options of fertility preservation (e.g., cryopreservation), respectively. CONCLUSION: IBD patients have a poor knowledge about the impact of IBD on fertility and pregnancy and HCPs do not sufficiently inform their patients. More information on these topics is needed for IBD patients.
Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Médicos , Complicações na Gravidez , Gravidez , Masculino , Humanos , Feminino , Doenças Inflamatórias Intestinais/complicações , Fertilidade , Doença de Crohn/complicações , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) consider that their diet is important for controlling symptoms and frequently ask their physician for additional guidance on this matter. The objectives of the present study of patients with IBD were to characterize the prevalence of exclusion diets and fasting and to identify associated risk factors. METHODS: Using an anonymous questionnaire, we screened patients attending our IBD nutrition clinic between November 2021 and April 2022 for exclusion diets. The avoidance of a food category completely was defined as total exclusion and avoidance most of the time was defined as partial exclusion. We also asked patients whether they fasted totally, intermittently, or partially. RESULT: A total of 434 patients with IBD were included. On inclusion, 159 patients (36.6%) totally excluded at least one food category and 271 (62.4%) partially excluded at least one food. Intermittent, total, or partial fasting was reported by 30.8% of the patients. Disease activity (odds ratio (OR) [95% confidence interval] = 1.7 [1.1-2.7], p = 0.0130) and treatment with a small-molecule or an investigational drug (OR = 4.0 [1.5-10.6], p = 0.0059) were independently associated with an exclusion diet. A history of stenosis (OR = 2.0 [1.2-3.2], p = 0.0063) and active disease (OR = 1.9 [1.2-3.1], p = 0.0059) were associated with fasting. CONCLUSION: In this real-world study, approximately two-thirds of our patients with IBD reported the partial or total exclusion of at least one food category and one third reported fasting. A systematic nutritional evaluation might improve clinical management and quality of care for patients with IBD both Crohn's disease and ulcerative colitis.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Colite Ulcerativa/complicações , Doença de Crohn/terapia , Doença de Crohn/complicações , Alimentos , JejumRESUMO
BACKGROUND AND AIM: Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP. METHODS: PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form. RESULTS: In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40-68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [nâ =â 12], thiopurines [nâ =â 10], infliximab [nâ =â 4], ciclosporin [nâ =â 2], methotrexate [nâ =â 1], and tacrolimus [nâ =â 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others. CONCLUSION: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy.