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BACKGROUND & AIMS: The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis. METHODS: We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018. RESULTS: Over a median follow-up period of 17.2 months (interquartile range, 8.8-23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4-4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07-5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21-6.41; P = .016), white blood cells ≥7 × 103/µL (HR, 2.419; 95% CI, 1.026-5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186-6.058; P = .018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed. CONCLUSIONS: In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course-these might be used in patient management and selection of treatment.
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Doença de Crohn , Adulto , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Humanos , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: Biomarker normalization and endoscopic remission are superior to clinical remission in achieving improved long-term clinical outcomes in patients with inflammatory bowel diseases. GOAL: To study whether higher maintenance adalimumab levels are associated with clinical remission, biomarker normalization, and endoscopic remission. STUDY: Data were collected retrospectively from the patients' medical records. We defined clinical remission as a Harvey Bradshaw Index ≤5 or a partial Mayo score ≤2 for Crohn's disease (CD) and ulcerative colitis (UC), respectively, biomarker normalization as a C-reactive protein <0.5 mg/dL and/or calprotectin <250 (mg/kg), endoscopic remission as a (simple endoscopic score-CD) ≤3/4 for ileal/extensive CD, respectively, or an endoscopic Mayo score ≤1 for UC, and deep remission as the combination of clinical and endoscopic remission with normal biomarkers. RESULTS: Ninety-seven patients were included (82 CD and 15 UC). Patients who achieved clinical remission, biomarker normalization, or endoscopic remission had higher serum trough adalimumab levels compared with patients not in remission [mean (M)±standard error (SE)=8.98±0.78 vs. 5.92±0.96 µg/mL; P=0.016, 9.38±0.85 vs. 5.48±0.87 µg/mL; P=0.002; 9.13±0.88 vs. 6.02±0.77 µg/mL; P=0.019, respectively]. Receiver-operating curve analysis showed that an adalimumab level of ≥8.25 µg/mL was associated with deep remission (sensitivity 84%, specificity 70%, area under the curve 0.775; P<0.001). CONCLUSION: Clinical remission, biomarker normalization, and endoscopic remission are positively associated with adalimumab trough levels. Adalimumab level of ≥8.25 µg/mL is associated with deep remission. This study provides additional data to guide therapeutic drug monitoring with adalimumab.
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Adalimumab/farmacocinética , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adalimumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Indução de Remissão , Estudos RetrospectivosRESUMO
BACKGROUND: An early treat-to-target approach in Crohn's disease (CD) patients is recommended to avoid complications. However, CD may not always progress despite lack of treatment, thus exposing some patients to unnecessary side effects. We aimed to examine whether newly diagnosed CD patients with an inflammatory phenotype can benefit from a watchful waiting approach. METHODS: This retrospective cohort study followed CD patients with an inflammatory phenotype who were diagnosed between 2010 and 2015 and followed for at least 1 year. A watchful waiting approach was defined as maintenance therapy with 5-ASA medication only or no treatment during the first year of diagnosis or longer. Disease complications were defined as need for surgery or change in disease phenotype. RESULTS: Eighty-six patients were included and followed-up for 57.0 ± 29.0 months. Thirty-seven patients were managed with a watchful waiting approach and 49 with an early therapeutic intervention. The majority of patients (83.8%) in the watchful waiting group did not develop disease complications. In this group, there was no difference in clinical disease severity (stools per day, 2.7 ± 1.7 vs 3.3 ± 1.0, P = 0.39; abdominal pain, 74.2 vs 50.0%, P = 0.24) between those who did not develop complications and those who did. Smoking was associated with a complicated course (multivariate analysis: OR = 1.98, 95% CI 1.06-3.71, P = 0.03). CONCLUSIONS: A watchful waiting approach of newly diagnosed CD patients with an inflammatory phenotype may be a feasible option, with low long-term complication rate specifically in nonsmoking patients.
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Doença de Crohn , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Humanos , Mesalamina , Fenótipo , Estudos Retrospectivos , Conduta ExpectanteRESUMO
BACKGROUND: There has been a paradigm shift in the treatment of Crohn's disease (CD) involving the rapid introduction of biologics and/or immunomodulators after diagnosis. We wished to assess whether this was applied to patients with newly diagnosed CD in a tertiary inflammatory bowel disease referral centre in Israel. METHODS: Newly diagnosed CD patients were stratified into 2 groups: the early group was diagnosed between 2005 and 2007 and the late group was diagnosed between 2010 and 2012. Baseline demographics, medical and surgical treatments, disease course and complications during those 2 periods were analyzed. RESULTS: Each group included 60 patients. Significantly higher rates of immunomodulators and biologics were administered to patients in the late group compared to the early group (81.7 and 36.7% compared to 56.7 and 18.3%, p = 0.004 and p = 0.021, respectively). On the other hand, steroid therapy was less prevalent in the late (36.7%) group compared to that of the early group (56.7%), p = 0.059. Medical and surgical CD outcomes, including exacerbations/hospitalizations and surgeries, were comparable for both groups. CONCLUSIONS: There was a change in treatment strategy between 2005-2007 and 2010-2012, as reflected in higher proportions of biologics/immunomodulators for patients with newly diagnosed CD. This was associated with a steroid-sparing effect.
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Produtos Biológicos/uso terapêutico , Doença de Crohn/terapia , Glucocorticoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adulto , Colectomia , Doença de Crohn/diagnóstico , Progressão da Doença , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Israel , Masculino , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & AIMS: There is controversy about whether levels of anti-tumor necrosis factor (TNF) and antidrug antibodies (ADAs) are accurate determinants of loss of response to therapy. We analyzed the association between trough levels of anti-TNF agents or ADAs and outcomes of interventions for patients with loss of response to infliximab or adalimumab. METHODS: We performed a retrospective study of pediatric and adult patients with inflammatory bowel disease and suspected loss of response to anti-TNF agents treated at medical centers throughout Israel from October 2009 through February 2013. We examined the correlation between outcomes of different interventions and trough levels of drug or ADAs during loss of response. An additional subanalysis was performed including only patients with a definite inflammatory loss of response (clinical worsening associated with increased levels of C-reactive protein or fecal calprotectin, or detection of inflammation by endoscopy, fistula discharge, or imaging studies). RESULTS: Among 247 patients (42 with ulcerative colitis), there were 330 loss-of-response events (188 to infliximab and 142 to adalimumab). Trough levels of adalimumab greater than 4.5 mcg/mL and infliximab greater than 3.8 mcg/mL identified patients who failed to respond to an increase in drug dosage or a switch to another anti-TNF agent with 90% specificity; these were set as adequate trough levels. Adequate trough levels identified patients who responded to expectant management or out-of-class interventions with more than 75% specificity. Levels of antibodies against adalimumab >4 microgram per mL equivalent (mcg/mL-eq) or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity. Patients with high titers of ADAs had longer durations of response when anti-TNF agents were switched than when dosage was increased (P = .03; log-rank test), although dosage increases were more effective for patients with no or low titers of ADAs (P = .02). An analysis of definite inflammatory loss-of-response events (n = 244) produced similar results; patients with adequate trough levels had a longer duration of response when they switched to a different class of agent than when anti-TNF was optimized by either a dosage increase or by a switch within the anti-TNF class (P = .002; log-rank test). CONCLUSIONS: The results of this retrospective analysis suggest that trough levels of drug or ADAs may guide therapeutic decisions for more than two-thirds of inflammatory bowel disease patients with either clinically suspected or definite inflammatory loss of response to therapy.
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Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos/sangue , Fatores Imunológicos/imunologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adalimumab , Adulto , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Fatores Imunológicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Infliximab , Israel , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Adulto JovemAssuntos
Endoscopia por Cápsula/métodos , Neoplasias do Colo/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Adulto , Idoso , Algoritmos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND AIMS: Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function. METHODS: Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing. RESULTS: Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors' microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (ß-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin. CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.
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The Crohn's Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018-2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07-55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies.
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Postoperative recurrence (POR) is the rule in patients with Crohn's disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16-0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).
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BACKGROUND: Educating patients regarding thier inflammatory bowel disease (IBD) is important for their empowerment and disease management. We aimed to develop a questionnaire to evaluate patient understanding and knowledge of IBD. METHODS: We have developed the Understanding IBD Questionnaires (U-IBDQ), consisting of multiple-choice questions in two versions [for Crohn's disease (CD) and ulcerative colitis (UC)]. The questionnaires were tested for content and face validity, readability, responsiveness and reliability. Convergent validity was assessed by correlating the U-IBDQ score with physician's subjective assessment scores. Discriminant validity was assessed by comparison to healthy controls (HC), patients with chronic gastrointestinal (GI) conditions other than IBD, and to GI nurses. Multivariate analysis was performed to determine factors associated with a high level of disease understanding. RESULTS: The study population consisted of IBD patients (n = 106), HC (n = 35), chronic GI disease patients (n = 38) and GI nurses (n = 19). Mean U-IBDQ score among IBD patients was 56.5 ± 21.9, similar for CD and UC patients (P = 0.941), but significantly higher than that of HC and chronic GI disease patients and lower than that of GI nurses (P < 0.001), supporting its discriminant validity. The U-IBDQ score correlated with physician's subjective score (r = 0.747, P < 0.001) and was found to be reliable (intra-class correlation coefficient = 0.867 P < 0.001). Independent factors associated with high U-IBDQ scores included academic education (OR = 1.21, 95% CI 1.10-1.33, P < 0.001), biologic therapy experience (OR = 1.24, 95% CI 1.01-1.53, P = 0.046), and IBD diagnosis at <21 years of age (OR = 2.97, 95% CI 1.05-8.87, P = 0.050). CONCLUSIONS: The U-IBDQ is a validated, reliable and short, self-reported questionnaire that can be used for assessing understanding of disease pathophysiology and treatment by IBD patients.
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Colite Ulcerativa , Doença de Crohn , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto , Inquéritos e Questionários , Adulto , Fatores Etários , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Compreensão , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Análise Discriminante , Feminino , Gastroenteropatias , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Adulto JovemRESUMO
Background and aim: Anti-TNFα is measurable in infants exposed in utero up to 12 months of age. Data about the exposure effect on the infant's adaptive immunity are limited. We aimed to prospectively evaluate the distribution and function of T and B cells, in infants of females with inflammatory bowel disease, in utero exposed to anti-TNFα or azathioprine. Methods: A prospective multi-center study conducted 2014-2017. Anti-TNFα levels were measured in cord blood, and at 3 and 12 months. T-cell repertoire and function were analyzed at 3 and 12 months by flow-cytometry, expression of diverse T cell receptors (TCR) and T-cell receptor excision circles (TREC) quantification assay. Serum immunoglobulins and antibodies for inactivated vaccines were measured at 12 months. Baseline clinical data were retrieved, and 2-monthly telephonic interviews were performed regarding child infections and growth. Results: 24 pregnant females, age 30.6 (IQR 26.5-34.5) years were recruited, 20 with anti-TNFα (infliximab 8, adalimumab 12), and 4 with azathioprine treatment. Cord blood anti-TNFα was higher than maternal blood levels [4.3 (IQR 2.3-9.2) vs. 2.5 (IQR 1.3-9.7) mcg/ml], declining at 3 and 12 months. All infants had normal number of B-cells (n = 17), adequate levels of immunoglobulins (n = 14), and protecting antibody levels to Tetanus, Diphtheria, Hemophilus influenza-B and hepatitis B (n = 17). All had normal CD4+, CD8+ T-cells, and TREC numbers. TCR repertoire was polyclonal in 18/20 and slightly skewed in 2/20 infants. No serious infections requiring hospitalization were recorded. Conclusion: We found that T-cell and B-cell immunity is fully mature and immune function is normal in infants exposed in utero to anti-TNFα, as in those exposed to azathioprine. Untreated controls and large-scale studies are needed to confirm these results.
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BACKGROUND: Women with inflammatory bowel diseases (IBD) often receive biologics to maintain remission during pregnancy. AIMS: To assess maternal and neonatal outcomes in patients with IBD treated with ustekinumab (UST) during pregnancy METHODS: In a multicentre, prospective cohort study, we recruited women with IBD treated with UST during pregnancy between 2019 and 2021. Outcomes were compared among patients treated with UST, anti-tumour necrosis factor α, (anti-TNF) and non-UST, non-anti-TNF therapies. UST-treated patients were matched 1:2 to controls according to age, body mass index and parity. Newborns were followed up to 12 months. RESULTS: We recruited 129 pregnant patients: UST 27; anti-TNF 52; non-UST, non-anti-TNF 50 (thiopurine or mesalazine 30, no therapy 20); Crohn's disease 25 (96.9%). Overall, pregnancy, neonatal and newborn outcomes were satisfactory, with no significant differences among patients treated with UST, anti-TNF and non-UST non-anti-TNF agents for obstetrical maternal complications [UST 3 (11.5%), anti TNF 12 (23.1%), non UST, non-anti-TNF 4 (8.2%), p = 0.095], pre-term delivery [1 (4.3%), 9 (18.4%), 4 (5.7%), p = 0.133], low birth weight [1 (4.2%), 5 (10.2%), 4 (8.3%), p = 0.679], or first year newborn hospitalisation [2 (9.1%), 4 (8.2%), 3 (6.1%), p = 0.885]. CONCLUSION: Pregnant patients with IBD treated with UST demonstrated favourable pregnancy and neonatal outcomes that were comparable with those in patients treated with anti-TNF or other therapy. Data are reassuring for patients with IBD and their physicians when considering UST during pregnancy.
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Produtos Biológicos , Doenças Inflamatórias Intestinais , Doença Crônica , Feminino , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mesalamina , Gravidez , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral , Ustekinumab/efeitos adversosRESUMO
BACKGROUND: The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. METHODS: We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18-55 years with mild-to-moderate Crohn's disease (defined by a Harvey-Bradshaw Index score of 5-14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 µ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov, NCT02231814. FINDINGS: Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. INTERPRETATION: CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. FUNDING: Azrieli Foundation and Nestle Health Science.
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Doença de Crohn/dietoterapia , Adulto , Proteína C-Reativa/metabolismo , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/terapia , Endoscopia Gastrointestinal , Nutrição Enteral , Fezes/química , Feminino , Humanos , Análise de Intenção de Tratamento , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Projetos Piloto , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. METHODS: This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] ofâ ≥5 andâ ≤11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAIâ <3. RESULTS: Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 pâ =â 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [pâ =â 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, pâ =â 0.35]. CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.
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Colite Ulcerativa , Transplante de Microbiota Fecal , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Colonoscopia , Dieta , Transplante de Microbiota Fecal/efeitos adversos , Humanos , Indução de RemissãoRESUMO
BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. OBJECTIVE: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. METHODS: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. RESULTS: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. CONCLUSION: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.
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(1) Background: Malnutrition is a highly prevalent complication in patients with inflammatory bowel diseases (IBD). It is strongly associated with poor clinical outcomes and quality of life. Screening for malnutrition risk is recommended routinely; however, current malnutrition screening tools do not incorporate IBD specific characteristics and may be less adequate for screening these patients. Therefore, we aimed to identify IBD-related risk factors for development of malnutrition. (2) Methods: A retrospective case-control study among IBD patients attending the IBD clinic of the Tel-Aviv Medical Center for ≥2 consecutive physician consultations per year during 2017-2020. Cases who had normal nutritional status and developed malnutrition between visits were compared to matched controls who maintained normal nutritional status. Detailed information was gathered from medical files, including: demographics, disease phenotype, characteristics and activity, diet altering symptoms and comorbidities, medical and surgical history, annual healthcare utility, nutritional intake and the Malnutrition Universal Screening Tool (MUST) score. Univariate and multivariate analyses were used to identify malnutrition risk factors. The independent risk factors identified were summed up to calculate the IBD malnutrition risk score (IBD-MR). (3) Results: Data of 1596 IBD patients met the initial criteria for the study. Of these, 59 patients developed malnutrition and were defined as cases (n = 59) and matched to controls (n = 59). The interval between the physician consultations was 6.2 ± 3.0 months, during which cases lost 5.3 ± 2.3 kg of body weight and controls gained 0.2 ± 2.3 kg (p < 0.001). Cases and controls did not differ in demographics, disease duration, disease phenotype or medical history. Independent IBD-related malnutrition risk factors were: 18.5 ≤ BMI ≤ 22 kg/m2 (OR = 4.71, 95%CI 1.13-19.54), high annual healthcare utility (OR = 5.67, 95%CI 1.02-31.30) and endoscopic disease activity (OR = 5.49, 95%CI 1.28-23.56). The IBD-MR was positively associated with malnutrition development independently of the MUST score (OR = 7.39, 95%CI 2.60-20.94). Among patients with low MUST scores determined during the index visit, identification of ≥2 IBD-MR factors was strongly associated with malnutrition development (OR = 8.65, 95%CI 2.21-33.82, p = 0.002). (4) Conclusions: We identified IBD-related risk factors for malnutrition, highlighting the need for a disease-specific malnutrition screening tool, which may increase malnutrition risk detection.
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Doenças Inflamatórias Intestinais/fisiopatologia , Desnutrição/diagnóstico , Desnutrição/etiologia , Avaliação Nutricional , Estado Nutricional , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Modelos Logísticos , Masculino , Desnutrição/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Processed foods have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Our goal was to develop a validated processed foods frequency questionnaire (PFQ) and assess its reliability and validity. METHODS: We recruited adult IBD patients to fill-in a PFQ in this prospective single-center study. Food intake was categorized into three groups of processed food levels: unprocessed, processed, and ultra-processed. Reliability was assessed by comparing the PFQ results of each patient at 2 time points. Validity was assessed by comparing the PFQ results to a 3-7 day food diary (FD), and by comparing urine sodium as a biomarker for the high intake of sodium that is mostly present in processed food. RESULTS: Eighty-six IBD patients were enrolled. Good test-retest reliability was indicated by intraclass correlation of 0.75-0.88 for the different food processing levels. Validity was fair-to-strong as assessed by correlations for different levels of processed food intake between FDs and PFQ, ranging between 0.43 and 0.64 (Pearsonr, P < 0.001), and further supported by higher mean urine sodium levels in patients with high processed foods consumption compared with low consumption (104.57 ± 53.26 vs. 78.62 ± 39.08 mmol/L, respectively, P = 0.022). Agreement between PFQ and the FD in categorizing patients to high and low processed food consumption groups was fair (Kappa 0.23-0.35). CONCLUSIONS: The PFQ is a reliable and valid tool for the assessment of processed foods consumption in IBD patients and can be utilized for studying the association between processed food consumption and IBD etiopathogenesis.
Assuntos
Fast Foods , Doenças Inflamatórias Intestinais , Adulto , Ingestão de Energia , Fast Foods/efeitos adversos , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Immune modulating therapies are associated with an increased risk of infections and malignancies. This is of particular concern in elderly inflammatory bowel disease patients. This study aims to compare the safety and efficacy of vedolizumab between young and elderly inflammatory bowel disease patients. METHODS: A binational, multicentre, retrospective, cohort study was performed from 2015 to 2019. Patients who underwent treatment with vedolizumab and were followed for at least 14 weeks were studied. They were divided according to age into groups: 40 years or less or 60 years or older. Clinical and endoscopic responses at weeks 14 and 52 and infection development were compared between young and elderly inflammatory bowel disease patient groups. RESULTS: There were 144 patients (82 Crohn's disease and 62 ulcerative colitis) in the elderly cohort and 140 patients (83 Crohn's disease and 57 ulcerative colitis) in the young cohort. The average age was 70.2 ± 7.3 years and 29.6 ± 5.7 years, respectively. Clinical and endoscopic responses were comparable between the groups (week 52 remission of Crohn's disease: 40% vs. 35%, P = 0.7; week 52 remission of ulcerative colitis: 48% vs. 51%, P = 0.84). Previous anti-tumour necrosis factor biological therapy was independently associated with poor clinical remission rates at week 52 (Crohn's disease: odds ratio 0.23, 95% confidence interval 0.06-0.79; P = 0.02 and ulcerative colitis: odds ratio 0.10 95% confidence interval 0.01-0.74; P = 0.024). There were significantly more infections in the elderly cohort (2% vs. 12%, P = 0.002), none of which were fatal. CONCLUSIONS: Vedolizumab is equally effective in elderly and young inflammatory bowel disease patients. The findings of this study demonstrate an increased risk of infections among the elderly treated with vedolizumab, which may be related to their age and underlying diseases.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Infecções/epidemiologia , Adulto , Fatores Etários , Idoso , Envelhecimento/imunologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Comorbidade , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Infecções/imunologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/imunologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Escócia/epidemiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Ustekinumab is an effective treatment of Crohn's disease (CD). Real-world data addressing the efficacy and safety of ustekinumab are scarce. AIM: Our aim was to assess the safety and efficacy of ustekinumab in a large national patient cohort. METHODS: A prospective multicenter study, in which we followed patients with active CD treated with ustekinumab for 24 weeks. Induction dose was intravenous ranging from 260 to 520 mg, according to body weight, followed by 90 mg doses given subcutaneously every 8 weeks. Clinical response was defined as a reduction of at least 1 severity category, as defined by Harvey-Bradshaw index (HBI). Patients with HBI < 5 were considered to be in clinical remission. Patients who stopped needing steroids at week 24 were defined as being in steroid-free clinical remission. RESULTS: A total of 106 CD patients from eight Israeli centers were included. All patients were previously exposed to at least one biological agent. Our cohort consisted of 65 (61.3%) females. Mean age was 41 ± 14 years with an average disease duration of 12.2 ± 8 years. A total of 96 (90.5%) patients continued treatment throughout week 24. Clinical response was observed in 52% of these patients with mean HBI reduction from 8.34 ± 3.8 to 6.8 ± 4.4 at week 24 (p = 0.001). Clinical remission was achieved in 33 patients (31.1%). Moreover, the number of patients requiring steroid treatment was reduced by 66% at week 24. Out of 106 patients, 11 patients (10.4%) discontinued treatment: 3 due to adverse events (2.8%), 7 due to a lack of response, and 1 who was lost to follow-up. Following 24 weeks of treatment, 15 patients reported minor adverse events. CONCLUSIONS: In a large real-world Israeli cohort of non-naïve-to-biological-treatment CD patients, ustekinumab was effective and safe in induction of clinical remission with a significant reduction in the number of patients requiring steroid treatment.
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Produtos Biológicos/administração & dosagem , Doença de Crohn/tratamento farmacológico , Ustekinumab/administração & dosagem , Administração Intravenosa , Adulto , Produtos Biológicos/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Israel , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão/métodos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/efeitos adversosRESUMO
INTRODUCTION: Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce. AIMS: To describe the effectiveness and safety of VDZ in maintenance treatment of IBD. METHODS: A multicenter retrospective national study. The primary outcome of was clinical response at week 52; main secondary aims included clinical remission at week 52, rates of secondary loss of response and treatment discontinuation. RESULTS: We included 193 (133-CD; 60-UC) patients from 9 Israeli IBD centers. At week 52, response was observed in 62/133 (46.7%) CD patients, including 28 (21%) in clinical remission; 71 (53.3%) discontinued treatment or did not respond. For UC, response at week 52 was observed in 27/60 (45%), including 20 (33%) in clinical remission; 33 (55%) discontinued treatment or did not respond. Secondary non-response by week 52 occurred in 19.4% and 23.5% of week 14 responders in CD and UC, respectively. Week 14 response was associated with treatment continuation at week 52: no predictors of secondary loss of response were identified. SUMMARY: VDZ is safe and effective for maintenance of response and remission in IBD; week 14 response is positively associated with long-term response in both UC and CD.