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1.
Clin Gastroenterol Hepatol ; 22(8): 1687-1696.e6, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38428709

RESUMO

BACKGROUND & AIMS: We assessed Modified Multiplier Simple Endoscopic Score for Crohn's Disease (MM-SES-CD) and Simple Endoscopic Score for Crohn's Disease (SES-CD) thresholds that are best associated with low likelihood of long-term disease progression. METHODS: Data from 61 patients with early Crohn's disease (CD) who participated in the CALM long-term extension study were used as the derivation cohort and validated using the McMaster inflammatory bowel disease database (n = 99). The primary outcome was disease progression (new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery) since the end of the CALM trial. Optimal MM-SES-CD and SES-CD thresholds were determined using the maximum Youden index. Receiver operating characteristic curve analyses compared threshold scores of remission definitions on disease progression. RESULTS: In the derivation cohort, based on the maximum Youden index, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared with patients in the derivation cohort with MM-SES-CD <22.5 (10/17 [58.8%] vs 3/44 [6.8%]; P < .001). Similarly, a significantly greater number of patients with SES-CD ≥ 4 had disease progression compared with those with a SES-CD <4 (11/25 [44.0%] vs 2/36 [5.6%]; P < .001). Compared with other clinical or endoscopic remission definitions, which demonstrated poor to fair accuracy, MM-SES-CD <22.5 performed the best for predicting disease progression (area under the curve = 0.81; 95% confidence interval, 0.68-0.94; P < .001). These thresholds were confirmed in the validation cohort. CONCLUSION: Achievement of MM-SES-CD <22.5 or SES-CD <4 in patients with ileocolonic or colonic CD is associated with low risk of disease progression and may be suitable targets in clinical trials and practice for endoscopic healing.


Assuntos
Doença de Crohn , Progressão da Doença , Humanos , Doença de Crohn/patologia , Masculino , Feminino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Medição de Risco , Adolescente
3.
Clin Gastroenterol Hepatol ; 22(7): 1475-1486.e4, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38369224

RESUMO

BACKGROUND AND AIMS: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability. METHODS: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization. RESULTS: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated. CONCLUSIONS: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Doenças Inflamatórias Intestinais , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/imunologia , Adulto , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Estudos Prospectivos , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Vacinação , Idoso , Adulto Jovem
4.
Dig Dis Sci ; 69(1): 45-55, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36920668

RESUMO

BACKGROUND: Early initiation of biologics in moderate-to-severe Crohn's disease (CD) may significantly alter disease progression, resulting in better patient outcomes. Limited real-world data exist on the impact of early biologic use in patients with CD in the United States. AIMS: We aimed to characterize biologic initiation and subsequent healthcare resource utilization (HCRU) in adults with recently diagnosed CD. METHODS: Patients with CD who initiated biologic treatment within 2 years of diagnosis (index date) were identified from medical and pharmacy claims (Merative L.P. MarketScan Database from 2010 to 2016) and classified as early (≤ 12 months post-index) or late (> 12-24 months post-index) biologic initiators. Propensity score matching balanced patient characteristics up to 1 year post-index. Differences in HCRU frequency and costs 1-2 years post-index were compared between the matched groups. RESULTS: After propensity score matching, 672 pairs of early and late biologic initiators were identified. Patients who initiated biologics early had fewer outpatient visits (15.5 vs 19.8, 95% confidence interval [CI] for difference: 2.7, 6.1) and lower total medical costs ($13,646.20 vs $22,180.70, 95% CI for difference: 4748.9, 12,320.1) 1-2 years post-index than late biologic initiators. Early biologic initiators had higher medication costs 1-2 years post-index ($33,766.30 vs $30,580.70, 95% CI: 546.1, 5825.1) but lower combined medical and medication costs ($47,412.50 vs $52,761.50, 95% CI: 801.5, 9896.40). CONCLUSIONS: While biologic treatments are costly, patients initiating biologics sooner after diagnosis appear to have better HCRU outcomes and require fewer healthcare resources at 1-2 years post-index, potentially leading to overall cost savings.


Assuntos
Produtos Biológicos , Doença de Crohn , Adulto , Humanos , Estados Unidos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Custos de Cuidados de Saúde , Custos de Medicamentos , Produtos Biológicos/uso terapêutico
5.
Am J Gastroenterol ; 119(1): 147-154, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37713528

RESUMO

INTRODUCTION: The American Gastroenterological Association (AGA) has compiled risk factors that may be predictive of disease complications in Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate the performance of the AGA risk factors for risk stratification in UC and CD. METHODS: We included participants of 2 cohorts: the Ocean State Crohn's and Colitis Area Registry cohort and the Mayo Clinic cohort. Baseline clinical risk factors were extracted according to the AGA pathway. Our primary end point was defined as follows: (i) any inflammatory bowel disease related-hospitalization, (ii) any inflammatory bowel disease-related bowel surgery, or (iii) any progression of disease. We analyzed the association of the number of AGA risk factors with our end point. Statistical multivariable modeling was performed with Cox proportional hazards model. RESULTS: A total of 412 patients with CD were included. Comparing ≥3 risk factors with 0-1 risk factor, we found a significantly increased risk of complications in both the Ocean State Crohn's and Colitis Area Registry cohort (hazard ratio [HR] 2.75, 95% confidence interval 1.71-4.41) and Mayo Clinic cohort (HR 2.07, 95% confidence interval 1.11-3.84). Diagnosis at younger age (HR 2.07), perianal disease (HR 1.99), and B2/B3 behavior (HR 1.92) were significantly associated with disease complications. We did not observe a consistent association between number of risk factors nor any specific individual risk factors and risk of disease complications in the 265 patients with UC included. DISCUSSION: We found a significant association between the number of AGA risk factors and the risk of disease complication in CD; this association was not significant in UC. The presence of ≥ 3 risk factors in CD leads to the highest risk of complications. The AGA care pathway is a useful tool to stratify patients who are at higher risk of disease complications in patients with CD.


Assuntos
Colite Ulcerativa , Colite , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Doença de Crohn/complicações , Doença de Crohn/terapia , Procedimentos Clínicos , Colite Ulcerativa/complicações , Doenças Inflamatórias Intestinais/complicações , Fatores de Risco , Colite/complicações
6.
Inflamm Bowel Dis ; 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37506265

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) can lead to long-term complications that significantly impact patients' quality of life and healthcare resource utilization. Prior studies have demonstrated improved short-term outcomes to early exposure of biologics in patients with Crohn's disease (CD) but not in patients with ulcerative colitis (UC). However, there are conflicting data on impact of early intervention on longer-term adverse events. Therefore, we conducted a systematic review and meta-analysis assessing the impact of early biologic treatment on rates of IBD-related surgery. METHODS: A systematic search was conducted in April 2022. Studies were included if biologic initiation was compared between patients starting early (<3 years of diagnosis or top-down treatment) vs later (>3 years of diagnosis or step-up treatment). Studies with <1 year of follow-up were excluded. The outcomes were colectomy and CD-related surgery for patients with UC and CD, respectively. Random-effects analyses were conducted to compare rates of IBD surgery between early and late biologic treatment. RESULTS: Eighteen studies were included in the meta-analysis. Three studies included patients with UC and 15 studies included patients with CD. In patients with CD, early biologic therapy was associated with lower odds of surgery (odds ratio, 0.63; 95% confidence interval, 0.48-0.84) compared with late treatment. Conversely, in patients with UC, the odds of colectomy were increased (odds ratio, 2.86; 95% confidence interval, 1.30-6.30). CONCLUSIONS: Early biologic treatment is associated with lower rates of surgery in patients with CD. In contrast, early biologic therapy appears to be associated with higher rates of colectomy in patients with UC, which may be confounded by disease severity.

7.
J Crohns Colitis ; 17(12): 1949-1961, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37492976

RESUMO

BACKGROUND AND AIMS: The benefit of continuing 5-aminosalicylic acid [5-ASA] treatment when escalating to advanced therapies in patients with inflammatory bowel disease [IBD] is unclear. Vedolizumab is a gut-selective monoclonal anti-α4ß7-integrin antibody used to treat moderate to severe IBD. Clinical trial data were analysed post hoc to assess the impact of 5-ASA co-treatment on vedolizumab efficacy and safety in patients with IBD. METHODS: Data were analysed from patients aged 18-80 years with moderate to severe ulcerative colitis [UC]/Crohn's disease [CD] receiving intravenous [IV]/subcutaneous [SC] vedolizumab. Efficacy data were from four studies [GEMINI 1 and 2 and VISIBLE 1 and 2]; safety data were from seven studies [GEMINI 1‒3 and long-term, VISIBLE 1, 2, and open-label extension]. The impact of 5-ASA co-treatment on clinical and endoscopic outcomes at Weeks 6 and 52 was assessed using multivariate analysis (adjusted odds ratios [aORs] with 95% confidence intervals [CIs]). RESULTS: There were no significant differences in UC clinical remission [Mayo score ≤2, no subscore >1] rates with vs without 5-ASA at Week 6 [20.7% vs 20.4%, respectively; aOR 0.77, 95% CI 0.43-1.38] or at Week 52 [45.1% vs 40.6%; aOR 1.14, 0.70-1.86], and in CD clinical remission [CD activity index score ≤150] rates at Week 6 [41.4% vs 35.1%; 1.26, 0.86-1.85] or at Week 52 [49.6% vs 37.8%; 1.35, 0.91-1.99]. The incidence of enteric and all infections in vedolizumab IV/SC-treated patients was low with and without 5-ASA. CONCLUSION: Continuation of concomitant oral 5-ASA after starting vedolizumab had no significant impact on clinical and endoscopic outcomes. CLINICAL TRIAL IDENTIFIERS: GEMINI 1: NCT00783718, EudraCT 2008-002782-32; GEMINI 2: NCT00783692, EudraCT 2008-00278-33; GEMINI 3: NCT01224171, EudraCT 2009-016488-12; GEMINI long-term safety study: NCT00790933, EudraCT 2008-002784-14; VISIBLE 1: NCT02611830, EudraCT 2015-000480-14; VISIBLE 2: NCT02611817, EudraCT 2015-000481-58; VISIBLE open-label extension: NCT02620046, EudraCT 2015-000482-31.


Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Mesalamina/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Resultado do Tratamento
8.
bioRxiv ; 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37333091

RESUMO

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon with sharply rising global prevalence. Dysfunctional epithelial compartment (EC) dynamics are implicated in UC pathogenesis although EC-specific studies are sparse. Applying orthogonal high-dimensional EC profiling to a Primary Cohort (PC; n=222), we detail major epithelial and immune cell perturbations in active UC. Prominently, reduced frequencies of mature BEST4+OTOP2+ absorptive and BEST2+WFDC2+ secretory epithelial enterocytes were associated with the replacement of homeostatic, resident TRDC+KLRD1+HOPX+ γδ+ T cells with RORA+CCL20+S100A4+ TH17 cells and the influx of inflammatory myeloid cells. The EC transcriptome (exemplified by S100A8, HIF1A, TREM1, CXCR1) correlated with clinical, endoscopic, and histological severity of UC in an independent validation cohort (n=649). Furthermore, therapeutic relevance of the observed cellular and transcriptomic changes was investigated in 3 additional published UC cohorts (n=23, 48 and 204 respectively) to reveal that non-response to anti-Tumor Necrosis Factor (anti-TNF) therapy was associated with EC related myeloid cell perturbations. Altogether, these data provide high resolution mapping of the EC to facilitate therapeutic decision-making and personalization of therapy in patients with UC.

9.
Therap Adv Gastroenterol ; 16: 17562848231176450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37337593

RESUMO

Over the last 2 years the lives of millions have changed because of the emergence of Coronavirus disease 2019 (COVID-19). Patients living with inflammatory bowel disease (IBD) represent a sizable population with their own sets of challenges to providers in the wake of so much uncertainty. The Centers for Disease Control considers immunocompromised individuals at higher risk of infection and complications from COVID-19. Early in the pandemic, the specific risks for IBD patients were unclear as guidance was based on expert opinion regarding the management of IBD during a COVID-19 era. Fortunately, after considerable work in the field, the overwhelming evidence suggests that IBD patients as a whole do not appear to be at increased risk for more severe disease from COVID-19. Certain risk factors such as age, steroids, comorbidities, combination immunomodulatory therapy, and IBD disease activity have been associated with worse outcomes. Most IBD medications are low risk, with the exception of immunomodulator monotherapy and combination therapy with thiopurine and anti-TNF. Vaccination remains safe and effective for all IBD patients, although additional booster doses may be necessary, particularly in patients taking anti-TNF agents.

10.
Gastroenterology ; 165(4): 976-985.e3, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37321356

RESUMO

BACKGROUND & AIMS: Early Crohn's disease (CD) treatment involves anti-tumor necrosis factor (TNF) agents, whereas ileocecal resection (ICR) is reserved for complicated CD or treatment failure. We compared long-term outcomes of primary ICR and anti-TNF therapy for ileocecal CD. METHODS: Using cross-linked nationwide registers, we identified all individuals diagnosed with ileal or ileocecal CD between 2003 and 2018 and treated with ICR or anti-TNF agents within 1 year of diagnosis. The primary outcome was a composite of ≥1 of the following: CD-related hospitalization, systemic corticosteroid exposure, CD-related surgery, and perianal CD. We conducted adjusted Cox's proportional hazards regression analyses and determined the cumulative risk of different treatments after primary ICR or anti-TNF therapy. RESULTS: Of 16,443 individuals diagnosed with CD, 1279 individuals fulfilled the inclusion criteria. Of these, 45.4% underwent ICR and 54.6% received anti-TNF. The composite outcome occurred in 273 individuals (incidence rate, 110/1000 person-years) in the ICR group and in 318 individuals (incidence rate, 202/1000 person-years) in the anti-TNF group. The risk of the composite outcome was 33% lower with ICR compared with anti-TNF (adjusted hazard ratio, 0.67; 95% confidence interval, 0.54-0.83). ICR was associated with reduced risk of systemic corticosteroid exposure and CD-related surgery, but not other secondary outcomes. The proportion of individuals on immunomodulator, anti-TNF, who underwent subsequent resection, or were on no therapy 5 years post-ICR was 46.3%, 16.8%, 1.8%, and 49.7%, respectively. CONCLUSION: These data suggest that ICR may have a role as first-line therapy in CD management and challenge the current paradigm of reserving surgery for complicated CD refractory or intolerant to medications. Yet, given inherent biases associated with observational data, our findings should be interpreted and applied cautiously in clinical decision making.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Estudos de Coortes , Fator de Necrose Tumoral alfa , Necrose , Estudos Retrospectivos , Resultado do Tratamento
11.
Aliment Pharmacol Ther ; 57(11): 1216-1230, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37051722

RESUMO

BACKGROUND: Sarcopenia, a loss of skeletal muscle mass or function, affects up to 50% of patients with inflammatory bowel disease (IBD) and is associated with poor clinical outcomes including increased hospitalizations, need for surgery and post-operative complications. Despite the high prevalence and clinical significance of sarcopenia in patients with IBD, few patients undergo routine muscle evaluation. AIM: The goal of this study was to review the mechanisms of sarcopenia in patients with IBD and understand novel modalities to assess and treat impaired muscle mass or function. METHODS: Pubmed and Cochrane databases were searched including articles published up to February 2023 utilizing the following keywords: "inflammatory bowel disease", "IBD", "Crohn's disease", "ulcerative colitis", "sarcopenia", "myosteatosis", "muscle health", and "frailty". RESULTS: The pathogenesis of sarcopenia in IBD is not well defined, however, there is evidence supporting the role of malabsorption, reduced protein intake, chronic inflammation, dysbiosis, decreased physical activity, medication effects and hormone signaling from visceral adiposity. Traditional sarcopenia assessment techniques include direct measurements on cross sectional imaging. However, given the time, cost and radiation exposure associated with cross sectional imaging, new bedside tools are now available to estimate muscle mass, including assessment of grip strength, mid upper arm circumference and body composition utilizing bioelectrical impedance analysis. In addition, novel biomarkers for assessing muscle mass and techniques utilizing point of care ultrasound have been proposed to make sarcopenia evaluation more streamlined in the IBD clinic. CONCLUSION: Sarcopenia is associated with poor clinical outcomes independent of IBD activity and therefore muscle health should be assessed in all IBD patients at routine intervals. Future studies to better our understanding of the pathophysiology as well as most effective management of sarcopenia in IBD will help guide clinical care and reduce disease related complications.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Sarcopenia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Sarcopenia/epidemiologia , Doença de Crohn/complicações , Colite Ulcerativa/complicações , Músculos
12.
Clin Gastroenterol Hepatol ; 21(11): 2928-2937.e12, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36787834

RESUMO

BACKGROUND: At diagnosis, up to one-third of patients with Crohn's disease (CD) have a complicated phenotype with stricturing (B2) or penetrating (B3) behavior or require early surgery. We evaluated protein biomarkers and antimicrobial antibodies in serum archived years before CD diagnosis to assess whether complicated diagnoses were associated with a specific serological signature. METHODS: Prediagnosis serum was obtained from 201 patients with CD and 201 healthy controls. Samples were evaluated with a comprehensive panel of 1129 proteomic markers (SomaLogic) and antimicrobial antibodies. CD diagnosis and complications were defined by the International Classification of Diseases-Ninth Revision and Current Procedural Terminology codes. Cox regression models were utilized to assess the association between markers and the subsequent risk of being diagnosed with complicated CD. In addition, biological pathway and network analyses were performed. RESULTS: Forty-seven CD subjects (24%) had a B2 (n = 36) or B3 (n = 9) phenotype or CD-related surgery (n = 2) at diagnosis. Subjects presenting with complicated CD at diagnosis had higher levels of antimicrobial antibodies six years before diagnosis as compared with those diagnosed with noncomplicated CD. Twenty-two protein biomarkers (reflecting inflammatory, fibrosis, and tissue protection markers) were found to be associated with complicated CD. Pathway analysis of the altered protein biomarkers identified higher activation of the innate immune system and complement or coagulation cascades up to six years before diagnosis in complicated CD. CONCLUSIONS: Proteins and antimicrobial antibodies associated with dysregulated innate immunity, excessive adaptive response to microbial antigens, and fibrosis precede and predict a complicated phenotype at the time of diagnosis in CD patients.


Assuntos
Anti-Infecciosos , Doença de Crohn , Humanos , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Proteômica , Fenótipo , Biomarcadores , Anticorpos , Fibrose
13.
Clin Gastroenterol Hepatol ; 21(10): 2629-2638, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36787837

RESUMO

BACKGROUND& AIMS: Tumor necrosis factor (TNF) antagonists often are used as first-line medications to treat moderate to severe inflammatory bowel disease (IBD), but many patients do not achieve or maintain response. Our aim was to compare the effectiveness of second-line treatments (ustekinumab, vedolizumab, or a second TNF antagonist) after TNF antagonist exposure in patients with Crohn's disease (CD) and ulcerative colitis (UC) from 2 electronic health records-based cohorts. METHODS: We identified patients with prior TNF antagonist exposure who switched to a different biologic in the Mount Sinai Health System (MSHS) electronic health records (CD, n = 527; UC, n = 165) and the Study of a Prospective Adult Research Cohort (SPARC) from the Inflammatory Bowel Disease Plexus Program of the Crohn's & Colitis Foundation (CD, n = 412; UC, n = 129). Treatment failure was defined as the composite of any IBD-related surgery, IBD-related hospitalization, new prescription of oral/intravenous corticosteroids, or need to switch to a third biologic agent. Time-to-event analysis was conducted with inverse probability of treatment-weighted data. RESULTS: Overall, treatment failure occurred in 85% of MSHS and 72% of SPARC CD patients. In SPARC, the likelihood of treatment failure was significantly lower with ustekinumab compared with vedolizumab as second-line treatment (adjusted hazard ratio, 0.66; 95% CI, 0.54-0.82; P < .001), a trend confirmed in MSHS (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.04; P = .15). In both cohorts, the superiority of ustekinumab compared with vedolizumab was shown when considering treatment failure as prescription of steroids or a third biologic agent. In UC, no differences between second-line treatment groups were identified. CONCLUSIONS: In 2 independent real-world cohort settings, second-line therapy in CD with ustekinumab after TNF antagonist treatment failure was associated with a lower likelihood of treatment failure than second-line vedolizumab.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Ustekinumab/uso terapêutico , Pontuação de Propensão , Estudos Prospectivos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Terapia Biológica , Resultado do Tratamento , Fator de Necrose Tumoral alfa
14.
Curr Gastroenterol Rep ; 25(3): 45-51, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36753033

RESUMO

PURPOSE OF REVIEW: Crohn's Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, "top-down" biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20-30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. RECENT FINDINGS: For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn's Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Sulfassalazina/uso terapêutico , Budesonida/uso terapêutico , Antibacterianos/uso terapêutico , Nutrição Enteral , Indução de Remissão
15.
Clin Gastroenterol Hepatol ; 21(6): 1598-1606.e5, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36642291

RESUMO

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Neoplasias , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Fator de Necrose Tumoral alfa , Fatores Biológicos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/induzido quimicamente , Inibidores do Fator de Necrose Tumoral , Produtos Biológicos/efeitos adversos
16.
Gastroenterology ; 164(4): 619-629, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36634824

RESUMO

BACKGROUND & AIMS: Better biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvß6 (anti-αvß6) autoantibodies have been described in patients with UC. We tested for the presence of anti-αvß6 antibodies in the preclinical phase of UC and studied their association with disease-related outcomes after diagnosis. METHODS: Anti-αvß6 autoantibodies were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense preclinical cohort (PREDICTS [Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects]). In a distinct, external validation cohort (Crohn's and Colitis Canada Genetic Environmental Microbial project cohort), we tested 12 pre-UC subjects and 49 matched controls. Furthermore, anti-αvß6 autoantibodies were measured in 2 incident UC cohorts (COMPASS [Comprehensive Care for the Recently Diagnosed IBD Patients], n = 55 and OSCCAR [Ocean State Crohn's and Colitis Area Registry], n = 104) and associations between anti-αvß6 autoantibodies and UC-related outcomes were defined using Cox proportional hazards model. RESULTS: Anti-αvß6 autoantibodies were significantly higher among individuals who developed UC compared with controls up to 10 years before diagnosis in PREDICTS. The anti-αvß6 autoantibody seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 time points. Anti-αvß6 autoantibodies predicted UC development with an area under the curve of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvß6 autoantibodies in preclinical UC samples was validated in the GEM cohort. Finally, high anti-αvß6 autoantibodies was associated with a composite of adverse UC outcomes, including hospitalization, disease extension, colectomy, systemic steroid use, and/or escalation to biologic therapy in recently diagnosed UC. CONCLUSIONS: Anti-integrin αvß6 autoantibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.


Assuntos
Colite Ulcerativa , Colite , Doença de Crohn , Humanos , Colite Ulcerativa/tratamento farmacológico , Autoanticorpos , Proteômica , Doença de Crohn/tratamento farmacológico , Biomarcadores , Colite/complicações
17.
Clin Gastroenterol Hepatol ; 21(5): 1348-1350, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35245701

RESUMO

Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.1-4 One way to investigate this treatment gap in CD is to look at the "net" remission rates in clinical trials defined as the actual percentage of patients enrolled during induction who are in remission at the end of maintenance. Indeed, most of the seminal clinical trials in CD used a "responder" methodology, where only patients who responded during induction were rerandomized to maintenance.


Assuntos
Produtos Biológicos , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Indução de Remissão , Produtos Biológicos/uso terapêutico
18.
Inflamm Bowel Dis ; 29(3): 423-429, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35590456

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of malnutrition. The goal of this study was to define the prevalence of malnutrition and micronutrient deficiencies in recently diagnosed IBD patients and to compare the performance of existing malnutrition screening tools in identifying IBD patients at increased risk for malnutrition. METHODS: This was a retrospective cohort study of adult patients with recently diagnosed IBD (≤18 months disease duration). A diagnosis of malnutrition was made utilizing the European Society for Clinical Nutrition and Metabolism malnutrition criteria. Serum micronutrient levels were included. The sensitivity of 5 malnutrition screening tools in identifying patients at moderate-high risk of malnutrition was determined based on the European Society for Clinical Nutrition and Metabolism malnutrition definition. Descriptive statistics summarized the data and univariate analyses tested associations. RESULTS: A total of 182 patients were included for analysis; 65 (36%) met criteria for malnutrition. A total of 135 (74%) patients had ≥1 micronutrient level checked and 105 (78%) had ≥1 deficiency. Patients with prior surgery (odds ratio [OR], 4.5; P = .004), active Crohn's disease (OR, 2.8; P = .03), and diarrhea (OR, 2.1; P = .02) were more likely to be malnourished. The Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool had the highest sensitivity (100%) in predicting those at moderate-high risk of malnutrition at the time of screening. CONCLUSIONS: Patients with recently diagnosed IBD have a high prevalence of malnutrition and micronutrient deficiencies. Both the Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool can be used to identify those at increased risk of malnutrition. Future studies and screening tool development are necessary to identify those at risk of developing malnutrition to facilitate timely referral for nutritional evaluation and prevent disease related complications.


This retrospective cohort study identified that patients with recently diagnosed inflammatory bowel disease have a high prevalence of malnutrition as well as micronutrient deficiencies and compared the utility of 5 available malnutrition screening tools in this population.


Assuntos
Doenças Inflamatórias Intestinais , Desnutrição , Adulto , Humanos , Estudos Retrospectivos , Prevalência , Desnutrição/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Estado Nutricional , Micronutrientes , Progressão da Doença
19.
Gut ; 72(7): 1271-1287, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36109152

RESUMO

OBJECTIVE: IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments. DESIGN: Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn's disease, n=421 UC and 243 controls) in the Mount Sinai Crohn's and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts. RESULTS: bMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time. CONCLUSION: Transcriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/patologia , Inflamação/genética , Inflamação/patologia , Doença de Crohn/patologia , Biópsia , Biomarcadores , Mucosa Intestinal/patologia
20.
Am J Gastroenterol ; 118(1): 129-137, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36114773

RESUMO

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 µg/mL (SD 67) and a median of 22 µg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Anticorpos , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Imunidade Humoral , Doenças Inflamatórias Intestinais/tratamento farmacológico , Necrose , SARS-CoV-2 , Vacinação
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