RESUMEN
BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs) have a high risk of venous thromboembolism (VTE). We assessed the timing and risk factors associated with readmission to the hospital for VTE among patients with IBD. METHODS: We collected data from the Nationwide Readmissions Database on IBD index admissions resulting in readmission to the hospital for VTE within 60 days, from 2010 through 2014. We used univariable and multivariable regression to assess risk factors associated with VTE readmission with unadjusted risk ratio (RR) and adjusted RR (aRR) as measures of effect. Time to VTE readmission was assessed in 10-day intervals, for up to 90 days. RESULTS: We identified 872,122 index admissions of patients with IBD; 1160 resulted in readmission with VTE. More than 90% of readmissions occurred within 60 days of discharge from the index admission. Factors associated with hospital readmission with VTE included prior VTE, longer length of hospital stay, comorbidities, having a flexible sigmoidoscopy or colonoscopy at index admission, and age older than 18 years. Additional risk factors included Clostridium difficile infection at index admission (aRR, 1.47; 95% CI, 1.17-1.85) and discharge to a skilled nursing facility or intermediate care facility (aRR, 1.39; 95% CI, 1.14-1.70) or discharge with home health services (aRR, 1.65; 95% CI, 1.41-1.94). CONCLUSIONS: Among patients admitted to the hospital with IBD, most readmissions with VTE occur within 60 days of discharge. Readmission with VTE is associated with C difficile infection and discharge to a skilled nursing facility, intermediate care facility, or with home health services. Studies are needed to evaluate the potential benefit of extending VTE prophylaxis for patients admitted to the hospital with IBD for up to 2 months after discharge, to minimize risk.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Tromboembolia Venosa , Adolescente , Hospitales , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Alta del Paciente , Readmisión del Paciente , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/epidemiologíaRESUMEN
OBJECTIVES: Few studies have examined the role of non-Clostridium difficile enteric infections in flares of inflammatory bowel disease (IBD). Our objective was to investigate enteric infection detected by multiplex PCR stool testing in patients with IBD. METHODS: We performed a cross-sectional analysis of 9403 patients who underwent 13,231 stool tests with a gastrointestinal pathogen PCR panel during a diarrheal illness from March 2015 to May 2017. Our primary outcome was the presence of an infection. Secondary outcomes included endoscopic and histologic predictors of infection, and IBD outcomes following testing. RESULTS: A total of 277 patients with Crohn's disease (CD), 300 patients with ulcerative colitis (UC), and 8826 patients without IBD underwent 454, 503, and 12,275 tests, respectively. Compared to patients without IBD, patients with IBD were less likely to test positive (CD 18.1%, UC 16.1%, no IBD 26.6%, p < 0.001). Compared to patients without IBD, CD had a higher prevalence of norovirus (p = 0.05) and Campylobacter (p = 0.043), whereas UC had a lower prevalence of norovirus (p = 0.001) and a higher prevalence of Campylobacter (p = 0.013), Plesiomonas (p = 0.049), and Escherichia coli species (p < 0.001). Of 77 patients who underwent endoscopy, there were no major endoscopic or histologic predictors of a positive test. Patients who tested negative were more likely to have IBD therapy escalated (p = 0.004). Enteric infection did not impact IBD outcomes following testing (log-rank 0.224). CONCLUSIONS: Non-Clostridium difficile enteric infections were identified in 17% of symptomatic patients with IBD. Endoscopic and histologic findings may not differentiate flare from infection. Norovirus and E.coli may play an important role in flare of IBD.
Asunto(s)
Infecciones Bacterianas/epidemiología , Colitis Ulcerosa/microbiología , Enfermedad de Crohn/microbiología , Enterocolitis/epidemiología , Intestinos/microbiología , Adolescente , Adulto , Anciano , Infecciones Bacterianas/microbiología , Campylobacter/aislamiento & purificación , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/patología , Estudios Transversales , Endoscopía Gastrointestinal , Enterocolitis/microbiología , Escherichia coli/aislamiento & purificación , Heces/microbiología , Femenino , Humanos , Intestinos/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Norovirus/aislamiento & purificación , Plesiomonas/aislamiento & purificación , Prevalencia , Índice de Severidad de la Enfermedad , Brote de los Síntomas , Adulto JovenRESUMEN
BACKGROUND: Patients with celiac disease and inflammatory bowel disease, two immune-mediated luminal conditions, have higher rates of certain infections than healthy counterparts. The prevalence of many gastrointestinal infections in these patients, however, is unknown. AIMS: Using a novel clinical stool pathogen PCR test, we investigated the hypothesis that patients with celiac disease/inflammatory bowel disease had different distributions of diarrheal pathogens than other patients. METHODS: We performed a retrospective cohort study of outpatients who underwent stool pathogen testing with the FilmArray Gastrointestinal PCR Panel (BioFire Diagnostics, Salt Lake City, UT) at our institution from January 1 to December 31, 2015. Rates of pathogens were measured in patients with or without celiac disease/inflammatory bowel disease. RESULTS: Of 955 patients, 337 had positive test for any pathogen, with 465 bacterial, parasitic, or viral pathogens identified. One hundred and twenty-seven patients (13.3%) had celiac disease or inflammatory bowel disease, of which 29/127 (22.8%) had a positive test, compared to 308/828 other patients (37.2%) (p = 0.002). Patients with celiac disease/inflammatory bowel disease had significantly fewer viruses (1.6 vs. 8.1% of patients; p = 0.008) and parasites (0 vs. 3.3%; p = 0.039), with nonsignificant trend toward fewer bacteria (21.3 vs. 29.2%; p = 0.063). Escherichia coli species were most common in both populations. CONCLUSIONS: Stool PCR identified numerous pathogens in patients with or without celiac disease/inflammatory bowel disease. Patients with celiac disease/inflammatory bowel disease were significantly less likely to have any pathogen identified, and had significantly fewer viruses and parasites. In this population, knowledge of common pathogens can guide diagnostic evaluation and offer opportunities for treatment.
Asunto(s)
Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/microbiología , Diarrea/microbiología , Heces/microbiología , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/microbiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Celíaca/diagnóstico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
BACKGROUND: In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS: We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS: The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P=0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Enfermedad de Crohn/clasificación , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Humanos , Quimioterapia de Inducción , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Inducción de Remisión , Índice de Severidad de la Enfermedad , UstekinumabRESUMEN
BACKGROUND & AIMS: Mucosal healing might alter midterm and long-term outcomes of patients with Crohn's disease (CD) and has become an important end point in clinical trials. However, the minimal degree of mucosal improvement (endoscopic response) required to alter midterm outcomes is not known. We aimed to determine the best definition of endoscopic response by evaluating data on the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic Index of Severity (CDEIS) from the Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease (SONIC trial). METHODS: We analyzed data from 172 patients who participated in the SONIC trial, were found to have endoscopic lesions at baseline, and underwent a second endoscopic examination at week 26 of treatment with infliximab, azathioprine, or both. Mucosal healing was defined as absence of ulcers. A central reader calculated SES-CD and CDEIS results. Different cutoff values were set for endoscopic response based on the SES-CD or CDEIS. The diagnostic ability of these different cutoff values was evaluated using receiver operating characteristic (ROC) curves, positive likelihood ratios (PLR), and negative likelihood ratios (NLR). Corticosteroid-free clinical remission (CFREM) at week 50 was used as a binary classifier. RESULTS: Based on analyses of ROC curves, PLR, and NLR, endoscopic response was defined as a decrease from baseline in SES-CD of at least 50%. At week 26, mucosal healing and endoscopic response were achieved in 48% and 65% of patients, respectively. Mucosal healing at week 26 was associated with CFREM at week 50, with 56% sensitivity, 65% specificity, a PLR of 1.60, and an NLR of 0.67. Endoscopic response at week 26 was associated with CFREM at week 50, with 74% sensitivity, 48% specificity, a PLR of 1.42, and an NLR of 0.54. Endoscopic response, defined as a decrease from baseline in CDEIS of at least 50%, yielded similar results. CONCLUSIONS: In patients with CD, mucosal healing and endoscopic response (defined as a decrease from baseline in SES-CD or CDEIS of at least 50%) at week 26 of treatment identified those most likely to be in CFREM at week 50. The ability of the proposed endoscopic response cutoff value to predict midterm CFREM should be validated in an independent, prospective cohort. Its correlation with changes in long-term disease progression still needs to be demonstration. ClinicalTrials.gov, Number: NCT00094458.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Azatioprina/uso terapéutico , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Endoscopía Gastrointestinal/métodos , Fármacos Gastrointestinales/uso terapéutico , Índices de Gravedad del Trauma , Adulto , Anticuerpos Monoclonales/farmacología , Azatioprina/farmacología , Estudios de Cohortes , Enfermedad de Crohn/patología , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Fármacos Gastrointestinales/farmacología , Humanos , Infliximab , Mucosa Intestinal/efectos de los fármacos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
BACKGROUND: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown. METHODS: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. RESULTS: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. CONCLUSIONS: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Azatioprina/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Antiinflamatorios , Anticuerpos Monoclonales/efectos adversos , Azatioprina/efectos adversos , Distribución de Chi-Cuadrado , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Infliximab , Infusiones Intravenosas , Modelos Logísticos , Masculino , Inducción de RemisiónRESUMEN
BACKGROUND AND AIMS: NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic (PK) profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and PK of NX-13 in patients with active ulcerative colitis (UC). METHODS: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4-10 were randomly assigned (3:3:3:1 ratio) to three NX-13 oral dose groups (250mg Immediate Release (IR), 500mg IR, or 500mg Delayed Release (DR) or placebo) once daily for 4 weeks. Safety and PK were the primary and secondary objectives, respectively. RESULTS: Thirty-eight patients (11 females) were recruited and randomized to placebo (5), NX-13 250mg IR (11), NX-13 500mg IR (11), or NX-13 500mg DR (11) and received at least one dose. There were no Serious Adverse Events (SAEs) or deaths during the trial. One patient (500mg DR, 1/11) withdrew for worsening of UC and a second (500mg IR, 1/11) on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population (36 patients), clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4. CONCLUSIONS: NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741.
RESUMEN
BACKGROUND: The role of intravenous (IV) cyclosporine in severe Crohn's colitis (CC) is poorly studied. AIM: Our primary aim was to determine the in-hospital colonic resection rate in patients with severe CC who received IV cyclosporine, and the potential predictors of resection among these patients. METHODS: An inpatient pharmacy query of all patients who received IV cyclosporine at Mount Sinai Medical Center for 12.5 years after January 1, 1996 was reviewed. Patients with CC or indeterminate colitis favoring Crohn's were included and their medical records were reviewed. Subsequent need for colonic surgery was assessed. A Kaplan-Meier plot with log-rank testing was performed to determine the rate of colonic surgery avoidance. Forward stepwise logistic regression was performed to determine independent predictors of surgery. RESULTS: Forty-eight patients met our inclusion criteria. Prior thiopurine and anti-tumor necrosis factor (anti-TNF) use was 85% and 69%, respectively. The median follow-up time was 12 months (range, 1 to 60 mo). 12.5% of patients required colonic resection during their admission for IV cyclosporine. Anti-TNF use in the 4 weeks preceding IV cyclosporine was the only predictor of surgery in this setting (P=0.05). The cumulative colonic surgery avoidance rate was 72±13% at 6 months and 59±15% at 12 months. CONCLUSIONS: The use of IV cyclosporine resulted in a low rate of in-hospitalization colonic surgery among CC patients with severe disease, the majority of whom previously failed anti-TNFs and thiopurines.
Asunto(s)
Colectomía/estadística & datos numéricos , Colitis/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Ciclosporina/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Administración Intravenosa , Adulto , Colectomía/métodos , Colitis/fisiopatología , Colitis/cirugía , Colon/cirugía , Enfermedad de Crohn/fisiopatología , Enfermedad de Crohn/cirugía , Ciclosporina/administración & dosificación , Femenino , Fármacos Gastrointestinales/administración & dosificación , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Omilancor is an oral, once-daily, gut-restricted, small molecule, first-in-class therapeutic for Crohn's disease (CD) and ulcerative colitis (UC) that targets the novel LANCL2 pathway. Through LANCL2 activation, omilancor increases the suppressive capacity of regulatory immune cells, including regulatory CD4+ T cells (Tregs), locally within the intestinal mucosa. In a Phase I study in normal healthy volunteers no changes in AEs or trends in safety laboratory trends were observed up to daily oral doses of 7500 mg/day. METHODS: In a Phase 2, proof of concept, double blind, parallel-group study, adult patients with Mayo Clinic scores (MCS) of 4 - 10 and endoscopic subscores of 2 or more were randomly assigned to groups given omilancor 440 mg QD (n=66), omilancor 880 mg QD (n=66) or placebo (n=66) for 12 weeks. The primary endpoint was clinical remission after 12 weeks as defined by rectal bleeding (RB) equal to 0, stool frequency (SF) equal to 0 or 1 and endoscopic appearance (MES) equal to 0 or 1. A modified intent to treat (mITT) population was defined by patients with RB > 0, histological activity and elevated fecal calprotectin (FCP) at baseline. Secondary endpoints included histological remission as defined by a Geboes score < 3.1 with absence of neutrophils in the lamina propria, endoscopic remission as defined by a MES < 2, normalization of FCP and pharmacokinetics (PK) of omilancor in stool, tissue and plasma. RESULTS: Oral omilancor was well tolerated with no trends in AE profile observed and most AEs of mild severity and no dose-limiting toxicities. In the mITT population, clinical remission was induced in 30.4% of omilancor treated patients relative to 3.7% of patients given placebo (Δ = 26.7, p = 0.01), thereby meeting the primary endpoint. Endoscopic remission was induced in 41.7% of patients treated with omilancor relative to 18.6% of patients given placebo (Δ = 23.1, p = 0.07). Histological remission was induced in 41.7% of patients treated with omilancor relative to 22.2% of patients given placebo (Δ = 19.5, p = 0.14). In patients with elevated baseline FCP, normalization occurred in 43.8% of the omilancor 880 mg group and 40.6% of the omilancor 440 mg group relative to 21.4% of the placebo group after 2 weeks (p = 0.048). PK analysis validated a gut-restricted profile with stable drug levels in stool over the 12-week treatment period and penetration into colonic biopsy tissue with limited systemic exposure. Reduction of patient reported outcomes occurred during the OLE with nearly 90% of patients reaching SF ≤ 1 and RB = 0 after 36 weeks of open-label treatment. CONCLUSIONS: Once a day oral dosing with omilancor was well-tolerated and induced clinical remission in a Phase II mild to moderate UC population. A Phase II study in CD and a Phase III program in UC (PACIFY) were initiated in 2021 and are currently recruiting.
RESUMEN
BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the mainstay of surgical treatment for patients with ulcerative colitis (UC) but is associated with an increased risk of infertility. We developed a simulation model examining the impact of initial surgical procedure on quality-adjusted life-years (QALYs) and fertility end points. METHODS: A patient-level state transition model was used to analyze outcomes by surgical approach strategy for females of childbearing age. Initial surgical options included IPAA, rectal-sparing colectomy with end ileostomy (RCEI), and ileorectal anastomosis (IRA). The primary outcome examined was QALYs, whereas secondary outcomes included UC and fertility-associated end points. RESULTS: IPAA resulted in higher QALYs for patients aged 20-30 years, as compared with RCEI. For patients aged 35 years, RCEI resulted in higher QALYs (7.54 RCEI vs 7.53 IPAA) and was associated with a 28% higher rate of childbirth, a 14-month decrease in time to childbirth, and a 77% reduction in in vitro fertilization utilization. When accounting for the decreased infertility risk associated with laparoscopic IPAA, IPAA resulted in higher QALYs (7.57) even for patients aged 35 years. CONCLUSIONS: Despite an increased risk of infertility, our model results suggest that IPAA may be the optimal surgical strategy for female UC patients aged 20-30 years who desire children. For patients aged 35 years, RCEI should additionally be considered, as QALYs for RCEI and IPAA were similar. These quantitative data can be used by patients and providers to help develop an individualized approach to surgical management choice.
Asunto(s)
Colitis Ulcerosa/cirugía , Infertilidad Femenina/epidemiología , Tratamientos Conservadores del Órgano/efectos adversos , Complicaciones Posoperatorias/epidemiología , Proctocolectomía Restauradora/efectos adversos , Adulto , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Tasa de Natalidad , Colectomía/efectos adversos , Colectomía/métodos , Simulación por Computador , Femenino , Humanos , Ileostomía/efectos adversos , Ileostomía/métodos , Íleon/cirugía , Infertilidad Femenina/etiología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tratamientos Conservadores del Órgano/métodos , Complicaciones Posoperatorias/etiología , Embarazo , Proctocolectomía Restauradora/métodos , Años de Vida Ajustados por Calidad de Vida , Recto/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: In patients with severe corticosteroid-refractory ulcerative colitis, cyclosporine or infliximab may be added in an effort to induce remission. If the patient then fails either of these drugs, it is unknown whether success can be achieved by using the other agent. The aim of this study was to assess outcomes of using cyclosporine after failure of infliximab, and vice versa. METHODS: We retrospectively reviewed the charts of 19 patients with corticosteroid-refractory ulcerative colitis who received either infliximab after failed cyclosporine or cyclosporine after failed infliximab. Acute salvage therapy was defined as having received the alternate drug within 4 weeks of discontinuing the first agent. RESULTS: Ten patients received infliximab after failing cyclosporine; 9 patients received cyclosporine after failing infliximab. Four patients (40%) in the infliximab-salvage group achieved remission, as did 3 (33%) in the cyclosporine-salvage group. Remission lasted a mean of 10.4 months (range, 4.4-17.03 mo) and 28.5 months (range, 5.0-41.5 mo), respectively. Severe adverse events included one patient who developed sepsis and died after receiving infliximab salvage. One patient who received cyclosporine salvage developed herpetic esophagitis, and another patient who received cyclosporine salvage developed pancreatitis and bacteremia. CONCLUSIONS: In patients with severe corticosteroid-refractory ulcerative colitis who fail treatment with either cyclosporine or infliximab, remission rates using acute salvage therapy by crossing over to the other drug occur in approximately one third of patients and have limited duration. Serious adverse events occurred in 16%, including 1 death, suggesting that the risks of acute salvage therapy may outweigh the benefits.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Terapia Recuperativa/métodos , Anticuerpos Monoclonales/efectos adversos , Bacteriemia/inducido químicamente , Ciclosporina/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Infliximab , Masculino , Pancreatitis/inducido químicamente , Estudios Retrospectivos , Sepsis/inducido químicamente , Resultado del TratamientoRESUMEN
BACKGROUND: Intravenous cyclosporine (i.v. CsA) is an effective therapy for patients with inflammatory bowel disease (IBD). However, data regarding its adverse events in these patients are limited. METHODS: A retrospective chart review of the initial 111 consecutive patients with IBD treated with i.v. CsA followed by a predetermined duration of oral therapy. RESULTS: One hundred eleven patients (64 UC, 47 CD; mean age 33 yr, range 16-68) received i.v. CsA at 4 mg/kg/day, then oral CsA at 8 mg/kg/day, with dose adjustment based on serum creatinine. The mean treatment duration was 9.3 months (range 1 wk to 34 months). Major adverse events occurred in 17 (15.3%) patients. Nephrotoxicity (serum creatinine > or = 1.4 mg/dL [123 micromol/L] or a rise by at least 33% over baseline not responding to dose adjustment) sufficiently severe to warrant discontinuation of therapy occurred in 6 (5.4%) patients. Serious infection occurred in 7 (6.3%) patients, seizures in 4 (3.6%) patients, anaphylaxis in 1 (0.9%) patient, and death in 2 (1.8%) patients. Minor adverse events (transient effects with complete resolution either spontaneously or with dose adjustment) comprised: paresthesias (51%), hypomagnesemia (42%), hypertension (39%), hypertrichosis (27%), headache (23%), minor nephrotoxicity (defined as above but with restoration of normal serum creatinine with dose adjustment; 19% of patients), abnormal liver function tests (19%), minor infections (15%), hyperkalemia (13%), and gingival swelling (4%). CONCLUSIONS: In our initial experience, limited duration CsA therapy was frequently associated with adverse events although the majority of these were minor and responded to dose adjustment. Although not all severe adverse events can be clearly attributed to CsA use alone, its high incidence suggests that vigorous monitoring by experienced clinicians at tertiary care centers may be required.
Asunto(s)
Ciclosporina/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anciano , Ciclosporina/administración & dosificación , Femenino , Humanos , Inmunosupresores/administración & dosificación , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Intestinal stenosis is a frequent complication of Crohn's disease, often leading to repeated bowel obstruction and surgery. The prevalence of small bowel stenosis has ranged from 20% to 40% and from 7% to 15% in patients with colonic disease. Although balloon dilation is the initial preferred approach, many patients eventually restenose and require surgical resection or stricturoplasty. Infliximab, a chimeric IgG1 kappa monoclonal antibody against TNF-alpha, has been effective in the treatment of enteric as well as fistulous complications of Crohn's disease. Repeated systemic administration has been successful for active inflammatory disease yet has been reported to be ineffective in the treatment of strictures. Although the TREAT registry has shown systemic infliximab to be safe in the long term, there is concern regarding infectious as well as neoplastic complications. METHODS: This report describes 3 patients refractory to all medical therapy including systemic infliximab. RESULTS: In all 3 patients, dilation of a colonic stricture was accomplished by injection of infliximab, via the sclerotherapy technique, into the distal and medial portions of the stricture. CONCLUSIONS: Infliximab was shown to be effective in the treatment of strictures in 3 patients.
Asunto(s)
Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Enfermedad de Crohn/tratamiento farmacológico , Obstrucción Intestinal/tratamiento farmacológico , Adulto , Enfermedades del Colon/tratamiento farmacológico , Femenino , Humanos , Enfermedades del Íleon/tratamiento farmacológico , Infliximab , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Enfermedades del Recto/tratamiento farmacológicoRESUMEN
BACKGROUND: The similar presentations in relapse of inflammatory bowel disease (IBD) and enteric infection pose substantial barriers to diagnosis and treatment. The objective of this study was to investigate the incidence, etiology, predictors, and treatment of enteric infection in patients with IBD. METHODS: We reviewed the records of 214 patients with IBD who underwent 295 gastrointestinal pathogen panel and Clostridium difficile infection (CDI) polymerase chain reaction (PCR) stool tests during an exacerbation of symptoms. We collected baseline characteristics, PCR outcomes, and medication exposures. We tested for associations via the Chi-square test and the t-test. Logistic regression analysis was used to identify predictors of enteric infection. RESULTS: Of 295 PCR tests ordered during an exacerbation of symptoms, 38 (12.9%) were positive for CDI and 41 (13.8%) were positive for 14 other pathogens, with E. coli species as the most common. A previous history of CDI or colonic involvement of IBD predicted CDI, whereas a previous colectomy predicted negative testing for CDI. The majority with CDI (24, 63.2%) received oral vancomycin and 15 (37.5%) with other enteric pathogens were treated for their infection. Patients with CDI had a longer median length of hospital stay (8.5 versus 4 days, P = 0.041). Patients who tested negative for enteric infections were more likely to have IBD medications added or up-titrated (P = 0.027). CONCLUSIONS: Enteric infection was detected in 79 (26.8%) symptomatic patients with IBD , with CDI the most frequent followed by E. coli. Negative stool PCR testing was associated with changes in IBD management. Broad enteric PCR testing should be considered during relapse of IBD.
Asunto(s)
Infecciones por Clostridium/epidemiología , Escherichia coli/aislamiento & purificación , Heces/microbiología , Enfermedades Inflamatorias del Intestino/complicaciones , Tiempo de Internación/estadística & datos numéricos , Adolescente , Adulto , Infecciones por Clostridium/tratamiento farmacológico , Colectomía/efectos adversos , Estudios Transversales , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/microbiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Recurrencia , Vancomicina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Prolonged antibiotic use is limited by several adverse effects, one of which is Clostridium difficile infection (CDI). The aim of this study was to determine the incidence of CDI in patients receiving chronic antibiotic treatment for Crohn's disease (CD). METHODS: We conducted a retrospective review of 100 patients with CD for which ≥6 months of outpatient antibiotic therapy was prescribed. Data were collected regarding demographics, CD phenotype, treatment history, and CDI. The incidence of CDI in our patient population was calculated and compared with historical controls. RESULTS: 100 patients were studied-60% of men, mean age 23.9 years at CD diagnosis. Eighty-two percent had disease involving the ileum, and 33% had disease involving the colon. The mean duration of antibiotic therapy was 39.6 months (range, 6-217 months). The most commonly prescribed classes of antibiotics were fluoroquinolones (84%), penicillins (57%), and cephalosporins (32%). Forty-nine percent of patients were treated with concomitant thiopurines, 45% with budesonide, and 41% with biologics. The overall incidence of CDI was 2%. This incidence of CDI was lower than previously reported for non-CD patients receiving chronic antibiotics for continuous-flow left ventricular assist device infections (12.5%) and orthopedic prosthesis infections (22.2%). CONCLUSIONS: The incidence of CDI is rare in patients receiving chronic antibiotic treatment for CD, and it seems significantly lower than for non-CD populations reported in the literature.
Asunto(s)
Antibacterianos/farmacología , Clostridioides difficile/efectos de los fármacos , Infecciones por Clostridium/epidemiología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/microbiología , Adolescente , Adulto , Anciano , Niño , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/microbiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , New York , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.
Asunto(s)
Neoplasias del Sistema Digestivo/etiología , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Animales , Neoplasias del Sistema Digestivo/inducido químicamente , Neoplasias del Sistema Digestivo/inmunología , Neoplasias del Sistema Digestivo/terapia , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/inmunología , Pronóstico , Factores de Riesgo , Factores de TiempoRESUMEN
The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.
Asunto(s)
Azatioprina/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Mercaptopurina/uso terapéutico , Azatioprina/historia , Quimioterapia Combinada , Fármacos Gastrointestinales/uso terapéutico , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Inmunosupresores/historia , Infliximab/uso terapéutico , Quimioterapia de Mantención , Mercaptopurina/historia , Inducción de Remisión , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohn's disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD. METHODS: Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 10 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohn's Disease Activity Index) at 4 and 6 weeks. RESULTS: Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects. CONCLUSIONS: A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.