Antitumor Necrosis Factor Agents to Treat EndoscopicPostoperative Recurrence of Crohn’s Disease: A Nationwide Study With Propensity-Matched Score Analysis

INTRODUCTION:Patients with Crohn's disease experiencing endoscopic postoperative recurrence (POR) may benefit from antitumor necrosis factor (TNF) agents but scarce data on this are available. Our aim was to assess the efficacy of anti-TNF in improving mucosal lesions in patients with endoscopic POR.METHODS:Multicenter, retrospective, study of patients with Crohn's disease who underwent therapy with anti-TNF agents for endoscopic POR (Rutgeerts score > i1). Treatment outcomes were assessed by the findings in the last ileocolonoscopy performed after anti-TNF therapy was initiated. Endoscopic improvement and remission were defined as any reduction in the baseline Rutgeerts score and by a Rutgeerts score < i2, respectively.RESULTS:A total of 179 patients were included, 83 were treated with infliximab and 96 with adalimumab. Median time on anti-TNF therapy at the last endoscopic assessment was 31 months (interquartile range, 13-54). Endoscopic improvement was observed in 61%, including 42% who achieved endoscopic remission. Concomitant use of thiopurines and treatment with infliximab were associated with endoscopic improvement (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.04-4.46; P = 0.03, and OR 2.34, 95% CI 1.18-4.62; P < 0.01, respectively) and endoscopic remission (OR 3.16, 95% CI 1.65-6.05; P < 0.01, and OR 2.01, 95% CI 1.05-3.88; P = 0.04, respectively) in the multivariable logistic regression analysis. These results were confirmed in a propensity-matched score analysis.DISCUSSION:In patients with endoscopic POR, anti-TNF agents improve mucosal lesions in almost two-thirds of the patients. In this setting, concomitant use of thiopurines and use of infliximab seem to be more effective in improving mucosal lesions.Fiorella Canete received a research grant from the Societat Catalana de Digestologia

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Efecto de dosis máximas de atorvastatina en la inflamación, la trombogénesis y la función fibrinolítica en pacientes con cardiopatía isquémica de alto riesgo

Introducción y objetivos. Se ha indicado que la utilización de dosis altas de estatinas podría reducir la aparición de nuevos eventos cardiovasculares en comparación con las dosis convencionales. Nuestro objetivo fue estudiar el efecto del incremento de la dosis de atorvastatina (80 mg/día) en diferentes marcadores del sistema inflamatorio (proteína C reactiva [PCR]), hemostático (fragmento F 1+2 de la protrombina [F1+2]) y fibrinolítico(activador tisular del plasminógeno antigénico [t-PA] y suinhibidor [PAI-1]). Pacientes y método. Se estudió a 27 pacientes concardiopatía isquémica de alto riesgo que presentaban cifras lipídicas superiores a las recomendadas a pesar del tratamiento con 40 mg/día de atorvastatina. Se compararon con 21 sujetos normocolesterolémicos sin enfermedad arteriosclerótica conocida. Se revaluó a 24 pacientesa los 3 meses del incremento de la dosis. Resultados. Los pacientes presentaron cifras elevadas de PCR, F1+2, t-PA, y PAI-1 en comparación con el grupo control (en todos, las variables tuvieron un valor de p <0,05). Tras incrementar la dosis de atorvastatina se ob-servó una reducción de las cifras de PCR, F1+2 y PAI-1 (p< 0,05). Se observó una correlación positiva entre losporcentajes de reducción de colesterol y del F1+2 (r =0,46; p = 0,023), sin que se hallara otra correlación significativa entre los demás parámetros. Conclusiones. Al incrementar las dosis de atorvastatina a 80 mg/día se consigue una reducción de los estadosinflamatorios, trombógenicos e hipofibrinolíticos en un grupo de pacientes con cardiopatía isquémica de altoriesgo y cifras elevadas de lípidos a pesar del tratamientocon dosis de 40 mg/día de atorvastatina

Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.This work was supported in part by grants from Fondo de Investigacion Sanitaria (www.isciii.es) (PI15/00713), Plan Nacional de I+D+I and Fondo Europeo de Desarrollo Regional-FEDER (http://www.ciencia.gob.es/portal/site/MICINN/menuitem.dbc68b34d11ccbd5d52ffeb801432ea0/?vgnextoid=e331aa27bfba7610VgnVCM1000001d04140aRCRD) (RD16/0025/0040), Fundacion Progreso y salud, Junta de Andalucia (https://www.sspa.juntadeandalucia.es/fundacionprogresoysalud/gestionconvocatorias/ugc/login.sol.jsp?id=10) (PI-0411-2014), and GEHEP-SEIMC (GEHEP-004).Peer reviewe