Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Effectiveness and safety of azathioprine for inflammatory pouch disorders: results from the RESERVO study of GETECCU.

Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.

Low risk of new dysplastic lesions in an inflammatory bowel disease population study with dye chromoendoscopy.

Background and study aims Rates of new dysplastic lesions or cancer progression after first dye chromoendoscopy in the era of high-definition endoscopy have yet to be determined. Patients and methods A multicenter, population-based, retrospective cohort study was performed in seven hospitals in Spain. Patients with inflammatory bowel disease and fully resected (R0) dysplastic colon lesions under surveillance with high-definition dye-based chromoendoscopy were sequentially enrolled between February 2011 and June 2017, with a minimum endoscopic follow-up of 36 months. The aim was to assess the incidence of developing more advanced metachronous neoplasia by analyzing possible associated risk factors. Results The study sample included 99 patients and 148 index lesions (145 low-grade dysplasia lesions and three high-grade dysplasia [HGD] lesions with a mean follow-up of 48.76 months [IQR: 36.34-67.15]). The overall incidence of new dysplastic lesions was 0.23 per 100 patient-years, 1.15 per 100 patients at 5 years and 2.29 per 100 patients at 10 years. A history of dysplasia was associated with a higher risk of developing any grade of dysplasia during follow-up ( P  = 0.025), whereas left colon lesions were associated with a lower risk ( P  = 0.043). The incidence of more advanced lesions at 1 year and 10 years was 1 % and 14 % respectively, with lesion size > 1 cm being a risk factor ( P  = 0.041). One of the eight patients (13 %) with HGD lesions developed colorectal cancer during follow-up. Conclusions The risk of dysplasia progressing to advanced neoplasia and, specifically, the risk of new neoplastic lesions after endoscopic resection of colitis-associated dysplasia, are both very low.

Incidencia e historia natural de la enfermedad inflamatoria intestinal en Castilla y León: estudio prospectivo, multicéntrico y poblacional / Incidence, and natural history of inflammatory bowel disease in Castilla y León: Prospective and multicenter epidemiological study

Introducción: La incidencia de la enfermedad inflamatoria intestinal (EII) está aumentando en todo el mundo. Objetivos: Evaluar la incidencia de EII en la comunidad autónoma de Castilla y León y describir las características clínicas de los pacientes al diagnóstico, el tipo de tratamiento recibido y la evolución clínica durante el primer año. Material y métodos: Estudio prospectivo, multicéntrico y poblacional en el que se incluyeron pacientes adultos diagnosticados de EII (enfermedad de Crohn [EC], colitis ulcerosa [CU] o colitis indeterminada [CI]) durante el año 2017 procedentes de 8 centros de Castilla y León. Se incluyeron variables epidemiológicas, clínicas y terapéuticas. Se calculó la incidencia global y por enfermedades. Resultados: Doscientos noventa pacientes fueron diagnosticados de EII (54,5% de CU, 45.2% de EC y 0,3% de CI), con una mediana de seguimiento de 9 meses (rango 8-11). La tasa de incidencia fue de 16,6 casos/100.000 habitantes-año (9/105 casos de CU y 7,5/105 casos de EC), con una proporción CU/EC de 1,2:1. Los pacientes con EC recibieron significativamente más corticoides sistémicos (47% vs. 30%; p=0,002), más tratamiento inmunomodulador (81% vs. 19%; p=0,000), más tratamiento biológico (29% vs. 8%; p=0,000) y mayor necesidad de cirugía (11% vs. 2%; p=0,000). Conclusiones: La incidencia de pacientes con CU en nuestro medio se incrementa, mientras que la de EC se mantiene estable, con una historia natural de la enfermedad peor (uso de corticoides, inmunosupresores, biológicos y cirugía) para los pacientes con EC comparado con los pacientes con CU en el primer año de seguimiento.(AU)

Introduction: The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Objectives: To evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year. Materials and methods: Prospective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated.Results290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8−11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/105 UC cases and 7.5/105 CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P=.002), immunomodulatory therapy (81% vs 19%; P=.000), biological therapy (29% vs 8%; P=.000), and surgery (11% vs 2%; p=.000) were significatively higher among patients with CD comparing with those with UC. Conclusions: The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.(AU)

Incidence, and natural history of inflammatory bowel disease in Castilla y León: Prospective and multicenter epidemiological study. / Incidencia e historia natural de la enfermedad inflamatoria intestinal en Castilla y León: estudio prospectivo, multicéntrico y poblacional.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) is increasing worldwide. OBJECTIVES: To evaluate the incidence of IBD in Castilla y León describing clinical characteristics of the patients at diagnosis, the type of treatment received and their clinical course during the first year. MATERIALS AND METHODS: Prospective, multicenter and population-based incidence cohort study. Patients aged >18 years diagnosed during 2017 with IBD (Crohn's disease [CD], ulcerative colitis [UC] and indeterminate colitis [IC]) were included from 8 hospitals in Castilla y León. Epidemiological, clinical, and therapeutic variables were registered. The global incidence and disease incidence were calculated. RESULTS: 290 patients were diagnosed with IBD (54.5% UC, 45.2% CD, and 0.3% IC), with a median follow-up of 9 months (range 8-11). The incidence rate of IBD in Castilla y Leon in 2017 was 16.6 cases per 10,000 inhabitants-year (9/105 UC cases and 7.5/105 CD cases), with a UC/CD ratio of 1.2:1. Use of systemic corticosteroids (47% vs 30%; P=.002), immunomodulatory therapy (81% vs 19%; P=.000), biological therapy (29% vs 8%; P=.000), and surgery (11% vs 2%; p=.000) were significatively higher among patients with CD comparing with those with UC. CONCLUSIONS: The incidence of patients with UC in our population increases while the incidence of patients with CD remains stable. Patients with CD present a worse natural history of the disease (use of corticosteroids, immunomodulatory therapy, biological therapy and surgery) compared to patients with UC in the first year of follow-up.

Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2 / Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection

Objetivo: Evaluar el resultado del cribado de hepatitis B y C en pacientes ingresados con COVID-19.Pacientes y métodos: Estudio transversal, prospectivo, realizado en dos hospitales españoles de tercer nivel. Se estudiaron marcadores de hepatitis B (HBsAg, anti-HBc) y C (anti-VHC, ARN VHC) a todos los pacientes hospitalizados con COVID-19 del 1 de marzo al 31 de diciembre de 2020.Resultados: En este periodo ingresaron 4662 pacientes con COVID-19: 56,3% fueron varones, la edad mediana fue 76 (0-104) años. Se realizó serología de hepatitis B a 2915 (62,5%) pacientes; 253 (8,75%) presentaban anti-HBc+y 11 (0,38%) HBsAg+. De los 11 pacientes, 4 desconocían el diagnóstico, 7 recibieron esteroides y uno recibió profilaxis. Hubo un caso de reactivación del VHB. Se determinaron anticuerpos anti-VHC a 2895 (62%) pacientes; 24 (0,83%) fueron positivos. De ellos, 13 pacientes estaban diagnosticados: 10 habían recibido tratamiento, uno se había curado espontáneamente y dos no habían sido tratados. De los 11 restantes, 10 tenían ARN VHC indetectable. En total, solo 3 (0,10%) pacientes tenían carga viral detectable. Sin embargo, ninguno recibió tratamiento (2> 90 años con comorbilidades, uno falleció por COVID-19).Conclusiones: El cribado de hepatitis C en pacientes ingresados por COVID-19 en nuestro medio ha mostrado menor utilidad de la esperada. La baja prevalencia de infección activa tras los tratamientos antivirales y la alta edad mediana de nuestra población limitan la detección de potenciales candidatos a tratamiento. El cribado de hepatitis B debería dirigirse a prevenir la reactivación en pacientes que precisen tratamientos inmunosupresores.(AU)

Aims: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients.Method: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection.Results: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0–104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19).Conclusion: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.(AU)

Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection. / Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2.

AIMS: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients. METHOD: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection. RESULTS: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0-104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19). CONCLUSION: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.

Influencia de la puntuación MELD basal en la eficacia del tratamiento de la hepatitis C con sofosbuvir y simeprevir / Influence of baseline MELD score in the efficacy of treatment of hepatitis C with simeprevir and sofosbuvir

INTRODUCCIÓN: Hay pocos estudios publicados acerca de los factores predictivos de respuesta al tratamiento de la hepatitis C con sofosbuvir y simeprevir. OBJETIVO: Conocer qué factores influyen en la respuesta a simeprevir (SIM) y sofosbuvir (SOF) en pacientes infectados por los genotipos 1 o 4 de la hepatitis C. PACIENTES Y MÉTODOS: Estudio prospectivo observacional de cohortes en 12 hospitales. La efectividad se evaluó con respuesta virológica sostenida (RVS12). RESULTADOS: Se incluyeron 204 pacientes (62,3% varones, edad media 55 años). Ciento ochenta y seis (91,2%) genotipo 1 (60,3% 1b, 25% 1a) y 18 (8,8%) genotipo 4. Ciento treinta y dos (64,7%) cirróticos (87,9% Child A), 33 (16,2%) F3, 31 (15,2%) F2, 8 (3,9%) F0-1. Un 80,8% MELD < 10. Noventa y tres (45,6%) naive. Se asoció ribavirina en 68 (33,3%). Carga viral basal media 2.151.549 UI/ML (DE: 2.391.840). Duración tratamiento 12 semanas en 93,1%. Cuatro suspendieron tratamiento: suicidio, brote psicótico, hiperbilirrubinemia y recurrencia hepatocarcinoma. Ciento noventa (93,1%) alcanzaron RVS12. No hubo diferencias RVS12 en función del genotipo, duración tratamiento, empleo de ribavirina, tratamiento previo, CV y plaquetas basales. En análisis univariante, negatividad carga viral a las 4 semanas (p = 0,042), ausencia de cirrosis (p = 0,021), albúmina basal ≥ 4g/dl (p:0,001) y MELD<10 (p < 0,0001) se asociaron con mayor RVS12. En estudio multivariante solo hubo relación significativa entre puntuación MELD basal < 10 y mayor RVS12 (p < 0,001). CONCLUSIONES: La combinación de simeprevir y sofosbuvir es muy eficaz en pacientes infectados por los genotipos 1 y 4 de la hepatitis C. Es un tratamiento seguro, especialmente en pacientes sin ribavirina. Esta combinación es más efectiva en pacientes con puntuación MELD inferior a 10

INTRODUCTION: There are few published studies on predictors of response to treatment with sofosbuvir and simeprevir in HCV patients. OBJECTIVE: The objective of the study was to analyse possible predictors of response to simeprevir (SMV) and sofosbuvir (SOF) in patients infected with hepatitis C genotypes 1 or 4. PATIENTS AND METHODS: Prospective observational cohort study in 12 hospitals. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). RESULTS: 204 patients (62.3% male, mean age 55 years) were included: 186 (91.2%) genotype 1 (60.3% 1b 25% 1a) and 18 (8.8%) genotype 4. 132 (64.7%) cirrhotic (87.9% Child A), 33 (16.2%) F3, 31 (15.2%) F2, 8 (3.9%) F0-1. 80.8% MELD<10. 93 (45.6%) naive. Ribavirin was added in 68 (33.3%). Mean baseline viral load 2,151,549 IU/ml (SD: 2,391,840). Treatment duration 12 weeks in 93.1%. 4 discontinued therapy: suicide, psychotic attack, hyperbilirubinaemia and liver cancer recurrence. 190 (93.1%) achieved SVR12. There were no differences in SVR12 depending on the genotype, treatment duration, ribavirin use, prior therapy, viral load (VL) or baseline platelets. In univariate analysis, undetectable VL at 4 weeks (p = 0.042), absence of cirrhosis (p = 0.021), baseline albumin ≥ 4g/dl (p = 0.001) and MELD < 10 (p < 0.0001) were associated with higher SVR12. In multivariate analysis, only baseline MELD score < 10 patients had higher SVR12 (p < 0.001). CONCLUSIONS: The combination of simeprevir and sofosbuvir in patients infected with genotype 1 and 4 hepatitis C is highly effective. It is a safe therapy, especially in patients without ribavirin. This combination was more effective in patients with a MELD score below 10

Influence of baseline MELD score in the efficacy of treatment of hepatitis C with simeprevir and sofosbuvir. / Influencia de la puntuación MELD basal en la eficacia del tratamiento de la hepatitis C con sofosbuvir y simeprevir.

INTRODUCTION: There are few published studies on predictors of response to treatment with sofosbuvir and simeprevir in HCV patients. OBJECTIVE: The objective of the study was to analyse possible predictors of response to simeprevir (SMV) and sofosbuvir (SOF) in patients infected with hepatitis C genotypes 1 or 4. PATIENTS AND METHODS: Prospective observational cohort study in 12 hospitals. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). RESULTS: 204 patients (62.3% male, mean age 55 years) were included: 186 (91.2%) genotype 1 (60.3% 1b 25% 1a) and 18 (8.8%) genotype 4. 132 (64.7%) cirrhotic (87.9% Child A), 33 (16.2%) F3, 31 (15.2%) F2, 8 (3.9%) F0-1. 80.8% MELD<10. 93 (45.6%) naive. Ribavirin was added in 68 (33.3%). Mean baseline viral load 2,151,549 IU/ml (SD: 2,391,840). Treatment duration 12 weeks in 93.1%. 4 discontinued therapy: suicide, psychotic attack, hyperbilirubinaemia and liver cancer recurrence. 190 (93.1%) achieved SVR12. There were no differences in SVR12 depending on the genotype, treatment duration, ribavirin use, prior therapy, viral load (VL) or baseline platelets. In univariate analysis, undetectable VL at 4 weeks (p=0.042), absence of cirrhosis (p=0.021), baseline albumin ≥ 4g/dl (p=0.001) and MELD<10 (p<0.0001) were associated with higher SVR12. In multivariate analysis, only baseline MELD score <10 patients had higher SVR12 (p<0.001). CONCLUSIONS: The combination of simeprevir and sofosbuvir in patients infected with genotype 1 and 4 hepatitis C is highly effective. It is a safe therapy, especially in patients without ribavirin. This combination was more effective in patients with a MELD score below 10.