Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Differences between pediatric and adult celiac disease.

INTRODUCTION: Celiac disease (CD) is a common autoimmune condition (involves 1-2% of the general population) that develops at any age in life but manifests differently in children and adults. OBJECTIVES: To analyze clinical differences in disease expression between both groups, as well as findings at the time of diagnosis. METHODS: A retrospective study of a series of patients diagnosed with CD during childhood (< 14 years) versus a series of adult patients (> 14 years). RESULTS: a total of 187 patients were included, of which 43 were children and 144 were adults. Among clinical manifestations in children classic presentation forms predominated -34 patients(79%) versus 20 adult patients (14%) (p < 0.001) (OR = 23.4;95% CI: 9.8-56.1). In contrast, atypical forms were predominant in the latter, and anemia was the most common finding in 61 patients (42%) versus 8 pediatric patients (19%) (p < 0.01). Adults had a greater diagnostic delay with a mean 10 ± 9 years versus 1 ± 2 years in children (p < 0.001). In adults, we found a higher frequency of associated autoimmune diseases (24.3 versus 9.3% in children) (p < 0.05). Regarding serum markers, TGt-2 was more commonly positive among children (88%) as compared to adults (31%) (p < 0.001); (OR = 21.4: 95% CI: 7.2-63.6). We found similar results with regard to the presence of villous atrophy, which was more common in children (95%) than in adults (33%) (p < 0.001) (OR = 41.0;95% CI: 9.5-76.7). As regards genetic markers, DQ2 was somewhat more common in children (97.7%) than in adults (90.3%) whereas DQ8 wasless common in children (2.3%) than in adults (9.7%), with no significant differences between groups. Patients negative for both markers were not included. CONCLUSIONS: Pediatric CD has clear differences when compared to adult CD, with classic forms predominating in the former, who also display a higher occurrence of positive serology and villous atrophy, and less diagnostic delay. In contrast, atypical forms predominate in the adult, with a lower occurrence of positive serology and milder histological forms. In these patients associated autoimmune conditions are more common and diagnostic delay is longer.

[Characteristics of patients with familial adenomatous polyposis in Spain. First results of the Spanish Registry of Familial Adenomatous Polyposis]. / Características de los pacientes con poliposis adenomatosa familiar en España. Resultados iniciales del Registro Español de Poliposis Adenomatosa Familiar.

BACKGROUND AND OBJECTIVES: Familial adenomatous polyposis is an inherited disorder characterized by the presence of multiple colorectal adenomas (more than 100 in the classic form and between 10 and 100 in the attenuated one), with a high risk of colorectal cancer development. To improve the diagnostic and therapeutic management of these patients, the Spanish Registry of Familial Adenomatous Polyposis was created in 2007.We aimed to evaluate the clinicopathological characteristics of patients with familial adenomatous polyposis in Spain. PATIENTS AND METHODS: All patients included in the Registry during one year were evaluated with respect to their demographic, clinical, pathological, and genetic characteristics. RESULTS: 243 patients of 156 unrelated families from 15 Spanish centers were included. One hundred thirty patients were male, and the mean age at diagnosis was 40 years. According to the clinical presentation, 127 corresponded to the classic form and 116 to the attenuated one. Colorectal adenoma with high-grade dysplasia was identified in 67 (28%) patients, and colorectal cancer in 42 (17%). Extracolonic manifestations were: duodenal involvement (n=46), gastric involvement (n=44), desmoid tumors (n=24), thyroid cancer (n=8), osteomas (n=6) and brain tumor (n=1). APC and/or MYH gene testing was performed in 140 (90%) families, detecting the causative mutation in 75 (54%) of them (70 in the APC gene and 5 in the MYH gene). CONCLUSIONS: During its first year of operability, a large number of patients and families were included in the Registry. The reduced prevalence of colorectal cancer as well as the large proportion of families submitted to gene testing demonstrated a high-quality clinical practice in Spain.

Diferencias entre la enfermedad celiaca infantil y del adulto / Diferences between pediatric and adult celiac disease

Introducción: la enfermedad celiaca (EC) es un proceso frecuente (afecta al 1-2% en población general), de naturaleza autoimmune, que aparece a cualquier edad de la vida, pero que se presenta de forma diferente en el niño que en el adulto. Objetivos: analizar las diferencias clínicas en las formas de expresión de la enfermedad entre ambos grupos, así como los hallazgos al momento del diagnóstico. Métodos: estudio retrospectivo de una serie de pacientes diagnosticados, en la infancia (< 14 años), frente a una serie de adultos (> 14 años). Resultados: se incluyeron un total de 187 pacientes, de los cuales 43 eran niños y 144 adultos. En las manifestaciones clínicas de los niños, predominaron las formas de presentación clá - sicas, 34 casos (79%) frente a los adultos 20 casos (14%) (p < 0,001) (OR = 23,4; IC-95%: 9,8-56,1). Por el contrario, en estos predominaron las formas atípicas, siendo la anemia el hallazgo más frecuente en 61 casos (42%) frente a 8 casos (19%) en los niños (p < 0,01). En los adultos existía un mayor retraso diagnóstico con una media de 10 ± 9 años, frente a los niños, que es de 1 ± 2 años (p < 0,001). Encontramos en los adultos una mayor frecuencia de enfermedades autoinmunes asociadas (24,3%), frente al 9,3% en niños (p < 0,05). Respecto a los marcadores serológicos, la TGt-2 fue más frecuentemente positiva en los niños (88%), que en los adultos (31%) (p < 0,001); (OR = 21,4: IC-95%: 7,2-63,6). Resultados similares encontramos en relación con la presencia de atrofia vellositaria, que estuvo presente más frecuentemente en los niños (95%) que en los adultos (33%) (p < 0,001) (OR = 41,0; IC-95%: 9,5-76,7). Respecto a los marcadores genéticos, el DQ2 fue algo más frecuente en niños (97,7%) que en adultos 90,3%, y el DQ8 ocurrió al contrario, siendo menos frecuente en niños (2,3%) que en adultos (9,7%), no encontrando diferencias entre ambos grupos. No se incluyeron pacientes negativos para ambos marcadores(AU)

Introduction: celiac disease (CD) is a common autoimmune condition (involves 1-2% of the general population) that develops at any age in life but manifests differently in children and adults. Objectives: to analyze clinical differences in disease expression between both groups, as well as findings at the time of diagnosis. Methods: a retrospective study of a series of patients diagnosed with CD during childhood (< 14 years) versus a series of adult patients (> 14 years). Results: a total of 187 patients were included, of which 43 were children and 144 were adults. Among clinical manifestations in children classic presentation forms predominated –34 patients (79%) versus 20 adult patients (14%) (p < 0.001) (OR = 23.4; 95% CI: 9.8-56.1). In contrast, atypical forms were predominant in the latter, and anemia was the most common finding in 61 patients (42%) versus 8 pediatric patients (19%) (p < 0.01). Adults had a greater diagnostic delay with a mean 10 ± 9 years versus 1 ± 2 years in children (p < 0.001). In adults, we found a higher frequency of associated autoimmune diseases (24.3 versus 9.3% in children) (p < 0.05). Regarding serum markers, TGt-2 was more commonly positive among children (88%) as compared to adults (31%) (p < 0.001); (OR = 21.4: 95% CI: 7.2-63.6). We found similar results with regard to the presence of villous atrophy, which was more common in children (95%) than in adults (33%) (p < 0.001) (OR = 41.0; 95% CI: 9.5-76.7). As regards genetic markers, DQ2 was somewhat more common in children (97.7%) than in adults (90.3%) whereas DQ8 was less common in children (2.3%) than in adults (9.7%), with no significant differences between groups. Patients negative for both markers were not included(AU)

Anemia ferropénica refractaria e intolerancia al gluten: respuesta a la dieta sin gluten / Refractory iron-deficiency anemia and gluten intolerance - Response to gluten-free diet

Introducción: la anemia ferropénica refractaria presenta un origen multifactorial, relacionado con diversas enfermedades digestivas, siendo las más frecuentes la enfermedad celiaca con malabsorción y la EII junto con la intolerancia al gluten aislada. Objetivos: determinar la prevalencia de marcadores serológicos, genéticos e histológicos de intolerancia al gluten y analizar la respuesta a la retirada del gluten de la dieta en estos pacientes. Métodos: se incluyeron de forma prospectiva y consecutiva una serie de pacientes con anemia refractaria. Se les aplicó un protocolo consistente en determinación marcadores serológicos (TGt-2), genéticos (HLA-DQ2/DQ8) e histológicos de enfermedad celíaca. Todos siguieron una dieta sin gluten durante una mediana de 3,6 años. Se interpretó como respuesta positiva la desaparición mantenida de la anemia durante el seguimiento. Resultados: se estudiaron 98 pacientes (84% mujeres) con una edad media de 54 años. Los ac. anti-TGt2 fueron positivos en el 5% de los casos. Un total de 67 casos (68%) presentaban el haplotipo HLA-DQ2 o DQ8 (+). Encontramos atrofia vellositaria (Marsh III) en el 13% de los casos y patrón inflamatorio (Marsh I o II) en el 13%. Los 72 casos restantes (74%) no presentaban alteraciones histológicas duodenales. Se compararon la edad, el tiempo de evolución de la anemia, número de transfusiones, número de dosis de hierro parenteral y tiempo en dieta sin gluten, en función de la presencia o no de atrofia vellositaria y de la positividad para el HLA-DQ2/8, sin encontrar diferencias significativas en ninguna de las variables analizadas. La respuesta fue positiva en el 92% de los casos. Conclusiones: la enfermedad celiaca con atrofia vellositaria es causa poco frecuente de anemia refractaria. Las formas de intolerancia al gluten sin lesión histológica asociada, representan cerca del 75% de los casos y desempeñan, por lo tanto, un papel importante en su aparición(AU)

Introduction: refractory iron-deficiency anemia has a multifactorial origin related to various gastrointestinal conditions, with celiac disease plus malabsorption and IBD together with isolated gluten intolerance being most common. Objectives: to determine the prevalence of serum, genetic, and histological markers for gluten intolerance, and to analyze the response to gluten withdrawal from the diet in these patients. Methods: a number of patients with refractory anemia were prospectively and consecutively enrolled. A protocol to measure serum (TGt-2), genetic (HLA-DQ2/DQ8), and histological markers for celiac disease was applied. All followed a gluten-free diet for a median 3.6 years. Sustained remission of anemia during follow-up was interpreted as positive response. Results: ninety-eight patients (84% females) with a mean age of 54 years were studied. Anti-TGt2 antibodies were positive in 5% of cases. A total of 67 cases (68%) were haplotype HLA-DQ2 or -DQ8 (+). We found villous atrophy (Marsh III) in 13% of patients, and an inflammatory pattern (Marsh I or II) in 13%. All remaining 72 patients (74%) had no histological duodenal changes. Age, anemia duration, number of transfusions, number of parenteral iron doses, and time on a gluten-free diet were all compared according to the presence or absence of villous atrophy and HLADQ2/ 8 positivity, and no significant differences were found for any of the analyzed variables. Response was positive in 92% of subjects. Conclusions: celiac disease with villous atrophy is rarely a cause of refractory anemia. Gluten intolerance with no histological lesions is seen in almost 75% of patients, and therefore plays a relevant role in its development(AU)

Características de los pacientes con poliposis adenomatosa familiar en España. Resultados iniciales del Registro Español de Poliposis Adenomatosa Familiar / Characteristics of patients with familial adenomatous polyposis in Spain. First results of the Spanish Registry of Familial Adenomatous Polyposis

Fundamento y objetivos: La poliposis adenomatosa familiar es una enfermedad hereditaria caracterizada por la presencia de múltiples adenomas en el colon y el recto (más de 100 en la forma clásica, y entre 10–100 en la forma atenuada), con un riesgo de cáncer colorrectal cercano al 100% si no se diagnostica y se trata de forma precoz. Con el objetivo de mejorar el diagnóstico y el tratamiento de estos pacientes en nuestro medio, en el año 2007 se creó el Registro Español de Poliposis Adenomatosa Familiar.Evaluar las características clinicopatológicas de los pacientes con poliposis adenomatosa familiar en España. Pacientes y métodos:Se evaluaron los pacientes incluidos en el registro durante el primer año de operatividad de este, en relación con las características demográficas, clínicas y genéticas.Resultados: En el período de estudio se incluyeron 243 pacientes pertenecientes a 156 familias no relacionadas procedentes de 15 centros. De estos, 130 eran hombres y la edad media al diagnóstico fue de 40 años. De acuerdo con la forma de presentación, 127 correspondían a la forma clásica y 116 correspondían a la forma atenuada. Se identificó la presencia de algún adenoma colorrectal con displasia de alto grado en 67 pacientes (28%), y de cáncer colorrectal en 42 pacientes (17%). Las manifestaciones extracolónicas fueron afectación duodenal (n=46), afectación gástrica (n=44), tumor desmoides (n=24), cáncer de tiroides (n=8), osteomas (n=6) y tumor cerebral (n=1). Se indicó la realización de análisis mutacional en los genes APC o MYH en 140 familias (90%): se completó en 85 de ellas, y se identificó la mutación causal en 75 familias (88%) (70 en el gen APC y 5 en el gen MYH) (AU)

Background and objectives: Familial adenomatous polyposis is an inherited disorder characterized by the presence of multiple colorectal adenomas (more than 100 in the classic form and between 10 and 100 in the attenuated one), with a high risk of colorectal cancer development. To improve the diagnostic and therapeutic management of these patients, the Spanish Registry of Familial Adenomatous Polyposis was created in 2007.We aimed to evaluate the clinicopathological characteristics of patients with familial adenomatous polyposis in Spain. Patients and methods: All patients included in the Registry during one year were evaluated with respect to their demographic, clinical, pathological, and genetic characteristics.Results: 243 patients of 156 unrelated families from 15 Spanish centers were included. One hundred thirty patients were male, and the mean age at diagnosis was 40 years. According to the clinical presentation, 127 corresponded to the classic form and 116 to the attenuated one. Colorectal adenoma with high-grade dysplasia was identified in 67 (28%) patients, and colorectal cancer in 42 (17%). Extracolonic manifestations were: duodenal involvement (n=46), gastric involvement (n=44), desmoid tumors (n=24), thyroid cancer (n=8), osteomas (n=6) and brain tumor (n=1). APC and/or MYH gene testing was performed in 140 (90%) families, detecting the causative mutation in 75 (54%) of them (70 in the APC gene and 5 in the MYH gene).Conclusions: During its first year of operability, a large number of patients and families were included in the Registry. The reduced prevalence of colorectal cancer as well as the large proportion of families submitted to gene testing demonstrated a high-quality clinical practice in Spain (AU)