Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs.

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.

Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life. / Prevalencia de déficit de hierro sin anemia en la enfermedad inflamatoria intestinal y su impacto en la calidad de vida.

INTRODUCTION: Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL. MATERIAL AND METHODS: 127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of <100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points. RESULTS: The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p<.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed. CONCLUSION: The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication.

Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission. / Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica.

BACKGROUND AND AIM: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade®); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. MATERIAL AND METHOD: Observational study with IBD patients treated with Remicade® for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. RESULTS: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. CONCLUSION: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade®.

Prevalencia de déficit de hierro sin anemia en la enfermedad inflamatoria intestinal y su impacto en la calidad de vida / Prevalence of iron deficiency without anaemia in inflammatory bowel disease and impact on health-related quality of life

Introducción: El déficit de hierro sin anemia asociada (DHSA) es un hallazgo frecuente en los pacientes no ingresados con enfermedad inflamatoria intestinal (EII), incluso en mayor proporción que la anemia. Sin embargo, no existen datos concluyentes de su presencia en nuestro medio ni del posible deterioro que conlleva en la calidad de vida relacionada con la salud (CVRS). Los objetivos de este trabajo fueron: establecer la prevalencia del DHSA, identificar posibles factores asociados y medir su impacto en la CVRS. Material y métodos: Se incluyeron 127 pacientes con EII, de manera consecutiva, en medio extrahospitalario en un estudio observacional, descriptivo, de corte transversal. Se definió DHSA como niveles de ferritina ≤30 ng/ml en ausencia de actividad inflamatoria o <100 ng/ml en su presencia, con índice de saturación de transferrina ≤16%, junto a niveles normales de hemoglobina. Se evaluó la CVRS mediante dos cuestionarios: CVEII-9 para los síntomas relacionados con EII, y FACIT-F para medir la presencia de fatiga, considerándola extrema ante una puntuación ≤ 30 puntos. Resultados: La prevalencia del DHSA fue del 37%. El sexo femenino (OR=2,9; p=0,015) y la presencia de actividad inflamatoria (OR=9,4; p=0,001) fueron las variables asociadas con su aparición. Los pacientes con DHSA presentaron cuestionarios de CVRS con menores puntuaciones de forma global; registrando una caída de 6,6 (p<0,001) y 4,3 (p=0,037) puntos en CVEII-9 y FACIT-F, respectivamente. Además, se observó un incremento en la presencia de fatiga extrema del 29,4%. Conclusión: La prevalencia de DHSA es considerable en los pacientes con EII en el ámbito extrahospitalario. Se asocia al sexo femenino y a la actividad inflamatoria, y supone un claro impacto negativo en la CVRS. Es necesaria una actitud más activa para el tratamiento de esta complicación (AU)

Introduction: Iron deficiency without anaemia (IDWA) is commonly found in outpatients with inflammatory bowel disease (IBD) in an even higher proportion than anaemia. However, its true prevalence and possible impact on health-related quality of life (HRQoL) are unknown. The objectives of this study were: to establish the prevalence of IDWA, identify possible associated factors and measure their impact on HRQoL. Material and methods: 127 patients with IBD in an outpatient setting were consecutively included in an observational, descriptive, cross-sectional study. IDWA was defined as ferritin levels of <100 ng/ml with inflammatory activity or ≤30 ng/ml without it, with transferrin saturation of ≤16%, and with normal haemoglobin levels. HRQoL was assessed using two questionnaires: the IBDQ-9 for symptoms related to IBD and the FACIT-F to measure the presence of fatigue. Fatigue was considered extreme with a score of ≤30 points. Results: The prevalence of IDWA was 37%. Variables associated with its occurrence were female gender (OR=2.9; p=.015) and the presence of inflammatory activity (OR=9.4; p=.001). Patients with IDWA presented HRQoL questionnaires with lower overall scores; decreases of 6.6 (p<.001) and 4.3 (p=.037) points in the IBDQ-9 and the FACIT-F were recorded, respectively. In addition, an increase of 29.4% in the presence of extreme fatigue was observed. Conclusion: The prevalence of IDWA is considerable in outpatients with IBD. IDWA is associated with female gender and inflammatory activity. It has a clear negative impact on HRQoL. A more active approach is needed to treat this complication (AU)

Evolución tras el intercambio a infliximab biosimilar en pacientes con enfermedad inflamatoria intestinal en remisión clínica / Evolution after switching to biosimilar infliximab in inflammatory bowel disease patients in clinical remission

Introducción y objetivo: Infliximab biosimilar (CT-P13) ha sido aprobado para las mismas indicaciones que infliximab original (Remicade(R)); sin embargo, hay pocos datos clínicos sobre el intercambio en la enfermedad inflamatoria intestinal (EII). El objetivo del estudio fue evaluar la eficacia, la seguridad, el perfil de biodisponibilidad y los factores asociados a la recidiva tras el intercambio a infliximab biosimilar en pacientes con EII en remisión clínica. Material y métodos: Estudio observacional con pacientes con EII tratados con Remicade(R) durante al menos 6 meses y en remisión clínica durante al menos 3 meses, a los que se realizó el intercambio a infliximab biosimilar. Se evaluó la incidencia de recidiva, los efectos adversos y los cambios en la biodisponibilidad del fármaco (niveles y anticuerpos). Resultados: Se incluyeron 36 pacientes (63,9% EC), con una media de seguimiento de 8,4 meses (±3,5). El 13,9% presentaron recidiva clínica. El mayor tiempo de remisión clínica previo al intercambio (HR=0,54; IC 95%=0,29-0,98; p=0,04) y niveles de infliximab detectables en el momento del intercambio (HR=0,03; IC 95%=0,001-0,89; p=0,04) se asociaron a menor riesgo de recidiva. No hubo diferencias entre niveles de infliximab en el momento del intercambio y en las semanas 8 y 16 (p=0,94). El 8,3% presentaron algún efecto adverso, requiriendo suspensión del fármaco en un paciente por neumonía grave. Conclusión: El intercambio a infliximab biosimilar en una cohorte de vida real de pacientes con EII en remisión clínica no parece tener un impacto significativo en los resultados clínicos a corto plazo. Los factores asociados con la recidiva fueron similares a los esperados en pacientes que continúan con Remicade(R) (AU)

Background and aim: The biosimilar of infliximab (CT-P13) has been approved for the same indications held by the infliximab reference product (Remicade(R)); however, there are few clinical data on switching in inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy, safety, bioavailability profile and factors associated with relapse after switching to biosimilar infliximab in IBD patients in clinical remission. Material and method: Observational study with IBD patients treated with Remicade(R) for at least 6 months and in clinical remission for at least 3 months who switched to infliximab biosimilar. The incidence of relapse, adverse effects and possible changes in drug bioavailability (trough level and antidrug antibodies) were evaluated. Results: Thirty six patients were included (63.9% CD) with a mean follow-up of 8.4 months (SD±3.5). The 13.9% had clinical relapse. The longer clinical remission time before switching (HR=0.54, 95% CI=0.29-0.98, P=.04) and detectable infliximab levels at the time of switching (HR=0.03, 95% CI=0.001-0.89, P=.04) were associated with a lower risk of relapse. No differences were found between infliximab levels at the time of switching and at weeks 8 and 16 (P=.94); 8.3% of the patients had some adverse event, requiring the suspension of biosimilar in one patient for severe pneumonia. Conclusion: Switching to biosimilar infliximab in a real-life cohort of IBD patients in clinical remission did not have a significant impact on short-term clinical outcomes. The factors associated with relapse were similar to those expected in patients continuing with Remicade(R) (AU)