OBJECTIVE: the recommendations of the Spanish Ministry of Health on vaccination in risk groups include mesalazine among the treatments with a possible negative effect on its effectiveness. However, this is not the recommendation of most experts. Our objective was to evaluate the effect of mesalazine on the humoral response to the SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). METHODS: VACOVEII is a Spanish, prospective, multicenter study promoted by GETECCU, which evaluates the effectiveness of the SARS-CoV-2 vaccine in patients with IBD. This study includes IBD patients who have recieved the full vaccination schedule and without previous COVID-19 infection. Seroconversion was set at 260 BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectivenes of the vaccine between patients treated with mesalazine and patients without treatment. RESULTS: A total of 124 patients without immunosuppressive therapy were included, of which 32 did not receive any treatment and 92 received only mesalazine. Six months after full vaccination, no significant differences are observed in the mean concentrations of IgG anti-S between both groups. In the multivariate analysis, antibody titers were independently associated with the use of mRNA vaccines and with SARS-CoV-2 infection. CONCLUSION: Mesalazine does not have a negative effect on the response to SARS-CoV-2 vaccines in IBD patients.
BACKGROUND: The response to SARS-CoV-2 vaccination decreases in inflammatory bowel disease (IBD) patients, specially under anti-TNF treatment. However, data on medium-term effectiveness are limited, specially using new recommended seroconversion rate (>260BAU/mL). Our aim was to evaluate the 6-month>260 BAU-seroconversion rate after full vaccination and after booster-dose. METHODS: VACOVEII is a Spanish multicenter, prospective study promoted by GETECCU. IBD patients full vaccinated against SARS-CoV-2 and without previous COVID-19 infection, treated or not with immunosuppressants, were included. The booster dose was administered 6 months after the full vaccination. Seroconversion was set at 260BAU/mL, according to most recent recommendations and was assessed 6 months after the full vaccination and 6 months after booster-dose. RESULTS: Between October 2021 and March 2022, 313 patients were included (124 no treatment or mesalazine; 55 immunomodulators; 87 anti-TNF; 19 anti-integrin; and 28 ustekinumab). Most patients received mRNA-vaccines (86%). Six months after full vaccination, overall seroconversion rate was 44.1%, being significantly lower among patients on anti-TNF (19.5%, p<0.001) and ustekinumab (35.7%, p=0.031). The seroconversion rate after booster was 92%. Again, anti-TNF patients had a significantly lower seroconversion rate (67%, p<0.001). mRNA-vaccine improved seroconversion rate (OR 11.720 [95% CI 2.26-60.512]). CONCLUSION: The full vaccination regimen achieves suboptimal response in IBD patients, specially among those anti-TNF or ustekinumab. The booster dose improves seroconversion rate in all patients, although it remains limited in those treated with anti-TNF. These results reinforce the need to prioritize future booster doses in patients on immunosuppressants therapy, specially under anti-TNF, and using mRNA-vaccines.
INTRODUCCIÓN: CT-P13 es un fármaco biosimilar de infliximab (IFX), efectivo en pacientes con enfermedad inflamatoria intestinal (EII). La medición de niveles de IFX y anticuerpos anti-IFX forma parte del tratamiento integral de dicha enfermedad. OBJETIVO: Comparar la respuesta clínica en función de un abordaje estrictamente clínico (CLN) o proactivo (PRO) basado en la medición de niveles en la semana 14, en la práctica clínica. MÉTODOS: Estudio prospectivo en pacientes que inician CT-P13 por EII. En el grupo PRO se midieron sistemáticamente los niveles de IFX y de anticuerpos postinducción (semana 14) y se intensificaron aquellos con niveles infraterapéuticos (<3μg/ml), independientemente de la respuesta clínica. RESULTADOS: Se incluyeron 77 pacientes (23 colitis ulcerosa y 54 enfermedad de Crohn). Ambos grupos, PRO (n=41) y CLN (n=36) presentaron una eficacia inicial y a largo plazo sin diferencias significativas. En la semana 14 hubo un 61% de remisión clínica (RC) (58,5% PRO, 63,9% CLN) y un 80,5% de al menos respuesta parcial (RP) (80,5% PRO, 80,6% CLN). En la semana 54 hubo un 68,8% de RC (61% PRO, 77,8% CLN) y un 76,6% de al menos RP (73,2% PRO, 80,6% CLN). De los pacientes en RC en la semana 14 (24 PRO, 23 CLN), 13 del grupo PRO fueron intensificados por niveles infraterapéuticos. En este subgrupo no se observaron diferencias significativas en la pérdida de respuesta secundaria (PRO 0%, CLN 8,7%). CONCLUSIÓN: Un manejo proactivo no mejoró las tasas de respuesta ni la remisión en el primer año. La intensificación de pacientes en RC y niveles infraterapéuticos postinducción no parece prevenir de forma significativa la pérdida de respuesta secundaria en el primer año
INTRODUCTION: CT-P13 is a biosimilar drug of infliximab (IFX), effective in patients with inflammatory bowel disease (IBD). The monitoring of levels of IFX and anti-IFX antibodies is now considered part of the integral management. OBJECTIVE: To compare the clinical response according to a strictly clinical (CLN) or proactive (PRO) approach based on the monitoring of levels in week 14, in clinical practice. METHODS: We conducted a prospective study in IBD patients starting CT-P13. In the PRO group, levels of IFX and post-induction antibodies were systematically measured (week 14) and those with infraterapeutic levels (<3μg/ml) were intensified, irrespective of the clinical response. RESULTS: We included 77 patients (23 ulcerative colitis and 54 Crohn's disease). Both PRO (n=41) and CLN (n=36) groups showed initial and long-term efficacy without significant differences. At week 14, 61% clinical remission (CR) (58.5% PRO, 63.9% CLN) and 80.5% at least partial response (PR) (80.5% PRO, 80.6% CLN). In week 54, 68.8% CR (61% PRO, 77.8% CLN) and 76.6% at least PR (73.2% PRO, 80.6% CLN). Of the patients in CR in week 14 (24 PRO, 23 CLN), 13 of the PRO group were intensified due to infra-therapeutic levels. In this subgroup no significant differences were observed in secondary loss of response (PRO 0%, CLN 8.7%). CONCLUSION: Proactive management does not improve response or remission rates in the first year. The intensification of clinical remission patients with post-induction infratherapeutic levels does not seem to significantly prevent secondary loss of response in the first year
Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Biosimilar Pharmaceuticals/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Cohort Studies , Infliximab/administration & dosage , Infliximab/pharmacology , Prospective Studies , Biological Therapy , Statistics, Nonparametric , Immunologic Factors , Anti-Inflammatory Agents
INTRODUCCIÓN: Ustekinumab, anticuerpo monoclonal que bloquea las interleucinas 12/23, ha demostrado en ensayos clínicos su eficacia para inducir y mantener la remisión clínica en la enfermedad de Crohn (EC). Su efectividad y su seguridad en la práctica clínica real es menos conocida y podría diferir respecto a los ensayos. OBJETIVO: Evaluar en la práctica clínica su efectividad y seguridad (pauta de inducción intravenosa esencialmente), como inducción y a largo plazo, en pacientes con EC refractarios a tratamiento biológico. MATERIAL Y MÉTODOS: Análisis retrospectivo multicéntrico (6 hospitales aragoneses), que incluye a todos los pacientes (N=69) con EC en tratamiento con ustekinumab (fuese con inducción intravenosa o subcutánea) que hubiesen alcanzado al menos 16 semanas de seguimiento. La respuesta o remisión clínica se ha evaluado en las semanas 16, 24, 32 y 48 mediante el índice de Harvey-Bradshaw. RESULTADOS: Se han incluido un total de 69 pacientes, edad media 42 años, 54% hombres. Un 89,86% (IC 95% [0,805, 0,949]) de los pacientes ha presentado mejoría clínica en la semana 16 (15,95% remisión, 73,92% respuesta). En el seguimiento posterior dicha respuesta se ha mantenido. Se han identificado mediante un modelo de regresión ordinal la edad (OR 0,95, p = 0.028) y el hábito tabáquico (OR 0,19, p = 0,027) como predictores de mala respuesta al tratamiento, mientras que la necesidad de cambio de biológico por efecto adverso (OR 96, p = 0,00017) y por pérdida de respuesta secundaria (OR 7,07, p = 0,034) han sido factores predictores de buena respuesta. No se han reportado efectos adversos graves que obligasen a interrumpir el tratamiento con ustekinumab. CONCLUSIÓN: Ustekinumab es efectivo y seguro en la práctica clínica real para lograr la inducción y el mantenimiento de la respuesta en pacientes con EC refractaria. El tabaco y la edad han mostrado ser predictores de mala respuesta, mientras que la indicación por efecto adverso a biológico previo y por pérdida de respuesta secundaria han mostrado ser predictores de buena respuesta
INTRODUCTION: Ustekinumab, a monoclonal antibody that blocks interleukins 12/23, has proven in clinical trials its efficacy in inducing and maintaining clinical remission of Crohn's disease (CD). Its effectiveness and safety in actual clinical practice is less known and may differ from trials. OBJECTIVE: To evaluate its effectiveness and safety in clinical practice (intravenous induction pattern essentially), such as induction and over the long term, in patients with CD refractory to biological treatment. MATERIAL AND METHODS: Multicentre retrospective analysis (6 hospitals in Aragón), which includes all patients (N=69) with CD undergoing treatment with ustekinumab (either with intravenous or subcutaneous induction), who had at least 16 weeks of follow-up. The clinical response or remission has been evaluated at weeks 16, 24, 32 and 48 using the Harvey-Bradshaw index. RESULTS: A total of 69 patients have been included, mean age 42 years, 54% men. A percentage of 89.86 (95% CI [0.805, 0.949]) of the patients presented clinical improvement at week 16 (15.95% remission, 73.92% response). In the subsequent follow-up, this response has been maintained. Age (OR 0.95, P=.028) and smoking habits (OR 0.19, P=.027) have been identified by an ordinal regression model as predictors of poor treatment response while the need for biological change due to adverse effect (OR 96, P=.00017) and due to loss of secondary response (OR 7.07, P=.034) have been predictors of good response. No serious adverse effects have been reported that forced them to stop taking ustekinumab. CONCLUSION: Ustekinumab is effective and safe in real clinical practice to achieve induction and maintenance of the response in patients with refractory CD. Tobacco and age have been shown to be predictors of poor response, while the indication for adverse effect to previous biological and for loss of secondary response has been shown to be predictors of good response
Humans , Male , Female , Adult , Middle Aged , Ustekinumab/therapeutic use , Crohn Disease/drug therapy , Treatment Outcome , Cohort Studies , Biological Treatment/methods , Retrospective Studies , Patient Safety , Administration, Intravenous
INTRODUCTION: CT-P13 is a biosimilar drug of infliximab (IFX), effective in patients with inflammatory bowel disease (IBD). The monitoring of levels of IFX and anti-IFX antibodies is now considered part of the integral management. OBJECTIVE: To compare the clinical response according to a strictly clinical (CLN) or proactive (PRO) approach based on the monitoring of levels in week 14, in clinical practice. METHODS: We conducted a prospective study in IBD patients starting CT-P13. In the PRO group, levels of IFX and post-induction antibodies were systematically measured (week 14) and those with infraterapeutic levels (<3µg/ml) were intensified, irrespective of the clinical response. RESULTS: We included 77 patients (23 ulcerative colitis and 54 Crohn's disease). Both PRO (n=41) and CLN (n=36) groups showed initial and long-term efficacy without significant differences. At week 14, 61% clinical remission (CR) (58.5% PRO, 63.9% CLN) and 80.5% at least partial response (PR) (80.5% PRO, 80.6% CLN). In week 54, 68.8% CR (61% PRO, 77.8% CLN) and 76.6% at least PR (73.2% PRO, 80.6% CLN). Of the patients in CR in week 14 (24 PRO, 23 CLN), 13 of the PRO group were intensified due to infra-therapeutic levels. In this subgroup no significant differences were observed in secondary loss of response (PRO 0%, CLN 8.7%). CONCLUSION: Proactive management does not improve response or remission rates in the first year. The intensification of clinical remission patients with post-induction infratherapeutic levels does not seem to significantly prevent secondary loss of response in the first year.
Biosimilar Pharmaceuticals , Colitis, Ulcerative , Inflammatory Bowel Diseases , Antibodies, Monoclonal , Biosimilar Pharmaceuticals/therapeutic use , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Prospective Studies , Remission Induction , Treatment Outcome
INTRODUCTION: Ustekinumab, a monoclonal antibody that blocks interleukins 12/23, has proven in clinical trials its efficacy in inducing and maintaining clinical remission of Crohn's disease (CD). Its effectiveness and safety in actual clinical practice is less known and may differ from trials. OBJECTIVE: To evaluate its effectiveness and safety in clinical practice (intravenous induction pattern essentially), such as induction and over the long term, in patients with CD refractory to biological treatment. MATERIAL AND METHODS: Multicentre retrospective analysis (6 hospitals in Aragón), which includes all patients (N=69) with CD undergoing treatment with ustekinumab (either with intravenous or subcutaneous induction), who had at least 16 weeks of follow-up. The clinical response or remission has been evaluated at weeks 16, 24, 32 and 48 using the Harvey-Bradshaw index. RESULTS: A total of 69 patients have been included, mean age 42 years, 54% men. A percentage of 89.86 (95% CI [0.805, 0.949]) of the patients presented clinical improvement at week 16 (15.95% remission, 73.92% response). In the subsequent follow-up, this response has been maintained. Age (OR 0.95, P=.028) and smoking habits (OR 0.19, P=.027) have been identified by an ordinal regression model as predictors of poor treatment response while the need for biological change due to adverse effect (OR 96, P=.00017) and due to loss of secondary response (OR 7.07, P=.034) have been predictors of good response. No serious adverse effects have been reported that forced them to stop taking ustekinumab. CONCLUSION: Ustekinumab is effective and safe in real clinical practice to achieve induction and maintenance of the response in patients with refractory CD. Tobacco and age have been shown to be predictors of poor response, while the indication for adverse effect to previous biological and for loss of secondary response has been shown to be predictors of good response.
Crohn Disease/drug therapy , Ustekinumab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adult , Drug Substitution , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Remission Induction , Retrospective Studies , Risk Factors , Severity of Illness Index , Smoking/epidemiology , Treatment Outcome , Ustekinumab/adverse effects
