Impact of mesalazine on the response to COVID-19 vaccination in patients with inflammatory bowel disease: Results of a prospective multicentre study of GETECCU (VACOVEII study). / Impacto de la mesalazina en la respuesta a la vacunación contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal. Resultados de un estudio prospectivo multicéntrico de GETECCU (VACOVEII).

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 260BAU/mL (centralized determination) and was assessed 6 months after full vaccination. In this subanalysis of the study, we compare the effectiveness 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.

A booster dose of SARS-COV-2 vaccine improves suboptimal seroconversion rates in patients with inflammatory bowel disease. Results of a prospective multicenter study of GETECCU (VACOVEII study).

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.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

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.

Sucrosomial Iron Supplementation for the Treatment of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients Refractory to Oral Iron Treatment.

Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p < 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients' QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%); they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients' QoL. In conclusion, SI should be considered in IDA-IBD patients.

Eficacia y seguridad de ustekinumab en la práctica clínica real. Estudio multicéntrico retrospectivo. Cohorte ARAINF / Efficacy and safety of ustekinumab in real clinical practice. Retrospective multicentre study. ARAINF cohort

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

Efficacy and safety of ustekinumab in real clinical practice. Retrospective multicentre study. ARAINF cohort. / Eficacia y seguridad de ustekinumab en la práctica clínica real. Estudio multicéntrico retrospectivo. Cohorte ARAINF.

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.

Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infection / Exactitud del test Ultra-Rapido de la Ureasa para el Diagnóstico de la infección por Helicobacter pylori

Background: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit(R) requires less than 1h. Objective: To determine URUT's diagnostic accuracy. Method: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1min, 5min, 30min and 60min and the RUT was checked over the course of 24h. Histology was used as the gold standard test. Results: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pyloripositive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p=0.3) but there was a tendency towards better results with the URUT. Conclusion: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pyloriinfection, and provides results in less than an hour (AU)

Introducción: El test de la ureasa (TRU) es un método simple, barato y relativamente rápido para el diagnóstico de la infección por Helicobacter pylori (H. pylori). Por tanto, es el método de elección en pacientes sometidos a gastroscopia. La mayoría de los kits requieren 24 h para obtener un resultado. En nuevo test ultrarrápido de la ureasa (TURU) de Biohit requiere menos de una hora. Objetivo: Determinar la exactitud diagnóstica del TURU. Método: Estudio multicéntrico, prospectivo y ciego, en el que se incluyó a pacientes dispépticos. Se obtuvieron 3 biopsias de antro y una de corpus durante la gastroscopia para análisis histológico estándar, TRU y TURU. El resultado del TURU se comprobó a los 1, 5, 30 y 60 min, mientras que el TRU se evaluó a lo largo de 24 h. La histología se utilizó como patrón oro. Resultados: Se incluyó a 144 pacientes, 68% mujeres, edad media 49 años, el 50% fueron positivos para H. pylori. TRU y TURU diagnosticaron correctamente el 85,9% y 90,0% de los casos, respectivamente. La duración media de espera para un resultado positivo del TRU fue 6 h. La sensibilidad, la especificidad y los valores predictivos negativo y positivo para el TRU fueron, respectivamente, del 82, el 90, el 89 y el 84%. Los resultados del TURU fueron equivalentes (el 85, el 94, el 94 y el 87%). Estos resultados mejoraron al excluir los pacientes que tomaban IBP (TRU: 86, 91, 93 y 83%; TURU: 91, 94, 96 y 89%). La comparación de distribución de diagnósticos correctos entre TRU y TURU no encontró diferencias estadísticamente significativas (test de McNemar p=0,3) pero existe una tendencia a mejores resultados con el TURU. Conclusión: El TURU es equivalente (o algo superior) al TRU tradicional en el diagnóstico de la infección por H. pylori y obtiene los resultados en menos de una hora (AU)

Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infection.

BACKGROUND: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit® requires less than 1h. OBJECTIVE: To determine URUT's diagnostic accuracy. METHOD: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1min, 5min, 30min and 60min and the RUT was checked over the course of 24h. Histology was used as the gold standard test. RESULTS: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pylori positive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p=0.3) but there was a tendency towards better results with the URUT. CONCLUSION: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pylori infection, and provides results in less than an hour.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. METHODS: All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. RESULTS: A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. CONCLUSIONS: The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias.