BACKGROUND: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. AIM: Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled, 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis, and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.
Objetivo: Estudiar la respuesta serológica (RS) y tolerabilidad frente a la vacuna contra la COVID-19 en pacientes con enfermedad inflamatoria intestinal (EII) y su relación con el tratamiento de la EII y tipo de vacuna. Métodos: Estudio observacional, transversal en pacientes con EII vacunados contra la COVID-19 sin infección previa conocida. La RS se analizó mediante la determinación de anticuerpos IgG frente a la subunidad S1. La seguridad se estudió mediante cuestionario para identificación de efectos adversos (EA). Resultados: Se incluyó a 280 pacientes con EII. Tipo de vacunas: Comirnaty® 68,8%; Spikevax® 10,8%, Vaxzevria® 18,3%, Ad26.COV2-S® 2,2%. Un 51,3% tuvo EA, siendo el 100% leves. Un 65% desarrolló anticuerpos IgG tras la vacunación. La RS fue superior para vacunas con tecnología ARNm (100% Spikevax®, 68,5% Comirnaty®) frente a las basadas en vector con adenovirus (38,0% Vaxzevria®, 33,3% Ad26.COV2-S®) (p <0,001). En el análisis multivariante la RS se relacionó con la edad (< 60 años; OR: 3,8, IC del 95%, 1,9-7,0; p <0,001). La RS en pacientes con aminosalicilatos fue del 65,4%, 61,4% con inmunosupresor, 65,8% con anti-TNF y 68,7% con biológicos no anti TNF (p = 0,9). Conclusiones: Un tercio de pacientes con EII no desarrolló anticuerpos con la pauta vacunal inicial frente al SARS-CoV-2. La RS a las vacunas basadas en tecnología ARNm fue superior y estuvo relacionada con la edad (mayor en pacientes más jóvenes). Los inmunosupresores y biológicos no disminuyeron la RS. Más de la mitad de los pacientes presentaron EA, leves en todos los casos.(AU)
Objective: To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. Methods: Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). Results: 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P<.001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.97.0; P<.001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P=.9). Conclusions: One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases.(AU)
Humans , Male , Female , Adult , Severe acute respiratory syndrome-related coronavirus , Coronavirus Infections/epidemiology , Pandemics , Serologic Tests , Inflammatory Bowel Diseases , Vaccines , Gastrointestinal Diseases , Gastroenterology , Cross-Sectional Studies
OBJECTIVE: To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. METHODS: Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). RESULTS: 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P<.001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.9-7.0; P<.001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P=.9). CONCLUSIONS: One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases.
COVID-19 Vaccines , COVID-19 , Inflammatory Bowel Diseases , Vaccines , Humans , Middle Aged , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , BNT162 Vaccine , ChAdOx1 nCoV-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Immunoglobulin G , Immunosuppressive Agents , Inflammatory Bowel Diseases/drug therapy , RNA, Messenger , SARS-CoV-2 , Vaccination
BACKGROUND: A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn's disease who have lost the response to the treatment. METHODS: This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. RESULTS: Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. CONCLUSION: Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn's disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.
Crohn Disease , Ustekinumab , Administration, Intravenous , Crohn Disease/therapy , Humans , Remission Induction , Treatment Outcome , Ustekinumab/adverse effects
