Valle García-sánchez - Academia.edu (original) (raw)

Papers by Valle García-sánchez

American Journal of Gastroenterology, 2020

INTRODUCTION To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflamma... more INTRODUCTION To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD). METHODS Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.

Therapeutic Advances in Gastroenterology, 2019

Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha ... more Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn’s disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. Methods: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn’s Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic...

Therapeutic Advances in Gastroenterology, 2019

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necro... more Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn’s disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remissio...

Journal of Crohn's and Colitis, 2019

Gastroenterology, 2011

Early Use of Azathioprine Has a Steroid Sparing Effect on Recently Diagnosed Crohn's Disease ... more Early Use of Azathioprine Has a Steroid Sparing Effect on Recently Diagnosed Crohn's Disease Patients Miquel Sans, Antonio Lopez-San Roman, Maria Esteve, Fernando Bermejo, Valle GarciaSanchez, Yolanda Torres, Eugeni Domenech, Marta Piqueras, Montserrat Aceituno, Maria Gomez-Garcia, Carlos Taxonera, Javier P. Gisbert, Ana Gutierrez, Fernando Gomollon, Daniel Ginard, Antonio Bernal, Antonio Z. Gimeno-Garcia, Carmen Munoz, Fermin Mearin, Miguel Minguez, Manuel Barreiro-de Acosta, Xavier Calvet, Juan Buenestado, Olga Merino, Maria Barrachina, Luis Bujanda, Miriam Manosa, Maria M. Calvo, Esther Garcia, Miguel A. Montoro, Jose Manuel Herrera Justiniano, Montserrat Andreu, Vicent Hernandez, Joaquin Hinojosa, Julian Panes

Gastroenterology Report, 2019

Background: This study is aimed at describing the prevalence of and risk factors associated with ... more Background: This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn's disease-related intestinal resection. Methods: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn's disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery.

Journal of Crohn's and Colitis, 2019

Journal of Crohn's & colitis, Jan 27, 2018

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting,... more Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis (GMA) to oral prednisone in patients with steroid-dependent UC. Randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone (40mg/day and tapering) to prednisone alone in patients with active, steroid-dependent UC (Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation). Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary end point was steroid-free remission (defined as a total Mayo score ≤2, with no subscore >1) at week 24, with no reintroduction of corticosteroids. One hundred and twenty-three patients we...

Scandinavian journal of gastroenterology, Jan 30, 2017

Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (U... more Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. E...

Gastroenterology, 2017

evaluated. Structural comparison was performed by multiple assays including peptide mapping using... more evaluated. Structural comparison was performed by multiple assays including peptide mapping using mass spectrometry and hydrogen/deuterium exchange (HDX). TNF-α neutralisation activity was measured by a luciferase reporter gene assay. The percentages of galactosylated, afucose plus high mannosylated, and charged glycan were determined. FcγRIIIa binding activity in surface plasmon resonance, AlphaScreen-based binding assay, and cell-based binding assay were assessed. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity in a NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMCs) were determined. Results: Analytical similarity of SB2 was demonstrated through extensive characterization studies. For example, the primary structure and higher-order structure of the reference infliximab and SB2 were similar (Figure 1). In the comparison of three infliximab products, the relative potency was similar for all 3 products (Figure 2A). In N-glycan analysis, as compared with the reference infliximab, a lower percentage of charged glycan with SB2 was noted, and a higher percentage of galactosylated glycan and a lower percentage of afucose plus high mannosylated glycans with CT-P13 were noted. The percentage of the relative FcγRIIIa binding affinity was lower with CT-P13 as compared with the reference infliximab (Figure 2B). The percentage of the relative ADCC activity in the NK92-CD16a cell line was lower with CT-P13 and higher with SB2 as compared with the reference infliximab but was similar for all 3 products in PBMCs (Figure 2C, 2D). Conclusion: Comparison of the three infliximab products showed that there was no difference in most quality attributes. FcγRIIIa binding and ADCC activity showed differences that were correlated with the N-glycan profile, but the differences were not demonstrated in the physiologically more relevant condition.

Medicine, 2017

To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic ... more To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID...

Biochemical pharmacology, Jan 15, 2016

The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would... more The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to...

Journal of gastroenterology, Jul 24, 2016

Inflammatory Bowel Diseases, 2016

on behalf of the USTEK Study Group Background: Ustekinumab is a fully human monoclonal antibody a... more on behalf of the USTEK Study Group Background: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. Methods: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. Results: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. Conclusions: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Inflammatory Bowel Diseases, 2016

Background: Psoriasis induced by anti-tumor necrosis factor-a (TNF) therapy has been described as... more Background: Psoriasis induced by anti-tumor necrosis factor-a (TNF) therapy has been described as a paradoxical side effect. Aim: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Methods: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Results: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel

Journal of Crohn's & colitis, Jan 19, 2016

The aim of this study was to evaluate the frequency of entero-urinary fistulas in a cohort of Cro... more The aim of this study was to evaluate the frequency of entero-urinary fistulas in a cohort of Crohn's disease (CD) patients, and to analyse the outcomes of medical and surgical therapy. This multicentre retrospective study included all CD patients with entero-urinary fistulas diagnosed by the presence of clinical symptoms and confirmed at surgery or by radiological or endoscopic techniques. We evaluated outcomes of medical and surgical therapy. We defined remission as absence of clinical symptoms with a radiological confirmation of fistula closure. Cox regression analysis was performed to evaluate predictive factors of achieving remission without need for surgery. Of 6081 CD patients screened, 97 had entero-urinary fistulas (frequency 1.6%). Seventy-five % of fistulas occurred in men. After a median follow-up of 91 months, 96% of patients were in sustained remission. Thirty-three patients (35%) received anti-TNF therapy. Of these, 45% achieved sustained remission (median follow-...

Gastroenterology, 2013

199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Am... more 199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Among the included patients, 4,734 used thiopurines with median duration of one year. Numbers of lymphoma cases identified were 119 and 18 among non-users and while using thiopurines respectively. The incidence rate of lymphoma among those who never used thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the 1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence rates of the fourth and more than four years were significantly different from the incidence rate of non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than four year of thiopurines use respectively (p ,0.001). Conclusion: In this nationwide cohort of UC patients, the incidence rate of lymphoma significantly increased after the third year of cumulative exposure to thiopurines. Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines Su1132

Digestive Diseases and Sciences, 2015

The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluate... more The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. Seventy-nine patients were included. Fifty-four patients (68.4 %) achieved short-term clinical response and 41 patients (51.9 %) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8 %) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95 % confidence interval (CI) 0.12-0.49; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4 %) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95 % CI 0.03-0.69; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.007). In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70 % of patients. In the long term, 58 % of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86 % reduction in the relative risk of colectomy.

American Journal of Gastroenterology, 2020

INTRODUCTION To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflamma... more INTRODUCTION To compare Engerix-B and Fendrix hepatitis B virus for primo vaccination in inflammatory bowel disease (IBD). METHODS Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs ≥100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs ≥100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P = 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in 13% of patients after 6 months and 20% after 12 months. Anti-HBs ≥100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs <100 IU/L after the vaccination.

Therapeutic Advances in Gastroenterology, 2019

Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha ... more Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn’s disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. Methods: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn’s Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic...

Therapeutic Advances in Gastroenterology, 2019

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necro... more Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn’s disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remissio...

Journal of Crohn's and Colitis, 2019

Gastroenterology, 2011

Early Use of Azathioprine Has a Steroid Sparing Effect on Recently Diagnosed Crohn's Disease ... more Early Use of Azathioprine Has a Steroid Sparing Effect on Recently Diagnosed Crohn's Disease Patients Miquel Sans, Antonio Lopez-San Roman, Maria Esteve, Fernando Bermejo, Valle GarciaSanchez, Yolanda Torres, Eugeni Domenech, Marta Piqueras, Montserrat Aceituno, Maria Gomez-Garcia, Carlos Taxonera, Javier P. Gisbert, Ana Gutierrez, Fernando Gomollon, Daniel Ginard, Antonio Bernal, Antonio Z. Gimeno-Garcia, Carmen Munoz, Fermin Mearin, Miguel Minguez, Manuel Barreiro-de Acosta, Xavier Calvet, Juan Buenestado, Olga Merino, Maria Barrachina, Luis Bujanda, Miriam Manosa, Maria M. Calvo, Esther Garcia, Miguel A. Montoro, Jose Manuel Herrera Justiniano, Montserrat Andreu, Vicent Hernandez, Joaquin Hinojosa, Julian Panes

Gastroenterology Report, 2019

Background: This study is aimed at describing the prevalence of and risk factors associated with ... more Background: This study is aimed at describing the prevalence of and risk factors associated with early post-operative complications after Crohn's disease-related intestinal resection. Methods: This was a retrospective analysis of data from the PRACTICROHN cohort. Adult Crohn's disease patients who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010 were included. The complications evaluated included death, ileus, anastomotic leak, abscess, wound infection, catheter-related infection, digestive bleeding and other extra-abdominal infections that occurred in the 30 days after surgery.

Journal of Crohn's and Colitis, 2019

Journal of Crohn's & colitis, Jan 27, 2018

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting,... more Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis (GMA) to oral prednisone in patients with steroid-dependent UC. Randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone (40mg/day and tapering) to prednisone alone in patients with active, steroid-dependent UC (Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation). Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary end point was steroid-free remission (defined as a total Mayo score ≤2, with no subscore >1) at week 24, with no reintroduction of corticosteroids. One hundred and twenty-three patients we...

Scandinavian journal of gastroenterology, Jan 30, 2017

Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (U... more Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. E...

Gastroenterology, 2017

evaluated. Structural comparison was performed by multiple assays including peptide mapping using... more evaluated. Structural comparison was performed by multiple assays including peptide mapping using mass spectrometry and hydrogen/deuterium exchange (HDX). TNF-α neutralisation activity was measured by a luciferase reporter gene assay. The percentages of galactosylated, afucose plus high mannosylated, and charged glycan were determined. FcγRIIIa binding activity in surface plasmon resonance, AlphaScreen-based binding assay, and cell-based binding assay were assessed. Antibody-dependent cell-mediated cytotoxicity (ADCC) activity in a NK92-CD16a cell line and in peripheral blood mononuclear cells (PBMCs) were determined. Results: Analytical similarity of SB2 was demonstrated through extensive characterization studies. For example, the primary structure and higher-order structure of the reference infliximab and SB2 were similar (Figure 1). In the comparison of three infliximab products, the relative potency was similar for all 3 products (Figure 2A). In N-glycan analysis, as compared with the reference infliximab, a lower percentage of charged glycan with SB2 was noted, and a higher percentage of galactosylated glycan and a lower percentage of afucose plus high mannosylated glycans with CT-P13 were noted. The percentage of the relative FcγRIIIa binding affinity was lower with CT-P13 as compared with the reference infliximab (Figure 2B). The percentage of the relative ADCC activity in the NK92-CD16a cell line was lower with CT-P13 and higher with SB2 as compared with the reference infliximab but was similar for all 3 products in PBMCs (Figure 2C, 2D). Conclusion: Comparison of the three infliximab products showed that there was no difference in most quality attributes. FcγRIIIa binding and ADCC activity showed differences that were correlated with the N-glycan profile, but the differences were not demonstrated in the physiologically more relevant condition.

Medicine, 2017

To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic ... more To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID...

Biochemical pharmacology, Jan 15, 2016

The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would... more The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to...

Journal of gastroenterology, Jul 24, 2016

Inflammatory Bowel Diseases, 2016

on behalf of the USTEK Study Group Background: Ustekinumab is a fully human monoclonal antibody a... more on behalf of the USTEK Study Group Background: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. Methods: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. Results: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. Conclusions: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.

Inflammatory Bowel Diseases, 2016

Background: Psoriasis induced by anti-tumor necrosis factor-a (TNF) therapy has been described as... more Background: Psoriasis induced by anti-tumor necrosis factor-a (TNF) therapy has been described as a paradoxical side effect. Aim: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Methods: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Results: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel

Journal of Crohn's & colitis, Jan 19, 2016

The aim of this study was to evaluate the frequency of entero-urinary fistulas in a cohort of Cro... more The aim of this study was to evaluate the frequency of entero-urinary fistulas in a cohort of Crohn's disease (CD) patients, and to analyse the outcomes of medical and surgical therapy. This multicentre retrospective study included all CD patients with entero-urinary fistulas diagnosed by the presence of clinical symptoms and confirmed at surgery or by radiological or endoscopic techniques. We evaluated outcomes of medical and surgical therapy. We defined remission as absence of clinical symptoms with a radiological confirmation of fistula closure. Cox regression analysis was performed to evaluate predictive factors of achieving remission without need for surgery. Of 6081 CD patients screened, 97 had entero-urinary fistulas (frequency 1.6%). Seventy-five % of fistulas occurred in men. After a median follow-up of 91 months, 96% of patients were in sustained remission. Thirty-three patients (35%) received anti-TNF therapy. Of these, 45% achieved sustained remission (median follow-...

Gastroenterology, 2013

199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Am... more 199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60 years. Among the included patients, 4,734 used thiopurines with median duration of one year. Numbers of lymphoma cases identified were 119 and 18 among non-users and while using thiopurines respectively. The incidence rate of lymphoma among those who never used thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the 1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence rates of the fourth and more than four years were significantly different from the incidence rate of non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than four year of thiopurines use respectively (p ,0.001). Conclusion: In this nationwide cohort of UC patients, the incidence rate of lymphoma significantly increased after the third year of cumulative exposure to thiopurines. Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines Su1132

Digestive Diseases and Sciences, 2015

The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluate... more The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. Seventy-nine patients were included. Fifty-four patients (68.4 %) achieved short-term clinical response and 41 patients (51.9 %) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8 %) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95 % confidence interval (CI) 0.12-0.49; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4 %) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95 % CI 0.03-0.69; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.007). In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70 % of patients. In the long term, 58 % of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86 % reduction in the relative risk of colectomy.