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Background: Ustekinumab is approved for ulcerative colitis (UC)., Aims: To assess the durability of ustekinumab in patients with UC and its short-term effectiveness, durability and tolerability in clinical practice., Methods: Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission., Results: We included 620 patients; 155 (25%) discontinued ustekinumab during follow-up (median 12 months). Rate of discontinuation was 20% per patient-year of follow-up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1-2.1), steroids at baseline (HR 1.5; 95% CI 1.06-2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09-2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid-free clinical remission. Moderate-severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2-0.5), male sex (OR 0.5; 95% CI 0.4-0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6-0.8) were associated with lower likelihood of steroid-free clinical remission at week 16. One hundred and seventy-six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune-mediated diseases., Conclusions: Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn's disease (CD) patients in real-world clinical practice., Methods: A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety., Results: A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever)., Conclusions: Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

Background: The impact of relapses on disease burden in Crohn's disease (CD) warrants searching for predictive factors to anticipate relapses. This requires analysis of large datasets, including elusive free-text annotations from electronic health records. This study aims to describe clinical characteristics and treatment with biologics of CD patients and generate a data-driven predictive model for relapse using natural language processing (NLP) and machine learning (ML)., Methods: We performed a multicenter, retrospective study using a previously validated corpus of CD patient data from eight hospitals of the Spanish National Healthcare Network from 1 January 2014 to 31 December 2018 using NLP. Predictive models were created with ML algorithms, namely, logistic regression, decision trees, and random forests., Results: CD phenotype, analyzed in 5938 CD patients, was predominantly inflammatory, and tobacco smoking appeared as a risk factor, confirming previous clinical studies. We also documented treatments, treatment switches, and time to discontinuation in biologics-treated CD patients. We found correlations between CD and patient family history of gastrointestinal neoplasms. Our predictive model ranked 25 000 variables for their potential as risk factors for CD relapse. Of highest relative importance were past relapses and patients' age, as well as leukocyte, hemoglobin, and fibrinogen levels., Conclusion: Through NLP, we identified variables such as smoking as a risk factor and described treatment patterns with biologics in CD patients. CD relapse prediction highlighted the importance of patients' age and some biochemistry values, though it proved highly challenging and merits the assessment of risk factors for relapse in a clinical setting., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The exploration of clinically relevant information in the free text of electronic health records (EHRs) holds the potential to positively impact clinical practice as well as knowledge regarding Crohn disease (CD), an inflammatory bowel disease that may affect any segment of the gastrointestinal tract. The EHRead technology, a clinical natural language processing (cNLP) system, was designed to detect and extract clinical information from narratives in the clinical notes contained in EHRs., Objective: The aim of this study is to validate the performance of the EHRead technology in identifying information of patients with CD., Methods: We used the EHRead technology to explore and extract CD-related clinical information from EHRs. To validate this tool, we compared the output of the EHRead technology with a manually curated gold standard to assess the quality of our cNLP system in detecting records containing any reference to CD and its related variables., Results: The validation metrics for the main variable (CD) were a precision of 0.88, a recall of 0.98, and an F1 score of 0.93. Regarding the secondary variables, we obtained a precision of 0.91, a recall of 0.71, and an F1 score of 0.80 for CD flare, while for the variable vedolizumab (treatment), a precision, recall, and F1 score of 0.86, 0.94, and 0.90 were obtained, respectively., Conclusions: This evaluation demonstrates the ability of the EHRead technology to identify patients with CD and their related variables from the free text of EHRs. To the best of our knowledge, this study is the first to use a cNLP system for the identification of CD in EHRs written in Spanish., (©Carmen Montoto, Javier P Gisbert, Iván Guerra, Rocío Plaza, Ramón Pajares Villarroya, Luis Moreno Almazán, María Del Carmen López Martín, Mercedes Domínguez Antonaya, Isabel Vera Mendoza, Jesús Aparicio, Vicente Martínez, Ignacio Tagarro, Alonso Fernandez-Nistal, Lea Canales, Sebastian Menke, Fernando Gomollón, PREMONITION-CD Study Group. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 18.02.2022.)

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

Introduction: controversial data have been reported on the potential association between celiac disease (CeD) and inflammatory bowel disease (IBD)., Objective: to study the prevalence of CeD in patients newly diagnosed cases with IBD., Methods: an observational, retrospective study was performed in patients with newly diagnosed IBD who were screened for CeD by anti-tissue transglutaminase antibodies (anti-tTG) measurements and an endoscopic duodenal biopsy. No patients had received corticosteroids, immunosuppressants or biologic drugs within the three months prior to gastroscopy. In the presence of Marsh 1, other causes were ruled out. CeD was diagnosed in patients positive for anti-tTG, compatible duodenal biopsy findings and a good response to a gluten-free diet., Results: a total of 163 patients were screened for CeD. Of these, six (3.7%) were positive for anti-tTG and four were diagnosed with CeD (three had ulcerative colitis, one had Crohn's disease). All patients with both CeD and IBD had normal IgA levels, positive anti-tTG and CeD genetic markers., Conclusions: the prevalence of CeD in our patients with IBD was higher than that reported in the literature for other series of patients with IBD. A combination of anti-tTG testing and CeD genetics may screen patients for CeD in this population of patients with IBD.

Acute tumour lysis syndrome (TLS) is a catastrophic complication of the treatment of certain neoplastic disorders. It most commonly occurs in association with hematologic malignancies and appears a few hours to a few days after initiation of specific chemotherapy, as the result from the release of intracellular components into the bloodstream due to abrupt malignant cell death. Acute spontaneous TLS is rare, and it has been described in leukemia and lymphoma and in some patients with solid tumors prior to institution of therapy. The syndrome is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and acute oliguric or anuric renal failure due to uric acid precipitation within the tubules (acute uric acid nephropathy) and to calcium phosphate deposition in the renal parenchyma and vessels.We report a case of acute spontaneous TLS in a patient with Crohn s disease treated with immunosuppressive drugs, who developed a plasmocytoma, in which serum uric acid concentration attained exceptionally high levels (44 mg/dL). The patient underwent acute oliguric renal failure, which required treatment with hyperhydration, urine alkalinization, urate oxidase and hemodialysis, with a fatal evolution.In conclusion, the present case report has several peculiarities: that of being one of the rare examples of spontaneous TLS, that of showing an exceptionally severe hyperuricemia, probably the highest ever reported in the literature, and that of the possible increased risk of tumours in patients with Crohn s disease taking inmunosuppressives and/or TNF antagonists.

Idiopathic thrombocytopenic purpura is an infrequent extraintestinal manifestation of inflammatory bowel disease. It is particularly rare in association with Crohn's disease. In these cases it presents certain peculiarities with respect to its normal clinical features, occurring more frequently when Crohn's disease is mainly colonic and usually appearing after the diagnosis of Crohn's disease has been made. Moreover, it usually complicates the clinical course of both diseases. We present a case of idiopathic thrombocytopenic purpura in a 14-year-old girl in whom the two diseases first presented simultaneously. The clinical course was poor and both diseases were refractory to habitual treatment.