Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab.

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.

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn's Disease Patients: The SUSTAIN Study.

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.

This large retrospective study demonstrated the short- and long-term effectiveness and safety of ustekinumab in patients with Crohn's disease in real-world clinical practice, including those with refractory disease.

Screening of hepatitis C virus infection in adult general population in Spain.

PURPOSE: The aim was to estimate seroprevalence and prevalence of hepatitis C virus (HCV) infection in a small health area of the Valencian Community, Spain. PATIENTS AND METHODS: This is a descriptive cross-sectional study aimed at estimation of HCV infection prevalence in the whole adult population (25-70 years old), that is, a pilot study for an eventual population-based screening program. RESULTS: A total of 5849 participants aged 25-70 years (51% male) were invited to participate by regular mail. Overall, 143 letters were returned owing to errors in the addresses. Of 5706 participants, 2637 (46.2%) participated in the study. Rapid test of anti-HCV antibody detection was positive in 30 cases (HCV seroprevalence 1.14%, 95% confidence intervals: 0.73-1.55%). Of those, seven were not aware of their condition. Participants who had a positive result in the rapid test of anti-HCV detection were given a confirmatory test by enzyme immune assay, and all had a positive result. RNA-HCV determination by quantitative PCR in positive anti-HCV patients showed positive viremia in 13 (43.3%) cases, of which five were not aware of the disease. Of the 17 patients who had negative viremia, two were unaware of their HCV status, one was a carrier of anti-HCV and was already aware of his condition, and 14 had been previously treated with satisfactory results. Regarding fibrosis, of the seven patients who were unaware of HCV infection, none of them had significant fibrosis. Moreover, 26 (86.7%) anti-HCV positive patients were reported to have one or more risk factors for HCV infection. CONCLUSION: HCV screening strategies applied to the general population are good means to diagnose and treat patients who are not aware of their infection, avoiding new transmissions as well as disease progression.