Hospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

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.

Project management, coordination, formal analysis, data preservation, first draft, revision and editing of the manuscript, methodology and research. Pilar Navajas Hernández: Data collection and preservation, revision and editing of the manuscript. María del Mar Martín Rodríguez: Data collection and preservation, revision and editing of the manuscript. Marta Lázaro Sáez: Data collection and preservation, formal analysis, first draft, revision and editing of the manuscript. Raúl Olmedo Martín: Data collection and preservation, revision and editing of the manuscript. Andrea Núñez Ortiz: Data collection and preservation, revision and editing of the manuscript. Federico Arguelles Arias: Data collection and preservation, revision and editing of the manuscript. María Carmen Fernández Cano: Data collection and preservation, revision and editing of the manuscript. Francisco Gallardo Sánchez: Data collection and preservation, revision and editing of the manuscript. Sandra Marín Pedrosa: Data collection and preservation, revision and editing of the manuscript.Javier González García: Data collection and preservation, revision and editing of the manuscript.Juan María Vázquez Morón: Project management, coordination, methodology, data collection and preservation, revision and editing of the manuscript. Conflicts of interest:A. Hernández has received payments as fees-for-service, participation in scientific meetings and funding for attendance from Abbvie, Ferring, Janssen, MSD, Pfizer, Sandoz and Takeda; M.M. Martín has received payments for advisory, participation in scientific meetings and attendance from MSD, Takeda, Janssen, Abbvie, Tillots Pharma, Chiesi and Ferring; M. Lázaro has received payments as fees-for-service, participation in scientific meetings and funding for attendance from Janssen, Pfizer and Takeda; R.Olmedo has received payments as fees-for-service and advisory from MSD, Abbvie, Takeda, Ferring, FAES Farma and Janssen; F. Arguelles has received payments for advisory, consultancy and research fundings from Janssen, MSD, Abbvie,

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.

Acknowledgments: we are grateful to Antonia Sáez Díaz, head of the Statistics Department, Axioma Comunicaciones, for her help with the statistical analysis.