8 research outputs found
Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohnâs Disease Patients: The SUSTAIN Study
Crohnâs disease; Effectiveness; UstekinumabEnfermedad de Crohn; Eficacia; UstekinumabMalaltia de Crohn; Efectivitat; UstekinumabBackground
Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohnâs 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 â„1 intravenous dose of ustekinumab for â„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 â„3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had â„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 work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data. Medical writing and editorial assistance for the preparation of this article was funded by Janssen-Cilag Spain. This assistance was provided by the following individuals, who are either employees of Springer Healthcare Communications (S.H.C.), or were contracted by S.H.C. to undertake editorial work in connection with the preparation of the article: Eliana Mesa, MD, Sheridan Henness, PhD, Fernando SĂĄnchez Barbero, PhD
Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohnâs Disease Patients on Ustekinumab
Malaltia de Crohn; Factors predictius; UstekinumabEnfermedad de Crohn; Factores predictivos; UstekinumabCrohnâs disease; Predictive factors; UstekinumabUstekinumab has shown efficacy in Crohnâs 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. Patientsâ 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.This work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data
Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohnâs 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 Crohnâs 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 Crohnâs 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 â„1 intravenous dose of ustekinumab for â„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 â„3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had â„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
Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885
The authors wish to make the following corrections to this paper [...]
Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study
(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery
Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohnâs Disease Patients on Ustekinumab
Ustekinumab has shown efficacy in Crohnâs 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. Patientsâ 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.