Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry

Abstract

Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims To evaluate the durability, effectiveness and safety of ustekinumab in UC in real-life. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at week 16. Results A total of 95 patients were included. At week 16, 53% of patients had response (including 35% of patients in remission). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at weeks 24 and 52, respectively. Thirty-six percent of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study

“…The finding that one-third of our patients were in CSFR following induction is consistent with recently published real world studies, though we acknowledge missing clinical data 5–8 14. Chaparro et al evaluated 95 patients from the Spanish ENEIDA registry and found CSFR rates of 30% and 32% at weeks 24 and 52, respectively 5.…”

“…Ustekinumab treatment persistence at week 52, either actual or estimated (for cohorts with a shorter follow-up), varied between 58% to 87% across real-world studies, including our own 5–8. The variability in persistence, which is often used as a proxy for assessing sustained effectiveness, may reflect the heterogeneity of included cohorts, varying treatment regimens, and study designs.…”

“…However, RCTs may not be suitable for effectiveness research due to poor external validity, a consequence of, among other things, strict inclusion criteria 4. Therefore, real-life data of ustekinumab in UC are needed, and remain very limited 5–8. The aim of this study was to supplement the body of observational research by describing the effectiveness and safety of ustekinumab in UC patients in everyday clinical practice.…”

Targeting IL12/23 in ulcerative colitis: update on the role of ustekinumab

“…Looking at potential predictors of response, multivariate analysis showed that baseline C-reactive protein (CRP) over the upper normal value was associated with a significantly lower probability of clinical remission at week 16 [odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1–0.7]. 22 …”

“… 16 – 18 Currently, few real-life data have been reported on the effectiveness of ustekinumab for UC treatment and, as it usually happens with new drugs, most of these studies included patients with prior exposure/failure to multiple biological drugs. 19 – 22 …”