Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Abstract

Summary Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real‐life long‐term data are currently available. Aims To assess the real‐world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. Results We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti‐TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid‐free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3‐10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. Conclusion After 52 weeks, over one‐half of patients with refractory UC were still treated by ustekinumab and one‐third were in steroid‐free clinical remission.

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.…”

“…Two smaller cohorts from Italy and the USA had similar outcomes, with a higher 12-month CSFR rate of 53% in the latter 6 8. It is worth noting that due to prescribing restrictions, only 3.6% (n=4) of our cohort were escalated to 4-weekly therapy, compared with 63% and 44% of the respective GETAID and US cohorts who received 4-weekly ustekinumab 7 8. This is likely to have influenced CSFR rates as ustekinumab dose intensification in UC has been shown to be effective in those failing 8-weekly treatment 15…”

“…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. Similarly, the French GETAID study of 103 patients demonstrated CSFR rates of 35% between weeks 12–16% and 32% at 12 months 7 14. Two smaller cohorts from Italy and the USA had similar outcomes, with a higher 12-month CSFR rate of 53% in the latter 6 8.…”

“…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.…”