Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis From 2 Tertiary IBD Centers in the United States

Abstract

Background Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from two US tertiary IBD centers. Methods Patients with moderately to severely active UC treated with ustekinumab at ______________ and ______________ between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1. Results Sixty-six UC patients were included. 92% of patients had prior exposure to biologics or tofacitinib. 43% and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF non-response and endoscopic Mayo score of 3 were negative predictors of clinical remission. 33% of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P<0.01) and lower stool frequency (P=0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). Conclusion In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.

The IL23-IL17 Immune Axis in the Treatment of Ulcerative Colitis: Successes, Defeats, and Ongoing Challenges

“…In particular, among 478 maternal pregnancies exposed to UST, 11 of them with UC, the prevalence of live births, spontaneous abortions and congenital anomalies were consistent with the general population and anti-TNF therapies. Real world data from the ENEIDA registry, the GETAID cohort and a US population were consistent with the known safety profile of UST (77)(78)(79). Three cases of leukocytoclastic vasculitis related to UST have been reported (79,95,96).…”

“…Real world data from the ENEIDA registry, the GETAID cohort and a US population were consistent with the known safety profile of UST (77)(78)(79). Three cases of leukocytoclastic vasculitis related to UST have been reported (79,95,96). To date, there are no data on safety for Risankizumab, Brazikumab and Guselkumab in UC.…”

“…The endoscopic activity, assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), showed a significant improvement from baseline, 3.8 ± 1.9 vs. 5.0 ± 1.2 (78). In two tertiary IBD centers in the US, among 66 patients almost all exposed to biologics or tofacitinib UST was effective in inducing clinical remission in 45% and 33% endoscopic and histologic remission at 1 year (79). Prior immunogenicity to anti-TNF did not confer a significantly risk of immunogenicity to UST in a cohort of 152 IBD patients, as the majority of real-worlds patients have likely failed anti-TNF biologics (80).…”

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

“…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.…”

Combination Therapy With Ustekinumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis

“…Regarding safety, some risks for systemic disease, cancer development and opportunistic infections, including leukocytoclastic vasculitis, non-melanoma skin cancers, prostate, colon, renal papillary, and rectal cancers, and cytomegalovirus colitis, legionella pneumonia, and ophthalmic and oral herpes simplex infections have been reported with the use of UST [ 1 , 15 ]. No adverse events occurred within 10 weeks of administration in the present study.…”