Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis

Abstract

Background and aims: Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease [CD] and 4 years in ulcerative colitis [UC].

Methods: In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w]. Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence intervals.

Results: In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including major adverse cardiac events and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab. Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic-naïve or who had a history of biologic failure. No lymphomas or cases of posterior reversible encephalopathy syndrome [formerly known as reversible posterior leukoencephalopathy syndrome] were reported.

Conclusion: The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support the well-established safety profile across all approved indications.

Clinical trials.gov numbers: NCT00265122, NCT00771667, NCT01369329, NCT01369342, NCT01369355, NCT02407236.

Keywords: Inflammatory bowel disease; safety; ustekinumab.

Graphical Abstract

Figure 1.

Rates of adverse events (A) and serious adverse events (B).

Figure 2.

Time to first event analysis for serious adverse events (A) and serious infections (B).

Figure 3.

Rates of infections (A) and serious infections (B).

Figure 4.

Opportunistic infections. OIs, opportunistic infections; TB, tuberculosis.

Figure 5.

Rates of all malignancies including non-melanoma skin cancer (NMSC) (A), malignancies other than NMSC (B), and NMSC (C).

Figure 6.

Observed rates of malignancies compared with expected (SEER) and standard incidence rations (SIR). ^aThe expected number of patients with malignancies is based on the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database (year 2019), adjusted for age, gender, and race. Only patients with race belonging to White, Black or African American, Asian, American Indian/Alaska Native, Native Hawaiian, or other Pacific Islander were included as SEER only contains incidence rates for these populations. One malignancy was not included as the patient’s race was unknown. ^b[SIR]; observed number of patients with malignancy divided by expected number of patients with malignancy. ^cConfidence intervals based on an exact method assuming that the observed number of events follows a Poisson distribution.