Safety Profile of Ustekinumab Favorable in Patients with IBD, History of BIologic Failure


Rates per 100 person-years for adverse events, infections, and major adverse cardiac events were similar between placebo and ustekinumab through up to 5 years.

Safety Profile of Ustekinumab Favorable in Patients with IBD, History of BIologic Failure

Edward V. Loftus, MD

New research suggested the overall rates of key safety events were similar between cohorts with inflammatory bowel disease (IBD) or ulcerative colitis (UC) receiving long-term ustekinumab or placebo.

These findings may be reassuring among the patient population with a history of prior biologic failure, study investigators said.

“The long-term safety profile of ustekinumab in IBD patients with a history of biologic failure was favorable and consistent with the overall IBD population and the well-established, long-term, cumulative safety profile of ustekinumab across approved disease indications,” wrote study author Edward V. Loftus, MD, Mayo Clinic College of Medicine and Science.

Loftus presented these data at the 2022 Digestive Disease Week Meeting in San Diego, California.

A significant number of patients may not respond to or lose response to, or are intolerant to, biologic agents and may require switching to a different biologic. The current integrated analysis incorporated ustekinumab phase 2/3 long-term safety data from IBD studies for up to 5 years in Crohn’s Disease (CD) and 2 years in UC in patients with a history of prior biologic failure.

The data from 5 phase 2/3 UST IBD studies were pooled, according to investigators. In phase 3, patients were given a single intravenous placebo or UST (130 mg or 6 mg/kg) induction dose and followed by a subcutaneous maintenance dose of placebo or ustekinumab (90 mg q8w or q12w).

All patients who received ≥1 dose of ustekinumab and were identified as having a history of prior biologic failure were included in the data analysis. Investigators noted concomitant immunomodulators and corticosteroids were permitted. In the pooled IBD group, safety outcomes are presented as events per 100 patient-years of follow-up and 95% confidence intervals (CIs).

For up to 5 years, a total of 847 IBD patients with a history of prior biologic failure received placebo (473 patient-years) and 1596 patients received ustekinumab (1970 patient-years). The average duration of follow-up was 2-fold longer for ustekinumab compared to placebo (64.18 weeks vs 29.06 weeks).

Data show the rates per 100 patient-years were similar between placebo and ustekinumab through up to 5 years for:

  • Adverse events (587.86 vs 487.13 per 100 patient-years)
  • Serious adverse events (40.35 vs 29.19 per 100 patient-years)
  • Infections (129.91 vs 118.95 per 100 patient-years)
  • Serious infections (6.97 vs 5.23 per 100 patient-years)
  • Major adverse cardiac events (0.21 vs 0.25 per 100 patient-years)

Overall, rates of non-melanoma skin cancer and malignancies were reported infrequently in ustekinumab patients with IBD, with similar rates between ustekinumab and placebo. Notably, the average duration of follow-up through 5 years was 2-fold longer for ustekinumab versus placebo (64.18 vs 29.06 weeks).

The overall rates of adverse events were similar between ustekinumab and placebo for individual events. Data show the most frequently reported adverse event was nasopharyngitis, while the most frequently reported infection was nasopharyngitis and upper respiratory tract infection.

Moreover, a total of 6 deaths were reported through up to 5 years in patients with a history of prior biologic failure treated with ustekinumab (0.3 per 100 patient-years). However, all were considered to have no relation to the study agent, according to investigators.

The study, “Long-Term Safety of Ustekinumab in IBD Patients with A History of Biologic Failure: Pooled Safety Analysis Through 5 Years in Crohn’s Disease and 2 Years in Ulcerative Colitis,” was presented at DDW 2022.

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