Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease:an integrated analysis of Phase II/III Clinical Development Programs

IntroductionTheoretical risks of biologic agents remain under study.ObjectiveThe aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials.MethodsPatients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]).ResultsAmong 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications.ConclusionsUstekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications.Trial registrationsClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355

Correction to:Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs

In the original publication of this article, the following correction should be noted in Table 5

Correction to: Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs.

In the original publication of this article, the following correction should be noted in Table 5

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

Previously published long-term safety data reported a favorable ustekinumab safety treatment profile for 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). In phase 3 studies, patients received a single IV placebo or ustekinumab (130mg or ~6mg/kg) induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab (90mg 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 interval. 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 MACE 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 previously failed a biologic. No lymphomas or cases of posterior reversible encephalopathy syndrome (PRES; formerly known as reversible posterior leukoencephalopathy syndrome [RPLS] were reported. The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favorable safety compared to placebo and continues to support the well-established safety profile across all approved indications