Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up

Abstract

SummaryBackground Long-term safety evaluations of biologics are needed to inform patient management decisions. Objectives To evaluate the safety of ustekinumab in patients with moderate-tosevere psoriasis treated for up to 5 years. Methods Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest [infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse cardiovascular events (MACE)] per 100 patient-years (PY) of follow-up were analysed by ustekinumab dose (45 or 90 mg) and by year of follow-up (years 1-5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population. Results Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ‡ 4 years (including 838 patients ‡ 5 years). At year 5, event rates (45 mg, 90 mg, respectively) for overall AEs (242AE6, 225AE3), SAEs (7AE0, 7AE2), serious infections (0AE98, 1AE19), NMSCs (0AE64, 0AE44), other malignancies (0AE59, 0AE61) and MACE (0AE56, 0AE36) were comparable between dose groups. Year-to-year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population. Conclusions No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis.

Squamous Cell Carcinoma of the Tongue in a Patient on Ustekinumab as the Treatment of Psoriasis

“…Another 5-year study by Papp et al also showed that the rates of malignancies other than NMSC were comparable between the ustekinumab 45 mg (0.59 per 100 PY) and 90 mg (0.61 per 100 PY) groups without increasing trend. Overall, the incidence of malignancies other than NMSCs in ustekinumab-treated patients (0.60 per 100 PY) was consistent with that expected in the general U.S. population (range 0.54-0.72 per 100 PY) [17]. There is no evidence of a shift towards a pattern of malignancy indicative of severe immunosuppression.…”

“…In general, malignancy excluding NMSC was not significantly increased in patients receiving long-term ustekinumab therapy when compared with The National Cancer Institute's Surveillance Epidemiology and End Results (NCI SEER) database [15,17].…”

“…To understand the potential risks of malignancies from ustekinumab therapy, five randomized placebo-controlled trials of ustekinumab for the treatment of moderate-to-severe plaque psoriasis and three meta-analyses of randomized controlled trials and open-label extension studies were identified through literature review [10][11][12][13][14][15][16][17][18]. In general, malignancy excluding NMSC was not significantly increased in patients receiving long-term ustekinumab therapy when compared with The National Cancer Institute's Surveillance Epidemiology and End Results (NCI SEER) database [15,17].…”

IL12/IL23 Inhibition in the Treatment of Psoriatic Arthritis

“…Overall, the rates of stroke and cardiovascular death were 0.03/100 PY and 0.07/100 PY, not statistically significant compared with placebo. There was no dose-dependent difference in the rate of overall risk of adverse events in patients who received 45 vs. 90 mg of UST [46]. The rate of other adverse events, including infections and malignancy were not statistically significant for either dose.…”

Biologicals in the Treatment of Plaque Psoriasis: Drug Selection by Means of the SOJA Method

“…An analysis of controlled clinical trials with ustekinumab showed an incidence of major cardiovascular events (MACE) of 0.44 per 100 patient years [82]. An analysis also including another IL12/23 antagonist (briakinumab) showed a significantly increased incidence of MACE vs. placebo [83].…”