Long-term Safety of Risankizumab From 17 Clinical Trials in Patients With Moderate-to-severe Plaque Psoriasis

K.B. Gordon; M. Lebwohl; K.A. Papp; H. Bachelez; J.J. Wu; R.G. Langley; A. Blauvelt; B. Kaplan; M. Shah; Y. Zhao; R. Sinvhal; K. Reich


The British Journal of Dermatology. 2022;186(3):466-475. 

In This Article


This integrated analysis of safety included data from 17 completed or ongoing clinical trials of risankizumab for moderate-to-severe psoriasis (3072 patients, 7927 PY of risankizumab exposure and treatment duration up to 5·9 years). The findings showed that the event rates for AEs and AEs of safety interest were consistent with the known safety profile of risankizumab and confirm its suitability for longer-term use.[3,19,20]

The EAER for serious infections in the long-term analysis set was 1·2 events per 100 PY, within the range reported in the PSOLAR study.[14,18] Evidence for the association between immunomodulating therapies and an increased risk of serious infection in psoriasis is inconclusive.[21–24] In addition to a role in the pathophysiology of psoriasis, the IL-23/T helper 17 pathway is involved in mucocutaneous defence against bacterial and fungal pathogens.[25–27] Thus use of risankizumab could, in theory, impair immune responses to Candida infection, increasing the risk of invasive infection. The EAER for Candida infections in the long-term analysis set was 0·6 events per 100 PY (Table S5) and there were no cases of deep or systemic candidiasis. These data are consistent with a recently performed comprehensive review of the literature, in which no evidence of an increased rate of systemic or deep Candida infections was found with inhibition of the p19 subunit of IL-23.[28] Furthermore, rates of two other opportunistic infections during long-term risankizumab treatment, herpes zoster (0·5 events per 100 PY) and tuberculosis (no incidences), are reassuring.

Patients with psoriasis may have higher rates of malignancy than the general population, regardless of treatment,[21] and the balance of IL-23 and IL-12 has been shown to affect the development of both antitumour and protumour immune responses.[29] In this integrated analysis of 7927 PY of risankizumab exposure, the EAERs of NMSC and non-NMSC malignant tumours were 0·7 events per 100 PY and 0·5 events per 100 PY, respectively, consistent with the rates reported in PSOLAR and lower than those in the MarketScan® psoriasis and nonbiologic-treated cohorts. Among patients with a prior history of cancer (n = 10), two patients experienced a recurrence of malignancy. These data suggest that risankizumab does not increase the risk of malignancy over that already associated with the pathophysiology of psoriasis, but that patients should be evaluated for risks of malignancy both before and during treatment.[30]

Patients with psoriasis are known to be at increased risk of other chronic health conditions as well, including cardiovascular and metabolic disorders.[31–34] Additionally, reports of MACE during phase II and III clinical trials of the anti–IL-12/23 antibody briakinumab in patients with psoriasis and in the setting of a large real-life database of patients who had received ustekinumab raised concerns about the short- and long-term cardiovascular safety of biologic therapies.[35,36] In this integrated analysis of risankizumab studies, the EAER of adjudicated MACE was low in both analysis sets (0·2 and 0·3 events per 100 PY in the short- and long-term analysis sets, respectively) and compares favourably with the range in the PSOLAR study for other biologic therapies (Figure 3).[14,18] Conversely, it has been shown recently that anti-IL biologics have a positive effect on lipid-rich atherosclerosis in patients with psoriasis.[37]

The treatment-emergent mortality rate in this integrated analysis was 0·5% (16 deaths, 0·2 events per 100 PY), with a standardized mortality ratio for treatment-emergent deaths of 0·32 (95% CI 0·18–0·53), suggesting that the risk of mortality was not increased in risankizumab-treated patients compared with the general population.

Limitations of this analysis include the lack of long-term comparators, possible selection of healthier patients to clinical trials in general, and that the EAER estimations were not adjusted for heterogeneity between trials. In addition, attrition over time might result in the population becoming more selected (healthy-user bias). Future analyses from these ongoing psoriasis trials are needed to confirm these results, as well as data from real-world, long-term registries.

In conclusion, this comprehensive analysis of more than 7000 PY of exposure to risankizumab supports the favourable safety profile of risankizumab in patients with moderate-to-severe psoriasis. Indeed, these data do not identify any new potential safety signals for risankizumab. These reassuring results should inform decisions that practitioners make regarding long-term treatment options for their patients with moderate-to-severe psoriasis.