Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

Abstract

Psoriasis is a chronic disease that requires long‐term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)‐23. This article reviews published data on the safety of these IL‐23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo‐ and active‐controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk–benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL‐23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL‐23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long‐term extension studies and patient registries will further establish the safety profile of IL‐23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.

Shewanella algae – A Novel Organism Causing Bacteremia: A Rare Case and Literature Review

“…It was noted that the most common infection reported was an upper respiratory tract infection. Infections classified as serious demonstrated no significant difference between the groups [ 11 ].…”

<p>Tildrakizumab: An Evidence-Based Review of Its Use in the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis</p>

“…Safety results of tildrakizumab are similar to what has been reported from analyses of phase III trials regarding other IL-23p19 inhibitors. 43 Rates of AEs and SAEs are also mostly comparable across groups in phase III studies of guselkumab and risankizumab. 43 However, one systemic review and meta-analysis on IL-23p19 blockers indicated an increased incidence rate of infections when treating with guselkumab and risankizumab.…”

“…43 Rates of AEs and SAEs are also mostly comparable across groups in phase III studies of guselkumab and risankizumab. 43 However, one systemic review and meta-analysis on IL-23p19 blockers indicated an increased incidence rate of infections when treating with guselkumab and risankizumab. 44 The reported infections did not evolve to serious infections or other serious events.…”

“…Selectively targeting the IL23p19 appears to avoid many of the adverse events associated with other biologics from the anti-TNF and anti-IL17 groups, 43 perhaps explained by the more specific mechanism of action of the IL23p19 inhibitors. Tildrakizumab seems to have a very favorable safety profile, as also seen with guselkumab and risankizumab, only nasopharyngitis being more frequent among patients treated with tildrakizumab compared to placebo.…”

Practical recommendations for systemic treatment in psoriasis in case of coexisting inflammatory, neurologic, infectious or malignant disorders (BETA‐PSO: Belgian Evidence‐based Treatment Advice in Psoriasis; part 2)

“…[58][59][60] For the IL23/p19 inhibitors: guselkumab, risankizumab and tildrakizumab; the IL17 receptor blocker: brodalumab; the IL17 inhibitors: ixekizumab and secukinumab, no increased risk for TB reactivation has yet been reported. [61][62][63][64] We also note that TB testing is no longer mandatory from a scientific point of view (but is still present as a reimbursement criterion) for IL17 and IL23 antagonists, as well as with apremilast and acitretin. We note however that there are limited data available with the IL12/23 inhibitor: ustekinumab; the IL23/p19 inhibitors: guselkumab, risankizumab and tildrakizumab; the IL17 receptor blocker: brodalumab in these patients.…”