Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review

Abstract

BackgroundAnti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated.ObjectivesThe purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity.ResultsA total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed.ConclusionsAnti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

Targeting Interleukin-17 as a Novel Treatment Option for Fibrotic Diseases

“…Given the strong pro-inflammatory role of IL-17, drugs that target IL-17 or the IL-17R are potential therapeutic candidates for inflammatory autoimmune diseases [ 126 , 127 ]. In 2016, anti-IL-17A monoclonal antibodies (mAbs), such as the IL-17 inhibitor secukinumab and the IL-17R inhibitor brodalumab, were both approved for the treatment of psoriasis [ 128 ]. More recently, the Food and Drug Administration has approved a novel drug, Ixekizumab, for the treatment of moderate-to-severe plaque psoriasis as well as active psoriatic arthritis.…”

“…More recently, the Food and Drug Administration has approved a novel drug, Ixekizumab, for the treatment of moderate-to-severe plaque psoriasis as well as active psoriatic arthritis. Ixekizumab is a humanized IgG4 mAb that selectively binds IL-17A and prevents interactions with IL-17R [ 128 ]. By targeting cells, it hampers the release of pro-inflammatory proteins, subsequently involving cellular components [ 127 ].…”

“…By targeting cells, it hampers the release of pro-inflammatory proteins, subsequently involving cellular components [ 127 ]. However, these drugs have unexpectedly demonstrated low efficacy in the diseases linked to IL-17, such as RA and MS [ 128 ]. Investigating in this context, Luo et al discovered that a molecular complex containing the adaptor molecule Act1 and the tyrosine phosphatase SHP2 mediates autonomous IL-17R signaling, sustaining an intense inflammatory state.…”

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management

“…These drugs can reduce inflammation and tissue injury associated with autoimmune diseases by targeting IL-17 or its receptors. Nonetheless, IL-17 inhibitors may have undesirable side effects, such as a higher risk of infections, allergies, or metabolic disorders (Wang et al 2023 ).…”

Disruption of IL-17 signaling in the respiratory mucosa results in invasive streptococcal infection

“…Accordingly, inborn IL-17 deficiency and therapeutics based on IL-17 inhibitors increase the risk of mucocutaneous candidiasis in humans (Davidson, van den Reek et al, 2022, Puel, Cypowyj et al, 2011, Puel, Cypowyj et al, 2012. Similarly, the most common adverse effects of anti-IL-17 therapy in patients with psoriasis is an increase in infections of the nasopharyngeal tract (Wang, Wang et al, 2023).…”