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

Abstract

Background: Anti-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.

Objectives: The 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.

Methods: PubMed, 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.

Results: A 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.

Conclusions: Anti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

Keywords: adverse events; anti-IL-17; biological agents; meta-analysis; systematic review.

Figure 1

Schematic diagram of the mechanism of action of anti-interleukin-(IL)-17 drugs. The mechanism of anti-IL-17 monoclonal antibodies in psoriasis and psoriatic arthritis. The pathogenesis of both psoriasis and psoriatic arthritis is closely related to the IL-23/IL-17 axis. First, dendritic cells secrete IL-23 to activate Th17 cells and then the activated Th17 cells secrete large amounts of IL-17, thereby triggering an inflammatory cascade. Next, the IL-17 family induces excessive proliferation of keratinocytes, resulting in localized papules, erythema, and silvery-white plaques on the skin. In addition, the IL-17 family act on the joint to activate synovial fibroblasts, osteoblasts, and osteoclasts, triggering local tissue inflammation. This study included three types of monoclonal antibodies that alleviate psoriasis and psoriatic arthritis by blocking IL-17A, IL-17R, and IL-17A/F, thereby interrupting the inflammatory cascade.

Figure 2

Box diagram of subgroup analysis. Box diagram of the incidence of changes in adverse events among different medication courses.

Figure 3

Heat map of different types of symptoms caused by different drugs. Red areas indicate greater relative probability of occurrence and lighter-colored areas indicate a slight or null relative probability of occurrence.