Impact of targeted therapies on the risk of cardiovascular events in patients with psoriasis and psoriatic arthritis: A systematic review and aggregate data meta‐analysis of randomized controlled trials

Abstract

Objective We aimed to investigate the effect of targeted therapies on cardiovascular risk in psoriasis (PsO) and psoriatic arthritis (PsA) via a meta‐analysis of randomized controlled trials (RCTs). Methods Pubmed, Embase, Cochrane Library, and Scopus were searched for RCTs reporting targeted therapies in patients with PsO/PsA published until 28 October 2021. The primary and secondary outcomes included the relationship between targeted therapies and all cardiovascular events (CVEs), major adverse cardiovascular events (MACEs), myocardial infarction (MI), heart failure, and stroke in PsO/PsA. The outcome risk ratios (RRs) were calculated using the Mantel–Haenszel fixed‐effect method. Results A total of 81 articles involving 88 RCTs were included. There was no statistically significant difference regarding the occurrence of all CVEs for all targeted therapies (RR = 1.03, 95% CI 0.74‐1.43, P = .85) compared to placebo in PsO/PsA. No statistically significant difference existed between drugs and placebo in patients with PsA on all CVEs (RR = 0.81, 95% CI 0.48‐1.36, P = .43). Surprisingly, the incidence of all CVEs was higher in the low dosage group compared to the high dosage group of all targeted therapies (RR = 1.97, 95% CI 1.19‐3.27, P = .008) and prominently anti‐interleukin‐17 agent (RR = 2.20, 95% CI 1.05‐4.58, P = .04). Conclusion Current targeted therapies are not associated with the risk of CVEs. Based on the existing evidence, we reported here that a dosage reduction of targeted therapies was not recommended.

Cardiovascular disease in spondyloarthritis: a narrative review of risk factors and the effect of treatments

“…Safety data from JAKi clinical trials has not shown increased risk of CVD in PsA [114]. A recent meta-analysis of over 80 PsA and psoriasis clinical trials found no differences in overall CV events or MACE in those taking JAKi compared with placebo or other medications including TNFi, IL17i, IL12/23i, and apremilast [115 ▪ ]. This study noted that the lower dosage of the therapies was associated with increased incidence of CV events, and effect most pronounced in IL17i use.…”

“…This study noted that the lower dosage of the therapies was associated with increased incidence of CV events, and effect most pronounced in IL17i use. This suggests control of inflammation with higher dose regimens may be beneficial and lower the risk of future CV events [115 ▪ ]. Refer to Table 4 for summary of selected studies.…”

Risk of incident autoimmune diseases in patients with newly diagnosed psoriatic disease: a nationwide population-based study

“…The treatment of psoriatic disease may affect the cardiovascular system. Conventional systemic treatments have been associated with an increased risk of major adverse cardiovascular events 11 ; however, targeted therapies have not shown an association 12 . Although defects in glucose metabolism among patients with psoriatic disease are not clearly established in previous studies, epidemiological studies suggest an association between type 2 diabetes and psoriatic disease 13 , 14 .…”

Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database

“…However, previous research ( Fang et al, 2022 ) showed that JAKi and TNFi in rheumatoid arthritis have comparable safety issues and mortality rates. Another meta-analysis ( Cai et al, 2023 ) showed that targeted therapies did not show a higher occurrence of all CVEs in PsO/PsA (RR = 1.03; 95% CI 0.74–1.43l; p = .85) compared to the placebo. Our findings showed that bDMARDs, especially infliximab, etanercept, and secukinumab, significantly presented a disproportionate signal of pericarditis compared to other medications for AS after accounting for confounding factors.…”