Study Highlights Cardiovascular Safety of Systemic Therapies for Psoriasis

New findings point to a possible link between apremilast and interleukin (IL)-17 with a lower incidence of major adverse cardiovascular events (MACE) in patients with psoriasis, whereas cyclosporine showed a higher incidence versus methotrexate.1

Juan José Lluch-Galcerá—from the Universitat Autònoma de Barcelona Departament de Medicina in Spain—and a team of other investigators authored the prospective cohort study that led to these findings. The investigative team highlighted that, prior to their research, there had been a general lack of data on cardiovascular safety with systemic agents in patients with psoriasis in terms of real-world evidence.

Additionally, the team highlighted that most of this information prior to their analysis, had been extrapolated from other inflammatory conditions.2 They noted that these conditions are not always useful for direct comparisons to psoriasis.

“This study aimed to evaluate the incidence of MACEs for the different systemic treatments used in patients with psoriasis, providing robust [real-world evidence] for conventional systemic treatments, small molecules and biologic therapy,” Lluch-Galcerá and colleagues wrote.1

The investigative team looked at data that had originated from BIOBADADERM, a national, prospective, multicenter registry that investigators had designed to track patients with psoriasis being treated with systemic therapeutics in real-world clinical settings. The BIOBADADERM registry included all prospective data gathered from January 2008 - November 2023 for those who both had moderate-to-severe psoriasis and had initiated a systemic option they had not previously implemented.

Contributions of safety data came from 19 dermatology departments located within tertiary care hospitals found across Spain.

Along with patients treated with biologics, Lluch-Galcerá and colleagues also incorporated a cohort of subjects being given a non-biologic, conventional systemic therapy for the first time. The team documented any cardiovascular events, including MACE, systematically. They implemented standardized definitions throughout the follow-up period.

Those included in BIOBADADERM were continuously monitored online, and the group subject to yearly on-site data validation audits. For each treatment, the duration of patients' exposure was calculated from the beginning of therapy to either the last dose that was recorded, November 2023, or the censoring date for those who had been lost to follow-up. Cardiovascular-related deaths were described by the team as fatal MACE.

Nine categories were used by the investigators to stratify subjects of the analysis based on the class of systemic drug they had received: traditional systemic agents such as methotrexate or cyclosporine, small molecules such as apremilast, TNFα inhibitors such as adalimumab or etanercept, IL-12/23 inhibitors such as ustekinumab, IL-23 inhibitors such as guselkumab or risankizumab, and IL-17 inhibitors such as brodalumab or secukinumab.

Lluch-Galcerá et al. wrote that their study's primary endpoint was the adjusted incidence rate ratio (IRR) for MACE. They compared individuals on methotrexate to those on other systemic therapeutic options.

At the study's conclusion, there were 5622 subjects involved in the investigators' analysis. This group contributed 11,368 treatment cycles and 21,762 person-years (PYs) of follow-up.

Apremilast was shown by the team to be associated with a substantially diminished risk of MACE compared to methotrexate (IRR = 0.17; 95% CI: 0.04–0.70). This was also observed for IL-17 inhibitors (IRR = 0.43; 95% CI: 0.20–0.91).

However, the investigative team highlighted an observed association between cyclosporine and a higher MACE risk relative to methotrexate (IRR = 3.59; 95% CI: 1.17–10.99). They did not identify statistically significant differences in MACE risk for the other systemic agents that the analysis had evaluated.

“The remaining systemic psoriasis treatments were not significantly associated with an increased risk of MACE,” they concluded.1 “Assessing [cardiovascular disease] in psoriasis patients is crucial, as different treatments can affect MACE incidence differently.”

References

1. Lluch-Galcerá JJ, Carrascosa JM, González-Quesada A, et al. Cardiovascular safety of systemic psoriasis treatments: A prospective cohort study in the BIOBADADERM registry. J Eur Acad Dermatol Venereol. 2025; 00: 1–12. https://doi.org/10.1111/jdv.20705.

2. Garcia-Doval I, Carretero G, Vanaclocha F, et al. Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials. Arch Dermatol. 2012; 148(4): 463–470.