Beyond skin: Integrating the cardiovascular impact of psoriasis therapies into disease management

Abstract

The association between moderate-to-severe psoriasis and increased cardiovascular morbidity and mortality is well established, with chronic systemic inflammation recognized as a central pathogenic mechanism.¹ Nevertheless, a patient's cardiovascular risk and the impact of psoriasis therapies on cardiovascular outcomes have not yet been fully integrated into the therapeutic algorithms that guide the selection of systemic treatments for psoriasis. In this context, the prospective, registry-based study by Lluch-Galcerá et al. offers clinically meaningful data and raises important considerations for future treatment recommendations and clinical decision-making.²

Drawing on more than 21,000 person-years of follow-up from 5622 patients across 11,368 treatment cycles from the BIOBADADERM registry—a well-established Spanish prospective multicentre cohort of patients with psoriasis treated with systemic therapies in routine clinical practice—the authors report differential incidence rates of major adverse cardiovascular events (MACE) across therapeutic classes. Notably, apremilast and IL-17 inhibitors were associated with a statistically significant lower risk of MACE compared to methotrexate, whereas cyclosporine was linked to an increased risk. Other therapeutic classes, including IL-12/23, IL-23 and TNF inhibitors, showed no significant difference versus methotrexate in adjusted models.

These findings merit attention on several levels. First, they provide real-world evidence (RWE) in a therapeutic area where data on the cardiovascular impact of psoriasis therapies remain scarce and are largely extrapolated from other immune-mediated inflammatory diseases.³ Moreover, randomized controlled trials (RCTs) in psoriasis are often underpowered and lack long-term follow-up, limiting their ability to detect rare events such as MACE. Thus, the present data fill a critical gap by evaluating cardiovascular outcomes in a large, representative cohort of patients with psoriasis treated in routine clinical practice.

Second, the observed protective association with apremilast and IL-17 inhibitors, although observational, is biologically plausible. Previous mechanistic and clinical studies have reported favourable effects of both drug classes on surrogate markers of cardiovascular risk, including lipid profiles, insulin sensitivity and inflammatory biomarkers. In particular, IL-17A blockade has been shown to attenuate vascular inflammation and endothelial dysfunction,⁴ while apremilast may exert cardioprotective effects via modulation of cAMP-mediated anti-inflammatory pathways.⁵ While causality cannot be inferred, these findings may signal a class effect with potential cardiometabolic relevance, particularly in patients with multiple risk factors.

Conversely, the increased cardiovascular risk associated with cyclosporine reinforces long-standing concerns. This agent's known hypertensive, dyslipidemic and nephrotoxic profile likely contributes to its adverse cardiometabolic effects, and its use should be approached with particular caution in patients with established cardiovascular disease or high baseline risk. The present study provides further empirical support for this position, emphasizing the importance of cardiovascular screening and monitoring when using cyclosporine.

Finally, it is also worth noting that methotrexate, used as the reference comparator, may confer its own cardiovascular benefits through suppression of systemic inflammation, potentially underestimating the relative safety of other therapies. Furthermore, the absence of statistically significant differences for some biologic classes should not be interpreted as evidence of equivalence. As acknowledged by the authors, the failure to detect differences may be due to low statistical power resulting from the small number of MACEs detected. However, the relatively narrow 95% confidence intervals suggest that these non-significant findings are unlikely to mask risks of major clinical relevance. This nuance reinforces the importance of interpreting null results with caution, especially in real-world studies with infrequent outcome events.

Beyond individual drug comparisons, this study contributes to a broader shift in psoriasis care: the transition from a skin-focused model to a systemic, comorbidity-conscious approach. While dermatologists increasingly recognize the relevance of cardiovascular risk in psoriasis, treatment choices remain largely driven by cutaneous efficacy, access and patient preference. Data such as those provided by BIOBADADERM should prompt a more systematic incorporation of cardiovascular considerations into clinical decision-making, especially in patients with elevated baseline risk.

In conclusion, the findings by Lluch-Galcerá et al. support the integration of cardiovascular risk assessment into the therapeutic selection process for patients with psoriasis. Future guidelines may benefit from incorporating cardiovascular safety profiles of systemic therapies, guided by RWE such as that presented here. As treatment options expand, optimizing outcomes will depend not only on achieving skin clearance but also on addressing the broader systemic burden of the disease.

Tiago Torres has received consultancy and/or speaker's honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz and UCB.