Biologic psoriasis treatment to lower cardiovascular risk?

Comparing and weighing the different research results, biologics used for psoriasis have not established the ability to lower cardiovascular (CV) risk [1]. Vigorously screening for CV risk factors seems to be the appropriate management for now.

Can the treatment of psoriasis directly impact the CV risk of patients? This is the question that Prof. Joel Gelfand (University of Pennsylvania, USA) strove to answer in his talk, explaining the different possible methods of research and their results.

Patients with psoriasis have an increased risk of mortality and major CV events (MACE), especially when their psoriasis is moderate to severe. Chronic inflammatory, metabolic irregularities, and CV disease are often present in psoriasis. Prof. Gelfand’s lab followed 8,760 psoriasis patients and 87,600 adults without psoriasis over an average time of >4 years [2]. After adjusting for comorbidities, a psoriasis body surface area (BSA) >10% entailed an increased mortality risk by 1.79 times. It has also been shown that the risk of developing diabetes escalates with higher BSA in psoriasis patients [3]. These findings seem to encourage doctors to choose aggressive treatments just because higher disease severity results in higher rates of mortality or diabetes. Yet, Prof. Gelfand advises to also take into account the potential side effects from treatment in this decision.

In studying CV disease in general, or in psoriasis in particular, researchers may either look at CV biomarkers or, ideally, at CV events, and they can choose between observational studies and RCTs. “In a perfect world we would be looking at RCTs of events,” Prof. Gelfand stated. A trial by Metha ate al. opted for a biomarker approach using 18-FDG PET/CT measurement of aortic vascular inflammation, as this inflammation is predictive of future CV events. The trial assessed treatment with adalimumab, phototherapy, and placebo over 12 weeks [4].

A within-groups comparison to baseline showed significance for phototherapy, but this disappeared when compared with placebo. In a 1-year, open-label extension with crossover to adalimumab, a significant 3.8% reduction of aortic vascular inflammation was revealed compared with baseline [4]. However, that significant change disappeared when comparing the start of adalimumab treatment with the end of the study (P=0.987) [4]. In 2 further RCTs that assessed secukinumab and ustekinumab, only the latter induced improvement in aortic vascular inflammation [5,6].

A number of observational studies have suggested that TNF blockers could lower the risk for myocardial infarction in both psoriasis and rheumatoid arthritis, but observational data has its limitations. Three RCTs that tested canakinumab, methotrexate, and colchicine with thousands of patients with pre-existing coronary disease revealed a reduction of events with canakinumab (HR 0.85) and colchicine (HR 0.77) but not with methotrexate [7-9]. However, there are also trade-offs to think about when using immunomodulatory therapy to prevent CV disease.

“Where does that leave us?” asked Prof. Gelfand. There are currently no therapies used for psoriasis that have proven to lower CV events in RCTs. Prof. Gelfand advised to follow the latest guidelines and screen patients for risk factors, perhaps more frequently in people with moderate-to-severe psoriasis getting phototherapy or biologics, and to consider using statins earlier in people with more severe psoriasis [10,11].

1. Gelfand JM. AAD Virtual Meeting Experience, 12-14 June 2020.
2. Noe MH, et al. J Invest Dermatol. 2018;138:228-230.
3. Wan MT, et al. J Am Acad Dermatol. 2018;78:315-322.
4. Mehta NN, et al. Circ Cardiovasc Imaging. 2018;11:e007394.
5. Gelfand JM, et al. J Invest Dermatol. 2020;140:85-93.
6. Gelfand JM, et al. J Invest Dermatol. 2020;ppi: S0022-202X(20)30157-3.
7. Ridker PM, et al. N Engl J Med 2017;377:1119-1131.
8. Ridker PM, et al. N Engl J Med 2019;380:752-762.
9. Tardif JC, et al. N Engl J Med. 2019;381:2497-2505.
10. Grundy SM, et al. Circulation. 2019;139:e1082-e1143

Posted on 6 August 20206 September 2023