Recent innovations in psoriasis

INTRODUCTION

It is a well-established fact that patients with psoriasis have an increased cardiovascular risk. In a study by Gelfand et al. on a large collective of patients in the UK with a total of 556,995 control patients and patients with mild (n=127,139) and severe psoriasis (n=3,837), a total of 11,194 myocardial infarctions (MIs ) were found in the control group (2%) against 2,319 (1.8%) and 112 (2.9%) MIs in the patients with mild and severe psoriasis groups [1]. An important observation was that the risk was higher in patients below the age of 50. In various regions of the world, similar results were found [2–5]. In a German health insurance database (n=1,344,071), metabolic syndrome and related conditions are more prevalent in those with psoriasis than those without psoriasis [6]. Therefore, it is of major importance that screening for cardiovascular risk factors is established in all national guidelines on the management of psoriasis. The joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities provide practical guidance for screening for vascular risk factors for psoriasis consultations (Table 1) [7].

The question arises at what age we should start with screening for cardiovascular risk factors in patients with psoriasis. In a study on paediatric psoriasis by the International Psoriasis Council (IPC), cardiovascular risk factors were observed in increased frequency in children with psoriasis as compared with children without psoriasis: waist circumference above the 90th percentile occurred in 9.3% of the control (n=19), 14.0% of the mild psoriatic patients (n=27), and 21.2% of the severe Table 1. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities [7]CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia) with national guidelines is recommended for all patients with psoriasis.Clinicians should consider early and more frequent screening for hypertension, diabetes, and hyperlipidemia in psoriasis patients who are candidates for systemic or phototherapy or who have psoriasis involving >10% of the BSA.Risk score models should be adapted for patients with psoriasis by introducing a 1.5 multiplication factor when the patient with psoriasis meets either criteria: disease severity of BSA >10% or candidate for systemic or phototherapy.CV risk management in psoriasis for hypertension and dyslipidemia should be carried out according to national guidelines. The target for blood pressure and lipid levels are based on risk calculated for psoriasis. Antihypertensives and statins may be used as in the general population. CV risk management should be performed by either a primary care physician or other healthcare provider experienced in CV risk management or the dermatologist.

Table 1. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities [7]

CV risk assessment (screening for hypertension, diabetes, and hyperlipidemia) with national guidelines is recommended for all patients with psoriasis.

Clinicians should consider early and more frequent screening for hypertension, diabetes, and hyperlipidemia in psoriasis patients who are candidates for systemic or phototherapy or who have psoriasis involving >10% of the BSA.

Risk score models should be adapted for patients with psoriasis by introducing a 1.5 multiplication factor when the patient with psoriasis meets either criteria: disease severity of BSA >10% or candidate for systemic or phototherapy.

CV risk management in psoriasis for hypertension and dyslipidemia should be carried out according to national guidelines. The target for blood pressure and lipid levels are based on risk calculated for psoriasis. Antihypertensives and statins may be used as in the general population. CV risk management should be performed by either a primary care physician or other healthcare provider experienced in CV risk management or the dermatologist.

The question arises at what age we should start with screening for cardiovascular risk factors in patients with psoriasis. In a study on paediatric psoriasis by the International Psoriasis Council (IPC), cardiovascular risk factors were observed in increased frequency in children with psoriasis as compared with children without psoriasis: waist circumference above the 90th percentile occurred in 9.3% of the control (n=19), 14.0% of the mild psoriatic patients (n=27), and 21.2% of the severe psoriatic patients (n=43) [8]. Also in paediatric patients with psoriasis, screening for cardiovascular risk factors is indicated.Insight into the pathogenetic relation between cardiovascular disease and psoriasis has revealed important shared pathways between psoriasis and the formation of atherosclerotic plaque. IL-17 has been suggested to be a potential mechanistic link between psoriasis and cardiovascular disease [9,10]. A 52-week, randomised, double-blind, placebo-controlled trial on secukinumab was carried out in patients with moderate-to-severe plaque psoriasis without clinical CV disease [11]. The primary outcome was endothelial function measured by flow-mediated dilation (FMD). Baseline FMD was significantly lower in psoriasis patients than in healthy volunteers (4.4 ± 3.9% vs 6.1 ± 3.3%; P<0.01). At week 52, FMD increased across groups. FMD was significantly higher than baseline in patients receiving the label dose of 300 mg secukinumab for 52 weeks (2.1%; P<0.0022).More recently, insights into the genetics of psoriasis and obesity and cardiovascular disease have been gained from Mendelian randomisation studies [12,13]. From these studies, it appeared that the genetic risk for obesity and cardiovascular disease causes psoriasis, but the reverse could not be shown: the genetic risk for psoriasis does not induce obesity or cardiovascular disease, which implies that psoriasis in itself might not be causal for cardiovascular disease.

However, psoriasis is an indicator disease for cardiovascular disease, which is compatible with the observation that cardiovascular risk factors can be present in patients with psoriasis at an early age. Furthermore, weight reduction and other lifestyle improvements should be advised early on. In line with the causal relationship between obesity in the direction of psoriasis is the observation that weight reduction may improve psoriasis involvement of the skin considerably [14].Anti-inflammatory treatments for psoriasis have been suggested to reduce cardiovascular risk. In particular, intensive treatment of psoriasis with anti-TNF, anti-IL-12/23, and anti-IL-17 have been claimed to have positive effects on cardiovascular comorbidity. A prospective observational study with biologic therapy versus non-biologics therapy revealed a significant improvement in coronary artery parameters after one year follow-up: total plaque burden and non-calcified plaque burden improved significantly [15].Various biologics used to treat psoriasis influence vascular inflammation and cardiometabolic parameters, thereby reducing cardiovascular risk [16–19]. Furthermore, methotrexate, cyclosporine, and tofacitinib have been suggested to impact vascular inflammation and biomarkers of cardiometabolic disease in psoriatic patients [20]. Also, the small molecule apremilast proved to induce beneficial changes in blood cardiometabolic biomarkers [21].

However, further prospective controlled studies are needed before we can conclude whether anti-inflammatory treatments of psoriasis improve cardiovascular comorbidities in patients with psoriasis.In studies on big data, substantial reductions of cardiovascular risk have been shown by anti-TNF; 3-year exposure to TNF antagonists resulted in a 51% reduction of the hazard for cardiovascular disease [22]. On the other hand, data from patient registries have been less convincing so far [23]. In a large prospective cohort study, the risk reduction of cardiovascular disease between three different biologic therapies and methotrexate could not be shown to be different [23]. Further well-designed prospective controlled long-term studies are needed before we can conclude whether anti-inflammatory treatments of psoriasis improve cardiovascular comorbidities in patients with psoriasis. So far, our knowledge of the impact of various anti-psoriatic treatments on cardiovascular disease and cardiovascular disease risk factors is fragmentary. But, should we wait for evidence from long-term controlled studies before taking advantage of the daily practice of these new compelling insights revealed by surrogate markers for cardiovascular disease? In a learning healthcare environment, we can treat our patients while capturing real-world evidence on the effect of the anti-psoriatic treatments on cardiometabolic risk factors and cardiovascular disease in patient registries, not only from the point of view of pharmacovigilance but from the point of view of a more holistic disease severity assessment, which is more than skin deep, considering cardiovascular risk and comorbidity.

Lessons from COVID-19

The pandemic COVID-19 has had its impact on patients with psoriasis. The virus SARS-CoV-2, responsible for COVID-19, invades host cells in the lung [24]. Binding of the spikes of the virus with angiotensin-converting enzyme (ACE)2 receptors is the first step. Viral replication follows and an immune response is induced which comprises a T-cell response and a differentiation of B cells into plasma cells, producing neutralising antibodies. Type I interferon is a critical cytokine in the first week of the COVID-19 infection. Crucial in the course of COVID-19 is whether a cytokine storm will complicate the immune response. It has been shown that TNF, IL-17, and IL-4 are key cytokines in the cytokine storm. The cytokine storm is responsible for the life-threatening course COVID-19 may have. It is intriguing that anti-TNF and anti-IL-17 are important treatment classes for psoriasis. In the first months of the COVID-19 pandemic, dermatologists felt unsure about the impact of systemic non-biologics and biologics on the course of COVID-19 and later on the course of the COVID-19 vaccination process.

In particular, the fear that patients on these drugs might have a more severe course of the disease as these drugs are contraindicated in active infections, but also the fear that these treatments may facilitate contracting COVID-19. Similar questions arose when vaccinations became available. Are vaccinations safe in patients who are on systemic treatments for psoriasis? Are vaccinations effective when patients are on these treatments?At first, decisions were based on the best insights into modes of action of anti-psoriatic drugs and the pathomechanism in COVID-19. Early in the pandemic, a registry was constructed and international organisations motivated dermatologists to collect information on patients with psoriasis, the treatments they received for psoriasis, and the course of COVID-19.To build evidence for the decision to continue or discontinue immunosuppressive medication in patients with psoriasis during the COVID-19 pandemic, another international patient registry was established: PsoProtect. This registry also collected detailed information on patients with psoriasis, who contracted COVID-19. The information collected in the registries provided evidence relevant to clinical practice on the treatment of psoriasis in COVID-19. COVID-19-related hospitalisation in patients on biologics proved to be lower than in patients on non-biologic systemic therapies [25]; however, it is remotely possible that patients on biologics had more rigorous isolation, which might be a confounding factor. In the population of patients with psoriasis, the well-known risk factors (older, male, non-white ethnicity, and comorbidities) caused higher hospitalisation rates. Similar trends were seen in other immune-mediated inflammatory diseases (IMIDs). Data from 3 international COVID-19 registries (including patients with rheumatic diseases, inflammatory bowel disease, and psoriasis collected from 12 March 2020 to 1 February 2021) were merged [26].

TNF inhibitor monotherapy implied a lower risk of a bad COVID-19 outcome compared with other immunomodulatory treatments in patients with IMIDs. This rapid development of partially harmonised, international patient registries was an important international achievement [27]. Real-world data have helped to formulate the lessons of this pandemic. One of those lessons is that biologics are safe in children with psoriasis and COVID-19 [28]. In 15% of the children, an aggravation of psoriasis was seen during the pandemic. Greater shielding among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes.

The question arises to what extent shielding causes the lower occurrence of severe COVID-19 development in those patients using targeted treatments [29]. In an international patient survey, 2,262 of 3, 720 participants (60.8%) reported risk-mitigating behaviour or 'shielding'. Patients receiving targeted therapies (biologics and Janus kinase inhibitors) reported shielding more frequently compared with those receiving no systemic therapy. Shielding was also associated with risk factors for severe COVID-19 comorbidity, indication for drugs for rheumatic musculoskeletal diseases and anxiety or depression.Anxiety and non-adherence regarding anti-psoriatic treatments have impeded the treatment of psoriasis during COVID-19 [30]. In patients with worsening psoriasis, anxiety to take the medication might be the reason for aggravation. Fears, anxieties, and confusion have to be addressed by an optimal doctor-patient relationship and, if needed, psychotherapy.Only 8% of individuals with psoriasis reported vaccine hesitancy [31]. This is reassuring for the efficacy of COVID‐19 vaccine uptake. Identifying individuals with concerns regarding COVID‐19 vaccination and providing personalised information will help to reduce the risk of patients with psoriasis in the ongoing pandemic.

Teledermatology and psoriasis

Teledermatology has been practised by dermatologists for years. During the COVID-19 pandemic, we had to learn how to work more and more in the virtual environment. There is, however, a large variation between dermatologists in enthusiasm and actual use of teledermatology for psoriasis. Some dermatologists are reluctant with respect to making the diagnosis and starting and maintaining treatment of psoriasis using teledermatology. Other colleagues are enthusiastic about the opportunities teledermatology is providing with respect to psoriasis care. During the COVID-19 pandemic, we had to make far more intense use of teledermatology for the treatment of psoriasis and interestingly, the popularity of teledermatology has increased. Teledermatology may be restricted to the dermatologist and the patient or it may be the consultation of both the general practitioner, the dermatologist, and the patient.

Storing and forwarding pictures is a highly efficient form of teledermatology, where the consultation by the patient and the reply by the dermatologist do not have to be synchronous. Live video conferencing is a more dynamic form of consultation, which is of course synchronous.The International Psoriasis Council (IPC) installed a working group of experts in telemedicine [32]. Statements on opportunities and limitations of telemedicine in the diagnosis and treatment of psoriasis were formulated by this group. Thirty‐six statements were agreed upon. Overall, the value and necessity for the implementation of teledermatology in dermatologic healthcare practices for psoriasis was regarded to be crucial by the group. Best practices on personalised care in psoriasis have to be developed and shared. Especially for early diagnosis of psoriasis, teledermatology provides opportunities but also limitations; in particular, in case the diagnosis is not so apparent. According to the working group, initiation and maintenance of topical treatments can be managed by teledermatology. Also, for maintenance treatments of patients with biologics, teledermatology provides an excellent approach with a low threshold approach contact possibility. For remote areas in the world, different forms of teledermatology can be successful. For some situations teledermatology may have limitations; for example, when whole skin inspection is needed and in case of functional tests (psoriatic arthritis).

In a learning healthcare environment, we have to take advantage of the opportunities of telemedicine and in-person consultations, reconciling the individuality of the patient and his/her psoriasis. Everyone has his own psoriasis and every person is unique, so, we have to personalise the treatment, making use of the classical in-person consultations where needed and possible and teledermatology where appropriate.The impact of the innovations described above for patients living with psoriasis and their dermatologist are clear:
(1) Cardiovascular comorbidities and psoriasis are associated. Screening for cardiovascular risk factors is also important in patients with a short history of psoriasis. Adequate treatment of these risk factors is important.
(2) Lessons from COVID-19 comprise the insight that COVID-19-related hospitalisation in patients on biologics was lower than in patients on non-biologic systemic therapies, and regarding vaccination: there is no reason to avoid vaccination in patients with psoriasis. For an up to date advice on COVID-19 and psoriasis, consult the IPC webpage: https://www.psoriasiscouncil.org/covid-19/ipc-statements-on-covid-19-psoriasis.
(3) Practical skills in teledermatology have advanced markedly during the COVID-19 pandemic. Compelling new findings and experiences have emerged that enrich treatment opportunities and improve access to care worldwide.

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Posted on 7 September 202322 November 2024