Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors

Purzycka-Bohdan, Dorota; Kisielnicka, Anna; Bohdan, Michał; Szczerkowska‐Dobosz, Aneta; Sobalska‐Kwapis, Marta; Nedoszytko, Bogusław; Nowicki, Roman

doi:10.3390/ijms22169063

Cited by 19 publications

(20 citation statements)

References 104 publications

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“…Cardiovascular risk factors are among the most common comorbidities in psoriasis [ 26 ]. The results of one observational study in patients with psoriasis suggest that a cumulative duration of exposure to low-grade chronic inflammation is associated with a high prevalence of vascular diseases and MACE events (1.0% per additional year of psoriasis duration) [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure

Griffiths

Gooderham

Colombel

et al. 2022

Dermatol Ther (Heidelb)

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Introduction We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab. Methods Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated. Results A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time. Conclusions The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00743-9.

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Section: Discussionmentioning

confidence: 99%

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure

Griffiths

Gooderham

Colombel

et al. 2022

Dermatol Ther (Heidelb)

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“…Since inflammation is the main process in the pathogenesis and development of psoriasis, it is recognized that other immune-mediated inflammatory diseases are common psoriasis comorbidities, e.g., psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel diseases [ 2 , 4 ]. It should be noted that psoriatic patients are more likely to develop severe vascular events such as myocardial infarction and stroke (up to 50%) than the general population [ 53 , 54 ]. In addition, among psoriatic patients, different endotypes with different risks, severity, and treatment options are distinguished based on hypertension, red cell distribution width, and the mean platelet volume [ 55 , 56 ].…”

Section: Psoriasis and The Local Endocrine Regulatorsmentioning

confidence: 99%

Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

Brożyna

Slominski

Nedoszytko

et al. 2022

IJMS

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Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.

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“…A combination of several exogenous and endogenous factors, including genetic predisposition, is well documented in the etiology and progression of both psoriasis and CVD [ 3 , 4 , 5 , 6 , 7 ]. The presence of systemic inflammation in combination with metabolic abnormalities might explain the high incidence of CVD in psoriatic patients [ 2 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Genetic and genome-wide association studies have recently allowed for the identification of a common genetic background of psoriasis and concomitant cardiovascular risk factors, suggesting pleiotropic mechanisms of interactions involving pro-inflammatory pathways [ 6 ]. However, other factors besides genetic background may explain the prevalence of CVD in psoriasis patients.…”

Section: Introductionmentioning

confidence: 99%

A Possible Link between Gut Microbiome Composition and Cardiovascular Comorbidities in Psoriatic Patients

Valentini

Silvestri

Bucalo

et al. 2022

JPM

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Cardiovascular disease (CVD) is one of the most common comorbidities that may affect psoriatic patients. Several exogenous and endogenous factors are involved in the etiology and progression of both psoriasis and CVD. A potential genetic link between the two diseases has emerged; however, some gaps remain in the understanding of the CVD prevalence in psoriatic patients. Recently, the role of the gut microbiome dysbiosis was documented in the development and maintenance of both diseases. To investigate whether gut microbiome dysbiosis might influence the occurrence of CVD in psoriatic patients, 16S rRNA gene sequencing was performed to characterize the gut microbiome of 28 psoriatic patients, including 17 patients with and 11 without CVD. The comparison of the gut microbiome composition between patients with and without CVD showed a higher prevalence of Barnesiellaceae and Phascolarctobacterium in patients with CVD. Among patients with CVD, those undergoing biologic therapy had lower abundance levels of Barnesiellaceae, comparable to those found in patients without CVD. Overall, these findings suggest that the co-occurrence of psoriasis and CVD might be linked to gut microbiome dysbiosis and that therapeutic strategies could help to restore the intestinal symbiosis, potentially improving the clinical management of psoriasis and its associated comorbidities.

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Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors

Cited by 19 publications

References 104 publications

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure

Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure

Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

A Possible Link between Gut Microbiome Composition and Cardiovascular Comorbidities in Psoriatic Patients

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