Interleukin‐17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation and associated comorbidities

Krueger, James G.; Brunner, Patrick M.

doi:10.1111/exd.13467

Cited by 97 publications

(95 citation statements)

References 122 publications

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“…An American study of 1776 patients with HS found that 57% of patients had at least one psychiatric disorder, thus making psychiatric disorders one of the most common comorbidities in patients with HS . Elevated levels of interleukin 17 (IL‐17) have been found in both depression and anxiety . Schlapbach et al .…”

Section: Discussionmentioning

confidence: 99%

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study

Jørgensen

Yao

Ghazanfar

et al. 2019

Acad Dermatol Venereol

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Aim To examine the burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa (HS). Methods Information on HS and ten systemic comorbidities was obtained by interview and clinical examination, including blood pressure, body mass index (BMI) and blood samples, in a cohort of consecutive HS outpatients. Results A total of 302 patients were included. About 86.6% had at least one comorbidity. The mean number of comorbidities per patient was 2.1. One or more cardiovascular comorbidities were observed in 76.5% with evidence of substantial unawareness and undertreatment; 48.4% had hypertension, 9.3% had diabetes, 57.7% had dyslipidaemia and 36.7% were obese. About 6.6% had inflammatory bowel disease, 6.3% had arthritis, 29.5% had a psychiatric diagnosis, 5.6% had psoriasis, 7.9% had obstructive lung disease, and 6.6% had polycystic ovary syndrome. These comorbidities occurred at different time points in relation to the onset of HS with evidence of shared as well as differential risk factors. Age (per year), HR = 0.87 (0.79–0.96), P < 0.006, age of onset of HS (per year), HR = 1.26 (1.14–1.40), P < 0.001, male sex, HR = 2.51 (0.88–7.16), P = 0.086, Hurley stage III (vs. Hurley I + II), HR = 3.46 (1.25–9.58), P = 0.017, BMI (per unit), HR = 1.12 (1.04–1.20), P = 0.002, and blood glucose (per unit), HR = 1.27 (1.16–1.39), P < 0.001 were significant predictors for onset of diabetes. Conclusion There is a substantial burden, unawareness and undertreatment of several systemic comorbidities in patients with HS. Comorbidities occur at different time points in relation to the onset of HS. This should lead to higher awareness among treating specialists.

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Section: Discussionmentioning

confidence: 99%

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study

Jørgensen

Yao

Ghazanfar

et al. 2019

Acad Dermatol Venereol

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“…Psoriasis is associated with a range of inflammatory and metabolic comorbidities, including obesity, diabetes, dyslipidemia, hyperuricemia and psychiatric conditions, and is associated with increased cardiovascular risk . The exact aetiology of comorbidity in psoriasis remains a topic of current research, but a state of systemic low‐grade inflammation induced by dysregulated Th1 and Th17 activation may contribute to the development of (pre)diabetes, obesity, non‐alcoholic fatty liver disease (NAFLD) and atherosclerosis …”

Section: Introductionmentioning

confidence: 99%

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

Gerdes

Pinter

Papavassilis

et al. 2019

Acad Dermatol Venereol

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Background Psoriasis is associated with metabolic, liver and cardiovascular comorbidity. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A, has shown significant and sustained efficacy in the treatment of moderate to severe psoriasis. Objectives This was an exploratory post hoc analysis of pooled data from three phase 3 studies in plaque psoriasis patient populations. The objective was to show the course of metabolic and liver parameters under secukinumab, etanercept or placebo treatment over time. A further objective was to assess the impact of selected comorbidities and metabolic characteristics on high‐sensitivity C‐reactive protein (hs‐CRP), as a surrogate marker of systemic inflammation. Methods Data from the phase 3 randomized controlled trials [FIXTURE (NCT01358578), ERASURE (NCT01365455) and SCULPTURE (NCT01406938); n = 3010] were included in this analysis. Patients were treated with secukinumab 150 mg or 300 mg, placebo or etanercept 50 mg (FIXTURE only) as active comparator. A set of metabolic and liver parameters was longitudinally assessed over 52 weeks. Multivariate regression analyses assessed the impact of selected comorbidities and metabolic characteristics on hs‐CRP levels at baseline and under treatment. Results Secukinumab treatment reduced hs‐CRP levels. Body weight and uric acid levels tended to decrease over 52 weeks with secukinumab. Secukinumab showed a neutral effect on fasting plasma glucose, lipid parameters and liver enzymes. Psoriatic arthritis, metabolic syndrome, obesity, impaired glucose metabolism, and hyperuricemia were each associated with increased hs‐CRP levels at baseline. Concomitant obesity attenuated the decline in hs‐CRP under treatment. Conclusions These analyses suggest neutral to favourable long‐term trends in metabolic and liver parameters under secukinumab treatment. Metabolic comorbidities were associated with increased hs‐CRP levels, reflecting the role of systemic inflammatory processes in their pathophysiology.

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“…However, several population‐based studies primarily based on Western populations revealed that psoriasis is an independent risk factor for an increased incidence of MI and ischemic events after adjusting cardiovascular risk factors . Highly increased levels of pro‐inflammatory molecules and cytokine‐activated leukocytes entering systemic circulation have been implicated in the resultant cardiovascular and metabolic comorbidities in psoriatic individuals . Indeed, certain transgenic mouse models of psoriatic inflammation were shown to be prone to developing thrombotic comorbidity which was protected by inhibition of IL‐23 or IL‐17A .…”

Section: Discussionmentioning

confidence: 99%

Increased risk of atherosclerotic cardiovascular disease among patients with psoriasis in Korea: A 15‐year nationwide population‐based cohort study

Kim¹,

Kim²,

Lee³

et al. 2019

The Journal of Dermatology

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The association between psoriasis and risk of atherosclerotic cardiovascular disease has not been thoroughly evaluated in a large longitudinal cohort of an Asian population. We conducted a nationwide population‐based retrospective cohort study encompassing more than 1.7 million Koreans with a 15‐year follow‐up period. The period prevalence of psoriasis was 0.33% among the baseline participants (1997–2000). In Cox proportional hazard analyses, the individuals with psoriasis had a higher adjusted hazard ratio (HR) for incidence of overall atherosclerotic cardiovascular disease (HR, 1.18; 95% confidence interval [CI], 1.09–1.27) compared with controls. Subgroup analyses revealed that the risk for myocardial infarction was commonly increased in both sexes with moderate to severe psoriasis (male: HR, 2.09; 95% CI, 1.35–3.24; female: HR, 3.23; 95% CI, 1.34–7.76), whereas the risk for ischemic stroke was specifically increased in female individuals with moderate to severe psoriasis (HR, 2.02; 95% CI, 1.24–3.30). Our data suggest that appropriate medical screening for possible cardiovascular comorbidities is warranted in Asian psoriatic patients according to disease severity and sex.

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Interleukin‐17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation and associated comorbidities

Cited by 97 publications

References 122 publications

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

Increased risk of atherosclerotic cardiovascular disease among patients with psoriasis in Korea: A 15‐year nationwide population‐based cohort study

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