Cardiovascular Risk Assessment in Patients With Severe Psoriasis Treated With Biologic Agents

Sponsor

University of Aarhus (Other)

Overall Status

Completed

CT.gov ID

NCT01356758

Collaborator

Aarhus University Hospital (Other), Aage Bangs Fond (Other), AbbVie (Industry), Region Midt Forskningsfond (Other)

126

Enrollment

Location

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Psoriasis is a common inflammatory disease of the skin and joints with a prevalence of 1-3% in the caucasian population of Northern Europe and the US. Similarly to other inflammatory diseases there is now substantial and accumulating evidence that psoriasis has a systemic inflammatory component.

It is known that patients suffering from psoriasis have increased prevalence of traditional cardiovascular risk factors, such as hypertension, dyslipidaemia, obesity, tobacco use and diabetes mellitus. This would logically explain an increased rate of cardiovascular events, but even when adjusting for theses risk factors, psoriasis carry an independent risk for developing cardiovascular disease.

Recent large epidemiological studies have shown a strong correlation between psoriasis and myocardial infarction.

Atopic dermatitis has been linked to ischemic stroke in one study, but besides this, the disease has not been associated with cardiovascular disease.

In conclusion, convincing and increasing evidence is supporting that psoriasis induce accelerated atherosclerosis and hence cardiovascular disease and mortality. In particular, this is seen in young patients with early disease onset.

Psoriasis is believed to be driven by cytokines produced by Th1 and Th17 lymphocytes. A number of these cytokines are suggested to be atherogenic. In contrast, another chronic inflammatory disease, atopic dermatitis, is predominantly driven by Th2 lymphocyte derived cytokines, some of which may inhibit atherosclerotic processes. It is therefore, of interest to compare the presence of cardiovascular disease in these two inflammatory skin diseases.

Hypothesis: That the risk of developing cardiovascular disease and especially coronary artery disease is increased in psoriasis patients and that this process can be influenced by treatment of psoriasis with biological treatment.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Atopic Dermatitis Atherosclerosis	Drug: biological treatment

Study Design

Study Type:

Observational

Actual Enrollment :

126 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Cardiovascular Risk Assessment in Patients With Severe Psoriasis Treated With Biologic Agents

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Psoriasis topical treatment Psoriasis topical treatment. No systemic drugs.
Psoriasis biological treatment Psoriasis biological treatment. Anti-Tnf and anti-il12/23.	Drug: biological treatment patients treated with anti-psoriatic biological agents Other Names: Adalimumab Etanercept Infliximab Ustekinumab
Severe atopic dermatitis Severe atopic dermatitis
Control No intervention. No inflammatory skin disease.

Outcome Measures

Primary Outcome Measures

Change in coronary calcium score (CAC score) [baseline: 0 months, and follow-up: approximately 12 months]
Psoriasis groups evaluated at 0 and approximately 12 months. AD group and controls at baseline only.
Repeated Coronary CT Angiography (CCTA) [0 and approximately 12 months]
Assessment according to the 18-segment model (as suggested by AHA): Changes in number of coronary plaques, stenosis, severity, composition. Changes in coronary plaque volume index. Psoriasis groups evaluated at 0 and approximately 12 months. AD group and untreated controls at baseline only.

Secondary Outcome Measures

Cardiovascular risk markers [0, 3 and 12 months]
hs-crp, homocystein, SBHG, apolipoprotein B, MBL, PAPP-A.
interleukines in blood [0, 3 and 12 months]
selected cytokines (amongst: TNFα, IL-1, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL17A, IL-19, IL-20, IL-23, IFN, ICAM-1, E-selectin)
traditional cardiovascular risk factors [0, 3 and 12 months]
monitoring of blood cholesterol levels and blood glucose.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Males and females aged 18 years or above.
Intervention group: Severe plaque psoriasis with indication for biological therapy according to national guidelines. Psoriasis Control group: Patients with similar disease activity who for personal reasons decline systemic treatment and only receive topical therapy. Atopic dermatitis group: Patients matched regarding sex, disease duration, body surface involvement, BMI and smoking habits.
Signed informed consent form prior to initiation of any study-mandated procedure.

Exclusion Criteria:

Significant arterial hypertension, unless well controlled with anti-hypertensive medication for at least 1 month before inclusion.
Lipid-lowering treatment, unless well controlled for at least 1 month before inclusion.
Congestive heart failure (NYHA group III and IV).
Reduced kidney function (eGFR below 60).
Oral methotrexate, ciclosporin, acitretin and fumarate esters within 1 month before inclusion. In the intervention group, patients receiving oral anti-psoriatic treatment for at least 6 months before the study start can be included, if they are maintained on the same dose during the study period.
UVB phototherapy and PUVA photochemotherapy within 1 month prior to study start.
Prior treatment with infliximab, etanercept, adalimumab or ustekinumab unless less than PASI-50% reduction have been observed during this treatment.
Investigational biological agents within 6 months prior to inclusion.
Any other investigational drug within 1 month or 5 half lives prior to inclusion, which ever is longer.
Concurrent immunosuppressive or anti-inflammatory treatment for immune diseases other than psoriasis and psoriatic arthritis.