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

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.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Psoriasis; Atopic Dermatitis
• Intervention / Treatment: Drug: biological treatment

• Study Type: Observational
• Enrollment (Actual): 126

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Dep. of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe psoriasis recruited from a dermatological in- and out patient clinic. Patients with severe atopic dermatitis.

Description

Inclusion Criteria:

1. Males and females aged 18 years or above.
2. 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.
3. Signed informed consent form prior to initiation of any study-mandated procedure.

Exclusion Criteria:

1. Significant arterial hypertension, unless well controlled with anti-hypertensive medication for at least 1 month before inclusion.
2. Lipid-lowering treatment, unless well controlled for at least 1 month before inclusion.
3. Congestive heart failure (NYHA group III and IV).
4. Reduced kidney function (eGFR below 60).
5. 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.
6. UVB phototherapy and PUVA photochemotherapy within 1 month prior to study start.
7. Prior treatment with infliximab, etanercept, adalimumab or ustekinumab unless less than PASI-50% reduction have been observed during this treatment.
8. Investigational biological agents within 6 months prior to inclusion.
9. Any other investigational drug within 1 month or 5 half lives prior to inclusion, which ever is longer.
10. Concurrent immunosuppressive or anti-inflammatory treatment for immune diseases other than psoriasis and psoriatic arthritis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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: Etanercept; Adalimumab; Infliximab; Ustekinumab
Severe atopic dermatitis
Control; No intervention. No inflammatory skin disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in coronary calcium score (CAC score)	Psoriasis groups evaluated at 0 and approximately 12 months. AD group and controls at baseline only.	baseline: 0 months, and follow-up: approximately 12 months
Repeated Coronary CT Angiography (CCTA)	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.	0 and approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular risk markers	hs-crp, homocystein, SBHG, apolipoprotein B, MBL, PAPP-A.	0, 3 and 12 months
interleukines in blood	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)	0, 3 and 12 months
traditional cardiovascular risk factors	monitoring of blood cholesterol levels and blood glucose.	0, 3 and 12 months

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: AbbVie; Aarhus University Hospital; Aage Bangs Fond; Region Midt Forskningsfond
• Investigators: Principal Investigator: Kasper F Hjuler, M.D., Aarhus University Hospital

Publications and helpful links

General Publications

• Hjuler KF, Bottcher M, Vestergaard C, Deleuran M, Raaby L, Botker HE, Iversen L, Kragballe K. Increased Prevalence of Coronary Artery Disease in Severe Psoriasis and Severe Atopic Dermatitis. Am J Med. 2015 Dec;128(12):1325-34.e2. doi: 10.1016/j.amjmed.2015.05.041. Epub 2015 Jun 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (Estimate): May 19, 2011

Study Record Updates

• Last Update Posted (Estimate): December 21, 2015
• Last Update Submitted That Met QC Criteria: December 18, 2015
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Skin Diseases, Papulosquamous; Psoriasis; Dermatitis; Atherosclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Etanercept; Adalimumab; Infliximab; Ustekinumab
• Other Study ID Numbers: j-nr 20100249

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided