Comorbidities

Peter Foley MBBS, BMedSc, MD, FACD Associate Professor of Dermatology, The University of Melbourne, Department of Medicine (Dermatology), St Vincent’s Hospital Melbourne Dermatology Investigation, Biological Therapies and Photobiology Clinics, St Vincent’s Hospital Melbourne Phototherapy and Biological Clinics, Skin and Cancer Foundation Inc (Victoria)

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Disclosures / Conflicts of Interest

• CSL – A, SP

• Galderma/PhotoCure – A, C, I, SP, T

• 3M/iNova/Valeant – A, I, SP

• LEO/Peplin – A, C, I, SP, T

• Roche – C, SP, T

• Ascent – C, SP, T

• Clinuvel – A, C, I

• GSK/Stiefel – A, I, SP

– A = advisory board

– C = consultant

– I = investigator (clinical trials)

– SP = speaker’s bureaux

– T = travel grants

• Abbott – A, SP

• BiogenIdec – A, I, SP

• Janssen-Cilag – A, C, SP

• Merck Serono - A, I, SP

• Schering-Plough/MSD – A, I, SP

• Wyeth/Pfizer – A, C, I, SP

• Amgen – A, I

• Novartis – A, I, SP, T

• Eli Lilly - I

• Celgene - I

• Australian Ultraviolet Services - C

• Aspen - SP

• BMS - I

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Psoriasis morbus fortiorium

“Psoriasis: the disease of people in good health”

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Comorbidities in Psoriasis

• A distinct number of concomitant disease entities have more frequently been observed than expected

• Such associations referred to as ‘comorbidities’ • May represent effect of shared risk factors

– Genetic predisposition – Environmental exposure – Factors related to long course of psoriasis – Factors related to treatment of psoriasis

• May represent an artifact because of increased surveillance of patients with psoriasis

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Comorbidities in Psoriasis

• Metabolic syndrome – Hypertension – Diabetes mellitus Type II – Dyslipidaemia

• Obesity • Cardiovascular disease and death • Psoriatic arthritis • Inflammatory Bowel Disease • Anxiety and Depression • Smoking and Alcohol • Lymphoma

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Co-morbidities In Psoriasis Patients

Hypertension Anxiety

Psoriatic arthritis

Depression

Diabetes Substance / Alcohol

abuse

All other forms of arthritis

Total (n=1000)

Moderate (n=398)

Severe (n=204)

Very Severe (n=397)

27%

23%

22%

17%

16%

16%

11%

10%

8%

2%

8%

31%

37%

28%

39%

23%

19%

22%

16%

15%

11%

3%

11%

15%

35%

23%

24%

25%

21%

16%

14%

13%

12%

2%

11%

23%

17%

20%

14%

10%

11%

12%

6%

7%

4%

1%

6%

44%

Obesity

Hypercholesterolaemia

Skin Cancer

Other

None

EU CHART study report 2004

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Psoriasis Co-morbidities in Australia

Co-morbidity n %

Obesity 328 48.7

Hypertension 178 26.4

Hyperlipidaemia 139 20.6

Depression 105 15.6

Diabetes 91 13.5

Non-melanoma skin cancer 61 9.1

Liver disease 60 8.9

Ischaemic heart disease 36 5.3

Other psychiatric illness 30 4.5

Other cancer 25 3.7

Melanoma skin cancer 18 2.7

Alcoholism 18 2.7

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Comorbidities of plaque psoriasis

– Increased risk of cardiovascular (CV) disease and CV risk factors1-6

• Including obesity,2,3 diabetes,1-3 metabolic syndrome,3,5 hypertension,1-3 hyperlipidaemia,1,2 and non-alcoholic fatty liver disease5

– The development of CV and/or metabolic disease may be linked to:

• Conventional risk factors for CVD/metabolic syndrome • Persistent systemic inflammation associated with chronic psoriasis7,8

– Psoriatic arthritis is a common complication, arising in up to one-third of psoriasis patients3

• Clinically unrecognized enthesitis may occur in early PsA9

• Dactylitis is associated with increased radiological damage10

– Psoriasis has also been associated with an increased risk of Crohn’s disease, chronic obstructive pulmonary disease, and gastroesophageal reflux disease1,2

1. Wu Y, et al. J Drugs Dermatol. 2008;7(4):373-7. 2. Mrowietz U, et al. Arch Dermatol Res. 2006;298(7):309-19. 3. Gottlieb AB, et al. J Dermatolog Treat. 2008;19(1):5-21. 4. Ludwig RJ, et al. Br J Dermatol. 2007;156(2):271-6. 5. Gisondi P, et al. J Hepatol. 2009;51(4):758-64. 6. Gisondi P, et al. Dermatology. 2009;218(2):110-3. 7. Kourosh AS, et al. Skin Therapy Lett. 2008;13(1):1-5. 8. Boehncke W-H, et al. BMJ. 2010;340:200-3. 9. McGonagle D. J Eur Acad Dermatol Venereol. 2009 Sep;23 Suppl 1:9-13. 10. Brockbank J, et al. Ann Rheum Dis. 2005;64:188-90.

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• Association with comorbidities

• Higher Psoriasis Disease Severity is Associated with Increased Comorbidities in Europe. Sato R, Piercy J, Kay S, Walker S, Singh A. (Wyeth Research / Adelphi Group Products)

BSA >= 10% severe BSA < 10% mild

Psoriasis Severity

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Inflammatory dysfunction is likely to contribute to the development of comorbidities in psoriasis

• Immune dysregulation and inflammation play an important role in the development and progression of psoriasis1,2

• As psoriasis progresses, persistent inflammatory dysfunction may drive the development of comorbid conditions such as cardiovascular disease1,2

1. Kourosh AS, et al. Skin Ther Lett. 2008;13(1):1-5. 2. Boehncke W-H, et al. BMJ. 2010;340:200-3.

The psoriatic march2

Cardiovascular disease

Atherosclerosis

Obesity

Endothelial dysfunction

Insulin resistance

Systemic inflammation

Psoriasis Smoking/alcohol

= association

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The psoriatic march and the development of comorbidities

Gisondi P, Girolomoni G. Actas Dermosifiliogr. 2009;100 Suppl 2:14-21.

Diabetes

Psoriasis

Psoriatic arthritis

NAFLD

Hypertension

Dyslipidaemia

Smoking

Cardiovascular diseases

Metabolic syndrome

Obesity

Genes Environmental

triggers

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Metabolic Syndrome

• For metabolic syndrome to be diagnosed, at least three of the following apply: – Waist circumference > 102 cm (men); 88 cm

(women) – Serum triglycerides >= 1.69 mmol/L – HDL cholesterol < 1.04 mmol/L (men); 1.29

mmol/L (women) – Blood pressure >= 130/85 mm Hg – Serum glucose >= 6.1 mmol/L

– NIH ATP III (Adult Treatment Panel), www.nhlbi.nih.gov/guidelines/cholesterol

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Metabolic Syndrome

• Psoriasis patients: – Have risk of developing metabolic

syndrome

– More severe psoriasis: risk

• Not known whether link is causative or a result of patient habits eg sedentary life, smoking, alcohol Cop

yrigh

t

Psoriasis is associated with an increased risk of the metabolic

syndrome

Type of rate OR and 95% CI OR 95% CI

Unadjusted 2.16 1.16-4.03

Multivariate† 1.96 1.02-3.77

0 3 2 1

Odds ratios (OR) for the metabolic syndrome* in a psoriasis population vs a control population

National Health and Nutrition Examination Survey, 2003-2006. (US; n = 71 cases, n = 2385 controls) Love TJ, et al. Arch Dermatol. 2011;147(4):419-24.

4

*Revised NCEP ATP III Definition †Adjusted for for age, sex, race/ethnicity, smoking status, and C-reactive protein (CRP) levels

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Hypertension, Diabetes, Dyslipidaemia

• All are more common in pts with psoriasis • Obesity, hypertension, heart failure and diabetes were as much

as two-fold more prevalent in 2,941 psoriatic inpatients compared to age-matched non-psoriatic patients (Henseler T and Christophers E, Disease concomitance in psoriasis. J Am Acad Dermatol 1995; 32: 982-6).

• Hypertension – rate due to obesity or use of cyclosporin – Smoking

• Diabetes Type II – Insulin resistance / metabolic syndrome – Associated with obesity

• Dyslipidaemia – Secondary to medication eg retinoids – Associated with obesity – Alcohol

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Obesity

• Common in psoriasis patients – Rates reaching 48%

– Prevalence ratio of 1.5 in patients with moderate to severe disease

– Weight loss may improve psoriasis • Through reduction of IL-6 and CRP

• Weight reduction after gastric bypass has resulted in remission of psoriasis

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Cardiovascular Disease and Death

• Psoriasis is an independent risk factor for atherosclerosis

• Severity of psoriasis is independent risk factor for MI regardless of presence of the metabolic syndrome

• Pts with PASI 10-20 and pts with PASI >20: – Similar 10-yr risk of coronary heart disease and stroke

• Compared with general population, 10-yr risk was: • 28% greater for coronary heart disease (P<0.001) • 11.8% greater for stroke (P=0.02)

Kimball et al (Am J Med 2010;123(4):350-357)

• Peripheral vascular disease increased in psoriasis patients

Prodanovich et al (Arch Derm 2009;145(6):700-3)

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Cardiovascular Disease and Death

• Young patients with severe psoriasis have MI / cardiovascular mortality – Psoriasis patients treated at least once as an inpatient had a 50%

increased risk for cardiovascular mortality compared to the general population

– Risk was clearly associated with: • severity of psoriasis • number of hospital admissions • admission at a young age

(Mallbris L, Akre O, Granath F, et al., Eur J Epidemiol 2004; 19:225-230)

• In UK: – Lifespan of patients with severe psoriasis decreased by 5% – Patients with onset < 25 yo: Lifespan shortened by 20 years

• Psoriasis most likely predisposes to increased risk of

cardiovascular disease by causing increase in TH-1 cytokines (TNF-α, IL2, IFNγ) – Cause upregulation of adhesion molecules and endothelins – Cause premature vascular damage and atherogenesis

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Adjusted relative risk of MI in patients with psoriasis based on patient age

1.29

3.10

1.08

1.36

Psoriasis may confer an independent risk of MI. The RR was greatest in young patients with severe psoriasis.

Gelfand JM, et al. Risk of myocardial infarction in patients with psoriasis. JAMA 2006; 296:1735-41.

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Severe psoriasis is associated with an increased risk of all-cause mortality

Gelfand JM, et al. Arch Dermatol. 2007; 143:1493-9.

Hazard

ratio

of m

orta

lity

vs

con

trols

(95

% c

onfi

denc

e int

erv

als)

Mild psoriasis (n=133,568) Severe psoriasis (n=3951)

3.0

0.5

0 95

Age (years)

85 75 65 55 45 35 All ages

1.0

1.5

2.0

2.5

3.5

Hazard ratio (95% confidence interval) for all-cause mortality vs controls

4.0

Retrospective, population-based cohort study (UK; n=137,519 cases, n=575,433 controls)

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Risk of obesity is significantly increased in patients with psoriasis

Prey S, et al. J Eur Acad Dermatol Venereol. 2010;24 Suppl 2:23-30.

Risk of obesity in psoriatic patients (odds ratio with 95% confidence interval)

Study*

*See slide notes for citations in full.

Herron 2005

Naldi 2005

Neimann 2006

Gisondi 2007

Kaye 2008

Cohen 2008

Naldi 2008

Driessen 2008

2.39

1.9

1.84

1.29

1.19

1.18

1.7

1.7

5.49

2 4 6 8 10

Matching

Not matching

Mild and moderate

Severe

Populations

Type of psoriasis

General population (databases)

Dermatological patients

Control

Cross sectional studies about risk

of obesity in psoriatic patients

(odds ratio with 95% confidence

interval).

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Obesity is a relevant risk factor for psoriasis and precedes development

of psoriasis

– Body mass index is a risk factor independently associated with onset of psoriasis1

– Increased adiposity and weight gain are strong risk factors for incident psoriasis in women2

– Obesity in early adulthood has also been shown to be a risk factor for psoriatic arthritis3

1. Naldi L et al. J Invest Dermatol 2005;125:61-7 2. Setty AR et al. Arch Intern Med 2007;167:1670-5 3. Soltani-Arabshahi R et al. Arch Dermatol 2010;147:721-6

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0

0.5

1.5

RR

fo

r d

eve

lop

ing

PsA

Increased BMI is associated with increased risk of psoriatic arthritis

Love JT, et al. Ann Rheum Dis. 2012;71(8):1273-7.

BMI <25 25-29.9 30-34.9 ≥35.0

1.0

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Psoriasis and obesity: a vicious cycle of systemic inflammation

Skin inflammation – psoriasis

Adapted from: Davidovici BB, et al. J Invest Dermatol. 2010;130(7):1785-96.

TNF; IL-1, IL-6, IL-8 IL-15, IL-18, IL-19, IL-20 IL-12, IL-23, IFN-γ, IL-l7 S100 proteins IL-10 (IL-4, IL-13)

TNF MCP-1, M-CSF Leptin, IL-6, IL-5, iNoS Adiponectin, PAI-1, renin-angiotensin (angiotensinogen) SHBG

Adipose tissue – obesity

Auto-inflammatory loop

Cytokines Leukocytes

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Weight gain may occur in patients receiving anti-TNF-a treatment

Mean weight (kg) change from baseline to Week 48

Adapted from: Saraceno R, et al. Pharmacol Res. 2008;57(4):290-5.

5

Me

an w

eig

ht

chan

ge (

kg)

1

0

3

4

2

Patients in group showing weight gain

48% 44% 40%

Infliximab n=50

1.53

p=0.0001

Etanercept n=50

2.18

p=0.007

Adalimumab n=30

2.57

p=0.0014

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1. Gisondi P, et al. J Eur Acad Dermatol Venereol. 2008;22(3):341-4. 2. Di Renzo L, et al. Dermatol Ther. 2011;24(4):446-51. 3. Prignano F, et al. Curr Med Res Opin. 2009;25(9):2311-6.

Weight gain may occur in patients receiving anti-TNF treatment

Mean body weight increased significantly from baseline in patients receiving etanercept (1.5±2.7 kg) (n=58) or infliximab (2.5±3.3 kg) (n=40) (p=0.004)1

A relative increase in bodyweight of 2.6±3.2% was observed in a mixed group of patients receiving either etanercept (n=28) or infliximab (n=12)2

– Blockade of TNF activity was associated with fat and lean mass gain in psoriasis and psoriatic arthritis patients

Increased bodyweight was recorded in the majority of patients receiving etanercept (54%) (n=62) or infliximab (53%) (n=36)3

In three studies in which patients with plaque psoriasis received anti-TNFs with follow up at 24 weeks:

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Psoriasis is associated with an increased risk of diabetes

Type of rate OR and 95% CI OR 95% CI P

Crude data 1.83 1.71-1.96 <0.00001

Age-adjusted 1.33 1.26-1.41 <0.00001

Age- and gender-adjusted

1.33 1.25-1.40 <0.00001

0 3 2 1

Odds ratios (OR) for diabetes in a psoriasis population vs a control population

Clalit Health Services database (Israel; n=15,757 cases, n=49,358 controls) Cohen AD, et al. J Eur Acad Dermatol Venereol. 2008;22(5):585-9.

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Cardiovascular Comorbidities

RA IBD Psoriasis

Hypertension

Dyslipidemia

Atherosclerosis

Metabolic syndrome

Thromboembolism ̶ ̶ Biomarkers of CV risk sICAM-1

homocysteine CRP IL-6

sICAM-1 homocysteine*

CRP IL-6

sICAM-1 homocysteine

IL-6 MCP-1

Increased mortality 2-3x 1.5x 3-4x

Reduced life expectancy

10-20 years unknown 3-20 years

*no association with increased CV risk

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Psoriatic Arthritis • Chronic inflammatory arthritis

– Causes progressive joint damage, reduced function – Uveitis frequently associated

• Prevalence 6-25% – Lack of consistency between studies concerning diagnostic criteria for PsA

• HLADR4 +ve: severe destructive form

• Usually develops after onset of psoriasis – Typically 10 years later

• Increased mortality in psoriatic arthritis – Previously active and severe disease, manifested by:

• Prior use of medications; and • Radiologic changes; and • Elevated ESR at presentation (Gladman et al, Arthritis Rheum 1998;41:1103-10).

• TNF-α – Plays central role in pathogenesis – Triggers osteoclastogenesis and bone resorption

• By stimulating both receptor activation of NF KappaB and its ligand • Expressed in bone marrow osteoclast precursors and stomal cells respectively

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1. Ibrahim G, et al. Clin Exp Rheumatol 2009;27(3):469-74. 2. Husni ME, et al. J Am Acad Dermatol 2007;57(4):581-7. 3. Gladman D, et al. Ann Rheum Dis 2008;68(4):497-501. 4. Tinazzi I, et al. Rheumatology (Oxford). 2012 Aug 9. [Epub ahead of print]

• Psoriasis Epidemiology Screening Tool (PEST)1

– 5-item questionnaire

– Sensitivity 92%; specificity 78%

• Psoriatic Arthritis Screening and Evaluation Tool (PASE)2

– 15-item questionnaire

– Sensitivity 82%; specificity 73%

• Toronto Psoriatic Arthritis Screen (ToPAS)3

– 12-item questionnaire

– Sensitivity 87%; specificity 93%

– Designed to detect PsA in any population, including non-psoriasis populations

• Early Arthritis for Psoriatic Patients (EARP)4

– 10-item questionnaire

– Sensitivity 85%; specificity 92%

Screening tools for psoriatic arthritis

PEST. Courtesy of Professor P Helliwell.1

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Depression and Anxiety • Prevalence of depression 10-62% amongst psoriasis patients

– Range due to inpatient (high) vs outpatient (low)

– Higher rates of suicidal ideation in severely affected psoriasis inpatients c/w pts with atopic dermatitis, acne

• PASI not a reliable predictor of depression risk

• Pruritus associated with depression in psoriasis patients ? poor sleep

• Impact that psoriasis has on quality of life is a stronger indicator of psychiatric morbidity than clinical severity

• Patients with PsA and skin psoriasis report significantly worse quality of life; joint pain associated with depression

• Perception of stigmatisation amongst psoriasis sufferers the most important predictor of depression

• Those who developed psoriasis young:

– Harbour stronger feelings of stigmatisation

– Lack of support correlated with depression

• Depression is:

– An independent risk factor for heart disease

– Associated with excess mortality, particularly from cardiovascular disease

• Anxiety found in up to 43% of psoriasis patients Hayes & Koo 2010

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Inflammatory Bowel Disease (Crohn’s Disease, Ulcerative Colitis)

• Crohn’s disease patients – 7x higher risk of developing psoriasis

• Psoriasis patients – 3x higher risk of Crohn’s disease

• Ulcerative colitis – Statistically significant association with psoriasis but

not as high as Crohn’s disease • Crohn’s disease, ulcerative colitis and psoriasis

share the same susceptibility loci (6P21), IL-23 receptor and IL-12B genes – IL-23 receptor encodes for a subunit of IL-23, pro-

inflammatory cytokine • Crohn’s disease and psoriasis primarily mediated by

Th-1 lymphocyte producing cytokines such as TNF-α and IFNg

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What is non-alcoholic fatty liver disease (NAFLD)?

Characterised by insulin resistance and strongly associated with type 2 diabetes and obesity1-3

Defined by fatty changes in the liver in the absence of a history of excessive alcohol consumption1

The spectrum of the disease ranges from simple steatosis to steatosis with evidence of hepatocellular inflammation (non-alcoholic steatohepatitis, or NASH), advanced fibrosis, and cirrhosis1,2

NAFLD may be primary (associated with the metabolic syndrome) or secondary (associated with nutrition, drugs, toxins, or metabolic or other diseases)1,2

1. Adams LA, et al. CMAJ. 2005;172(7):899-905. 2. Angulo P. N Engl J Med. 2002;346(16):1221-31. 3. Bhatia LS, et al. Eur Heart J. 2012;33(10):1190-200.

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Prevalence of NAFLD in psoriasis patients vs controls

0

20

40

100

80

Psoriasis patients (n=130)

NA

FLD

pre

vale

nce

(%

)

* 60

Control (n=260)

*p<0.0001

Prevalence of NAFLD in psoriasis patients by disease severity

0

20

40

100

80

PASI <10 (n=59)

NA

FLD

pre

vale

nce

(%

)

* 60

PASI ≥10 (n=71)

*p<0.01

Psoriasis is associated with non-alcoholic fatty liver disease (NAFLD)

Gisondi P, et al. J Hepatol. 2009;51(4):758-64.

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Bhatia LS, et al. Eur Heart J. 2012;33(10):1190-200.

NAFLD is a CV disease risk factor

IR: insulin resistance

Excess caloric intake Sedentary lifestyle

Genetic susceptibility

Deranged adipokine profile

Ectopic fat in other organs e.g. heart

Hyperinsulinaemia Plasma FFA

Visceral and subcutaneous

fat and/or adiposopathy

Adipose tissue IR

Skeletal muscle lipids

Ectopic fat

Skeletal muscle IR

Adipose tissue IR

NASH

Hepatic IR

Hepatic steatosis

CV risk (↑ endothelial dysfunction, ↑ dyslipidaemia,

hypercoaguability, ↑ inflammation, ↑ atherosclerosis, CV lipotoxicity)

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Smoking and Alcohol

• Smoking – Positive correlation between smoking and psoriasis

• >20 cigarettes per day assoc. with 2.2x in more severe forms of psoriasis

• Female smokers: 3.3x risk of psoriasis

• Palmoplantar pustulosis has strongest association

– Pathophysiology of smoking: • Psoriasis involves a neutrophil – predominantly inflammatory infiltrate

• Smoking thought to alter the morphology and function of neutrophils

• Also causes damage via oxidation – Anti-oxidant levels are low in psoriasis patients, making them more susceptible to

oxidative damage

• Alcohol – Psoriasis patients have higher prevalence of excess alcohol intake

– Disease severity positively correlated with alcohol intake

– Excess alcohol intake shown to precipitate psoriasis

– Excess alcohol consumption a known association with anxiety and depression

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Traditional systemic treatments for psoriasis may impact CV risk factors

Methotrexate1-3

– Few studies are available in the psoriasis population and data are not conclusive

– One study suggested no significant impact on risk of MI, with a trend towards reduced risk in younger patients1

– Another study indicated that moderate doses may reduce the risk of vascular disease versus non-treated psoriasis patients2

– May induce hyperhomocysteinaemia, a risk factor for thrombosis3

– May favour steatohepatitis4

Ciclosporin3

– May increase blood pressure (induce or worsen hypertension)

– May alter glucose tolerance

– May promote hyperlipidaemia

Retinoids3

– May promote hyperlipidaemia

1. Abuabara K, et al. Br J Dermatol. 2011;165(5):1066-73. 2. Prodanovich S, et al. J Am Acad Dermatol. 2005;52(2):262-7. 3. Gisondi P, Girolomoni G. Actas Dermosifiliogr. 2009;100 Suppl 2:14-21. 4. Adams LA, et al. CMAJ. 2005;172(7):899-905.

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Therapeutic Potential for Biologics in Managing Comorbidities

• Metabolic Syndrome – Insulin resistance

• Biologics inhibit pro-inflammatory cytokines, potentially improving insulin sensitivity • Isolated cases of psoriasis and rheumatoid arthritis pts with diabetes developing

unpredictable hypo- or hyperglycaemia after commencing anti-TNF-α treatment

– Body Mass Index and weight • Reports of anti-TNF-α medications associated with significant weight gain and

increases in BMI (Gisondi et al, J Eur Acad Dermatol Venereol 22:341-344, 2008)

• Weight gain may aggravate preexisting metabolic syndrome • Biologics with a fixed-dose regimen may have a compromised efficacy in heavier

individuals (Clark et al. J Am Acad Dermatol 2008; 58:443-6)

• Fully human monoclonal anti-p40 antibody not associated with weight gain

– Blood lipids • Biologics’ effects on blood lipids: mixed and unclear results

• Cardiovascular Disease – Biologics inhibit pro-inflammatory cytokines

• Potentially decreasing cardiovascular risk and mortality – TNF-α antagonist contraindicated in pts with moderate-severe forms of

congestive heart failure

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Therapeutic Potential for Biologics in Managing Comorbidities

• Psoriatic Arthritis – Clinical trials have shown that TNF-α

antagonists: • Markedly inhibit inflammation • Reduce structural joint damage

– Radiographic evidence of inhibition of progressive joint disease

• Inflammatory Bowel Disease – Crohn’s disease and ulcerative colitis

• Anti-TNF-α antibodies have proven beneficial effect • Etanercept: Lack of efficacy

– Report of development of Crohn’s disease in treated pts

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Biologic treatments for psoriasis: impact on CV risk factors

Data gathered from rheumatoid arthritis populations receiving anti-TNFs indicate potential for:1

– Reduced insulin resistance

– Control of inflammation (CRP, IL-6)

– Increased HDL-cholesterol

– Decreased risk of arteriosclerotic plaque formation

In a retrospective study of patients with psoriasis or psoriatic arthritis (n=8845), those treated with TNF inhibitors (n=1673) showed:2

– Significant reduction in MI risk vs topical agents

– Significantly lower MI incident rate vs topical agents

1. Kaplan MJ. Vasc Health Risk Manag. 2008;4(6):1229-35. 2. Wu JJ, et al. Arch Dermatol. Epub 20 Aug 2012.

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Management of Comorbidities

• Look closely for comorbidities – eg signs of insulin resistance

• Be aware of the risk profile – e.g. early onset, severe psoriasis

increase risk

• For all psoriasis patients: – Take complete history

• DLQI, Smoking, Alcohol

– Physical examination • incl. blood pressure

– Laboratory screening • incl. fasting glucose and lipids

– CXR, ? ECG

– Regular monitoring of risk factors • Disease associated

• Medication associated

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Management of Comorbidities

• Encourage lifestyle changes (diet, exercise, stop smoking) • High body mass index is associated with a reduced short-term

clinical response to all systemic treatments (Naldi et al. Dermatology 2008; 217:365-73)

• Weight loss improves the response of obese patients with

moderate-to-severe chronic plaque psoriasis to low-dose ciclosporin therapy

(Gisondi et al. Am J Clin Nutr 2008; 88:1242-7)

• Early referral, eg: – Metabolic syndrome: refer to endocrinologist / cardiologist – Diabetes: refer to diabetic educator / endocrinologist – Anxiety / Depression: Psychologist / psychiatrist – Liaise closely with GPs eg hypertension control, lipid-lowering meds

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Psoriasis: Beyond the Skin

• Need to recognise psoriasis as a chronic inflammatory disorder

• Choices for therapy should take into account adverse effects of drugs on co-morbidities and dangerous drug interactions

• Therapy of psoriasis is influenced by and may affect other organ systems and co-morbid diseases; – High index of suspicion of side effects associated

with systemic treatments

• Therapy of psoriasis may benefit from treating associated metabolic disorders

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Psoriasis: Beyond the Skin

• Inflammation associated with moderate-to-severe psoriasis confers a higher cardiovascular morbidity and mortality risk; therefore long-term disease control with systemic therapy may reduce cardiovascular morbidity and mortality in psoriasis patients.

• Patients with psoriasis need a global approach, taking into account their cardiovascular risk profile.

• Assessment of psoriasis severity should take a broader view than just a PASI assessment; address comorbidities such as: – Cardiovascular risk factors – Psoriatic arthritis – Psoriasis symptoms (pruritus, cutaneous pain, burning, bleeding,

desquamation) – Quality of life

• Broader assessment may indicate earlier treatment than when

using PASI alone to assess psoriasis severity

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QUESTIONS?

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