Effectiveness of TNF-α blockers and

IL-12/IL-23 blockers in the treatment of

Psoriasis.

Preliminary observations.

Wojciech Francuzik, Kinga Byczkowska

Student working group

at The Clinic of Skin Diseases and Medical Mycology,

Poznań University of Medical Sciences.

Supervisor: Professor Zygmunt Adamski MD PhD

Biological Agents

● Used in dermatology, rheumatology and

gastroenterology

● Block pathways of inflammtion

pharmatching.com

Interleukin IL-12 in the pathogenesis of

psoriasis

Dendritic Cells

Macrophages

Keratinocytes

Mast cells

Granulocytes Th0

Th1

NK Other

cytokines

IgG

IL-12

Interleukin IL-23 in the pathogenesis of

psoriasis

Langerhans C

Macrophages

Keratinocytes

Th17

Th17

activ

e

Induce

s

CD8+ cytotoxicit

y

IL-23

TNF-α in the pathogenesis of psoriasis

Langerhans C

Macrophages

Keratinocytes

Mast cells

● Elevated concentration in changed skin

● Induces migration of macrophages

● Stimulates LC maturation

● Stimulates proinflammatory cytokines production

● Induces proliferation of keratinocytes

Structure of cytokines important in the

pathogenesis of psoriasis

Nature Reviews Immunology

TNF-α

Acts trough:

TNF-RI

TNF-RII

Current Protocols.com

The agents used in the treatment of

psoriasis

Infliximab Etanercept Adalimumab Ustekinumab

Chimeric

antibody

Human

antibody

Human

fusion protein

Human

antibody

TNF-α blockers

IL-12, IL-23

Blocker

p40 subunit

i.v. 5mg/kg

0-2-4-8 w

Than every 8 w

s.c. 50 mg

Every week

i.m. 40 mg

Every 2 weeks

s.c. 45mg

0-4-12 w

Than every 12 w

Aim of this study:

To verify which biologic agent (infliximab,

adalimumab, etanercept, ustekinumab) used in

the treatment of psoriasis is the most effective

in reducing skin changes.

Materials and methods:

51 psoriatic patients

Infliximab Etanercept Adalimumab Ustekinumab

15 12 11 13

PASI 0

(at day 0)

PASI 0

(at day 0)

PASI 0

(at day 0)

PASI 0

(at day 0)

After 4 weeks

of therapy

PASI 4 PASI 4 PASI 4 PASI 4

After 12 weeks

of therapy

PASI 12 PASI 12 PASI 12 PASI 12

● Calculating a percentile PASI reduction after 4

weeks of therapy

● Calculating a percentile PASI reduction after 12

weeks of therapy

Materials and methods:

Pred4= PASI 4

PASI 0

Pred12= PASI 12

PASI 0

Results:

● There is a difference beetween means in the 4 agents

groups during fist 4 weeks of treatment

P=0.0196 (Kruskal-Wallis test)

I: infliximab, E: etanercept, A: adalimumab, U: ustekinumab

Results:

● There was a difference beeteween means of Pred4

between groups treated with etanercept and

adalimumab P=0.0074 (Mann Whitney test)

Etanercept group mean = 51,42%

Adalimumab group mean = 72,00%

● There was a difference beeteween means of Pred4

between groups treated with etanercept and

infliximab P=0.0089 (Mann Whitney test)

Infliximab group mean = 73,07%

Etanercept group mean = 51,42%

Results:

● There was NO difference beeteween means of Pred4

inside each group considering common psoriasis and

psoriatic arthritis patients

● There was NO difference beeteween means of Pred4

inside each group considering patients with family

history of psoriasis and those without

● There was NO difference beeteween means of Pred12

between all groups

P=0.5238 (Kruskal-Wallis test)

Results:

● There was difference beeteween means of Pred4

between male and female patients in infliximab

group P=0,0077 (Mann Whitney test)

Im: infliximab in males, Ik: ifliximab in females

Results:

● There was difference beteween means of Pred4

between male patients in all groups.

● Significant difference was observed between

infliximab, etanercept and adalimumab groups.

I: infliximab, E: etanercept, A: adalimumab, U: ustekinumab, m for male patients

Infliximab treated

group

Adalimumab treated group

Conclusion

● The effectiveness of reducing PASI score was most

rapidly seen in infliximab group

● Etanercept group had longer response to therapy

time

● All agents were equally effective in reducing skin

changes during 12 weeks of treatment

● Male patients seamed to respond faster to Infliximab

than female patients.

● Male patients showed more varied response to

different agents than female patients

Thanks to:

● Professor Zygmunt Adamski MD PhD

● Staff of the Skin Disease Department of The

Regional Hospital in Poznań

Immunologia, Gołąb J, Jakóbisiak M, Lasek W (red.).

PWN Warszawa 2004

Tracey D, Klareskog L, Sasso EH et al. Tumor necrosis factor

antagonist mechanism of action: a comprehensive review.

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Krueger JG. The immunologic basis for the treatment of psoriasis

with new biologic agents. J Am Acad Dermatol 2002; 25: 20-33

Liebwohl MG, Use of Etanercept in the dermatology setting.

Am J Acad Dermatol 2005; 6: 49-59