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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.
Pharmacol Ther 2008; 117:224-79
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

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Effectiveness of TNF-α blockers and IL-12/IL-23 blockers in the treatment of Psoriasis. Preliminary observations.

  • 1. 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
  • 2. Biological Agents ● Used in dermatology, rheumatology and gastroenterology ● Block pathways of inflammtion pharmatching.com
  • 3. Interleukin IL-12 in the pathogenesis of psoriasis Dendritic Cells Macrophages Keratinocytes Mast cells Granulocytes Th0 Th1 NK Other cytokines IgG IL-12
  • 4. Interleukin IL-23 in the pathogenesis of psoriasis Langerhans C Macrophages Keratinocytes Th17 Th17 activ e Induce s CD8+ cytotoxicit y IL-23
  • 5. 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
  • 6. Structure of cytokines important in the pathogenesis of psoriasis Nature Reviews Immunology TNF-α Acts trough: TNF-RI TNF-RII Current Protocols.com
  • 7. 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
  • 8. 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.
  • 9. 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
  • 10. ● 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
  • 11. 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
  • 12. 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%
  • 13. 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)
  • 14. 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
  • 15. 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
  • 18. 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
  • 19. 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. Pharmacol Ther 2008; 117:224-79 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