PATHOGENESIS AND

MANAGEMENT OF PSORIASIS
ASSALAMUALAIKUM WARAKHMATULLAHI
WA BAROKATUH
SUGENG ENJANG

Sunardi Radiono,
Malang Dermato - venereology update 2014
24 - 25 JanuarI 2014

Presentation out line

1.Clinical pearl
2.Basic
pathogenesis
3.Management keys

Clinical pearls: Batasan pengertian

PENYAKIT PERADANGAN KULIT KHRONIK DENGAN DASAR
AUTOIMUN BERSIFAT PROGRESIF DAN RESIDIF , DITANDAI
ADANYA HIPERPROLIFERASI KERATINOSIT DAN
INFILTRASI SEL RADANG LIMFO-HISTIOSITIK PADA DERMIS

PREVALENSI DAN INSIDENSI

0,1 1 % ASIA, 2,5% KAUKASOID
DOMINAN DI PERKOTAAN/ KEHIDUPAN MODERN
14% TOTAL KUNJUNGAN DI RS SARDJITO YOGYAKARTA
1 2,5 % RS LAIN DI INDONESIA

VARIASI KLINIS

P. VULGARIS/
PLAKAT

P.
INVERSA

P. GUTTATA

Pitting nail,
dystrophic nail, and
onycholysis
P. KUKU

Lake of
pustule
P.PUSTULOSA
GENERALISATA

P.ARTROPATI

Psoriasis erythrodermia
reactive psoriasis
exfoliation > 75% body surface
DEMAM/ MENGGIGIL
AL MENINGKAT > 10.000/ML

PERBAIKAN KLINIS SETELAH

FOTO TERAPI NB-UVB 8
MINGGU

PENANDA KLINIS
Auspitz sign ;
pin point bleeding when pull
off
the scale
Wax drop
phenomen/FENOMENA
TETESAN LILIN
The micaceous scale becoming dull if scratched
SKUAMA JERNIH/
KERUH
LESI BERDERET/ LINEAR ATAU PADA
DAERAH PROMINEN MERUPAKAN TANDA
ERUPSI ISOMORFIK/ KOEBNER SIGN

Burden of psoriasis
Impairments in quality of life are comparable to those
seen with cancer, diabetes and heart disease1,2
Early onset,
lifelong disease
with a chronic
relapsing nature

Embarrassment
Social exclusion
Stigmatisation
Difficulties with
sexual activities

Loss of working days

Unable to secure
employment
Missed school

Interpersonal
relationships33

Mental health55
Depression
Anxiety
1. Rapp SR, et al. J Am Acad Dermatol 1999; 41: 401407
2. Dubertret L, et al. Br J Dermatol. 2006;155:72936
3. Krueger G, et al. Arch Dermatol. 2001;137:2804
4. Finlay AY, Coles EC. Br J Dermatol. 1995;132:23644
5. Fortune DG, et al. Dermatol Clin. 2005;23:68194

Comorbidities in Psoriasis
Patients

Psoriasis patients are at increased risk for:

Obesity (~2-fold)1,2
Smoking (~2-fold)1
Diabetes (~1.5-fold)2
Hypertension (~2-fold)2
Heart failure (~2-fold)2
Myocardial infarction
(mild psoraisis: ~1.5-fold; severe psoriasis: ~7-fold) 3
Increased inpatient cardiovascular mortality (from coronary
artery disease, cerebrovascular disease, pulmonary
embolism) (~1.5-fold)4
Depression (5.5% have suicidal ideation)5
Mortality (severe psoriasis: ~1.5 fold)6

OBAT PEMICU SEBAGAI PSORIASIS

PATOGENESIS : KONSEP DASAR

FAKTOR
GENETIK
FAKTOR
LINGKUNG
AN

Psoriasis is the result of a complex cutaneous immune

reaction with a major inflammatory component

Activation

Antigenpresentin
g cells

Preferential
development of
Th1- and Th17type T-cells

Mediators such as
IL-12, IL-23, TNF-
and IFN- drive
cellular changes

sterile
abscesses
in the
epidermis

Influx
of
neutro
-phils

Psoriasis

Migration and
proliferation within
the skin
Homing
mechanisms
involve
chemotactic
factors such as IL-8
and CCL27

Angiogenesis

Capillary
abnormalities
in the upper
dermis

Hyperproliferation
of keratinocytes

Pathirana
Pathirana D,
D, et
et al.
al. JJ Eur
Eur Acad
Acad Dermatol
Dermatol Venereol.
Venereol. 2009;23
2009;23 (Suppl
(Suppl 2):170
2):170

PATHOGENESIS ; PERKEMBANGAN PROSES

INFLAMASI
KOMPLEKS REAKSI RADANG
AUTOIMUN DENGAN TARGET
JARINGAN
EPIDERMIS/KERATINOSIT

HIPERPROLIFERASI
TIPE WOUND
HEALING YANG TAK
TERKONTROL

Gambaran tahapan patogenesis lesi psoriasis (dikutip dari Sabat

PATOGENESIS : AKTIVASIS SISTEM SINYAL

Aktivasi suatu sitokin

proinflamasi pada
PENDERITA oleh sebab
apapun, dapat mimicu
orkestra sitokin
tersebut

Interaksi antara sitokin

utama dan imunosit pada
lesi psoriasis
(dikutip dari Sabat et
al., 2007).

ILUSTRASI PERAN SENTRAL

Th17 PADA PROSES
INFLAMASI PSORIASIS (Martin et
al.,2012)

Manajemen psoriasis
1.Pertimbangan umum
2.Algoritme pemilihan model terapi
3.Terapi topikal
4.Fototerapi
5.Terapi sistemik
6.Terapi kombinasi
7.Terapi biologik

Pertimbangan umum :
1. kenali sifat alamiah psoriasis
PSORIASIS KHRONIK, RESIDIF (KAMBUHAN) DAN
PROGRESIF
MUDAH TERJADI TAKIFILAKSIS
SULIT ADHEREN/TAAT DENGAN PROGRAM TERAPI
MEMILIKI DAMPAK NYATA TERHADAP KUALITAS HIDUP
PENDERITA
RIWAYAT TERAPI YANG KOMPLEKS
SERING DENGAN MANIFESTASI EFEK SAMPING OBAT
EDUKASI /DAN SOSIALISASI KE
KELUARGA

SESUAIKAN PERSEPSI DOKTER

DAN PASIEN
Dalam riset
klinik/DOKTER

Dalam praktek/
PASIEN

Target
PASI >50
PASI >75
PASI >50 < 75

SEMBUH >> BEBAS LESI

( PASI 100 )

PASI >50 SETELAH 16 MINGGU MULAI PENGOBATAN DAPAT DIJADIKAN ACUAN

BAHWA OBAT DAPAT DITERUSKAN SECARA TUNGGAL
PASI < 50 OBAT DAPAT DIGANTI ATAU DIKOMBINASI DENGAN OBAT LAIN.

Mrowietz U, et al. Arch Dermatol Res 2011;303:110

Smith CH, et al. Br J Dermatol 2009;161:9871019

UPAYAKAN MEMBUAT TAKSIRAN KASAR DERAJAT

BERAT PENYAKIT SERTA TETAPKAN
FAKTOR PENYULIT/CONCOMITANT CONDITION YANG
ADA
Severity of symptoms
Psoriasis Area and Severity index
(PASI)
Physicians Global Assessment
(PGA)
Body surface area (BSA)

Health-related quality of life (HRQoL)

SF-36 (generic measure of HRQoL)
Dermatology Life Quality Index (DLQI)
Skindex
Psoriasis-specific quality of life index
(PsoQoL)
Psoriasis Disability Index (PDI)

Body surface area affected >10%

OR
Psoriasis Area Severity Index (PASI)
>10
OR
Dermatology Life Quality Index (DLQI)
>10

Assessments of disease
severity should consider
both symptom severity
and impact on quality of
life
Finlay AY. Br J Dermatol. 2005;152:8617

SELALU INGAT:

KADANG PSORIASIS DAPAT SEMBUH

DENGAN TERAPI YANG SANGAT
SEDERHANA

JAGA JANGAN SAMPAI PASIEN

KEHILANGAN HARAPAN
SEMBUH
Say with love

Say with love

Ajarkan untuk tetap bersyukur kepada Tuhan walau
menderita sakit

2. Algoritme pengobatan
psoriasis vulgaris berdasar
berat penyakit (Jerman)
Chronic Plaque
Psoriasis
Base
Therapy
Mild
BSA
<10%
PASI
<10
Moderat
e
BSA
>10%
PASI
>10

Severe

Topical
Therapy

Systemic
therapy
+ Topical Therapy

Calcineurin
inhibitors
Dithranol
Corticoids
Laser
Tazarotene
Tar
Vitamin D3

Ciclosporin
Fumaric acid
ester
Methotrexate
Photo: UV-B
Balneo-photo
PUVA

Retinoids

Systemics are
recommended for the
treatment of moderate
to severe psoriasis

Attending: climate
therapy
Attending:
psychosocial
therapy
Adalimuma
b
Etanercept
Infliximab
Ustekinuma
b

Nast A, et al. J Dtsch Dermatol Ges. 2011;9 (Suppl

2):S1S104

PERTIMBANGAN PEMILIHAN OBAT

TOPIKAL PSORIASIS
DASAR PEMILIHAN
Luas lesi, lokasi lesi dan pilihan pasien
Efektif dalam jangka pendek (6-8
minggu)
dengan hasil yang nyata (perbaikan
lebih 20%)
Catatan: perhatikan pengalaman pasien
dengan efikasi obat topikal yang telah
dipakainya

OBAT TOPIKAL PSORIASIS

BAHAN

KADAR

EFEK

EFEK
SAMPING

As. Salisilat

24%

Keratolitik

Ter (lcd/ocd)

6 30 %

Anti mitotik/ anti

inflamasi

Bau/kotor

Kortikosteroid

Variatif

Antralin/ di
thranol

0,5 4 %

Iritasi
0,1 0,3

Analog vit.D3
Tazaroten
Inhibitor
kalsineurin

Antimitotik, anti
inflamasi dan vasi
konstriksi

Atrofi, striae,
supresi
adrenal

Anti mitotik
-

Maturasi keratinosit dan

0,05 0,1 regulasi pertumbuhan
%
Iritasi dan
Maturasi sel dan
erupsi pada
keratolitik
kombinasi
dengan UVB
Rasa terbakar

Keamanan obat topikal untuk scalp

psoriasis

KORTIKOSTEROID UTK PSORIASIS

MENGAPA HARUS BERUJUNG DEMIKIAN ?

MEKANISME AKSI KORTIKO STEROID TOPIKAL

(Uva et al., 2012)

STRATEGI UNTUK MENCAPAI KEAMANAN

PENGGUNAAN KORTIKOSTEROID JANGKA PANJANG
Pilih
steroid
sesuai
Hati-hati
pemakai
an pada
anakanak

Hati-hati
pada kulit
tipis

Steroid
aman

kombina
si

Ingat
rekomend
asi

< 50 g/ minggu

Uva et al., 2012, Int J Endocrinology

Foto terapi

BROAD BAND(BB) DAN NARROW BAND(NB)-UVB1

FOTO-KEMOTERAPI (Psoralen UVA)
LASER EXCIMER
KLIMATO TERAPI DAN BALNEO TERAPI

KEUNGGULAN
DAPAT DIKOMBINASI DG OBAT TOPIKAL/ SISTEMIK (Metotreksat, ter,
anthralin, retinoid sistemik)
COCOK UTK YANG TIDAK RESPONSIF TERHADAP TERAPI TOPIKAL

KELEMAHAN FOTO TERAPI

HARUS ADA ALAT
PENGUKURAN /PENERAAN YANG BENAR
PASIEN RAJIN KE KLINIK
EFEK SAMPING JANGKA PENDEK DAN PANJANG

E.S. JANGKA PENDEK : RASA TERBAKAR, TERBAKAR SURYA,

HIPERPIGMENTASI, ERUPSI PSORIASIS
ES JANGKA PANJANG: KEGANASAN (TU-PUVA)

PEMILIHAN PENGOBATAN SISTEMIK

GAGAL DG OBAT TOPIKAL

LESI PLAK LUAS/ ERITRODERMI TERUTAMA
ORANG TUA
PPG
ARTRO PATI BERAT
SERING HARUS DIRUJUK KE RS
MEMENUHI RUMUS 10
Body surface area affected (BSA) > 10%,
or
PASI score > 10, or
DLQI > 10

JENIS OBAT

DOSIS

Metotreksat

2,5 22,5 MG/

MINGGU

Siklosporin A
(Cs-A)

2,5- 5 mg /kg
BB/hr

ESO
Hepatotoksik,sto
matitis,
mielosupresi dll.

EFIKASI
PASI 50 - 75%
PASI 50- 90%

Nefrotoksisitas
Kurang efektif

Mikofenolit
mofetil
Ester asam
fumarat

500 700 mg bid. Penyakit infeksi

berat, keganasan
Penyakit gastro
intestinal khronik,
gangguan ginjal,

PASI 50 80%

PASI 90 80%
80 160 mg 2
kali/ minggu
6- Thioguanine
500 1500 mg/
hari
Hidroksi urea

supresi sumsum
tulang, hepato
toksik
Supresi sungsum
tulang

PASI 75 60%

Biologic Treatments

Biologic Therapies:
Indication for Use in Europe
(No standard developed in Indonesia at moment)

Moderate to severe plaque psoriasis

in adult patients who failed to
respond to, or who have a
contraindication to, or are intolerant
to other systemic therapy including
ciclosporin, methotrexate or PUVA

Nomenclature of Biologic
Therapies
Suffix indicates class of biologic
therapy1
cept = human receptor fusion protein
e.g. etanercept
ximab = chimaeric monoclonal
antibody
e.g. infliximab
zumab = humanized monoclonal
antibody
e.g. efalizumab
1. Johnston SL. J Clin Pathol. 2007;60(1):8-17.

Biological Therapies:
Comparison of Dosing and
Administration
Efalizumab1

Method of
administration

Subcutaneous Subcutaneous
0.7 mg/kg
induction
dose

Posology

Etanercept2

Then 1 mg/kg
(maximum
200 mg per
single dose)

Self-administered
Weight-based
dosing

1. Efalizumab SPC 2. Etanercept SPC.

3. Infliximab SPC. 4. Adalimumab SPC.

25 mg twice
weekly
OR
50 mg twice
weekly for 12
weeks, then
25 mg twice
weekly if
necessary

Infliximab3

Adalimumab4

Intravenous
infusion

Subcutaneous

5 mg/kg
0, 2, 6 weeks
induction
treatment

80 mg
induction
dose

Then every
8 weeks

Then 40 mg
every other
week

Biological Therapies:
Comparison of Structure and
Function

Type of biologic

Target

Mode of action

Efalizumab1

Etanercept2

Infliximab3

Adalimumab4

Humanised
monoclonal
antibody

Human
TNF-receptor/IgG1Fc fusion
protein

Chimaeric
monoclonal
antibody

Fully human
monoclonal
antibody

LFA-1

TNF-, TNF-

TNF-

TNF-

Blocks T cell
functions

Blocks TNF-
activity

Blocks TNF-
activity

Blocks TNF-
activity

1. Efalizumab SPC 2. Etanercept SPC.

3. Infliximab SPC. 4. Adalimumab SPC.

Efalizumab

Murine anti-CD11a

Structure
Humanised monoclonal antibody

Target
CD11a

Presumed mechanism of action

Prevents the interaction between
LFA-1 on T-cells and ICAM-1 on
APCs/endothelium to block the
migration,
adhesion and activation of T cells

Human IgG

Etanercept

Structure
Human fusion protein composed
of TNF receptor type II (TNF-R p75)
and human IgG1 Fc fragment

Target
TNF- (and TNF-)

Presumed mechanism of action

Attenuates inflammatory action
of TNF by interfering with binding to cellsurface receptors

Etanercept Mechanism
of Action 1
Macrop
hage
or
activat
ed
T cell

TNF
rece
ptor
1. Etanercept SPC.

Target cell

Infliximab
Structure

Murine anti-TNF-

Chimaeric monoclonal antibody

with
mouse variable region and
human
IgG1 region

Target
TNF-

Presumed mechanism of
action
Attenuates inflammatory action
of TNF- by interfering with
binding
to cell-surface receptors
1. Infliximab SPC.

Human

Infliximab Mechanism of
Action 1
Macrop
hage
or
activat
ed
T cell

Receptorbound
TNF
Solubl
e
TNF
Transmembra
ne-bound
TNF
TNF
rece
ptor

Target cell

Adalimumab Mechanism of
1
Action
Macrop
hage
or
activat
ed
T cell

Receptorbound
TNF
Solubl
e
TNF
Transmembra
ne-bound
TNF
TNF
rece
ptor

Target cell

Initial PASI 75 and PASI 90 with

current biologic agents
PASI 75 and PASI 90 responses infliximab (week 10 data)
and efalizumab, etanercept, adalimumab (week 12 data)

100
80

80

68

Patients (%)

60
40
20

37

34
22

21
11

57

49

Efalizumab1
1 mg/kg

PASI 75

Etanercept2 Etanercept2
25 mg
50 mg

Infliximab3
5 mg/kg

Adalimumab4
40 mg/kg

PASI 90

1. Efalizumab SPC. 2. Papp KA et al. Br J Dermatol. 2005; 152:1304-12. 3. Reich K et al. Lancet. 2005; 366:1367-1374.
4. Menter A et al. J Am Acad Dermatol. 2008; 58:106-115.

Comparison of Tolerability and

Safety1-4
Efalizumab

Etanercept

Infliximab

Adalimumab

Most common
adverse events

Flu-like symptoms

Injection-site
reactions

Infusion-related
reactions

Injection-site
reactions

Immunogenicity
issues

Infusion/injectionsite related
reactions

Main risks

Tuberculosis & Tuberculosis & Tuberculosis &

Psoriasis flare
other infections other infections other infections
or rebound
(Black-box
(Black-box
(Black-box
Thrombocytopenia
warning)
warning)
warning)

Jenang sela wader kali sesonderan

Nyuwun ngapura yen wonten lepat
kawula
Sugeng siang
Wasalammualaikum warahmatullahi
Wa barokatuh

Management Options for Psoriasis:

Oral Systemic Therapies
Oral retinoids vitamin A analogues (acitretin is the
principal licensed product in this class) which reduce
epidermal proliferation and differentiation
Methotrexate a folic acid antagonist that
interferes with purine synthesis and thus inhibits DNA
synthesis and cell replication; it also has specific Tcell suppressive activities
Ciclosporin an immunosuppressant that inhibits
the activation of T cells and may also exert a direct
effect on epidermal keratinocytes.
Fumaric acid esters non-specific T cell inhibitors
producing changes in cytokine production that are
beneficial in psoriasis (used mainly in Germany, for
severe psoriasis)

Oral Methotrexate
1
(MTX)
Methotrexate is one of the most commonly used

oral systemic agents for psoriasis

Potential for adverse effects necessitates careful
selection and monitoring of patients
Proposed mechanism
of action

Inhibits DNA synthesis and cell replication; also has specific

T-cell suppressive activities

Dosing

7.5-22.5 mg per week

Efficacy

> 60% PASI 75 response

Major toxic effects

Foetal death or abnormalities, myelosuppression,

hepatotoxicity, pneumonitis, stomatitis

Monitoring required

Yes

Consider to off treatment when cumulative dose of MTX

1.5 grams
1. reach
Menter A, Griffiths
CEM. Lancet. 2007; 370:272-84.

Oral Systemic Agents can be Highly

Effective
in the Treatment of Moderate to Severe
PASI 75 at week 16 in patients treated with MTX or CsA for
psoriasis
Psoriasis
1

PASI 75 (%)

Subjects achieving

100
80

71
60

60

30/42

26/43

40
20
0

Methotrexate
15 mg/week

1. Heydendeal VMR et al. N Engl J Med. 2003; 349:658-665.

ciclosporin
3 mg/kg/day

Pengobatan siklosporin pd psoriasis

Intervention

Therapeutic recommendation

Methotrexate

Less desirable for short-term induction therapy than for long-term therapy due
to its slow onset of action

Ciclosporin

Use primarily for induction therapy in adults with moderate-to-severe

psoriasis insufficiently treated with topical therapy and/or
phototherapy

Retinoids (oral)

Not a first choice monotherapy, but combine with phototherapy

Should not be used in women of child-bearing age

Fumaric acid esters

Effective induction therapy in adults with moderate-to-severe psoriasis

Use a combination of fumaric acid esters and topical treatments

Phototherapy

Induction therapy for moderate-to-severe psoriasis

Narrowband UVB is first choice
PUVA recommended when UVB insufficiently effective

Biologics (adalimumab,
infliximab, etanercept)

Use primarily for induction therapy in adults with moderate-to-severe psoriasis

insufficiently treated with conventional systemics and/or phototherapy

*Supported by the European Dermatology Forum (EDF), the European

Academy of Dermatology and Venereology (EADV) and the International
Psoriasis Council (IPC)
Pathirana D, et al. J Eur Acad Dermatol Venereol.
2009;23 (Suppl 2):169

Ciclosporin is an effective drug for shortterm management

of moderate-to-severe psoriasis
Ciclopsorin is associated with a range of
adverse effects including nephrotoxicity

Proposed mechanism
of action

Calcineurin inhibitor which interferes with early

events in T cell activation, preventing the
production of cytokines (IL-2) and activated T cells

Dosing

2.5-5 mg/kg/day

Efficacy

> 60% PASI 75 response

Major toxic effects

Nephrotoxicity, hypertension, immunosuppression

(increased risk of infection or malignancy)

Monitoring required

Yes (creatinine, blood pressure)

1. Menter A, Griffiths CEM. Lancet. 2007; 370:272-84.

Mechanism of action of ciclosporin

Ciclosporin induces immunosuppression by inhibiting the first
phase of T-cell activation
Signal
Ca2+
CsA

T-cell receptor

Ion channel

Extracellular
Intracellular

CsA
CpN

Ca2++
CaN

CpN

NF-ATc

Dephosphorylation
P
NF-ATc

NF-ATn

T-cell

+
Nucleus

This tool may contain scientific/medical information on unapproved

products or product uses. This information is for educational purposes
only. Please consult the applicable prescribing information for details on
approved uses of products.

Interleukin 2 gene
Modified from Stepkowski SM. Expert Rev Mol Med. 2000;2:123

Ciclosporin is a critical-dose drug

Switching between formulations may lead to clinically
important changes in bioavailability and efficacy
With the use of ciclosporin generics, an average of 20% lower bioavailability can be expected,
which means that efficacy may be unsatisfactory in isolated cases 1
Conventional and generic formulations of ciclosporin are characterised by considerable intraand inter-individual variability in absorption2
The Medicines and Healthcare Products Regulatory Agency (MHRA) in the
UK states that:3
Ciclosporin must be prescribed and dispensed by brand name
Patients should be stabilised on a single brand of ciclosporin
All products that contain ciclosporin are interchangeable only if careful
therapeutic monitoring takes place
Prescribing and dispensing of ciclosporin should be by brand name to
avoid inadvertent switching
1. Pathirana D, et al. J Eur Acad Dermatol Venereol. 2009;23(Suppl 2):5-70
2. Colombo D & Egan CG. Int J Immunopathol Pharmacol. 2010;23:117783
3. MHRA Drug Safety Update. 2009; 3:12. Available at:
http://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON065444

Pemakaian siklosporin dapat diatur sesuai

keadaan pasien
Several treatment schedules are available for the use of
ciclosporin in psoriasis1
Intermittent short-term
therapy

Short course (1216 weeks) until significant

improvement is achieved, after which treatment is
withdrawn
If relapse occurs, treatment is reinstituted at the
previously effective dose

Prevention of relapse2

Treatment with ciclosporin for two days per week

weekend therapy
Can be used to maintain remission status

Rescue therapy

Used in severe flares of disease until an alternative

maintenance treatment is instituted

Long-term continuous
therapy

Clinical improvement maintained with the lowest

effective dose

Combination therapy

Ciclosporin can be combined with topical therapies, such

as corticosteroids, anthralin, or vitamin D3 analogues,
and other systemic treatments, such as methotrexate,
fumaric acid esters and mycophenolate mofetil
Other combinations used in clinical practice include
ciclosporin and biologics and ciclosporin and retinoinds (see
notes)

Rotational therapy

2.

1. Amor KT et al. J Am Acad Dermatol. 2010;63:92546

Colombo D et al. Int J Immunopathol Pharmacol. 2010;23:114352

Treatment with ciclosporin can be rotated with the

Managing nephrotoxicity
Increases in serum creatinine can be reversed by dose
reduction or withdrawal of treatment
Serum creatinine to 3050% above baseline value
(even if within normal range)

Serum creatinine to 50% above baseline

value
(even if within normal range)

Reduce dose by at least 25%

Reduce dose by at least 50%
Repeat measurement within 30 days
Repeat measurement within 30 days

Creatinine to <30% above baseline value

Creatinine remains 30% above baseline value

Continue ciclosporin treatment

Stop ciclosporin therapy

Pathirana D, et al. J Eur Acad Dermatol Venereol. 2009;23:570

Efficacy of continuous therapy

Continuous maintenance therapy with

ciclosporin is effective in the treatment of severe
psoriasis
PASI scores in patients with severe psoriasis receiving ciclosporin 2.5
mg/kg/day for up to 30 months (Part 1: dose-finding period, part 2:
maintenance phase)1
In patients treated for 6
30 months with
ciclosporin
(1.255 mg/kg/day),
withdrawal of treatment
did not lead to severe
deterioration of
the disease1

2.5 mg/kg/day

35

PASI score

30
25
20
15
10

n=39

n=50

n=5

5
0
0

36
Part 1

12
Part 2

30 (months)
Duration of
treatment

1.

In another study,
maintenance of clinical
response until month 10
was reported in 6877% of
patients with severe
plaque psoriasis treated
with a maintenance dose
Mrowietz U, et al. J Am Acad Dermatol. 1995;33:47075
2.
ofLaburte C, et al. Br J Dermatol. 1994;130:36675
2.5 mg/kg/day2

Ciclosporin and pediatric

psoriasis
In about one third of patients, psoriasis starts
In about one third of patients, psoriasis starts
in the first or second decade of life1
Efficacy and safety2,3
Reports indicate a favourable response with ciclosporin in childhood psoriasis. In carefully
selected and closely monitored patients (serum creatinine levels and blood pressure),
ciclosporin (2-4 mg/kg/day) can produce a relatively rapid clinical response
Long-term experience with ciclosporin in the pediatric population is derived from
transplantation, and risks for malignancy and lymphoproliferative disorders appear minimal in
children due to limited courses of therapy

In children or adolescents suffering from severe

psoriasis, the possibility of early onset physical comorbidities, psychological disturbances and
impairment in quality of life can create the need for
aggressive treatments4
1. Benoit S & Hamm H. Clin Dermatol. 2007:55562
2. Perrett CM, et al. J Dermatolog Treat. 2003;14:113-8
3. Pereira TM, et al. J Eur Acad Dermatol Venereol. 2006;20:6516
4. Sticherling M, et al. J Dtsch Dermatol Ges. 2011;9:81524

Ciclosporin and nail psoriasis

Nail psoriasis represents a treatment challenge for

dermatologists due to a slow response to treatment
In a retrospective study of 84 patients with
moderate to severe psoriasis and nail psoriasis,
systemics and biologic treatments improved
nail psoriasis1
The efficacy of ciclosporin was higher than that
of other systemic agents (acitretin, methotrexate,
PUVA, REPUVA, NUVB)1
In a randomised study in 37 patients, methotrexate
and ciclosporin were both moderately effective on
psoriatic nails2

Clinical practice and published papers indicate that ciclosporin is a

valuable treatment option for nail psoriasis
1. Snchez-Regaa M, et al. J Eur Acad Dermatol Venereol. 2011;25:57986
2. Gmel M, et al. J Eur Acad Dermatol Venereol. 2011;25:10804

Efalizumab Safety and

Tolerability1
Commonest side effects are mild
headache, chills, myalgia, and low-grade
fever
Haemolytic anaemia and
thrombocytopenia have been recorded
in some cases - it is recommended that
efalizumab is discontinued should those
conditions develop
Aseptic meningitis and inflammatory
polyradiculoneuropathy reported in
post-marketing surveillance

Rebound with
Efalizumab
Rebound is defined as:
Worsening of psoriasis over baseline
value (e.g. PASI >125%) or new
pustular, erythrodermic or more
inflammatory psoriasis occurring
within 2 months of stopping therapy.1

Efalizumab causes psoriasis

rebound in 5% of patients who
discontinue treatment2

Biologic Treatments: Etanercept

Etanercept Safety and

Tolerability
Injection-site reactions were the most common
adverse events (14% vs placebo 6%)1
Other common adverse events included:
infections, allergic reactions, formation of
antinuclear antibodies, pruritus and fever1

Serious adverse effects occurred with

frequency comparable
to placebo and included:
malignancies, asthma, infections, injection-site
reactions, pancytopenia and aplastic anaemia,
and interstitial lung disease.1

Etanercept has received a black box warning

for risk of reactivation of TB2
1. Etanercept SPC.
2. FDA. Safety Update on TNF- Antagonists: Infliximab and Etanercept. Available from:
www.fda.gov/OHRMS/DOCKETS/ac/01/briefing.

Infliximab Safety and

Tolerability

In clinical studies and post-marketing

surveillance, infusion-related reactions are the
most common adverse events
(20% vs 10% placebo)1
Safety precautions and warnings for infliximab
also include:
infections (some of which have been fatal),
hepatitis B reactivation, hepatobiliary events,
certain combination therapies, vaccinations,
autoimmune processes, neurological events,
malignancies and lymphoproliferative disorders,
heart failure, and surgery1

Antinuclear antibody formation seen in ~50%

infliximab-treated patients (~20% controls) lupus and lupus-like syndromes are uncommon 1
1. Infliximab SPC.
The
FDA
has Infliximab
issued
a black-box
warning for
2. FDA.SafetyUpdate
on TNF-
Antagonists:
and Etanercept.
Document 3779b2_01_cber_safety%20_revision2.

Biologic Treatments: Adalimumab

Structure
Fully human monoclonal
antibody

Target
TNF-

Presumed mechanism of
action
Attenuates inflammatory
action
of TNF- by interfering with
binding
to cell-surface receptors
Apoptosis of TNF--positive
macrophages and T cells

Human anti-TNF-

Adalimumab Safety and

Tolerability

Injection-site reactions were the most

commonly reported adverse event (14% vs 8%
placebo or active control) 1
May result in the formation of autoimmune
antibodies although new onset lupus-like
syndrome is rare (2/3441 patients in clinical
studies) 1
Common adverse reactions included:
infections, dizziness, headache, neurologic
sensation disorders, cough, nasopharyngeal pain,
diarrhoea, abdominal pain, stomatitis and mouth
ulceration, nausea, increased hepatic enzymes,
musculoskeletal pain, pyrexia and fatigue1

Special warnings and precautions:

A black box warning from the FDA for risk of
tuberculosis and other infections (some of which
have been fatal), hepatitis B reactivation, allergic